FA FAMILY NEWSLETTER · 2018-03-12 · Overview, Gene Discovery, and Stem continued on page 24 FA F...

Evaluations by the participantsrated this meeting as outstanding.Highlights included presentations on

#33 A Semi-annual Publication of the Fanconi Anemia Research Fund, Inc. Spring 2003

Oral Cancer in FA Patients.........2

Clone with Subtle Abnormality on Chromosome 3 Predicts MDS, AML in FA Patients.......3

Model Presented for Understanding Head & NeckSquamous Cell Carcinoma.....3

The FA Research Fund SolidTumor Initiative.........................4

Family News.................................11

Fundraising ..................................20

HIGHLIGHTS

Fanconi AnemiaScientific Symposium

The Wyndham Franklin PlazaHotel in Philadelphia was the site ofthe Fourteenth Annual Fanconi Ane-mia Scientific Symposium held fromDecember 2-5, 2002. One hundredfifty-eight researchers attended thismeeting to hear oral presentationsfrom 46 scientists regarding theresults of their research into Fanconianemia. In addition, 26 scientistsdetailed their research through posterpresentations. Countries representedby participants in the Symposiumwere Brazil, Canada, England,France, Germany, Israel, Italy, Japan,Mexico, The Netherlands, Spain,Turkey, and the United States.

Topics covered five areas:Overview, Gene Discovery, and Stem

continued on page 24

FA FAMILYNEWSLETTER

Annual Family Meeting: Mark Your CalendarThe Fanconi Anemia Research Fund has reserved Camp Sunshine from

August 8–12 for the Annual Family Meeting. Camp Sunshine, on SebagoLake in Casco, Maine, has an outstanding program for children and parentsalike. The FA Research Fund complements this program by inviting physi-cians and researchers who specialize in Fanconi anemia to discuss their treat-ment programs and/or research protocols. The Family Meeting is invaluableto parents who would like to talk with experts in a relaxed atmosphere, hearcomprehensive information about FA treatment, or just relax with other FAparents. A scholarship program is available for FA families who need assis-tance in traveling to Maine.

Camp Sunshine provides free lodging and meals. Suzanne Lauck, FamilySupport Coordinator, will send information in the late Spring regardingFamily Meeting registration. ◆

Cell Differentiation; Cancer andLeukemia; Functions of FA Proteinsin DNA Repair and Hematopoiesis;Novel Therapies; and Bone MarrowTransplantation.

Post-transplantComplications inFrance

Eliane Gluckman, Hôpital Saint-Louis, Paris, France, reported onpost-transplant complications in FApatients transplanted in France from1981 through 1996. She compared37 FA patients to 73 non-FA patientsin terms of incidence and severity ofgraft-versus-host disease (GVHD),and GVHD resistance to cortisonetherapy. In all categories, FA patientsdid worse than non-FA patients.

FA and Breast Cancer RiskAt the December Scientific Symposium, Arleen Auerbach of The Rocke-

feller University, New York, presented data on the risk of breast cancer in FApatients and carriers. Of 367 female patients in the International FanconiAnemia Registry (IFAR), only three have had breast cancer. These patientswere ages 29, 40 and 42 at the time of breast cancer diagnosis. Auerbachbelieves this represents a significantly increased risk of breast cancer in FApatients compared to an age-matched non-FA population; twenty times theexpected number of breast cancers was observed in FA females. However, ofthe 754 patients (males and females) in the recent analysis of the IFAR data,60 developed AML (2,314 times the number expected based on an age-matched normal population) and 19 had squamous cell carcinoma of thehead and neck (500 times the expected number). Thus, while the risk of allcancer is significant for FA patients, these patients are not especiallypredisposed to breast cancer relative to their extraordinary risk for AML andsquamous cell carcinoma, particularly of the head and neck.

Auerbach is also conducting an extensive study of FA carriers. The risk ofcancer in carriers is unknown at the present time. However, carriers of thethree most common FA genes (FANCA, FANCC and FANCG) do not appearto have an increased risk of breast cancer. ◆

2 FA Family Newsletter

MEDICAL NEWS


Singh Discusses Oral Cancer in FA PatientsBhuvanesh Singh, MD, Memorial

Sloan-Kettering Cancer Center, NewYork City, addressed our recentScientific Symposium, providingnew, potentially very helpful insightinto the cancers that affect FApatients. Singh noted that 39 FApatients have developed squamouscell carcinoma (SCC) among the 754in the International Fanconi AnemiaRegistry. Of these carcinomas, 47%are cancers of the head and neck.The cumulative incidence of SCC inFA patients is 19% by the age of 40.

FA patients develop SCC at anearlier age than the non-FA popula-tion. Surgery is the primary therapy,since FA patients do not tolerateradiation or chemotherapy well.

Singh noted significant differ-ences between FA patients with head& neck squamous cell carcinoma(HNSCC) and this same disorder inthe general population. Use oftobacco and alcohol is associatedwith more than 85% of the non-FA

head and neck cancers, but only 16%of these cancers in FA patients.Among 19 FA patients withHNSCC, 10 (or 53%) developed arecurrence of the tumor within tenmonths, and 63% developed two ormore cancers during their life span.Comparable rates are far lower in thegeneral population.

Singh was able to study 24 tumorsamples from FA patients with headand neck cancer. While mutations ofthe p53 gene are found in 36% ofnon-FA head and neck cancers,Singh’s group found no p53 muta-tions in the FA tumors. Of specialsignificance, 83% of the FA tumorswere positive for human papillomavirus (HPV), compared to 28% inthe non-FA population. These datasuggest that HPV may play a

Bhuvanesh Singh, MD

significant role in SCC developmentin FA patients.

Singh concluded that there is anurgent need to develop new ways oftreating and preventing this compli-cation in FA patients. ◆

Spring 2003 3

Model Presented for Understanding Head &Neck Squamous Cell Carcinoma

Ruud Brakenhoff, PhD, Depart-ment of Otolaryngology, VrijeUniversiteit (Free University) MedicalCenter, Amsterdam, proposed a novelmodel for understanding the develop-ment of head and neck squamous cellcarcinoma (HNSCC) in the generalpopulation. He noted that 10-30% ofnon-FA HNSCC patients developlocal recurrences in spite of tumor-free margins after surgery, suggestingthe presence of undetected cancercells or precancerous lesions related tothe tumor. Based on research toelucidate the basis of this clinicalproblem, researchers gained novelinsight into the process of HNSCCcarcinogenesis.

Brakenhoff described four biol-ogical states that characterize the

evolution of these tumors: 1) theswitch from a normal epithelial stemcell to a genetically altered stem cell;2) the switch from a single genetical-ly altered stem cell into a large pre-cancerous field of genetically alteredstem cells; 3) progression of a clonein the field into invasive carcinoma;and 4) development of metastaticcarcinoma.

A critical event that influencescancer risk is the development ofgenetically altered fields, whichdisplace the normal mucosa and canextend up to 10 cm in diameter.When a malignant tumor isremoved, the remaining pre-cancer-ous field can give rise to new tumors.

Understanding the critical molec-ular steps in this progression model

Ruud Brakenhoff, PhD

Heidemarie Neitzel, PhD

Clone with Subtle Abnormality on Chromosome3 Predicts MDS, AML in FA Patients

Heidemarie Neitzel, PhD, Insti-tute for Human Genetics, Charité,Berlin, reported that a particularchromosomal abnormality, defined asgains of the chromosomal segment3q26q29, represents an ominousfinding in FA patients.

Bone marrow from 54 FApatients was tested using threemethods: conventional cytogenetics,comparative genomic hybridization(CGH), and fluorescence in situhybridization (FISH). Twenty-eightpatients had no chromosomal abnor-mality, while 26 patients had clonalaberrations. Of these 26, 19 hadabnormalities on the long arm ofchromosome 3, indicating a signifi-cant overrepresentation of 3q aberra-tions in these FA patients. Neitzel’slaboratory observed a considerable

increase in this clone over time,suggesting that this abnormalityconfers a proliferative advantage tothese cells.

Neitzel compared the clinicalcourse of FA patients without thechromosome 3 abnormality andthose with this aberration. Patientswithout abnormalities of chromo-some 3q did significantly better.Only one of these patients developedMDS and one leukemia. In the 19patients with an abnormal 3q, how-ever, 13 developed MDS and 4leukemia. These data reveal that 3qabnormalities are strongly associatedwith a poor prognosis.

Neitzel concludes that detectionof 3q aberrations is imperative andcan be achieved by screening FAbone marrow and FA peripheral

blood with interphase FISH. Ideally,blood should be screened every 3months. Neitzel advises that patientswith this abnormality shouldstrongly consider bone marrowtransplantation before this cloneevolves further. ◆

could lead to early diagnosis andtreatment of these precursor lesions.Currently, non-invasive methods fordetecting these fields, as well asstrategies for treatment, are beingdeveloped. ◆


The FA Research Fund Solid Tumor Initiative:A Progress Report

The FA Research Fund has taken a number of actions in the last year toadvance research into the solid tumor malignancies for which FA patients areat extremely high risk in their late teens and adulthood. These tumors includesquamous cell carcinoma of the head and neck, esophagus, gastrointestinaltract, and gynecological system, all of which respond extremely poorly tostandard cancer treatment.

To address this issue, the Fund has done the following:

• Convened the first FA and Cancer Conference in Chicago in April, 2002.Twenty leading researchers and treating physicians were invited to attendthis conference to advise the Fund in addressing the issue of solid tumors.As a result of this meeting, a number of researchers are now investigatingFA.

• Funded a recent research project to study mouth cancer in FA patients.

• Published a newsletter entitled Fanconi Anemia: A Cancer-Prone Disease toacquaint solid tumor researchers with the Fund and with Fanconi anemia.

• Staffed the Fund’s display booth at the American Association of CancerResearch (AACR) conference, at the American Society of Clinical Oncolo-gy conference, and at the Sixth Research Workshop on Head and NeckCancer to interest researchers in studying FA-related cancer.

• Invited Steven Engroff, MD, University of Maryland, to speak with FAparents and adult FA patients about head and neck cancer at the Fund’sRegional Meeting in Columbia, MD, in June 2002. Similarly, Dr. Engroffspoke with FA parents at the FA Family Meeting, Camp Sunshine, Maine,in August, 2002. Blanche Alter, MD, MPH, National Cancer Institute,also presented information regarding FA and cancer epidemiology at bothmeetings.

• Invited cancer researchers to the FA Scientific Symposium held inPhiladelphia in December. This outreach resulted in a separate session onsolid tumors and the presence of a number of cancer researchers new toFanconi anemia research.

• Sent a letter to all major cancer institutes in the United States, Canada,and Europe regarding the high incidence of solid tumors plaguing FApatients to acquaint institute researchers with the need for research intothe disease and the ability of the Fund to sponsor that research.

• Developed the FA Courier to encourage FA patients to donate researchmaterials (including tumor samples) so that researchers studying FA solidtumors will have sufficient material for research projects.

• Organized a Standards for Clinical Care Conference for March, 2003,which will include development of a chapter on squamous cell carcinomaof the head and neck for the next edition of the Fanconi Anemia: Standardsfor Clinical Care handbook. ◆

FDA Halts CertainGene Therapy Trials

On January 14, 2003, the FDAhalted 27 gene therapy trials afterlearning that a second child withsevere combined immunity disease,treated in France, had developedleukemia. Three trials were previous-ly halted after the first child devel-oped this complication.

All 30 trials involve attempts toinsert a retroviral vector into a blood-producing stem cell. Only 15% of200 gene therapy trials in the USwere affected by this ruling. Trialsinvolving other gene-delivery vectorsand targets other than blood stemcells are not affected.

The possibility that a retroviralvector could lodge near a cancer-causing gene and turn it on, orwithin a tumor-suppressor gene andturn it off, has always been a theoret-ical concern. Until these two cases,however, the risk was consideredquite low. There have been 40 or 50similar trials in the US involving 100patients. Most had limited or no suc-cess, but none has caused a cancer-like complication. Gene therapistswonder if there is something aboutthis specific disease and this specifictrial that caused these two unfortu-nate outcomes.

Nine children have benefitedconsiderably from the French trial.Scientists must balance risks againstbenefits in deciding how next toproceed. ◆

Spring 2003 5

Researchers Explore Novel Therapies for FAAt our recent Scientific Symposium, researchers presented their work on novel therapies that have the potential to

correct FA bone marrow cells (or epithelial cells) without stem cell transplantation.

• Catherine Verfaillie, Universityof Minnesota, discussed herongoing work with multipotentadult progenitor cells (MAPC).These cells can be isolated fromthe bone marrow, grown in largequantities, and can differentiateinto a variety of different cellsand tissues. Because of thesetraits, they may be ideal cells fortreating both blood and epithelialcells of FA patients.

• Francesco Galimi, Laboratory ofGenetics, The Salk Institute, usesa lentiviral vector to transducestem cells. This vector has theadvantage of transducing non-dividing stem cells and canreduce the ex vivo (outside of thebody) gene transfer time fromdays to hours. Using this vector,Galimi is able to cure the bonemarrow of FA mice. Galimi isnow testing the capability oflentivectors to correct the Fan-coni gene defect in cells derivedfrom FA patient marrow andcord blood. Because of the diffi-culty in isolating a large numberof stem cells from FA patients,early results have been disap-pointing.

John Wagner, MD, asks questions of the presenters in the Novel Therapies section of theScientific Symposium.

• Christopher Walsh, Mount SinaiHospital, says the fact that only asmall number of CD34+ cells (atype of stem cell) can be isolatedfrom the marrows of FA patientshas hampered early gene therapyexperiments. A rare, alternatestem cell population called SP(side population) cells mightprovide a better target for genetherapy. FA patients with goodblood counts have an almostnormal number of these cells. Asblood counts decline, so does thepopulation of SP cells. Genetherapy experiments with FAmice, using SP cells and a lentivi-ral vector, have produced promis-ing results.

• Marcus Grompe, Oregon Healthand Science University, discussedthe drawbacks of current meth-ods of gene therapy that rely onviral vectors to carry genes intocells. One characteristic of FA is

the loss of stem cells; it is hard toisolate the necessary number ofthese cells and even harder totransduce them with a normalgene. A further complication isthe need to manipulate thesefragile cells ex vivo. Grompebelieves that gene transfermethods which could be applieddirectly in the patient (in vivo)might be preferable. He is cur-rently working on two separatemethods of gene transfer that donot use viruses and allow forinsertion of naked DNA into thegenome. One technique uses agene delivery system called“Sleeping Beauty transposon” andthe other a method called “inte-grase.” Early experiments in micehave produced very promisingresults: FA group C blood stemcells have been corrected directlyin vivo and without using a genetherapy virus. ◆


Transplant Results from GermanyWolfram Ebell, MD, of Humboldt University, Berlin, stated that there are

149 FA patients in the German registry. Since the 1980s, 84 German patientshave received stem cell transplants.

Ebell presented data on 20 patients recently transplanted in Germany. Forspecific details the reader can request the abstract of this presentation via theenclosed form. Ebell does not use irradiation, but rather a protocol consistingof fludarabine, busulfan (for most patients), and pre/post immunosuppres-sion. He does not T-cell deplete marrow or peripheral blood. Thirteen ofthese 20 patients, or approximately 60%, survive. Ebell noted several trends:

• Patients with aplastic anemia only did better than patients with myelodys-plasia (MDS). Patients with frank leukemia had the poorest survival rate.

• Younger patients (0-10) did better than older patients (11-20).

• Patients given bone marrow did better than those receiving peripheralblood stem cells.

• Patients without prior androgen usagedid better than those with priorandrogen usage.

• Abnormal clones alone (in the absenceof progression to MDS or AML) donot predict a poorer outcome.

• Patients with a subtle clonal abnor-mality on chromosome 3 do poorlywithout a transplant, suggesting thatthese patients might be good candi-dates for immediate stem cell trans-plants. (See article on page 3 entitled“Clone with Subtle Abnormality onChromosome 3 Predicts MDS, AMLin FA patients.”) ◆ Wolfram Ebell, MD

Arleen Auerbach, PhD and Farid Boulad, MD at the Fanconi Anemia Scientific Symposium.

Results of Transplantsat Memorial Sloan-Kettering

Farid Boulad, MD, MemorialSloan-Kettering Cancer Center, NewYork, reported on nine FAhematopoietic stem cell transplantsperformed at his center between May1998 and May 2002. Two patientshad aplastic anemia, six had myelo-dysplastic syndrome, and one acutemyelogenous leukemia at the time oftransplant. Seven patients were heavi-ly transfused, and seven had receivedtreatment with oxymetholone priorto transplantation. Four patientsunderwent related mismatcheddonor transplants with respectivematching at 4/6(7/10), 4/6(8/10),5/6(8/10) and 5/6(9/10) HLA-anti-gens. Five patients underwentunrelated donor transplants withrespective matching at 5/6(7/10),5/6(8/10), 5/6(8/10), 5/6(9/10) and6/6(10/10) HLA-antigens.

The preparatory regimen includ-ed single dose total body irradiation,fludarabine, and cyclophosphamide.Seven patients received peripheralblood stem cells, and two receivedbone marrow; all were T-cell depleted.

All 9 patients engrafted. With amedian follow-up of 18 months, 7 of9 are alive and 6 of 9 are alive dis-ease-free. Two patients with a signifi-cant history of infection died of pul-monary infection. One patientrelapsed with MDS 8 months posttransplant. This patient is presentlyin remission, 3 months following asecond transplant after receiving highdose busulfan and fludarabine.

All patients experienced rapidengraftment, early immune reconsti-tution, and no or minimal GVHD.Given the severity of disease prior totransplant and the degree of donormismatch, these results are extremelypromising. ◆

Spring 2003 7

Transplant Outcomesin Minnesota

John Wagner, MD, University ofMinnesota Medical School, Min-neapolis, reviewed recent transplantoutcomes at his center. Just threeyears ago, only 18% of FA patientssurvived unrelated donor transplants.Patients experienced high levels oftoxicity from the preparatory regi-men, graft rejection, graft-versus-hostdisease (GVHD), and opportunisticinfection. Today, many of these prob-lems have been overcome and out-comes have improved dramatically.The probability of survival in stan-dard risk patients is 100% for FApatients with an HLA identical donor(N=7), and 81% for FA patients witha matched unrelated donor (N=25).

However, patients with one ormore high risk features have a statisti-cally lower probability of survival.Factors associated with survival areyounger age (patients 18 or youngerdo better than older patients);absence of leukemic blasts; HLAmatched marrow or HLA 0-1antigen mismatched umbilical cordblood; and absence of systemicinfection. High risk patients have a33% probability of survival (N=11).

As a result of these findings,Wagner recommends that standardrisk patients should be considered fortransplant with the onset of marrowfailure and prior to administration oftherapies such as androgens andtransfusions. High risk patients,however, should delay transplant andconsider options such as androgentherapy. Other approaches are beingexplored for these patients.

Infection remains the primarycause of death. Wagner noted that18% of high risk patients developedan aspergillus fungal infection,compared to 5% of standard riskpatients. ◆

John Wagner, MD

L to R: Wolfram Ebell, MD, Farid Boulad, MD, Eliane Gluckman, MD, Richard Harris, MD, and John Wagner, MD, respond to audience questions during the

Bone Marrrow Transplantation session of the Scientific Symposium.

Cincinnati ModifiesProtocol for AlternateDonor Transplants

Richard Harris, Children’s Hospi-tal Medical School, Cincinnati, Ohio,described a new trial using T-celldepleted peripheral blood progenitorcells (PBPC) from unrelated orrelated mismatched donors, in aneffort to decrease graft-versus-hostdisease (GVHD). Harris reported oneight FA patients transplanted withthis protocol. The preparatoryregimen included total body irradia-tion, cyclophosphamide (Cytoxan),ATGAM, and fludarabine. Fourpatients had a major HLA-A or -Bmismatch donor, while four werecompletely matched. Six were heavilytransfused; three had been onandrogens.

Engraftment was rapid in allpatients. Five remained engrafted.However, three experienced majorengraftment problems. One patientrelapsed with myelodysplasia, wasre-transplanted, and died ofaspergillus fungal infection. A secondwas re-transplanted, again lost thegraft, and is transfusion dependent.A third received donor lymphocyteinfusions and is presently 100%engrafted.

Harris concludes that heavily T-cell depleted PBPC from alterna-tive donors results in a very low riskof GVHD in FA patients. Long-termengraftment is a major problem.Harris has modified this protocol toincrease the dose of cyclophos-phamide and fludarabine, in thehope of preventing graft failure. ◆


Fanconi Anemia Research Fund Honors ResearchersFive exceptional researchers were honored for their work on FA during the 14th Annual Scientific Symposium.

Dave Frohnmayer, vice-president of the Board of Directors of the FA Research Fund, made the awards on behalf ofthe Fund during the Presenters’ Dinner.

John Wagner, MD, University ofMinnesota, Minneapolis, receivedthe first Pioneer Award for Thera-peutic Advancement bestowed by theFund. The Board of Directorsacknowledged Wagner’s outstandingcontribution to the science relatingto stem cell transplantation of FApatients. Frohnmayer noted thatWagner’s pioneering work, includingthe use of fludarabine, has increaseddramatically the odds of FA patientssurviving a transplant, especiallyfrom an unrelated donor. Frohn-mayer also acknowledged Wagner’sexceptional leadership in pushing FAscience forward.

Arleen Auerbach, PhD, TheRockefeller University, New York,received the Lifetime AchievementAward. Frohnmayer acknowledgedthe exceptional contribution thatAuerbach has made to the field of FAresearch by establishing the premierFA diagnostic center in the world atThe Rockefeller University. Frohn-mayer also expressed the Board’s pro-found appreciation for Auerbach’stireless dedication to FA research andfor her compassion in helping count-less families understand the geneticsof the disorder.

Eliane Gluckman, MD, HôpitalSt. Louis, Paris, received the LifetimeAchievement Award. Frohnmayerhighlighted the exceptional contribu-tion that Gluckman has made to thefield of FA research and to the clini-cal care of FA patients. The Board ofDirectors noted her exceptional workas a pioneer in cord blood trans-plants, in FA bone marrow trans-plants, and in FA research in Europe.Frohnmayer cited Gluckman’s leader-ship and outreach to the FA medicaland scientific community regardingFA solid tumors as a catalyst for theFA and Cancer Conference hosted bythe Fund in early 2002.

Arleen Auerbach, PhDDave Frohnmayer and Eliane Gluckman, MD

Dave Frohnmayer and John Wagner, MD

We are what we repeatedly do.

Excellence, then, is not an act,

but a habit.

~Aristotle

elucidation of FANCD2. Because ofGrompe’s accomplishment, FA hasbeen vaulted out of the realm of anorphan disease into a much broaderand faster-paced scientific arena.Frohnmayer expressed profoundappreciation for Grompe’s dedicationand long-term commitment to FApatients and FA research, from estab-lishing the FA Cell Repository atOregon Health & Science Universityto continuing innovative research.

In presenting the Award of Meritto D’Andrea, Frohnmayer acknowl-edged the remarkable contributionthat D’Andrea has made to the fieldof FA research by unlocking thesecrets of the FA protein pathway,and through the discovery that theBRCA2 gene is identical toFANCD1. Frohnmayer expressed thegratitude of the FA Research Fundthat D’Andrea has consistently been

Spring 2003 9

Fanconi Anemia Research FundHonors Researcherscontinued from previous page

Alan D’Andrea, MD andMarkus Grompe, MD

To conclude the ceremonies,Frohnmayer bestowed the Award ofMerit, the highest award given by theFund, on two outstanding research-ers, Markus Grompe, MD, OregonHealth & Science University,Portland, and Alan D’Andrea, MD,Dana-Farber Cancer Institute,Boston. Only two other researchers,Manuel Buchwald, PhD, SickChildren’s Hospital, Toronto, andHans Joenje, PhD, Free University,Amsterdam, have received this honorsince the inception of the Fund in1989.

Frohnmayer acknowledged theexceptional contribution thatGrompe has made to the field of FAresearch through the discovery and

Standards for Clinical Care Consensus ConferenceThe FA Research Fund is spon-

soring a Standards for Clinical CareConsensus Conference at the O’HareHilton Hotel in Chicago fromMarch 6 - 8, 2003. The purpose ofthe workshop is to develop an updat-ed consensus regarding clinical carefor FA patients.

Eva Guinan, MD, Dana-FarberCancer Institute, who moderated thefirst Consensus Conference in 1998,will moderate this conference as well.The physicians in attendance willdevelop consensus regarding optimalstandards of care for FA patients intheir areas of expertise. The FAResearch Fund will publish theresults in an updated edition of the1999 Standards for Clinical Carehandbook.

The 1999 edition will be expand-ed by the inclusion of chapters

entitled Hand and Arm Anomalies(chaired by Scott Kozin, MD,Shriners’ Hospital, Philadelphia);Diagnosis and Treatment of Gas-trointestinal Abnormalities (chairedby Sarah Jane Schwarzenberg, MD,University of Minnesota); Diagnosisand Treatment of GynecologicalAbnormalities (chaired by PamelaStratton, MD, National Institutes ofHealth); Experimental Therapies(chaired by Bruce Blazar, MD, Uni-versity of Minnesota); and SquamousCell Carcinoma of the Head andNeck (chaired by Bhuvanesh Singh,MD, Memorial Sloan-KetteringCancer Center).

The 1999 chapters that will beupdated and the chairs of those ses-sions include Diagnostic Work-Up(Blanche Alter, MD, MPH, NationalCancer Institute); Treatment of

Hematologic Abnormalities (AkikoShimamura, MD, Dana-Farber Can-cer Institute); Diagnosis and Treat-ment of Growth Failure andEndocrinopathies (Michael P. Wajn-rajch, MD, Cornell Medical Center);Matched Sibling Donor Hematopoi-etic Cell Transplantation (RichardHarris, MD, Cincinnati Children’sHospital); and Alternate DonorHematopoietic Cell Transplantation(John Wagner, MD, University ofMinnesota). ◆

a leader in FA research, setting thepace, taking risks, and pushing thisscience forward. ◆


Risks of RadiationTherapy in FA Cancer Patients

Blanche Alter’s article on“Radiosensitivity in Fanconi’s anemiapatients” was published in Radiologyand Oncology (62:345-347, 2002).Alter describes literature reports of 14FA patients with squamous cell carci-noma who were given radiationtherapy. Three of these patients hadreceived a bone marrow transplant;eleven had not. Possible toxicity wasreported in six of these 14 patients:1/1 with vaginal cancer, 4/10 withhead and neck or esophageal cancer,and 1/3 with oral cancer followingbone marrow transplant.

Most of the patients whosecancers were treated with radiationtherapy died shortly thereafter (at 3months for the patient with vaginalcancer, 3-12 months for eight of theuntransplanted ten patients withhead and neck or esophageal cancer,and 3-6 months for all three of thepost-BMT oral cancer patients). Theonly survivors were two untrans-planted patients with oral cancer whowere alive at 3 and 10 monthsfollowing radiation therapy.

Alter notes “although radiationtherapy may be blamed for the out-comes, the poor survival may be areflection of the advanced stage ofthe tumors for which definitivesurgery was inadequate and radiationwas required.”

Alter concludes that it wouldappear prudent to use surgical inter-ventions as much as possible. Herarticle stressed the importance ofusing careful surveillance in an effortto detect precancerous lesions. ◆

Blanche Alter, MD, MPH

Mutations of FANCA Found in Non-FA Patientswith Aplastic Anemia or Myelodysplasia

Johnson Liu, Mount Sinai Hospi-tal, New York, reported that severalnon-FA patients suffering from aplas-tic anemia (AA) or myelodysplasia(MDS) had mutations in FANCA.His laboratory studied 80 non-FApatients with AA or MDS. Three ofthese patients had a disease mutationin FANCA. These are either inherited

or acquired mutations. Thesefindings suggest that FA carriersmight be at risk for the developmentof AA or MDS, following a secondgenetic “hit” or an environmentaltoxic exposure. ◆

Eighty-seven percent of the FApatients had acute GVHD, and mostof these patients went on to developchronic GVHD. Sixty-two percentdeveloped Grade II-IV GVHD.

Although FA and non-FA patientshad a similar 10-year outcome, FApatients resistant to cortisone therapyexperienced an additional cluster oflethal events beginning at 5 yearspost-transplant. This late mortality,restricted to FA patients, was closelyrelated to head and neck carcinomas.These cancers did not appear in thefirst five years post-transplant, butthe cumulative incidence of cancerwas 20% in transplanted FA patientsafter ten years, and 53% after 15years. Gluckman concludes that theimpact of acute GVHD on survivalis not limited to the early post-trans-plant period and is a major risk factorfor head and neck cancer. Preventionof GVHD is crucial. (Eds. Note:Recent transplant protocols havegreatly reduced the incidence ofGVHD in FA transplants.) ◆

Post-transplant Complications inFrancecontinued from page 2

Editors’ Note andDisclaimer

Statements and opinionsexpressed in this newsletter arethose of the authors and notnecessarily those of the editorsor the Fanconi AnemiaResearch Fund. Informationprovided in this newsletterabout medications, treatmentsor products should not be con-strued as medical instruction orscientific endorsement. Alwaysconsult your physician beforetaking any action based on thisinformation.

Spring 2003 11

FAMILY NEWS

It has been three years since myunrelated bone marrow transplant,and I am very proud to say that mylife has never been so normal. WhileI have struggled with what some havecalled chronic graft-versus-hostdisease, my platelets, hemoglobin,and white count have been perfectlynormal since I came home to Orlan-do, Florida from Minneapolis inFebruary of 2000. Problems that Ihave faced since transplant haveincluded chronic lung and sinusinfections as well as problems gainingand maintaining weight. Althoughthese problems are serious since myimmune system is still gettingstronger, the majority of the prob-lems have been treated with normalmedical practices without the needfor immune suppressants and/or

steroids. The chronic infections havenot been a problem since November2002, when I received my first flushot since my transplant. Since thenI have been perfectly healthy, and Ihaven’t even experienced normal coldsymptoms.

I am currently a junior at theUniversity of Central Florida pursuinga double degree in Legal Studies andInternational Political Science. I enjoystaying active in my university com-munity: I am currently the vice-presi-dent of the United Nations Associa-tion of UCF, the Treasurer for PhiAlpha Delta Law Fraternity Interna-tional, and a founding father of SigmaNu Fraternity International. I havebeen working for Sears Heating andCooling for the past two years, and Iam looking forward to establishing an

Chris Byrd: Life After Transplantinternship with a local law firm thissummer. I enjoy scuba diving and thebeach, although I have to wear T-shirts and a ton of sunscreen to pro-tect my sensitive skin from the sundue to full body radiation.

My advice to anyone consideringan unrelated bone marrow transplantis to keep a positive attitude and tolook forward to all of the new andexciting opportunities that wait in alife free from the blood-relatedaspects of Fanconi anemia. I wouldlike to encourage anyone who hasany questions or would like to knowabout my life and experiences to con-tact me, preferably by e-mail [email protected]. As you can see, Iam usually very busy but I will domy best to respond as soon as possi-ble. Stay positive and God bless. ◆

“Where There’s a WILL, There’s a Way”by Kayla Lackey, Charlotte, NC, www.willpowerfund.org

William Tyler Lackey—“Will” toall who know him—is a 4-year-oldlittle boy who was diagnosed with FAon September 25, 2002. Like every-one else, we have a story, a story thatspeaks of fear, anger, hope and love.

Our story begins with the weekprior to September 25th when Willwas seen by a pediatric hematologistto whom we were referred after wediscovered that Will’s platelets were alittle low at 115,000. That was thefirst time I’d ever heard of Fanconianemia. I was forewarned to preparemyself for the test results to comeback positive and was told that Will“fit the profile.” Results were due toWill Lackey

be back in two weeks. The next week was spent learning.

I read everything I could find onFanconi anemia. I surfed the webuntil the wee hours of the morning. I was determined to “be ready.” I e-mailed Suzanne at the FARF andasked for access to the e-group, arequest that was denied at the time,because we were not yet diagnosed.We exchanged e-mail several timesduring that week, and she was won-derful at guiding me in the rightdirection, even though I was still anoutsider—an outsider who hoped shewould never be accepted.



Fighting FAby Erik Kjos-Hanssen, [email protected]

”We think Johan (then age 11)has leukemia. He should go to ahospital in another city in Norwaynext week.” So said the voice in atelephone call I received at work on aFriday in 1995. That call became thelocal 9/11 in our family and was thestart of a long journey. Some dayslater, the diagnosis was rescinded, butthe doctor did not know what causedJohan’s low haemoglobin level of 10.Johan was later given the diagnosis ofaplastic anemia.

FA is really a dramatic disease. Forparents getting the diagnosis for theirnewborn baby, there is no time torest. It becomes an uphill fight fromday one. How these parents work fortheir children! Anyone who hasn’texperienced it will never know. Oursituation was different. The first 6-7years of Johan’s childhood were love-ly, and my wife Turid, our daughterRagnhild, Johan, and I had a veryfine time together. Then our sonbecame more and more “lazy” whenwe were exercising together. As goodparents, we fought much with Johanover that topic. Had we only knownabout his low haemoglobin (hgb)level we could have avoided lots oftears and bad parental feelings later!

The next years became a reallyhard time. Johan’s hgb fell to 6.0 in2000, and he required bi-weeklyblood transfusions. My task was totell my teenager every quarter thatthe hgb had dropped slightly, andthen the question came: “What willhappen if this continues?” Myresponse that the best doctors inNorway were involved was counteredby “This is what scares me. I wouldbe calmer if it were the doctor on thecorner who is treating me.”

Our “problem” was that no blood

sample was tested for FA. In all theseyears we had to see doctors, motivateJohan, discuss with the frustratedteacher who claimed that Johan wasdifficult and unmotivated at school(although his situation was known),calm the grandparents, and workwith our own feelings. An over-whelming agenda. Personally, I felt itvery difficult to combine intensebusiness work with phone calls todoctors discussing vital issues for myson. In hindsight, I see that our fami-ly had a really hard time in all theseyears. But apparently, this became a“project” for my wife and myself, andit brought us closer together. On theother hand, it did also put tensioninto our relationship because thematuring of our own feelings was notaligned. Being a manager, I had to beopen at work about my situation,while Turid working at home neededmore time to work with her feelings.I also learned that we as parentsneeded to absorb the bad news our-selves some days before we couldcommunicate it to Johan and others.

In our situation we struggled withmuch uncertainty because we didn’tknow the enemy: what was the

disease? We discussed for hourswhether it was the food, the house,the air, the previous medicine,the…?? We arrived, of course, at thesame conclusion every time—nobody had a clue.

After “waiting” for five years,things started to happen in 2000. AtEaster, a blood sample was sent toLondon to test for FA. Positive!Again, I got the message by phone ona Friday. I searched the Internetimmediately and found the FA hand-book and much other information atwww.fanconi.org. During the week-end I read all the information andbecame really scared. The doctordidn’t know much about FA andcouldn’t tell us much. As we finallyfound the diagnosis, we hoped for atreatment, but the hope was turnedinto horror. It was hard to tell a 16-year-old boy about FA. And howmuch and when should you tell?After a couple of months, the haema-tologist told us that no treatment wasavailable and Johan had to rely onblood transfusions in the future.

Every family experiencing FA goesthrough lots of dramas and

Johan skiing in Norway, Easter 2002


Spring 2003 13

dilemmas. Johan’s objective duringhis teenage years was to “be just anormal kid.” Nobody should knowthat he had FA. As parents, however,we had to decide who needed toknow about Johan’s situation andwhat should be told when.

The turning point came in thesummer 2000. I had a cold, had tostay in-house, and surfed the Internetagain. Then I read about the upcom-ing Family Meeting at Lake Geneva.Immediately I decided to join,although I found it crazy to travelfrom Norway to Wisconsin for theweekend. I overcame those obstruc-tions and travelled. I had no expecta-tions, but I felt that the camp was thelast effort to be tried. How the hopesfor the future changed during mystay! When I came there, I met otherparents of FA children for the firsttime. I learned a lot about the diseaseand oxymetholone (Oxy) treatment.It was really an emotional chaos. Imet so many nice parents, kids, doc-tors and FARF staff. We are not usedto praying for each other in Norway,but it was good to know that manypeople were praying for our family inthe US!

Things happened fast when Icame back to Norway. Johan was puton Oxy in October. It worked verywell, and he had his last blood trans-fusion in November 2000. Johan hastoday a normal hgb level and is by allmeans very active. His motivationand interest for schoolwork haveimproved significantly. Last Christ-mas, Johan and I had a real speedskating contest over a quarter mile ata lake. I was beaten, but both thewinner and the loser were ecstatic!

To sum up, every FA family couldwrite books describing their hopes,sorrow and anger. Living this “roller

Fighting FAcontinued from previous page

coaster life” is much more intensethan any “normal” family could everunderstand. It is good therapy forparents to learn more about FA. Theworldwide network of skilled peopleis vital whenever you need it, espe-cially for those of us living in small

Mark Your Calendars: Regional Meeting in Minneapolis

The Fanconi Anemia Research Fund is sponsoring a regional meeting inMinneapolis, Minnesota on Saturday, May 17, 2003. John Wagner, MD, andMargaret MacMillan, MD, from the Blood and Marrow Transplant Programat the University of Minnesota Medical School, have arranged an outstandingprogram for FA parents and FA adults.

The preliminary program will address the basic understanding of Fanconianemia, as well as novel treatment strategies. The speakers and their topicswill include:Margaret MacMillan, MD: Blood and Marrow Transplantation for FA

Betsy A. Hirsch, PhD: Interpreting the Cytogenetic Report

Phuong Nguyen, MD: Marrow Aspirate Findings in FA

Frank Ondrey, MD: Head and Neck Cancer in FA

Sarah Jane Schwarzenberg, MD: Feeding Intolerance and AbdominalProblems in FA

Anna Petryk, MD: Diabetes and Hormonal Problems in FA

John Wagner, MD: Preimplantation Genetic Diagnosis to Prevent Diseaseand Select for HLA

Catherine Verfaillie, MD: Future Applications of Adult Stem Cell and GeneTherapyIn addition to these presentations, the day will include a reception at the

Science Museum of Minnesota, workshops with cytogenetics and hematol-ogy, tours of the local housing facilities used by families during treatment,and tours of the Fairview University Medical Center Bone Marrow Trans-plant Unit and Bone Marrow Transplant Clinic. Depending on the numberof parents who will be able to arrive early on Friday, May 16, 2003, Dr. Wag-ner has offered to arrange a possible excursion to the National Marrow DonorProgram.

Regardless of whether you live in this particular geographic region, wehope you will join us at this meeting. It is open to all FA parents and adultFA patients. The FA Research Fund has a scholarship program to which youcan apply if you need financial assistance to attend. If you are interested inattending or have questions about the meeting, please contact the Fund officeby April 16 at [email protected], by fax at 1-541-687-0548 or by phone at 1-800-828-4891. ◆

countries with only a handful of FApatients. The FA camp is “a must”for all parents to establish the net-work and get updated on FAresearch.

Enjoy the good moments, gainenergy, and fight FA! ◆


peritoneal dialysis. Six long weekslater, with his lungs having furtherdeteriorated, Alex was removed fromventilator support. He quietly passedaway on December 13, just 9 daysshort of his 15th birthday. What Iknow is that the doctors and nursesat FUMC all fought hard for Alex, asdid we, but in the end we were doingmore to him than for him, and so weset him free.

We are so grateful to Alex for thetime he blessed our life and thethings he taught us. He’s the onewho showed us that this disease didnot define who he was. Heapproached it with a Zen-like atti-tude: never giving in to it, yet neverfighting it. He taught us how to bepresent in the moment, somethinghe practiced daily. During transplanthe even mentioned that he neverworried about what tomorrow wouldbe like, that he couldn’t do anythingabout it anyway, so he might as welljust stay focused on today. Alex washappy and good-natured and laughedeasily, especially when watchinginane movies (Dumb and Dumber, InSearch of the Holy Grail). He wasloyal and loving with a strong sense

In Memory of Alex Eddyby Sharon Swanson

Woo Hoo!! That was the send-offwe gave Alex on the day he departedthis world. It was one of Alex’sfavorite expressions (being thediehard Simpson’s fan that he was).Saying goodbye to Alex was hard, yetjoyous. He is now free of a body thatlimited him, free of invasive tubes,free of pain. He can now be more“real” than any of us can imagine andcan only hope for.

Alex was a unique child from theday he was born, December 22,1987. The 22nd, the day after theWinter Solstice, is the day lightbegins returning to the earth. So, Icalled him my “Child of the Light,”and it was true: he always carried alight within. Adults in particularwere drawn to Alex and his inner“light.” Alex was quiet and gentle innature, caring and affectionate.Everything Alex undertook, he didwith a passion. Whether he was thebest or even good at what he did wasnot as important as experiencing the“activity” to the fullest. He lovedmany things: baseball, fishing,nature, playing card games (Pokemonand Magic the Gathering), collectinganything and everything, playing thetenor sax, and doing anything thatallowed him to be part of a group,whether it was being on a team, cubscouts, or attending a family gather-ing. Alex was a disciplined studentwho excelled in school, but hatedbusywork. He had dreams of one dayattending a college like Harvard.

Alex was not diagnosed with FAuntil he was 6 years old. He hadalways been extremely thin as a child,had some café-au-lait spots, andslightly “different-looking” thumbs,but no other physical anomalies. Ablood test taken when he had the fluled to his diagnosis. From that day

forward our world came crashingdown around us, but over time welearned to live with the disease. Infact, while Alex was on oxymeth-olone, our life was almost “normal.”The disease was more of a nuisance,with only hints of its life-threateningqualities lurking in the background.

In October 2001, we traveled toFairview University Medical Center(FUMC) in Minneapolis, met withDr. MacMillan, and had Alex’s annu-al bone marrow biopsy. The biopsyshowed there were very few cells leftin Alex’s bone marrow and that, as aresult, oxymetholone would not beeffective much longer. Dr. MacMil-lan recommended that we proceed totransplant, given the success rate ofthe latest protocol and since amatched unrelated donor had alreadybeen identified. After much researchand soul searching, we determinedthat the transplant was Alex’s bestchance for securing a longer life. Wescheduled his bone marrow trans-plant for June 2002, allowing Alex tofinish the 8th grade, get his braces offand, most important to him, finishhis last season of baseball.

We drove from Shreveport,Louisiana and arrived in Minneapolison June 8; the transplant date wasJune 25. While it was tough, Alexdid quite well through transplant andwas discharged on day +25. But that’swhen Alex’s luck ran out. Alex wasadmitted to the hospital 7 moretimes in the following months forrepeated fevers, Grade 2 graft-versus-host disease, changes to his medica-tions and, finally, for adenovirus.During our last admission, Alex suf-fered seizures, followed by a loss ofability to oxygenate, which requiredhim to be put on a ventilator. He alsodeveloped kidney failure, requiring

Alex Eddy


Spring 2003 15

Jeremy Brand5/30/95 - 10/16/02

Alex Eddy12/22/87 - 12/13/02

Jordan Farris1/16/85 - 9/20/02

Carlotta Frontani7/8/92 - 11/4/02

Henry Strongin Goldberg10/25/95 - 12/11/02

Clifton Langhorne9/13/75- 1/13/02

Jason Masters5/5/95 - 1/18/03

Haley Race7/20/00 - 11/13/02

Erica Seiford9/4/85 - 1/5/03

Heavenly Sheldon4/22/99 – 8/30/02

Tian Sheldon7/28/95 - 11/26/02

Guillermina Villegas7/26/00 - 11/8/02

In LovingMemory

Lessons in Life

adapted by Joanne Cacciatore for bereaved parents

I’ve learned people don’t care how much you know until they knowthat you care.

I’ve learned to avoid judging others so I think what I say, not say whatI think.

I’ve learned that it’s taking me a long time to become the person I wantto be.

I’ve learned that a child who has lived just moments can be yourgreatest teacher.

I’ve learned that you can keep going long after you think you can’t.

I’ve learned that we are responsible for what we do, no matter how wefeel.

I’ve learned that heroes are people who do what needs to be done,regardless of their personal circumstances.

I’ve learned that learning to forgive takes a lot of practice.

I’ve learned that friends can become strangers, and strangers canbecome friends.

I’ve learned that ignorance isn’t an excuse for the lack of compassion.

I’ve learned that ignorance begets ignorance.

I’ve learned that some people will never, ever ‘get it.’

I’ve learned some people love you dearly, but just don’t know how toshow it.

I’ve learned that true love continues to grow, even over the longestdistance.

I’ve learned that the community of sorrow is the strongest of all.

I’ve learned that it isn’t always enough to be forgiven by others.Sometimes you have to learn to forgive yourself.

I’ve learned that no matter how bad your heart is broken, the worlddoesn’t stop for your grief.

I’ve learned that your life can be changed in a matter of minutes.

I’ve learned that writing, as well as talking, can ease emotional pains.

I’ve learned to trust myself.

I’ve learned that the people you care most about in life are taken fromyou too soon.

I’ve learned that you should always leave loved ones with lovingwords. It may be the last time you see them.

I’ve learned that love isn’t measured by the amount of time you havewith someone.

I’ve learned that some sorrow is so deep that it has no words. But so islove.

What has your child taught you?


On October 25, 1995, Henrymade me a mom and a better person.Before he could even smile or talk,Henry taught me what was impor-tant and what just didn’t matter atall; and he taught me to savor eachmoment, to love, to laugh and todwell in possibility.

And together as a family we havedone just that, packing more smileand laugh-producing times togetherin seven years than many do in a life-time. We have lived and loved asthough we could one day lose Henry,while simultaneously pushing loveand science to their limit to ensurethat we would have him in our livesforever. Henry has driven a tractor,fallen in love, danced with 10women at one time, and laugheduntil he fell over. Just two days ago,Henry finally got the biggest, baddestSwiss Army knife, which he heldonto ’til the very end. We have livedevery day with Henry to its fullest.We have had ice cream for dinner;transitioned from the hospital to run-ning a lemonade stand in a matter ofminutes; gone to Cactus Cantinaseven nights a week; and acquiredevery single Pokemon figure made. Atlast count we had 188. He met Presi-dent Clinton, Cal Ripken, Batman,the entire Minnesota Twins, andmore significantly, they got to meethim. We did all those things becauseat that moment in time we could andbecause, though we always hopedthings would get better, we knewenough to go when the going wasgood. Just in case.

As I’m sure all of you know,Henry just made everything better.He was wise well beyond his years,and he was so much fun. It’s almostas if all the good things in life werecreated with Henry in mind. No one

had greater appreciation for Disney-world, Funland, Sullivans or any ofthe other fun things in life thanHenry. He was a great lover of musicand could sing “Brick House” anddance with the best of them. I willcherish my memories of Allen andHenry dancing together in ourhome.

It is such a privilege to be Henry’smother, and I am thankful every daythat Allen and I found one anotherand created such a wonderful, love-filled family.

It’s no surprise that Henry hashad an ongoing fascination withsuperheroes. He put on a Batmancostume for Halloween when he wastwo and didn’t take it off until we leftfor Minnesota two and one-half yearslater. Henry didn’t need it anymoresince he had received sufficient train-ing and, at that point, he hadachieved superhero status in his ownright. As my brother Andrew said,“Batman should wear a Henry shirt.”

My dad used to tell me that a daywithout me was a day without sun-shine. Now I know what he was talk-ing about. Sweetie, you are every-thing enjoyable in life. You are alemonade stand on a hot summerday. You are the first piece in a box ofGodiva chocolate; kite flying on thebeach; the final encore at a Spring-steen show; s’mores at a campfire; apiñata at a birthday party; fireworkson the Fourth of July; a ride on aFerris wheel; the glow of candlelightduring a thunder storm; finding asand dollar on the beach; pennycandy; class outside; the last ski runof the day; meeting your child for thefirst time. The loss of you drenchesmy heart in sorrow.

One nightfall, the evening beforewe left for Henry’s transplant, Henry

With Love, From MomThis eulogy was delivered by Laurie Strongin Goldberg for her son, Henry

and Jack were taken by the magic offireflies and started to run aroundour yard, catching one after another.Each catch was a victory and was metwith curiosity and excitement. Someof those bugs sacrificed their lives atthe clumsy, but curious, hands ofthese three- and four-year-old boys.

I watched and let myself feel whatit’s like to be a kid, filled with curios-ity and wonder about the world. Atsome point I noticed that Henry haddisappeared, so I went inside to seewhat had become of him. I wentupstairs and slowly opened his bed-room door and heard a whispertelling me to come in quick and toshut the door. I found Henry lyingon his back watching the fireflies,which he had brought upstairs one-by-one and set free, light up hisroom.

I’m not sure how Cactus Cantinaor Max’s Ice Cream will survive with-out you, and I sure wish that Daddy,Jack, Joe and I didn’t have to. I missyou so, so much already, honey. Ourjob now is to ensure that everythingis better because of you. So, like you,we will draw our swords, but don’texpect the same resiliency. You set thebar high. Give us a while, and we willmake you proud, my son.

So today we say farewell to yourbody, and every day from now on wewill cherish your soul and spirit, forthey live within us now. Goodbye,Henry. ◆

Henry Strongin Goldberg

Spring 2003 17

by Kari Doctor

My identical twin sister, Alissa,and I were diagnosed with Fanconianemia 26 years ago at the age of 3months. After a brief explanation,my parents were told that if we devel-oped the anemia, the only possibilityof a “cure” was a very experimentalbone marrow transplant and that wewould probably not live past the ageof 10.

Alissa was born without thumbsand a shorter left arm, which is miss-ing the radius bone. She had surg-eries to rotate, shorten and move herindex fingers into position asthumbs. Alissa has incredible dexteri-ty and loves to crochet, make jewelry,and quilt. She also had several surg-eries to straighten her left arm andstabilize her wrist. The Shriners’ doc-tors investigated lengthening herarm, but found that it would not befeasible. I, Kari, had surgery at theage of 15 months to correct a renalproblem. As a result of scar tissueblockage in the ureter tube, I lostthat kidney.

We underwent blood countsevery 3-6 months as we were growingup, which were always within thenormal range. When we were 13, thedoctor called and told our motherthat she no longer needed to bring usin because everything looked like itwas going to be fine. That was a wel-come message, but not a surprise.When we were three years old, Godgave our mother the assurance andpeace that we were going to be okay.We were not aware of the seriousnessof our diagnosis until we wereteenagers.

Growing up was much more of achallenge for Alissa because kidsteased her because of her birth

Identical Twins GrowUp with FA

of right and wrong, particularly whenit came to how you treat others. Heoften became indignant at bothfriends and adults for their behavior.He never tried to be popular, almostshunning that, wanting to be stub-bornly true to who he was.

I have no regrets about our choiceto go to transplant or the care wereceived at FUMC. People facing asimilar decision should feel confidentthat they would be in the best ofhands. During my stay, I saw manyFA children (and even one adult) gothrough transplant and return home.I maintained a web page as we wentthrough this experience, which wasextremely therapeutic. More impor-tant, it opened us to an extendedcommunity of family and friends,both old and new (which includedmany of you) who joined us andsupported us on this journey. Thiscommunity transformed this verydifficult experience into one of beau-ty and love; into one of many gifts,not just of loss; into a future of hope,rather than despair. For that, Ihumbly thank you. ◆

Alex Eddycontinued from page 14

defects. But I feel God has blessedour lives and used our situations todevelop our character for His pur-poses. Alissa has an incredible empa-thy and love for children. She hasworked with children for 9 yearsnow, volunteered at a handicappedmission in Mexico for 3 months, andearned her degree in early childhoodeducation. I have my own business asa graphic artist.

Neither of us has ever developedany blood-related problems associat-ed with Fanconi anemia. However,my husband and I sought geneticcounseling last year before trying tostart a family and have since gonethrough testing of skin (fibroblast)samples that has confirmed the diag-nosis and, also, blood samples thatshow that our blood has been“cured.” Those tests were performedon Alissa with the same results. Wefeel God has given us a promise inJeremiah 29:11, “‘For I know theplans I have for you,’ declares theLord, ‘plans for welfare and not forcalamity to give you a future and ahope.’” ◆

Kari Doctor and her twin sister Alissa Burk


Elma Dueck (second row on right), her siblings, and her parents

Elma Dueck’s Journey with Fanconi Anemiaby Kenneth Dueck, her husband

On December 23, 1970, Elmawas born in a remote region in Mexi-co, hours from the nearest pavedroads. After migrating to the USA(Oklahoma) in 1979, she worked onher family’s dairy farm, milking, andgardening.

Soon after we married in 1991,one of her sisters had complicationsduring pregnancy (Elma had 6 sistersand 4 brothers). After CBCs on othersiblings, it was discovered that severalothers had low blood counts or oddplatelets. Elma was one of them.

In 1992 Elma and I pursued theissue some and had a bone marrowbiopsy. While results were not nor-mal, doctors didn’t pinpoint theproblem as Fanconi anemia.

Our oldest daughter was born byC-section in 1993. In 1996 our sonwas born naturally. In 1998, whilepregnant with our third child, Elma’sblood counts dropped lower, and shehad to have a blood transfusion.After a natural delivery, her countsdid fine again. About a year later, inOctober 1999, she discovered thather blood counts had dropped signif-icantly. After that, she had to have 3units of blood approximately every 5weeks. Elma’s blood work was sent toThe Rockefeller University in NewYork in January 2000. The resultcame back positive for FA.

A bone marrow transplant wasrecommended, but we weren’t at allready for it, as Elma’s double cousin’schild had a bone marrow transplantfor FA in Canada and did not sur-vive. Eventually it seemed that heronly choice was a bone marrowtransplant, as oxymetholone didn’tdo much for her.

We chose Minneapolis as thetransplant center. They seemed to

that could happen, but nobody gotthem all (Elma got a good bit ofthem though!). On January 24, Elmawent into the hospital where shereceived four days of chemotherapyand one of radiation. The transplantwas on January 31, 2002. On Febru-ary 10, the white blood cells startedto come in. By the 20th, she wasreleased from the hospital.

Except for a seizure soon aftertransplant, things went pretty muchas expected with mouth sores, noteating and hair loss. On day +21 thebone marrow biopsy showed 100%donor, which has remained that way.Then the GVHD (graft-versus-hostdisease) set in! Itchy rash from headto foot (she was reminded of Job inthe Bible), plus diarrhea and nausea,which responded well to steroids.

have the most experience with adultFA bone marrow transplants. Bonemarrow transplant was urged as soonas possible, but they needed 1/5 of amillion dollars up front. That seemedan impossible amount.

But God had a way. Our churchpitched in tremendously and, in acouple of months time, we had suffi-cient funds to go ahead. God alsoprovided a 6/6 match in one ofElma’s sisters who doesn’t have FA.Three of her sisters and one brother(two of whom are now deceased) alsowere diagnosed with FA.

On January 4, 2002 we arrived inMinneapolis for the work-up andtransplant. Our 3 children and mysister were with us. The childrencame to visit their mom practicallyevery day in the hospital. The doctorrecited a long list of complications continued on page 19

Spring 2003 19

But, the itch didn’t, so she had tohave a course of ATG. It took 3courses of ATG to subdue theGVHD. In the meantime, CMV(cytomegalovirus) flared up.

In early May Elma was hospital-ized to treat the CMV. So, on Day+100 she was in the hospital insteadof on the way home. While in thehospital, we discovered that she hadaspergillus fungus in her lung, forwhich she is still taking medicine.Then her mouth and esophagus gotso sore, she could hardly swallowwater. Finally, after about ten andone-half weeks in the hospital, Elmawas released. Things seemed to be onthe mend.

Soon we noticed that she was get-ting weaker, and the therapist set towork. However, Elma was then diag-nosed with Guillain-Barré syndrome.When dealing with Guillain-Barrésyndrome, more than therapy is

Fundraising Assistance Did you know that 85 percent of the donations to the FA Research

Fund are raised by FA families? The staff of the Fund stands ready to assist you with your fundraising

efforts. We’ll help you write or edit your fundraising letter; photocopy it;provide the postage; and mail it from our office, using your mailing list. Ifyou’re going to hold a fundraising event, we’ll provide similar help.

The FA Research Fund asks FA parents to make certain that any eventthey hold is covered by liability insurance. This insurance for a one-timeevent is often available through a family’s homeowners insurance as arelatively inexpensive insurance rider. Please contact the Fund if you needassistance obtaining or paying for this required insurance.

When a donation is received, we’ll send a letter of thanks from theFund with a tax receipt, and we’ll notify you that a donation has beenmade in your name. One request: Please ask your donors to write theirdonation check to the “Fanconi Anemia Research Fund.”

Our sincere thanks go to all of you for your efforts to raise funds tocombat this devastating disease.

Elma Dueck with her three children

needed, so into the hospital she went.She came out three weeks later. Shestill couldn’t turn on her side in bedby herself, but grew stronger steadily,if slowly. We returned home in Janu-ary 2003. We were welcomed backby our very supportive church (after

Elma Dueck’s Journey withFanconi Anemiacontinued from previous page

2 months, they still show up almostevery evening with a meal!).

Elma’s older sister Frieda Martens(who had FA) got aplastic anemia,some severe infections, and passedaway in December at age 42. Fiveweeks later her brother Larry Plett,who had FA and was sick withleukemia, died at age 37.

The transplant with its complica-tions has been much more difficultthan we anticipated. The bone mar-row appears to be working, althoughthere are a number of ongoing com-plications. God is faithful! He hasgiven grace and strength as needed.Also, you realize how many friendsyou have and what they are worth ina time like this. The facilities,doctors, nurses and staff at FairviewUniversity Medical Center wereexcellent! ◆


I am pleased to report that manyFA families stepped up to the plateduring 2002 to raise money for FAresearch and to decrease the depen-dence of the Fund on the fundraisingefforts of only one family, the Frohn-mayers. While the FA Research Fundfaced the same disheartening decreasein donations that affected other non-profit organizations due to the pooreconomy, we were heartened thatdonations decreased by only 18%from the previous year.

The excellent news is that whilethe Frohnmayers raised 54% of thetotal funds donated during 2002, theremaining FA families increased theirpercentage of funds raised from 31%in 2000, to 43% in 2001, to a whop-ping 46% in 2002! Clearly, the trendis in the right direction, and I’mextremely grateful for your efforts.

Even better was the news that,whereas 40 FA families raised $1,000or more in 2001, 53 families did soin 2002. That is a tremendousaccomplishment, as we continue oururgent effort to assist the Frohnmay-ers in raising funds for a cure for FA.

Of the FA families in the UnitedStates, 118 made a donation or raisedfunds for FA research in 2002. If youhave not yet participated in raisingfunds, we urge you to do so, as we allwork together to beat this unrelent-ing and devastating disease.

Thanks to all who were activepartners with the Fund in raisingmoney for our critically urgent causeduring 2002! ◆

FA Families Increase Fundraising Effortsby Mary Ellen Eiler

FUNDRAISING

Our daughter, Shannon, wasdiagnosed with FA two years ago.This year we sent out fundraising let-ters for the first time. We hadthought about doing it last year, witha custom letter we would write andsend out ourselves. However, life’snormal time pressure and some con-cerns over asking friends and relativesfor money resulted in the projectnever getting started.

This year we decided that havingFA is far worse than any possiblesocial embarrassment from asking fordonations, so we decided if ourdaughter can live with FA, we canhelp raise money for research. Theresearch sponsored over the past 14years by FARF has already helped ourfamily, and the Fund is currentlysponsoring research that could helpShannon directly.

To make sure the project got donethis year, we decided to take theFund up on their standing offer todo the administrative work—theprinting and mailing of the letters.We decided that it didn’t matter thatmuch exactly what the letter said aslong as it covered the basics (what isFA and how the research supportedby the Fund has helped), so we creat-ed a letter by slight modification to atemplate provided by the Fund. Inthe end, it is only important to giveothers the opportunity to donate, notexactly what is said. We prepared amailing list of the addresses of ourparents, other relatives, our friends,and friends of our parents. Once theletter and mailing list were ready, wee-mailed it to one of the employees at

the Fund, who prepared all the lettersand had them mailed out in one day.So far the fund has received dona-tions of several thousand dollars fromour letter.

We urge you all to give the peopleyou know the opportunity to donateby sending out fundraising letters.The Fund office staff is enthusiasticto help you. Any amount your lettersraise will help expand the amount ofresearch that can be funded—as thereare more great research proposalsthan there are funds for them. ◆

Getting Started with Fundraisingby Andrew & Jennifer Gough

Shannon Gough

Spring 2003 21

The Athens and DiMercurio Families Sponsor the Downriver Dash

Vicki and Andrew Athens, with Fabrizio, Antonino, and Marie DiMercurio at the Downriver Dash.

A Scary Way toFundraise

Steve Holmes and Kerry Robin-son of Sammamish, WA, were look-ing through the alumni bulletin ofthe University of Oregon when theysaw an article about the Frohnmayerfamily and how Fanconi anemia hadaffected them. Touched by the loss ofKatie and Kirsten Frohnmayer andby the efforts of Lynn and Dave todefeat FA, Steve and Kerry decidedto act. Their children suggested hold-ing a haunted house as a fundraiser.They have done just that for threeHalloweens now, raising funds for FAresearch. One of the guests whoattended the haunted house evensecured a matching grant fromMicrosoft!

Steve and Kerry’s neighborshelped with the effort, transforminga garage into the haunted house.They constructed a plastic labyrinthof walls inside and dressed up inscary costumes (but not too scary, indeference to the little ones whoattend!). Last year the house includeda torture chamber, a “nut” room, agraveyard, a mad surgeon’s operatingroom and an insane fortuneteller.Cookies, candy and apple cider arealso part of the attraction of this verycreative event. ◆

Harley Raffle Raises Funds for FA Research

Credit Card DonationsCredit card donations can bemade to the FA Research Fundvia PayPal. Look for the PayPalbutton below the Donations lineon the home page of the FARFweb site (www.fanconi.org).

The Board of Directors of BPositive, a non-profit organizationstarted by FA parents Mark andDianne Pearl in Chesterfield, MO,donated $15,000 to the FA ResearchFund after a very successful raffle intheir community. The BourbeuseValley Harley-Davidson dealer inVilla Ridge, Missouri, sold B Positivea Harley at cost, and the members ofgroup then sold 1,500 raffle tickets

for $10 each. On top of that success,the gentleman who won the Harleydonated the bike back to B Positive,resulting in $15,000 of totalproceeds! Buoyed by this success,members of B Positive will hold the2nd Annual Harley-Davidson rafflein 2003! Our thanks to this greatgroup! ◆

FA parents Vicki and AndrewAnton-Athens and Marie andAntonino DiMercurio of Michigansponsored the Second Annual Down-river Dash on September 14, 2002,to raise funds for FA research. Therace, a 5K run/walk, also included aKids Dash. Through registration feesfor the run, this event raised $7,000

in the last two years. The DownriverDash is an occasion of fun and exer-cise for all, as well as a wonderful wayto make a community aware ofFanconi anemia and to raise moneyfor research. Thanks go to the Athensand DiMercurios for this excellenteffort! ◆


From July 1 through December31, 2002, FA families raised$441,673 for Fanconi anemiaresearch. The Fund also received$9,079 from the United Way and theCombined Federal Campaign. Ourthanks to all of you who have workedso hard to raise critically-neededresearch dollars.

$30,000 and upDave & Lynn FrohnmayerPat & Mary DiMarino

$10,000 - $19,999Laurie Strongin & Allan GoldbergChristie & Randy KelleyDeane Marchbein & Stuart Cohen

$5,000 - $9,999Vicki & Andrew Anton-AthensJoseph Chou & Frances WangAndrew & Jennifer GoughJeff & Judy HoffmanCharles & Katy HullLorraine & Kevin McQueenLeighsa & Stephen PerlishJack & Lisa NashAndrea & Bob Sacks

$1,000 - $4,999Mark & Linda BaumillerRandy & Nancy BloxomChris & Susan CollinsBrian & Margaret CurtisBill & Pat DanksDonna DellaRattaEd & Janice DuffyBeth & Jeff JanockJohn & Karilyn KelsonGregory & Lynette LowrimoreSteve & Allison McClayGil & Peggy McDonnellDianne & John PloetzRandy & Stephanie RaceErik & Lori SaloBryan & Karen Siebenthal

Mark & Susan TragerWilliam & Mary UnderrinerMichael & Beth VangelMarc & Sandi Weiner

Up to $999Ken & Jeanne AtkinsonRichard & Sharon AtwoodLily & Keith BaggettCherie BankAudrey & John BarrowJohn & Francene BerglundJohn & Elaine BeyerRoel & Diane BrandEd & Barbara BrookoverDonald & Danielle BurkinJoelle & Joachim CarvahloJames ColonJohn & Kim ConnellyCharles & Dahne DeeksCarol & James DillonMarie & Antonino DiMercurioBrian & Jennifer DormanGene & Lynn EddyPaige EllisEzat & Laila FaizyarDavid & Mary Ann FiaschettiPat & Maria GleasonJack & Tina GreerAlan & Rachel GrossmanMitchell & Tirzah Haik

Roger & Eleanor HermanRonnie HickmanRobert & Jennifer KieselDavid KwonAyala LauferPeg LeRouxGayle LicariEric & Beth LosekampCecelia MelolingAndrea & Matthew MorrisSheila MuhlenBob & Alice NicholsonRobert & Mary NoriLuis & Lucina PerezBrad & Lisa PittsHal & Bobbie PorterLynn & Shirley QuiliciJan & Lucia RasmussenMarcia ReardonLynn & Rick SabloskyBill & Connie SchenoneJim & Carol SiniawskiJeff & Debby SlaterKaren SteingartenGreg & Brandi StuartPaul & Debra SundsvoldRichard & Janice ThomasWaldo & Michell ValenzuelaKim & Michael Williams

Family Fundraising Efforts

Use of LogoThis is just a reminder to our FAfamilies: please use our logo orletterhead only after you haveconsulted the staff of the FAResearch Fund and received theirapproval. This is necessary to besure our messages are accurateand consistent. It also helps toavoid legal complications. We arehappy to collaborate on fundrais-ers and mailings.

Spring 2003 23

Investigator: Hans Joenje, PhD, Free University, AmsterdamTitle: Complementation Analysis in Fanconi AnemiaAmount: $58,707

Investigator: Catherine Verfaillie, MD, and Uma Lakshmipathy, PhD,University of Minnesota, Minneapolis

Title: FANCC Gene Correction by Homologous Recombination inMultipotent Adult Progenitor Cells

Amount: $105,500

Investigator: Bruce Blazar, MD, and Jakub Tolar, MD, University ofMinnesota, Minneapolis

Title: Multipotent Adult Progenitor Cell Effects on Tissue Repair afterBone Marrow Transplant in Fanconi Anemia

Amount: $70,000

Investigator: Catherine Verfaillie, MD, and Balkrishna Jahagirdar, MD,University of Minnesota, Minneapolis

Title: Transplantation of Adult Stem Cells for Treatment of FanconiAnemia

Amount: $107,737

Investigator: Maureen Hoatlin, PhD, Oregon Health & ScienceUniversity, Portland

Title: Development of a Xenopus Model for Fanconi AnemiaAmount: $59,751

Investigator: Maureen Hoatlin, PhD, Oregon Health & ScienceUniversity, Portland

Title: Retroviral Expression Cloning of FANCI and FANCJAmount: $54,360

Your FA Research Dollars at Work in 2002

WILL, there’s a way.” Although Willis probably at least 2 years away fromtransplant, we wasted no time. Weheld 3 bone marrow drives before theend of 2002 and added 118 names tothe list of donors. Many of thosehave also gone on to give blood andplatelets. We appeared on the localnews, and we have raised awarenessin our community regarding FA andthe importance of marrow donations.

I still have my fair share of dayswhen I wonder WHY, but now Iknow that I am not in this alone. Tothose of you in the FA family that Ihave spoken with, THANK YOU.There have been many days thatthose conversations with other par-ents were what carried me through.This is not an easy disease to dealwith. Thank God there are friendsout there who understand. ◆

To my surprise, it did not taketwo weeks—it was only one week tothe day that I got that terrible callthat changed my life forever. I washome from work early that day. Willwas sent home from day care becauseof a fever. It was 2:30 p.m. when thephone rang—it was our doctor. Ourconversation was very brief: “The testresults confirmed FA. We will meetin one week to discuss.” End ofconversation.

I felt like I had been hit with aton of bricks. My body fell to thefloor, screaming in pain. I couldn’tthink, I couldn’t talk, and I couldn’tbelieve it—my son, the light of mylife, was going to die from a dreadfuldisease that I couldn’t even under-stand. WHY?!?! I called my bestfriend, and I couldn’t speak. I wascrying into the phone, “He has it, hehas it!” We then cried together. Thiswas our worst day in over 20 years offriendship.

My second call was to Suzanne atthe FARF. Although I’d never mether, I knew she was the one person Ineeded to talk to on that terrible day.I was right. We talked for about anhour and, even though my heart wasstill shattered into a million pieces, I hung up that phone with a newsense of hope and understanding.

It has been four months since thatterrible day. I know more about FAthan I ever wanted to. I have learnedso much in such a short time, and Ihave to say “thank you” to the staff atFARF. They have been so helpful. I came to them at my lowest point. I had already given up, and theyinspired me to make a difference. Istarted a nonprofit organizationcalled WILL POWER in honor ofWill. Our slogan is “Where there’s a

Where There’s a WILL, There’s a Waycontinued from page <None>


the function of the FA proteins; therelationship of FA to DNA repairand homologous recombination;research regarding the relationship ofhuman papilloma virus to the squa-mous cell carcinoma that affects FApatients; novel methods of possiblegene therapy; and the ongoing effortsby transplanters to increase the suc-cess rate for FA patients undergoingbone marrow transplants.

1801 Willamette St., #200Eugene, OR 97401phone: (541) 687-4658

(800) 828-4891 (USA only)FAX: (541) 687-0548e-mail: [email protected] site: www.fanconi.org

Newsletter EditorsLynn & Dave Frohnmayer Mary Ellen EilerJoyce Owen, PhD

Layout and DesignTanya Harvey, Wild Iris Design

StaffExecutive Director:Mary Ellen Eiler

Family Support Coordinator:Suzanne Lauck

Board of DirectorsBarry Rubenstein, JD, PresidentDavid Frohnmayer, JD, Vice PresidentRuby Brockett, Secretary/TreasurerDeane Marchbein, MDKevin McQueenMark PearlRobert D. SacksMichael L. VangelPeter von Hippel, PhDJoyce Owen, PhD, Director EmeritusLynn Frohnmayer, Advisor to the Board

Scientific Advisory BoardGrover C. Bagby, Jr., MD, ChairManuel Buchwald, PhD, OCRichard Gelinas, PhDEva Guinan, MDHans Joenje, PhDChristopher Mathew, PhDStephen Meyn, MD, PhDRaymond J. Monnat, Jr., MDMaria Pallavicini, PhDLeona D. Samson, PhDKevin M. Shannon, MDNeal Young, MD

PrintingImage Masters Printers

�The Fifteenth Annual

International FA ScientificSymposium

OCTOBER 16-19, 2003

Renaissance Houston HotelHouston, Texas

Scientific Symposiumcontinued from page 1

Included as an insert in thisnewsletter is a listing of the Sympo-sium presentations, giving the nameof the presenter and the title of his orher presentation. If you would like acopy of one or more of theseabstracts, indicate your request onthe enclosed form and return it tothe FA Research Fund office. ◆

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