Not for publication or presentation · PDF fileNot for publication or presentation . ......

Not for publication or presentation

A G E N D A CIBMTR WORKING COMMITTEE FOR PEDIATRIC CANCER San Diego, CA Wednesday, February 11, 2015, 12:15 – 2:15 pm

Co-Chair: Carrie Kitko, MD, The University of Michigan, Ann Arbor, MI; Telephone: 734-615-5706; Fax: 734-647-9271; E-mail: [email protected]

Co-Chair: Gregory Hale, MD, All Children's Hospital, St. Petersburg, FL Telephone: 727-767-5681; Fax: 727-767-4379; E-mail: [email protected]

Co-Chair: Parinda Mehta, MD, Cincinnati’s Children’s Hospital Medical Center, Cincinnati, OH; Telephone: 513-636-5917; Fax: 513-803-1969; E-mail: [email protected]

Statisticians: Jennifer Le-Rademacher, PhD; CIBMTR Statistical Center, Milwaukee, WI; Telephone: 414-955-4849; Fax: 414-955-6513; E-mail: [email protected]

Heather Millard, MPH, CIBMTR Statistical Center, Milwaukee, WI; Telephone: 414-805-0703; Fax: 414-805-0714; E-mail: [email protected]

Scientific Director: Elizabeth Thiel, MD, CIBMTR Statistical Center, Milwaukee, WI; Telephone: 414-805-0700; Fax: 414-805-0714; E-mail: [email protected]

1. Introduction

a. Minutes and Overview Plan from February 2014 meeting (Attachment 1) b. Introduction of incoming Co-Chair: Angela Smith, MD, MS; University of Minnesota Medical Center,

Fairview; Email: [email protected]; Telephone: 612-626-2778

2. Accrual Summary (Attachment 2)

3. Presentations, published or submitted papers

a. PC10-01 Bitan M, He W, Zhang M-J, Abdel-Azim H, Ayas MF, Bielorai B, Carpenter PA, Cairo MS, Diaz MA, Horan JT, Jodele S, Kitko CL, Schultz KR, Kletzel M, Kasow KA, Lehmann LE, Mehta PA, Shah N, Pulsipher MA, Prestidge T, Seber A, Shenoy S, Woolfrey AE, Yu LC, Davies SM. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood. 2014 Mar 6;123(10):1615-20.

b. PC10-02b Hitzler JK, He W, Doyle J, Cairo M, Camitta BM, Chan KW, Diaz Perez MA, Fraser C, Gross TG, Horan JT, Kennedy-Nasser AA, Kitko C, Kurtzberg J, Lehmann L, O'Brien T, Pulsipher MA, Smith FO, Zhang M-J, Eapen M, Carpenter PA. Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome. Pediatr Blood Cancer. 2014 Jun;61(6):1126-8.

c. PC10-04 Kelly MJ, Horan JT, Alonzo TA, Eapen M, Gerbing RB, He W, Lange BJ, Parsons SK, Woods WG. Comparable survival for pediatric acute myeloid leukemia with poor-risk cytogenetics following chemotherapy, matched related donor, or unrelated donor transplantation. Published Pediatr Blood Cancer. 2014 Feb;61(2):269-75.

1

Not for publication or presentation

d. PC10-03 Mehta PA, Zhang M-J, Eapen M, He W ---, Seber A, Gibson B, Camitta B, Kitko C, Dvorak C,

Nemecek ER, Frangoul H, Abdel-Azim H, Kasow KA, Lehmann L, Gonzalez-Vicent M, Diaz MA, Ayas M, Qayed M, Carpenter P, Jodele S, Lund T, Leung W, Davies S. Transplant Outcomes for Children with Hypodiploid Acute Lymphoblastic Leukemia: The CIBMTR Experience. Submitted.

4. Studies in progress (Attachment 3)

a. PC14-03 Landmark analysis for updated relapse/LFS estimates for pediatric pts (M Bitan/S Davies)

Protocol Development

b. PC14-01 AutoHCT for Wilm's tumor (M Malogolowkin) (Attachment 4) Data File Preparation

c. PC09-01 Allo in children with T-ALL (M Burke) Manuscript Preparation

Dropped studies

a. PC14-02 Trends in pediatric HCT (E Thiel)

5. Proposals

a. PROP 1411-23 Outcome of hematopoietic stem-cell transplantations in CNS-positive pediatric AML patients (T Schechter/H Frangoul/L Sunge) (Attachment 5)

b. PROP 1411-76 Impact of cytogenetic and molecular features in children receiving allogeneic hematopoietic stem cell transplant (HSCT) for acute leukemia (AC Dietz/MA Pulsipher) (Attachment 6)

Dropped Proposals

a. PROP 1409-03 Use of prophylactic intrathecal chemotherapy post hematopoietic stem cell transplant in de novo pediatric acute lymphoblastic leukemia (R Mitchell/AK Keating) Dropped due to low number of patients with documented prophylactic intrathecal chemotherapy post-transplant.

b. PROP 1411-19 Outcomes in children with T-Cell ALL following allogeneic hematopoietic cell transplantation in CR1 (MJ Burke/MR Verneris) Dropped due to feasibility.

c. PROP 1412-09 Risk factors for pediatric AML relapse after allogeneic HSCT (LA Broglie/S Chaudhury) Dropped due to overlap with PC14-03.

6. Other Business

2

Not for publication or presentation Attachment 1

MINUTES AND OVERVIEW PLAN CIBMTR WORKING COMMITTEE FOR PEDIATRIC CANCER Grapevine, TX Friday, February 28, 2014, 12:15 pm – 2:15 pm

Co-Chair: Adriana Seber, MD, Instituto De Oncologia Pediatrica, Sao Paulo, Brazil Telephone: 55-11-5080-8487; Fax: 55-11-5080-8480; E-mail: [email protected] Co-Chair: Carrie Kitko, MD, University of Michigan Medical Center, Ann Arbor, MI Telephone: 734-615-3342; Fax: 734-647-9271; E-mail: [email protected] Co-Chair: Gregory Hale, MD, All Children's Hospital, St. Petersburg, FL

Telephone: 727-767-5681; Fax: 727-767-4379; E-mail: [email protected] Statisticians: Wensheng (Vincent) He, MS, CIBMTR, Milwaukee, WI Telephone: 414-805-0670; Fax: 414-805-0714; E-mail: [email protected] Jennifer Le-Rademacher, PhD; CIBMTR, Milwaukee, WI Telephone: 414-955-4849; Fax: 414-955-6513; E-mail: [email protected] Scientific Director: Elizabeth Thiel, MD, MS, Medical College of Wisconsin, Milwaukee, WI Telephone: 414-805-0700; Fax: 414-805-0714; E-mail: [email protected]

1. Introduction Dr. Carrie Kitko welcomed the audience and introduced the new co-chair, Dr. Parinda

Mehta from Cincinnati Children's Hospital Medical Center. A souvenir was presented to departing chair Dr. Adriana Seber. The Working Committee membership, goals and expectations, guidelines for voting on proposals and rules of authorship were discussed. The minutes from the 2013 meeting were approved.

2. Accrual summary (Attachment 2) Numbers of transplants for pediatric malignancy stratified by graft type and donor were

presented as part of the meeting documents.

3. Presentations, published or submitted papers Four papers were published in 2013. These include:

a. PC10-02a Hitzler JK, He W, Doyle J, Cairo M, Camitta BM, Chan K, Diaz Perez MA, Fraser C, Gross TG, Horan JT, Kennedy-Nasser AA, Kitko C, Kurtzberg J, Lehmann L, O'Brien T, Pulsipher MA, Smith FO, Zhang M-J, Eapen M, Carpenter PA. Outcome of Transplantation for Acute Myelogenous Leukemia in Children with Down Syndrome. Biology of Blood & Marrow Transplantation. 2013 Jun 1; 19(6):893-897.

b. PC10-04 Kelly MJ, Horan JT, Alonzo TA, Eapen M, Gerbing RB, He W, Lange BJ, Parsons SK, Woods WG. Comparable survival for pediatric acute myeloid leukemia with poor-risk cytogenetics following chemotherapy, matched related donor, or unrelated donor transplantation. Pediatric Blood & Cancer. 2014; DOI 10.1002/pbc.24739. Epub 2013 Aug 19.

3


c. PC10-02b Hitzler JK, He W, Doyle J, Cairo M, Camitta BM, Chan K, Diaz Perez MA, Fraser C, Gross TG, Horan JT, Kennedy-Nasser AA, Kitko C, Kurtzberg J, Lehmann L, O'Brien T, Pulsipher MA, Smith FO, Zhang M-J, Eapen M, Carpenter PA. Outcome of Transplantation for Acute Lymphoblastic Leukemia in Children with Down Syndrome. Pediatric Blood & Cancer. 2014; DOI 10.1002/pbc.24918.

d. PC10-01 Bitan M, He W, Zhang M-J, Abdel-Azim H, Ayas MF, Bielorai B, Carpenter PA, Cairo M, Diaz Perez MA, Horan JT, Jodele S, Kitko C, Schultz KR, Kletzel M, Kasow KA, Lehmann L, Mehta PA, Shah N, Pulsipher MA, Prestidge T, Seber A, Shenoy S, Woolfrey AE, Yu LC, Davies SM. Transplantation for Children with Acute Myeloid Leukemia: A Comparison of Outcomes with Reduced intensity and Myeloablative Regimens. Blood. 2014; DOI 10.1182/blood-2013-10-535716

5. Studies in progress a. PC10-03 HCT for Hypodiploid ALL (P Mehta)

Dr. Stella Davies presented the summary of this study for Dr. Mehta. The primary objective was to evaluate the outcomes after allogeneic transplantation in children with hypodiploid ALL and identify the risk factors associated with the outcomes. After reviewing the cytogenetics forms, 78 patients from 52 centers were eligible and included in the final analysis. Multivariate analysis confirmed both disease status and number of chromosomes were independently associated with mortality; mortality risks were higher for transplants in CR2 (HR 2.16, p=0.05) and when chromosomes were <=43 (HR 2.15, p=0.05). Despite the obvious limitation of small numbers of patients and the retrospective nature of our study, the results suggest that compared to historical results from chemotherapy only treatment, pediatric patients with hypodiploid ALL, may have improved outcomes when transplanted in CR1, and benefit may be most notable in those with ≤43 chromosomes. The manuscript will be drafted and is anticipated to be submitted by June, 2014.

b. PC09-01 Allo in children with T-ALL (M. Burke) Dr. Kitko presented the summary of this study for Dr. Burke. The primary objective was to evaluate the outcomes after allogeneic transplantation in children with T-cell ALL and in CR2, and identify the risk factors associated with the outcomes. One hundred twelve patients of 18 years or younger with the diagnosis of T-ALL in CR2 reported in the CIBMTR from 2000 to 2011 were included. The 5-year estimate of disease free survival (95% confidence interval) is 44% (34% – 53%). The preliminary multivariate analysis result shows that site of first relapse and donor HLA type were independently associated with relapse; site of first relapse and year of transplant were independently associated with treatment failure. Relapse risks were higher for patients with bone marrow relapse prior to transplant compared to relapse in CNS or testes, for mismatched unrelated transplants, and for patients with early relapse. Risks of treatment failure were higher for patients with bone marrow relapse prior to transplant and when transplanted between 2000-2005 compared to 2006-2011. Audience questioned what the main message of the paper will be. This will be the largest pediatric HCT study of T-cell ALL ever reported. The transplant outcomes may be slightly better than literature reported outcomes of patients treated with chemotherapy only. There was also a question from audience on comparing outcomes of TBI containing regimen versus Non-TBI regimen. The numbers of patients for the

4


two groups are too small. A manuscript is anticipated to be submitted by June, 2014.

6. Future/proposed studies

a. PROP 1311-32 Outcome of Total body irradiation (TBI) versus non-TBI (chemotherapy) based conditioning regimens for allogeneic hematopoietic cell transplantation in MLL gene rearranged Acute myeloid leukemia (H Rangarajan, P Satwani) Dr. Rangarajan presented the proposal. The aim of the proposal is to compare outcomes of patients treated with TBI based versus chemotherapy based myeloablative conditioning regimens for MLL gene rearranged AML. There are 124 eligible patients in the CIBMTR database at the research level; 82 patients received Non-TBI regimen and 42 received TBI containing regimen. The characteristics of these patients were presented. Given the heterogeneity of the two groups and small sample size, the committee members were not convinced the study would be feasible. The recommendation from the committee members was not to pursue the study any further. Therefore this was not approved.

b. PROP 1311-35 Outcome of matched sibling donor hematopoietic cell transplantation for children with acute myelogenous leukemia in first complete remission as compared to beyond first complete remission (C Weiner, P Satwani) Dr. Satwani presented the proposal. The objective of the proposal is to Compare outcomes of children with standard and high risk AML who receive a matched sibling donor (MSD) HCT in CR1 to those who received a MSD HCT beyond CR1. There are 371 eligible patients in the CIBMTR database at the research level; 308 patients in CR1, 48 in CR2 and 15 in relapse/PIF. The committee members questioned scientific merit of this proposal and were not convinced the study would add much to the existing literature or change clinical practice. Consequently, the recommendation from the committee members was not to pursue this further.

The meeting adjourned at 1:30 PM.

5


Working Committee Overview Plan for 2014-2015

a. PC10-03 Allogeneic transplantation for hypodiploid acute lymphoblastic leukemia. We

anticipate submitting the manuscript for peer-review by June 2014. b. PC09-01 Allogeneic transplantation for T-cell acute lymphoblastic leukemia. We

anticipate submitting the manuscript for peer-review June 2014. Oversight Assignments for Working Committee Leadership (March 2014)

Adriana Seber PC10-03 Allogeneic transplantation for hypodiploid acute lymphoblastic

leukemia. Carrie Kitko PC09-01 Allogeneic transplantation for T-cell acute lymphoblastic leukemia.

Gregory Hale Transplant data for Wilm’s Tumor patients

6


Accrual Summary for the Pediatric Cancer Working Committee

Characteristics of patients aged 18 years with acute and chronic leukemia, myelodyplastic syndrome and lymphoma reported to the CIBMTR between 2000 - 2014*.

HLA-identical sibling HCT TED,

N (%) Research,

N(%)

Acute myeloid leukemia 2157 536

Bone Marrow 1482 (69) 372 (69)

Peripheral blood 642 (30) 151 (28)

Cord Blood 33 ( 2) 13 ( 2)

Acute lymphoblastic leukemia 2750 554

Bone Marrow 1947 (71) 337 (61)


Cord Blood 64 ( 2) 29 ( 5)

Chronic myeloid leukemia 422 130

Bone Marrow 268 (64) 89 (68)


Cord Blood 5 ( 1) 0

Myelodysplastic Syndrome 423 113

Bone Marrow 317 (75) 88 (78)


Cord Blood 10 ( 2) 5 ( 4)

Hodgkin lymphoma 41 7

Bone Marrow 17 (41) 2 (29)


Non-Hodgkin lymphoma 259 57

Bone Marrow 164 (63) 28 (49)


Cord Blood 3 ( 1) 2 ( 4) * Cases in 2014 continue to be reported

7


Characteristics of patients aged 18 years with acute and chronic leukemia, myelodyplastic syndrome and lymphoma reported to the CIBMTR between 2000 and 2014*

Other related donor HCT TED,

N (%) Research,

N(%)


Bone Marrow 220 (42) 82 (53)


Cord Blood 9 ( 2) 5 ( 3)


Bone Marrow 297 (47) 81 (49)


Cord Blood 8 ( 1) 4 ( 2)


Bone Marrow 45 (54) 21 (55)


Cord Blood 2 ( 2) 2 ( 5)


Bone Marrow 56 (46) 22 (61)



Bone Marrow 5 (38) 3 (75)



Bone Marrow 28 (46) 9 (45)


Cord Blood 1 ( 2) 0 * Cases in 2014 continue to be reported

8


Characteristics of patients aged 18 years with acute and chronic leukemia, myelodyplastic syndrome and lymphoma reported to the CIBMTR between 2000 and 2014*

Unrelated donor HCT TED,

N (%) Research,

N(%)


Bone Marrow 1177 (39) 603 (37)


Cord Blood 1177 (39) 789 (48)


Bone Marrow 1770 (42) 847 (39)


Cord Blood 1584 (38) 1024 (47)


Bone Marrow 286 (61) 166 (61)


Cord Blood 84 (18) 57 (21)


Bone Marrow 501 (46) 236 (40)


Cord Blood 410 (37) 284 (48)


Bone Marrow 14 (48) 5 (45)


Cord Blood 3 (10) 3 (27)


Bone Marrow 141 (45) 61 (38)


Cord Blood 98 (31) 65 (41) * Cases in 2014 continue to be reported

9


Characteristics of patients aged 18 years with acute leukemia and lymphoma reported to the CIBMTR between 2000 and 2014*

Autologous HCT TED,

N (%) Research,

N(%)


Bone Marrow 53 (19) 3 ( 7)


Cord Blood 1 (<1) 0


Bone Marrow 5 ( 8) 1 (20)


Cord Blood 2 ( 3) 0


Bone Marrow 69 ( 5) 4 ( 3)



Bone Marrow 52 (10) 1 ( 2)

Peripheral blood 450 (90) 50 (98) * Cases in 2014 continue to be reported

10


Number of patients aged 18 years with solid tumor reported to the CIBMTR between 2000 and 2014*

Autologous Allogeneic

TED Research TED Research

Testicular 53 8 1 1

Bone sarcoma(No Ewing sarcoma) 106 22 3 1

Central nervous system tumors 639 137 0 0

Wilm’s Tumor 208 27 6 2

Neuroblastoma 3249 476 47 16

Retinoblastoma 83 11 1 1

Ewing sarcoma 430 64 22 4

Extragonadal germ cell tumor 175 17 1 0

Medulloblastoma 909 156 2 0

PNET 43 12 1 1

Rhabdomyosarcoma 88 11 20 3

* Cases in 2014 continue to be reported

11


TO: Pediatric Cancer Working Committee Members FROM: Elizabeth Thiel, MD; Scientific Director for the Pediatric Cancer Working Committee RE: Studies in Progress Summary PC14-03: Personalized Prognostic Information for Pediatric Leukemia Survivors (M Bitan, S Davies) This study proposes to identify important risk factors for mortality, relapse and GVHD that will allow personalized prognostication for those who survive at least 1 year post-transplant without relapse of their disease. For this, the study will evaluate children with first myeloablative allogeneic (matched family or unrelated donor) HCT for acute myeloid leukemia or acute lymphoid leukemia from 1991-2011. Protocol is in development.

PC14-01: Auto Transplantation for Children with Wilm's Tumor (M Malogolowkin) Wilm’s tumor is the most common renal tumor in children affecting approximately one per 10,000 children younger than 15 years of age worldwide. The significant success of initial therapy for the majority of patients has made it challenging to investigate the best therapy for the limited number of patients that do not do well. This study proposes to evaluate overall survival of children receiving autologous hematopoietic stem cell transplant for Wilm’s Tumor. Data file preparation is underway.

12


CIBMTR PC14-01

INVESTIGATING THE OVERALL SURVIVAL FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION FOR PATIENTS WITH WILMS TUMOR

FINAL PROTOCOL

Study Chair: Marcio H. Malogolowkin, MD Professor of Pediatrics Chief, Hematology-Oncology-Transplant Children's Hospital of Wisconsin

Email: [email protected] Study Statistician: Michael T. Hemmer, MS CIBMTR Statistical Center Medical College of Wisconsin 9200 W. Wisconsin Avenue Milwaukee, WI 53226 USA Telephone: 414-805-4638 Fax: 414-805-0714 Email: [email protected]

Jennifer Le-Rademacher, PhD CIBMTR Statistical Center Medical College of Wisconsin 8701 Watertown Plank Rd Milwaukee, WI 53226 USA Telephone: 414-955-4849 Fax: 414-955-6513 Email: [email protected]

Scientific Director: Elizabeth Thiel MD, MS

CIBMTR Statistical Center Medical College of Wisconsin 8701 Watertown Plank Road Milwaukee, WI 53226 USA Telephone: 414-456-4606 Fax: 414-456-6530 E-mail: [email protected]

13


Working Committee Co-Chairs: Gregory Hale, MD All Children's Hospital, St. Petersburg, FL Telephone: 727-767-5681 Fax: 727-767-4379 E-mail: [email protected] Parinda Mehta, MD

Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue

Cincinnati, OH 45243 Telephone: 513-636-4913 Fax: 513-636-3549 E-mail: [email protected]

Carrie Kitko, MD

University of Michigan Medical Center 1500 E. Medical Center Drive Ann Arbor, MI 48109 USA Telephone: 734-615-3342 Fax: 734-647-9271

E-mail: [email protected]

14


SPECIFIC AIM: To study the overall survival of children receiving autologous hematopoietic stem cell transplant (AutoSCT) for Wilms Tumor.

SCIENTIFIC JUSTIFICATION:

Wilms tumor is the most common renal tumor in children affecting approximately one per 10,000 children younger than 15 years of age worldwide.i Modern multimodality treatment with chemotherapy, radiation and improved surgical techniques has resulted in improved survival rates of 90%ii. Even so, 15% of favorable histology patient and almost 50% of patients with anaplastic Wilms tumor relapse or fail to go into remissioniii. The significant success of initial therapy for the majority of patients has made it challenging to investigate the best therapy for the limited number of patients that do not do well.

Several groups have treated high-risk Wilms tumor patients, usually those that have relapsed, with high dose chemotherapy followed by AutoSCT. Overall survival rates following AutoSCT range from 32-60%iv. Survival rates of comparable patients who have not received AutoSCT have been reported to be around 47-63%v. However, due to small numbers of patients among AutoSCT verses no AutoSCT studies, it is extremely difficult for primary oncologists to make a decision regarding referring patients for AutoSCT.

PATIENT ELIGIBILITY POPULATION:

Diagnosis: Wilms Tumor

Age: Younger than 21 years at date of initial diagnosis

Years of transplant: 1990-2012

OUTCOMES:

Primary:

Event-Free Survival (EFS): Time to event (death, relapse, progression). Patients remaining alive and in complete remission will be censored at last follow-up. There are no competing risks. Secondary:

Relapse: the recurrence of the primary disease. The outcome will be evaluated by cumulative incidence estimates, with transplant-related mortality as a competing risk.

Transplant-related mortality (TRM): Death in the first 28 days post-transplant or death in continuous remission. The outcome will be evaluated by cumulative incidence estimates, with relapse as a competing risk.

Progression-Free Survival (PFS): Time to treatment failure (death or relapse). Patients remaining alive and in complete remission will be censored at last follow-up. There are no competing risks.

Overall Survival: time to death from any cause. Patients are censored at date of last follow-up.

VARIABLES TO BE DESCRIBED:

Age at diagnosis:

Age at transplantation:

Gender: male, female, missing

Disease status at transplantation:

Time from diagnosis to transplantation, months:

Year of transplantation:

Graft type: bone marrow (BM), peripheral blood stem cells (PBSC), missing

Conditioning regimen: alkylating agents vs. platinum agents

Planned tandem/subsequent transplant: yes vs. no vs. missing

15


VARIABLES TO BE ANALYZED:

Disease status at transplantation: 1st relapse vs. > 2nd relapse/CR vs. persistent/progressive disease vs. no relapse vs. missing

Time from diagnosis to transplantation, months: < 12 vs. 12-18 vs. > 18

Graft type: BM vs. PBSC

Year of Transplantation: 1990-1994 vs. 1995-1999 vs. 2000-2004 vs. 2005-2012

Conditioning regimen: Alkylating agents vs. Platinum agents

Planned tandem/subsequent transplant: yes vs. no vs. missing

STUDY DESIGN: Patient-, disease-, and transplant-related variables will be summarized. Median and range will be given for continuous variables. Frequency and percentage will be listed for categorical variables. The probabilities of overall survival will be calculated using the Kaplan-Meier estimator. (If secondary outcomes are considered, the probabilities of progression-free survival will be estimated by the Kaplan-Meier estimator. The cumulative incidences of relapse and TRM will be estimated using the cumulative incidence function.) In multivariate analysis, the Cox proportional hazards model will be used to identify significant risk factors. Variables to be considered in the multivariate models are listed above. The assumption of proportional hazards for each factor will be tested using time-dependent covariates. When the test indicated differential effects over time (non-proportional hazards), models will be constructed breaking the post transplant time course into two periods, using the maximized partial likelihood method to find the most appropriate breakpoint. The proportionality assumptions will be further tested. A stepwise model selection approach will be used to identify all significant risk factors. Factors which are significant at a 5% level will be kept in the final model. Two-way interactions will be tested for all variables remained in the final model. REFERENCES:

i Breslow N, Olshan A, Beckwith JB, Green DM., Epidemiology of Wilm’s Tumor, Med Pediatr Oncol. 1993:172-81. ii Ha Tc, Spreafico F, Graf N, Dallorso S, Dome JS, Malogolowkin, Furtwangler R, Hale JP, Moroz V, Machin D, Pritchard-Jones K. An International Strategy to Determine The Role of High Dose Therapy in Recurrent Wilm’s Tumors. Eur J Cancer. 2013 Jan: 49 (1): 194-210. iii Ha Tc, Spreafico F, Graf N, Dallorso S, Dome JS, Malogolowkin, Furtwangler R, Hale JP, Moroz V, Machin D, Pritchard-Jones K. An International Strategy to Determine The Role of High Dose Therapy in Recurrent Wilm’s Tumors. Eur J Cancer. 2013 Jan: 49 (1): 194-210. iv Ha Tc, Spreafico F, Graf N, Dallorso S, Dome JS, Malogolowkin, Furtwangler R, Hale JP, Moroz V, Machin D, Pritchard-Jones K. An International Strategy to Determine The Role of High Dose Therapy in Recurrent Wilm’s Tumors. Eur J Cancer. 2013 Jan: 49 (1): 194-210. v Ha Tc, Spreafico F, Graf N, Dallorso S, Dome JS, Malogolowkin, Furtwangler R, Hale JP, Moroz V, Machin D, Pritchard-Jones K. An International Strategy to Determine The Role of High Dose Therapy in Recurrent Wilm’s Tumors. Eur J Cancer. 2013 Jan: 49 (1): 194-210.

16


Table 1. Characteristics of patients who underwent autologous transplant for Wilm's Tumor from 1990-

2013, as reported to the CIBMTR.

Characteristics of patients: 1990-1994 1995-1999 2000-2004 2005-2012

Number of patients 35 76 59 107

Number of centers 16 43 39 57

Region of center

US 34 (97) 60 (79) 40 (68) 84 (79)

Canada 0 8 (11) 3 (5 ) 10 (9 )

International 1 (3 ) 8 (11) 16 (27) 13 (12)

Patient-related

Age at diagnosis, median(range), years 4 (1 - 12) 4 (<1 - 16) 5 (1 - 21) 4 (1 - 19)

Age at diagnosis, years

0-4 21 (60) 45 (59) 29 (49) 65 (61)

5-9 13 (37) 24 (32) 24 (41) 32 (30)

10+ 1 (3 ) 7 (9 ) 6 (10) 10 (9 )

Age at transplant, median(range), years 6 (1 - 14) 6 (1 - 18) 7 (2 - 22) 7 (2 - 23)

Age at transplant, years

0-4 11 (31) 27 (36) 12 (20) 28 (26)

5-9 20 (57) 34 (45) 35 (59) 60 (56)

10+ 4 (11) 15 (20) 12 (20) 19 (18)

Gender

Male 15 (43) 37 (49) 28 (47) 48 (45)

Female 20 (57) 38 (50) 30 (51) 59 (55)

Missing 0 1 (1 ) 1 (2 ) 0

Disease status in CR or not

CR 7 (20) 20 (26) 32 (54) 69 (64)

Not in CR 20 (57) 45 (59) 19 (32) 34 (32)

Missing 8 (23) 11 (14) 8 (14) 4 (4 )

17


Table 1. (continued) 1990-1994 1995-1999 2000-2004 2005-2012


Disease status

CR2 5 (14) 5 (7 ) 24 (41) 53 (50)

CR3+ 0 1 (1 ) 6 (10) 16 (15)

CR unknown 2 (6 ) 21 (28) 5 (8 ) 0

REL1 - sensitive 5 (14) 5 (7 ) 4 (7 ) 3 (3 )

REL1 - resistant 3 (9 ) 0 0 2 (2 )

REL1 - untreated 1 (3 ) 2 (3 ) 1 (2 ) 0

REL1 - unknown 0 2 (3 ) 0 3 (3 )

REL2 - sensitive 1 (3 ) 0 4 (7 ) 1 (<1)

REL3+ - sensitive 0 1 (1 ) 0 0

REL3+ - untreated 0 1 (1 ) 0 0

REL3+ - unknown 0 0 0 1 (<1)

REL unknown 0 1 (1 ) 6 (10) 1 (<1)

Progression 1 (3 ) 6 (8 ) 0 4 (4 )

Stable disease 5 (14) 4 (5 ) 0 0

Partial response 4 (11) 14 (18) 1 (2 ) 16 (15)

Missing 8 (23) 13 (17) 8 (14) 7 (7 )

Disease status

Relapsed once (REL1 / CR2) 14 (40) 14 (18) 29 (49) 61 (57)

Relapsed more than once (REL2+ / CR3+) 1 (3 ) 3 (4 ) 10 (17) 18 (17)

Persistent/Progressive Disease 6 (17) 10 (13) 0 4 (4 )

Missing 14 (40) 49 (64) 20 (34) 24 (22)

Disease status/Time from dx to tx, months

Rel once, < 12 7 (20) 4 (5 ) 7 (12) 8 (7 )

Rel once, 12-18 2 (6 ) 4 (5 ) 11 (19) 27 (25)

Rel once, >= 18 5 (14) 6 (8 ) 11 (19) 26 (24)

Rel > once, < 24 1 (3 ) 0 4 (7 ) 3 (3 )

Rel > once, >= 24 0 3 (4 ) 6 (10) 15 (14)

PPD 6 (17) 10 (13) 0 4 (4 )

Unknown, < 12 3 (9 ) 8 (11) 5 (8 ) 2 (2 )

Unknown, 12-24 2 (6 ) 14 (18) 4 (7 ) 10 (9 )

Unknown, >= 24 1 (3 ) 14 (18) 3 (5 ) 5 (5 )

Missing 8 (23) 13 (17) 8 (14) 7 (7 )

18


Table 1. (continued) 1990-1994 1995-1999 2000-2004 2005-2012


Transplant-related

Time from diagnosis to transplant, median(range),

months

12 (3 - 120) 17 (5 - 108) 18 (2 - 132) 19 (<1 - 208)

Time from diagnosis to transplant, months

< 6 2 (6 ) 3 (4 ) 4 (7 ) 1 (<1)

6-12 15 (43) 18 (24) 12 (20) 11 (10)

12-18 6 (17) 18 (24) 15 (25) 38 (36)

18-24 6 (17) 7 (9 ) 10 (17) 21 (20)

24-36 5 (14) 17 (22) 10 (17) 15 (14)

>36 1 (3 ) 13 (17) 8 (14) 21 (20)

Graft type

BM 24 (69) 20 (26) 6 (10) 7 (7 )

PBSC 11 (31) 54 (71) 51 (86) 100 (93)

Missing 0 2 (3 ) 2 (3 ) 0

Regimen groups *

Alkylating agents 21 (60) 59 (78) 27 (46) 47 (44)

Platinum agents 8 (23) 5 (7 ) 13 (22) 54 (50)

Missing 6 (17) 12 (16) 19 (32) 6 (6 )

Year of transplant

1990 3 (9 ) 0 0 0

1991 4 (11) 0 0 0

1992 10 (29) 0 0 0

1993 6 (17) 0 0 0

1994 12 (34) 0 0 0

1995 0 15 (20) 0 0

1996 0 15 (20) 0 0

1997 0 12 (16) 0 0

1998 0 16 (21) 0 0

1999 0 18 (24) 0 0

2000 0 0 16 (27) 0

2001 0 0 6 (10) 0

2002 0 0 11 (19) 0

2003 0 0 13 (22) 0

2004 0 0 13 (22) 0

2005 0 0 0 15 (14)

2006 0 0 0 4 (4 )

2007 0 0 0 14 (13)

2008 0 0 0 19 (18)

2009 0 0 0 12 (11)

19


2010 0 0 0 7 (7 )

2011 0 0 0 13 (12)

2012 0 0 0 9 (8 )

2013 0 0 0 14 (13)

Time from transplant to second transplant,

median(range), months

7 (7 - 7) 3 (3 - 3) 1 (1 - 23) 1 (1 - 2)

Time from transplant to second transplant, months

No 2nd transplant 34 75 53 101

< 1 0 0 2 (33) 1 (17)

1-2 0 0 2 (33) 4 (67)

2-6 0 1 1 (17) 1 (17)

6-12 1 0 0 0

12-24 0 0 1 (17) 0

Cause of death

Primary disease 17 (77) 38 (83) 22 (79) 36 (90)

IPN 0 2 (4 ) 0 0

Infection 1 (5 ) 1 (2 ) 1 (4 ) 0

Organ failure 1 (5 ) 3 (7 ) 1 (4 ) 1 (3 )

Other 0 0 2 (7 ) 1 (3 )

Missing 3 (14) 2 (4 ) 2 (7 ) 2 (5 )

Follow-up of survivors, median (range), months 128 (17-241) 93 (1-198) 92 (1-147) 31 (1-94)

Abbreviations: CR = Complete remission, REL = Relapse, BM = Bone marrow, PBSC = Peripheral Blood Stem Cells, CY =

Cyclophosphamide, LPAM = Melphalan, BU = Busulfan, THIO = Thiotepa, CARB = Carboplatinum.

*: Alkylating agents are defined as CY+LPAM, BU+CY, BU+LPAM, LPAM, CY+THIO, CY;

Platinum agents are defined as CARB+LPAM, CY+CARB, CARB.

Criteria Excluded N

First allogeneic transplant reported for Wilm’s Tumor from 1990-2012 356 Age < 21 years at diagnosis 34 322 Excluded patients with disease status of PIF, CR1, VGPR1, PR1 45 277

20


Study Proposal 1411-23 Study Title: Outcome of hematopoietic stem-cell transplantations in CNS-positive pediatric AML patients Tal Schechter, MD, The Hospital for Sick Children, Toronto, Canada, [email protected] Haydar Frangoul, MD, MS, Vanderbilt University, [email protected] Lillian Sunge, MD, PhD, The Hospital for Sick Children, Toronto, Canada, [email protected] Hypothesis: We hypothesis that pediatric AML patients who had CNS involvement prior to HSCT will have similar overall survival using busulfan-based conditioning regimen or total-body irradiation based conditioning regimens. Specific Aims: Aim 1: To assess the overall survival (OS) and event free-survival (EFS) of pediatric AML patients with CNS involvement who underwent HSCT Aim 2: To determine the effect of total-body irradiation-based (TBI) vs. busulfan-based regimens on EFS and OS in CNS-positive pediatric AML patients. Aim 3: To determine the effect of a cranial irradiation boost on EFS and OS in CNS-positive pediatric AML patients. Aim 4: To evaluate the effect of risk factors such as time point of CNS positivity (primary diagnosis of AML vs. relapse), remission status, number of remissions, cytogenetics and donor type on OS and EFS in CNS-positive pediatric AML patients who underwent allogeneic HSCT. Scientific Justification: Childhood acute myeloid leukemia (AML) is a heterogeneous disease that with intensive chemotherapy and supportive care has survival rates of ∼ 70%.1 The proportion of patients with central-nervous system (CNS) involvement at diagnosis or relapse ranges between 5 and 12% and merits CNS-directed therapy.1,2 CNS involvement at time of diagnosis was not found to affect overall survival (OS) in AML patients but it does increase the risk for CNS relapse.3 Little is known about the prognostic impact of CNS involvement on HSCT outcomes in pediatric AML patients. In addition, the optimal conditioning therapy is not known for these patients. In a recent single-center retrospective study of adult patients, nearly 12% had CNS-positive disease prior to transplant. Conditioning regimens included busulfan-based or total-body irradiation (TBI)-based regimens. Intrathecal therapy and cranial irradiation boosts were used in a subsets. Adult patients with CNS involvement prior to transplant experienced a poorer transplant outcome compared to patients without CNS involvement. Patients who did not receive cranial radiation had a 6% 5-yr OS. Interestingly, CNS-positive patients receiving TBI as part of the conditioning regimen had a trend toward worse OS than those who did not receive TBI.2 Although many CNS-positive AML patients have undergone HSCT, knowledge regarding the recommended conditioning regimen and patients’ outcome is scarce, especially in pediatric patients.

21


There is a need for complete cohort evaluation of such transplants for clinicians to be able to understand appropriate indications, complications and outcomes after HSCT.

Patient Eligibility Population: Inclusion criteria: All pediatric AML patients (age <18 years) with CNS-positivity at any time point prior to HSCT who underwent a first myeloablative transplant between 1995 - 2012. CNS positive AML: according to the AAML1031 criteria:

Any number of blasts on a cytospin prep in an atraumatic (< 100 RBCs) lumbar puncture.

Blasts in a traumatic tap in which the WBC/RBC ratio in the CSF is twice that in the peripheral blood.

Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome). Extra-ocular orbital masses are not considered CNS leukemia.

Radiographic evidence of an intracranial, intradural mass consistent with a chloroma Haploidentical transplants and ex-vivo and in-vivo T-cell depleted patients will be excluded.

Data Requirements: This retrospective review of the CIBMTR database will not require collection of supplemental data or submission of data from organizations outside of CIBMTR. The specific variables to be analyzed from the existing CIBMTR data collection forms will include:

CIBMTR Form ID Form Name Data Requested

Form 2000 Recipient Baseline Data

Age Gender Ethnicity Primary disease: Form 2010 (full)

Cytogenetics

Time of CNS involvement

Location of relapse (BM/CNS/BM+CNS/Chloroma) Donor type :

family donor/unrelated donor

stem cell used

Degree of HLA match between the donor and recipient

Gender mismatch

Number of cord units used Preparative regimens (chemotherapy, TBI, cranial boost) GVHD prophylaxis regimen and doses

Form 2100 100 Days Post- HSCT Data

GVHD data:

Day 0-day 100: Acute GVHD Grading and staging and organs involved.

Time after HSCT to develop GVHD

22


Response to therapy.

chronic GVHD and severity Outcome /secondary graft-failure Time of neutrophil engraftment

infectious complication

Patients outcome: Treatment related mortality/ relapse

Form 2200 Six Months to Two Years Post-HSCT Data

Diagnosis of:

Chronic GVHD (limited or extensive) and organ involved

Patients outcome: Treatment related mortality/ relapse

Form 2300 Yearly Follow-up For Greater Than Two Years Post-HSCT Data

Diagnosis of:

Chronic GVHD (limited or extensive)

Patients outcome and causes of treatment-related mortality/relapse

Sample Requirements: N/A Study Design: This study will be a retrospective review of data already collected through the CIBMTR database. Specifically, each aim and proposed analysis is outlined below: Aim 1: To assess the OS and EFS of pediatric AML patients with CNS involvement who underwent HSCT We will describe survival using the Kaplan Meier method in which events will be considered relapse, second malignancy or death post HSCT. Given that the aim is descriptive, the sample size justification is based upon the precision to estimate outcomes. The specific precision will differ depending on the pattern of censoring. However, if approached as a proportion, if we assume that there are 300 children who meet eligibility criteria with an EFS of 30% at five years, then the two-sided 95% confidence interval will range from 19% to 41% which is sufficiently precise for our purpose. Aim 2: To determine the effect of TBI-based vs. busulfan-based regimen on EFS and OS in CNS positive pediatric AML patients. Survival by preparative regimens will be described using the Kaplan-Meier method and preparative regimen will be compared using the log-rank test. Aim 3: To determine the effect of cranial boost on EFS and OS in CNS positive pediatric AML patients. Analysis will be the same as Aim 2, with comparison of groups who did and did not receive cranial boost using the log rank test. Aim 4: To evaluate the effect of risk factors such as time of CNS positivity (diagnosis/relapse), remission status, number of remissions, cytogenetics and donor type on OS and EFS in CNS positive pediatric AML patients between patients who underwent allogeneic HSCT

23


In order to evaluate factors that may influence OS and EFS in CNS positive pediatric AML patients, we will build univariate and multiple Cox regression models. Multiple regression models will use a backwards section approach. Clinical relevance: In children with AML, the prognostic impact of CNS involvement prior to HSCT and

the optimal conditioning regimen for CNS-positive AML are unknown. The proposed retrospective analysis of the CIBMTR database is likely to close this gap in knowledge and provide evidence to guide clinical decision making in this challenging situation

References:

1. Creutzig U et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel Blood 2012:120(16); 3187-3205

2. Mayadev JS et al. The Impact of Cranial Irradiation Added to the Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia with Central Nervous System Involvement. Int J Radiat Oncol Biol Phys 2011;80(1):193-198

3. Johnston DL et al. Risk factors and therapy for isolated central nervous system relapse of pediatric acute myeloid leukemia. J Clin Oncol 2005;23(36):9172-9178.

24

http://bloodjournal.hematologylibrary.org/search?author1=Ursula+Creutzig&sortspec=date&submit=Submit


Characteristics of ≤18 year old patients who underwent HCT for AML, with CNS-positivity any time

prior to transplant, reported to the CIBMTR from 2000-2013

Variable N (%)

Number of patients 387

Age in years, median (range) 7 (<1-19)

<10 years 241 (62)

≥ 10 years 146 (38)

Sex

Male 219 (57)

Female 168 (43)

Graft type

Bone marrow 150 (39)

Peripheral blood 49 (13)

Cord blood 188 (48)

Donor type

HLA-identical sibling 71 (18)

Twin 1 (<1)

Other relative 19 ( 5)

Unrelated donor 296 (77)

Conditioning regimen

TBI-based 196 (51)

Bu-based 187 (48)

Other* 4 ( 1)

GVHD prophylaxis

Ex vivo T-cell depletion alone 11 ( 3)

CD34 selection alone 7 ( 2)

Cyclophosphamide + others 1 (<1)

FK506 + MMF +- others 24 ( 6)

FK506 + MTX +- others (except MMF) 48 (12)

FK506 + others (except MTX, MMF) 11 ( 3)

CSA + MMF +- others (except FK506) 77 (20)

CSA + MTX +- others (except FK506, MMF) 112 (29)

CSA + others (except FK506, MTX, MMF) 78 (20)

Other GVHD prophylaxis 18 ( 5)

Year of transplant

2000 17 ( 4)

2001 20 ( 5)

2002 26 ( 7)

2003 28 ( 7)

2004 30 ( 8)

2005 27 ( 7)

25


Variable N (%)

Year of transplant (continued)

2006 31 ( 8)

2007 25 ( 6)

2008 39 (10)

2009 47 (12)

2010 37 (10)

2011 21 ( 5)

2012 17 ( 4)

2013 22 ( 6)

Median follow-up of survivors in months, median (range) 53 (2-157)

*Melphalan+Thiotepa

Selection criteria Excluded Included

Patients ≤18 years old receiving first HCT for AML in 2000-2013

2364

Underwent myeloblative conditioning regimen 397 RIC (9)

NMA (24) TBD (243)

Missing (121)

1967

CNS-positivity at any time prior to transplant 1580 387

Consent 0 387

26


Study Proposal 1411-76 Study Title: Impact of cytogenetic and molecular features in children receiving allogeneic hematopoietic stem cell transplant (HSCT) for acute leukemia Andrew C. Dietz, MD, MS, University of Utah & Primary Children’s Hospital, [email protected] Michael A. Pulsipher, MD, University of Utah & Primary Children’s Hospital,

[email protected] Hypotheses:

1. Individual or combinations of pre-HSCT cytogenetic and molecular abnormalities will be associated with HSCT survival and may allow for further definition of HSCT specific cytogenetic and molecular risk stratification

2. HSCT will abrogate the effects of some traditionally high-risk cytogenetic and molecular lesions Specific Aims:

1. To study the impact of cytogenetic and molecular lesions on HSCT survival 2. To examine HSCT survival through multivariate analysis other key transplant variables in order

to establish the independent prognostic implication of specific cytogenetic and molecular features

Scientific Justification: The work-up of and risk stratification for acute leukemia in childhood classically involves age, presenting white blood cell count (WBC), presence of extrameduallary disease, and morphologic, immunophenotypic, molecular, and cytogenetic evaluation of leukemia cells.1-3 Based on initial high-risk stratification or subsequent relapse, patients are considered eligible for allogeneic HSCT as more intensive treatment.4, 5 While the impact of molecular and cytogenetic features at diagnosis is more well known, the impact of those same features on the allogeneic HSCT process is less well known. For childhood acute lymphoblastic leukemia (ALL), initial immunophenotypic separation into T-cell disease versus B-cell disease is important. Patients with T-cell ALL only rarely have the cytogenetic abnormalities seen in B-cell ALL, and overall the impact of various abnormalities is not as well known.6 For patients with B-cell ALL, excluding the mature B-cell phenotype, the impact of molecular and cygogenetic features is much better known. There are favorable abnormalities such as hyperdiploidy and t(12;21) or ETV6-RUNX1.7 There are unfavorable abnormalities such as hypodiploidy, iAMP21, the Philadelphia chromosome or t(9;22), and MLL gene (11q23) translocations.7 There are also abnormalities originally found to be unfavorable such as t(1;19) or E2A-PBX1, that may be able to be overcome by intensified up front therapy.8 More rare cytogenetic changes such as t(17;19) or E2A-HLF appear to be extremely deleterious in case reports and small series,9 and yet more have unknown significance. For childhood acute myeloid leukemia (AML), favorable molecular and cytogenetic features include t(8;21), inv(16), t(15;17), NPM1 mutations, and CEBPA mutations.10-14 Unfavorable features include abnormalities in chromosomes 3, 5, and 7, as well as FLT3 mutations.10-12 MLL gene (11q23) rearrangements can portend good prognosis as with t(1;11), neutral prognosis as with t(9;11), or poor prognosis as with t(4;11), t(6;11), and t(10;11).12, 15 More rare cytogenetic changes such as t(6;9) and t(1;22) have also been associated with poorer prognosis,16, 17 and yet more have unknown significance.

27


The ability of allogeneic HSCT to overcome or mitigate high-risk features is well established.4, 5 However, the prognosis of most cytogenetic or molecular risk factors through the HSCT process is not as well established, which is the reason why this concept has been studied already through the CIBMTR for adult AML18 and why there is a study in progress for adult ALL through the Acute Leukemia Working Committee of the CIBMTR (LK13-02, PI’s Lazaryan and Bachanova). Patient Eligibility Population:

Patients aged 18 or younger who underwent allogeneic HSCT for acute lymphoblastic leukemia or acute myeloid leukemia in first or second complete remission at participating CIBMTR centers between 2000 and 2013

Data Requirements: Data will primarily come from CIBMTR Data Collection Forms 2010 (AML), 2011 (ALL), and all follow-up forms. Demographic data such as age at transplant, gender, and race will be collected as well as clinical data. Clinical data will include age at diagnosis, year of transplant, initial white blood cell count, presence/site of extramedullary disease, all cytogenetic and molecular classifications, disease status (CR1 versus CR2) at transplant, performance score at transplant, conditioning regimen (myeloablative versus reduced intensity; TBI versus non-TBI), donor source, CMV status, GVHD prophylaxis, date of relapse, date of death, reason for death, date of last contact. Sample Requirements: No samples are required for this study Study Design: This will be a retrospective observational cohort study through the CIBMTR. Available cytogenetic reports will be reviewed for validation. Initial groupings of cytogenetic findings will be based on the known cytogenetic risk groups for AML and ALL at diagnosis. The primary outcome will be overall survival (OS) with secondary outcomes of relapse, non-relapse mortality (NRM), and event free survival (EFS) in which events will be defined as death or disease relapse. EFS and OS will be estimated by the Kaplan-Meier method and compared using log-rank testing. Cumulative incidence curves of NRM and relapse will be compared using Gray testing. Clustering of proportional hazards will be used to refine groupings and create the HSCT-specific risk stratification. This will be done separately for AML and ALL. References: 1. Smith M, Arthur D, Camitta B, et al. Uniform approach to risk classification and treatment

assignment for children with acute lymphoblastic leukemia. J Clin Oncol 1996;14:18-24. 2. Locatelli F, Schrappe M, Bernardo ME, Rutella S. How I treat relapsed childhood acute

lymphoblastic leukemia. Blood 2012;120:2807-2816. 3. Rubnitz JE. How I treat pediatric acute myeloid leukemia. Blood 2012;119:5980-5988. 4. Oliansky DM, Rizzo JD, Aplan PD, et al. The role of cytotoxic therapy with hematopoietic stem

cell transplantation in the therapy of acute myeloid leukemia in children: an evidence-based review. Biol Blood Marrow Transplant 2007;13:1-25.

5. Hahn T, Wall D, Camitta B, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: an evidence-based review. Biol Blood Marrow Transplant 2005;11:823-861.

6. Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 2005;23:6306-6315.

28


7. Moorman AV, Ensor HM, Richards SM, et al. Prognostic effect of chromosomal abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: results from the UK Medical Research Council ALL97/99 randomised trial. The Lancet Oncology 2010;11:429-438.

8. Uckun FM, Sensel MG, Sather HN, et al. Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group. J Clin Oncol 1998;16:527-535.

9. Minson KA, Prasad P, Vear S, et al. t(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature. Case reports in hematology 2013;2013:563291.

10. Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116:354-365.

11. Harrison CJ, Hills RK, Moorman AV, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol 2010;28:2674-2681.

12. Reinhardt D, Von Neuhoff C, Sander A, Creutzig U. [Genetic prognostic factors in childhood acute myeloid leukemia]. Klinische Padiatrie 2012;224:372-376.

13. Brown P, McIntyre E, Rau R, et al. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 2007;110:979-985.

14. Ho PA, Alonzo TA, Gerbing RB, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 2009;113:6558-6566.

15. Balgobind BV, Raimondi SC, Harbott J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489-2496.

16. Sandahl JD, Coenen EA, Forestier E, et al. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica 2014;99:865-872.

17. Bernstein J, Dastugue N, Haas OA, et al. Nineteen cases of the t(1;22)(p13;q13) acute megakaryblastic leukaemia of infants/children and a review of 39 cases: report from a t(1;22) study group. Leukemia 2000;14:216-218.

18. Armand P, Kim HT, Zhang MJ, et al. Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant 2012;18:280-288.

29


Characteristics of ≤18 year old patients who underwent allogeneic HCT for AML or ALL, in CR1 or CR2,

reported to the CIBMTR from 2000-2013

Variable N (%)

Number of patients 3894

Age in years, median (range) 9 (<1-19)

<10 years 2067 (53)

≥ 10 years 1827 (47)

Sex

Male 2270 (58)

Female 1624 (42)

Disease

AML 1725 (44)

ALL 2169 (56)

Graft type

Bone marrow 1770 (45)

Peripheral blood 731 (19)

Cord blood 1393 (36)

Donor type

HLA-identical sibling 905 (23)

Twin 12 (<1)

Other relative 151 ( 4)

Unrelated donor 2826 (72)

Conditioning regimen

TBI-based 2597 (67)

Bu-based 1171 (30)

Other 126 ( 3)

GVHD prophylaxis

Ex vivo T-cell depletion alone 219 ( 6)

CD34 selection alone 76 ( 2)

Cyclophosphamide + others 6 (<1)

FK506 + MMF +- others 182 ( 5)

FK506 + MTX +- others (except MMF) 544 (14)

FK506 + others (except MTX, MMF) 111 ( 3)

CSA + MMF +- others (except FK506) 547 (14)

CSA + MTX +- others (except FK506, MMF) 1397 (36)

CSA + others (except FK506, MTX, MMF) 682 (18)

Other GVHD prophylaxis 130 ( 3)

Year of transplant

2000 316 ( 8)

2001 318 ( 8)

2002 323 ( 8)

30


Variable N (%)

2003 316 ( 8)

2004 372 (10)

2005 362 ( 9)

Year of transplant (continued)

2006 359 ( 9)

2007 310 ( 8)

2008 281 ( 7)

2009 276 ( 7)

2010 210 ( 5)

2011 113 ( 3)

2012 145 ( 4)

2013 193 ( 5)

Median follow-up of survivors in months, median (range) 61 (2-174)

Selection criteria Excluded Included

Patients ≤18 years old receiving first alloHCT for AML or ALL in 2000-2013

5348

In CR1 or CR2 1359

3989

Consent 95 3894

31

Not for publication or presentation · PDF fileNot for publication or presentation . ......

Documents

Transcript of Not for publication or presentation · PDF fileNot for publication or presentation . ......