Goals of This Talk:

• Review potential benefits of protons

• Clinical protocols using protons

• Review- What have we learned to date?

Goals of This Talk:

Review potential benefits of protons

Clinical protocols using protons

Review- What have we learned to date?

Reasons for BMT in LeukemiaReasons for BMT in Leukemia

• Poor prognosis chromosomal abnormalities

• Prior myelodysplasia

• Secondary AML

• Prolonged Induction

• Relapsing/Refractory Disease

Reasons for BMT in LeukemiaReasons for BMT in Leukemia

Poor prognosis chromosomal abnormalities

Prior myelodysplasia

Secondary AML

Prolonged Induction

Relapsing/Refractory Disease

E.D. Thomas - 1990 Nobel Prize in MedicineE.D. Thomas - 1990 Nobel Prize in Medicine

• Pioneered bone marrow transplant conditioning regimen

• Established single fraction, low dose rate TBI regimen along with Cytoxan

• Used dogs and Cobalt sources in 1950s and 1960s.

E.D. Thomas - 1990 Nobel Prize in MedicineE.D. Thomas - 1990 Nobel Prize in Medicine

Pioneered bone marrow transplant conditioning regimen

Established single fraction, low dose rate TBI regimen along with Cytoxan

Used dogs and Cobalt sources in 1950s and 1960s

Late Effects

• Cataracts• Growth & development• Fertility & sexual function• Pneumonitis• Veno-occlusive disease• Renal damage• Psychosocial development• Secondary malignancies

Late Effects

• Cataracts

• Growth & development

• Fertility & sexual function

• Pneumonitis

Late Effects

• Veno-occlusive disease

• Renal damage

• Psychosocial development

• Secondary malignancies

Late Effects

• Cataracts

• Growth & development

• Fertility & sexual function

• Pneumonitis

Late Effects

• Veno-occlusive disease

• Renal damage

• Psychosocial development

• Secondary malignancies

Secondarymalignancies

Psychosocialdevelopment

Renaldamage

Veno-occlusivedisease

Pneumonitis

Fertility & Sexual

Function

Growth & Development

Cataracts

Late Effects

Late Effects:Late Effects:

• Posterior subcapsular cataract

• Almost all patients w/ single fraction

• 18% with fractionated

• Surgery almost always well tolerated

• Steroids increase risk

Cataracts

Late Effects:Late Effects:

• Endocrine dysfunction• growth hormone esp.. poor in those receiving prior

craniospinal XRT

• subclinical hypothyroidism in ~70%

• subnormal sex steroid concentrations

• Growth plate damage

• Seen in chemo only regimens alsoSeen in chemo only regimens also

Growth &Development

Late Effects:Late Effects:

• > 95 % of males w/ permanent azoospermia– no change w/ fractionation

• Most female patients stop menstruating, but some can recover ( 20%)

• Some pregnancies documented

Fertility & Sexual

Function

Late Effects:Late Effects:

– Clinical Symptoms• dyspnea

• fever

• non-productive cough

• hypoxia

– Within 90 days of transplant

– High mortality

Classical ground glass appearance

Pneumonitis

Late Effects:Late Effects:

– Pathology• edema and fibrin

exudation

• endothelial hypertrophy

• thickened alveolar septa Late Pneumonitis w/ pulmonary fibrosis

Pneumonitis

Late Effects:Late Effects:

• TBI– Total dose

– Dose rate

– Fractionation

• Other Chemo– Bleomycin

– Cytoxan

– Ara C

– Busulfan

• Infectious– CMV

– Pneumocystis

– Fungal

• Patient Factors– Age

– Increased wt

– Male gender

– CML

– GVHD

• Disease– Malignancy

– Remission status

– Original Stage

• Lung XRT– Mean Lung Dose

– V20

– Previous thoracic irradiation

Pneumonitis

Late Effects:Late Effects:

– Clinical Symptoms• sudden weight gain

• jaundice

• hepatomegaly

• ascites

• high bilirubin

– Incidence• 10 - 20 % of patients,

~50% mortality

Pathology - obliteration of small vessels

More frequent w/ Busulfan

Veno-occlusivedisease

Late Effects:Late Effects:

• Increase Cr, BUN, • Decrease GFR• Anemia, HTN, peripheral edema, inc. LDH• Increased risk

• Ara C Amphotericin B• GVHD Busulfan• TBI dose• Cyclosporine

RenalDamage

Late Effects:Late Effects:

• Influenced by genetics, chemotherapy ( alkylating agents)

• Witherspoon et al (Seattle) reported RR=6.69 in 2246 patients

• Many B-cell lymphomas, sarcomas

• Patients with genetic immunodeficiency at higher risk (i.e.. Wiskott Aldrich)

Secondarymalignancies