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Goals of This Talk:

Goals of This Talk:. Review potential benefits of protons Clinical protocols using protons Review- What have we learned to date?. Reasons for BMT in Leukemia. Poor prognosis chromosomal abnormalities Prior myelodysplasia Secondary AML Prolonged Induction Relapsing/Refractory Disease.

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Goals of This Talk:

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  1. Goals of This Talk: • Review potential benefits of protons • Clinical protocols using protons • Review- What have we learned to date?

  2. Reasons for BMT in Leukemia • Poor prognosis chromosomal abnormalities • Prior myelodysplasia • Secondary AML • Prolonged Induction • Relapsing/Refractory Disease

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

  4. Late Effects - Cataracts • Posterior subcapsular cataract • Almost all patients w/ single fraction • 18% with fractionated • Surgery almost always well tolerated • Steroids increase risk

  5. Late Effects - Growth Development • 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 also

  6. Late Effects - Fertility & Sexual Function • > 95 % of males w/ permanent azoospermia • no change w/ fractionation • Most female patients stop menstruating, but some can recover ( 20%) • Some pregnancies documented

  7. Late Effects - Pneumonitis • Clinical Symptoms • dyspnea • fever • non-productive cough • hypoxia • Within 90 days of transplant • High mortality Classical ground glass appearance

  8. Late Effects - Pneumonitis • Pathology • edema and fibrin exudation • endothelial hypertrophy • thickened alveolar septa Late Pneumonitis w/ pulmonary fibrosis

  9. TBI Total dose Dose rate Fractionation Other Chemo Bleomycin Cytoxan Ara C Busulfan Late Effects - Pneumonitis • Disease • Malignancy • Remission status • Original Stage • Infectious • CMV • Pneumocystis • Fungal • Patient Factors • Age • Increased wt • Male gender • CML • GVHD • Lung XRT • Mean Lung Dose • V20 • Previous thoracic irradiation

  10. Late Effects - Veno-occlusive Disease • 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

  11. Late Effects - Renal • Increase Cr, BUN, • Decrease GFR • Anemia, HTN, peripheral edema, inc. LDH • Increased risk • Ara C Amphotericin B • GVHD Busulfan • TBI dose • Cyclosporine

  12. Late Effects - 2nd Malignancies • 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)

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