Goals of This Talk:

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

• gt 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
Late Effects - Pneumonitis

• TBI
• Total dose
• Dose rate
• Fractionation

• Infectious
• CMV
• Pneumocystis
• Fungal

• Disease
• Malignancy
• Remission status
• Original Stage

• Patient Factors
• Age
• Increased wt
• Male gender
• CML
• GVHD

• Lung XRT
• Mean Lung Dose
• V20
• Previous thoracic irradiation

• Other Chemo
• Bleomycin
• Cytoxan
• Ara C
• Busulfan

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 RR6.69 in
  2246 patients
• Many B-cell lymphomas, sarcomas
• Patients with genetic immunodeficiency at higher
  risk (i.e.. Wiskott Aldrich)