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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 Leukemia. - PowerPoint PPT Presentation
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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