Download Survivorship Issues - Massachusetts General Hospital

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
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Poor prognosis chromosomal abnormalities
Prior myelodysplasia
Secondary AML
Prolonged Induction
Relapsing/Refractory Disease
Reasons for BMT in Leukemia
Poor prognosis chromosomal abnormalities
Prior myelodysplasia
Secondary AML
Prolonged Induction
Relapsing/Refractory Disease
E.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 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
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Cataracts
Growth & development
Fertility & sexual function
Pneumonitis
Veno-occlusive disease
Renal damage
Psychosocial development
Secondary malignancies
Late Effects
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•
•
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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
Cataracts
Growth &
Development
Secondary
malignancies
Psychosocial
development
Late Effects
Renal
damage
Fertility &
Sexual
Function
Pneumonitis
Venoocclusive
disease
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:
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
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
Late Effects:
Pneumonitis
– Clinical Symptoms
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dyspnea
fever
non-productive cough
hypoxia
– Within 90 days of
transplant
– High mortality
Classical ground glass appearance
Late Effects:
Pneumonitis
– Pathology
• edema and fibrin
exudation
• endothelial
hypertrophy
• thickened alveolar
septa
Late Pneumonitis w/ pulmonary fibrosis
Late Effects:
• TBI
– Total dose
– Dose rate
– Fractionation
• Patient Factors
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Age
Increased wt
Male gender
CML
GVHD
• Disease
Pneumonitis
• Infectious
– Malignancy
– Remission status
– Original Stage
– CMV
– Pneumocystis
– Fungal
• Other Chemo
• Lung XRT
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Bleomycin
Cytoxan
Ara C
Busulfan
– Mean Lung Dose
– V20
– Previous thoracic
irradiation
Late Effects:
Venoocclusive
disease
– Clinical Symptoms
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sudden weight gain
jaundice
hepatomegaly
ascites
high bilirubin
– Incidence
• 10 - 20 % of patients,
~50% mortality
Pathology - obliteration of small
vessels
More frequent w/ Busulfan
Late Effects:
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Renal
Damage
Increase Cr, BUN,
Decrease GFR
Anemia, HTN, peripheral edema, inc. LDH
Increased risk
• Ara C
• GVHD
• TBI dose
• Cyclosporine
Amphotericin B
Busulfan
Late Effects:
Secondary
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)