How Andy Warhol Treated Myelodysplastic Syndrome

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How Andy Warhol Treated MyelodysplasticSyndrome
Mike Martin, MD Grand Rounds
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MDS

• Approx. 5,000 Dx annually
• Median age 65-70 years old
• Insult is to the hematopoietic stem cell
• Accumulate genetic mutations
• Growth advantage

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Who to treat?
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Who to treat? And how?
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EPO

• Phase II trials have RR of 25
• Endpoints inconsistently defined at time of most
  studies
• EPO lt500 predicts response
• Best in non-transfusion dependent
• Addition of G-CSF increased to 40
• 50 patient Phase II trial
• Dose escalation 30-gt75-gt150mcg
• 38 response rate
• CR Hgb of 11.5, PR inc by 1.5 and 100
  transfusion independence

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G/GM-CSF

• 2 trials with lack of efficacy at decreasing
  infection or impacting OS
• Qualitative defects

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IL-11

• Low dose 10mcg/kg/day
• 5 of 11 patients with plt increase
• Median increase was 95,000, duration measured in
  weeks
• Grade 1 peripheral edema and myalgias
• Too small to comment on changes in bleeding risk,
  etc

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Lenalidomide 5q Minus
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5q Minus
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Arsenic Trioxide

• Mitochondrial membrane depolarization and
  downstream apoptosis through reactive o2 species
• Specific pro-apoptotic pathways

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Schiller et al JCO 2006

• 250mcg/kg x 5days qweek x2, then 2 weeks off
• 70 patients
• HI rates 34-39 in low risk
• HI rates 6-9 in high risk
• 33 gained transfusion independence
• 2 TR deaths
• 44 c Grade ¾ thrombocytopenia
• 11 c Grade ¾ febrile neutropenia

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Immunosuppression

• Lymphocyte mediated suppression of myeloid CFUs
• Select group of potential responders
• HLA-DR15
• FAB RA
• lt 60 years old
• Short duration of transfusion dependence
• RR 60
• Thymoglobulin
• Cyclosporine
• Combined

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Cure?
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• Median age 38
• 5 early and 8 late graft failure
• 14 2-year relapse
• 29 2-year DFS
• 54 2-year TRM
• Correlated with age, HLA mismatch and recipient
  CMV

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• 452 patients
• Median age 38
• 9 graft failure
• 23 3-year relapse
• 40 3-year DFS

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37 3-year TRM
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Conundrum?
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Induction effect?
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