Myelodysplastic (MDS) Syndrome and Leukemia After Autotransplantation for Lymphoma: a Multicenter Case-Control Study

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 12, 2001

Presenter: D. J. Rizzo
Affiliation: NCI, Bethesda, MD


  • Increased survival has been seen in pateints with Hodgkin?s disease and Non-Hodgkin?s lymphoma who underwent autotransplantation, with a 40-50% long-term disease-free-survival rate.
  • However, previous reports indicate that pts receiving autotransplants for lymphoma have an increased risk of MDS/Leukemia.
  • The separate contributions of pre-tranplant and tranplant-related therapy to this risk are not well chararcterized.

Materials and Methods:

  • Case-control study of 56 pts with MDS/leukemia from 955 pts receiving autotransplants for HD and 1784 for NHL, 1989- 1995 at 12 institutes in North America with follow up through Dec. 31, 1996.
  • Three age-, sex- and latency-matched controls were randomly selected for each case.
  • Medical records reviewed to determine all pre- and post- transplant therapy and related procedures.


  • In multivariate analyses, pre-transplant chemotherapy is the largest contributor for risk of developing MDS/leukemia. With 4- and 10- fold increased risks in pts given mechlorethamine (MOPP-like regimen) and chlorambucil (p <0.05), compared to those given only cyclophosphamide- based treatment (2 fold).
  • Risk increased with increasing dose of mechlorethamine > 50 mg/m2 (Relative risk 4.8) and increasing duration of chlorambucil ( > 10mos, RR 16.8)
  • For total body irradiation (TBI), no substantial increased risk observed for dose < 12Gy (RR1.4). However, for doses of 13.2 Gy, there was statistically significant 4-5 fold (p=0.02) increased risk.
  • Peripheral blood vs bone marrow stem cell transplantation had statistcally significant 2 fold increased risk (p<0.05) in univariate but not in multivariate analyses.
  • No assoication between graft purging or use of mobilization chemotherapy/growth factors and MDS/leukemia.

Authors' Conclusions

  • The types and intesity of conventional pre- transplant chemotherapy has the strongest impact on developing MDS/leukemia after autotransplantation.
  • Although some transplant-related factors (grafting, TBI, high dose chemotherapy, purging, priming) may also play a role these findings required confirmation on other patient populations.

Clinical/Scientific Implications:

  • Additional information reported by presenter that 33/37 patients who had post-transplant cytogenetic study showed positivity for cytogenetic evidence for MDS. Further reviews of patients?s pre-transplant cytogenetic status of MDS is underway.
  • Avoidance of using MOPP or MOPP-like regimen should be undertaken in order to decrease incidence of secondary MDS/leukemia as increasing numbers of patients undergoing bone marrow or peripheral stem cell transplantation.

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