Myelodysplastic syndrome after autologous transplantation for lymphoma: the price of progress.

P ROGRESS, IT SEEMS, never occurs without unintended or unwanted problems. For example, the internal combustion engine revolutionized transportation, but with it came highway fatalities, air pollution, and the strip mall. Must it be the same in medicine? Miller et al’s description’ of patients who developed myelodysplastic syndrome and/or acute leukemia after high-dose therapy and autologous hematopoietic stem cell rescue for lymphoma brings up the issue again. The short-term safety (< 10% acute mortality) of autologous transplantation as a treatment modality for non-Hodgkin’s lymphoma and Hodgkin’s disease has been previously e~tablished.’.~ Most importantly, patients with relapsed non-Hodgkin’s lymph~ma’~~ and refractory Hodgkin’s not generally considered curable with conventional salvage chemotherapy, may achieve long-term disease-free survival after undergoing transplantation. In patients who are selected on the basis of continued sensitivity of their tumors to chemotherapy and who have minimal residual disease before transplant, the long-term disease-free survival rate may be 40% to 50%.’s4 The use of this expensive technology has clearly benefited many patients and could help a great many more in the future. The success of myeloablative therapy in this population has convinced many investigators to study the role of autologous transplantation in patients with non-Hodgkin’s lymphoma in first remission who have low-grade disease or in those with intermediateor high-grade disease at significant risk to relapse on the basis of advanced stage at Therefore, the experience described by transplant physicians at the University of Minnesota’ and preliminary reports from several other centersg”’ concerning the development of myelodysplasia as a late complication after autologous transplantation mandates careful examination. When one learns of a 15% actuarial incidence of myelodysplasia after autologous bone marrow transplantation,’ many questions arise. Is the problem actually of such a significant magnitude or is this just an aberration at one center caused by one particular approach or by the inevitable vicissitudes of statistics (ie, bad luck)? Could it be an artifact caused by an inability to diagnose myelodysplasia as accurately after transplant as in the patient who walks in off the street, never having previously met a medical oncologist? Can we identify patients who are at particularly high risk to develop myelodysplasia after transplantation? Is myelodysplasia really a “complication” of transplant or is it just a consequence of successful antilymphoma therapy? More patients with lymphoma who have received many alkylating agent-containing chemotherapeutic regimens may now be long-term survivors. Should our approach to patients with advanced or poor prognosis lymphoma be altered based on this description of a potentially new setting for iatrogenic leukemia? And I’ve just begun to ask. Myelodysplasia after autologous transplant for lymphoma, if not a real problem, is certainly being reported with increas-