Abstract
Treatment-related myelodysplastic syndromes and acute myeloblastic leukemia (t-MDS/AML) have emerged as relevant complications of autologous stem cell transplantation (ASCT) for follicular lymphoma. Given the fact that also fludarabine-cyclophosphamide combination chemotherapy, which is increasingly used for primary treatment in CLL, has been implicated in induction of secondary stem cell disorders, t-MDS/AML might be a substantial problem after ASCT for CLL, too. Therefore the purpose of this study was to analyze the incidence and characteristics of t-MDS/AML among those patients who were autografted for CLL and registered in the EBMT database. For each case submitted between 1992 and 2004, centers received a questionaire asking for follow-up information with particular focus on t-MDS/AML.
Results: Of 1139 patients identified from the database, a reply was received for 457. After these 457 autotransplants, 18 cases of t-MDS/AML were observed, giving a crude rate of 3.9%. Median time from ASCT to t-MDS/AML was 28 (10–73) months. Patients with t-MDS/AML had received 2 (1–3) lines of conventional chemotherapy prior to ASCT, containing alkylating agents in 92% and fludarabine in 71% of the patients. Only a single patient had been pretreated with combined fludarabine-cyclophosphamide. High-dose regimens comprised total body irradiation in 71% of the t-MDS/AML cases; and mobilized peripheral blood was used as stem cell source in 92%, containing 2.9 (1.4–7.8) CD34+ cells/kg. Treatment of t-MDS/AML consisted of chemotherapy in 17%, ASCT in 6%, and allo-SCT in 17%, whereas the majority of the patients received supportive care only. Median survival from diagnosis of t-MDS/AML was 8 months with 2 of the 3 allografted patients being alive 10 and 13 months post diagnosis, respectively.
Conclusions: The incidence of t-MDS/AML after ASCT for CLL does not seem to exceed the range reported for follicular lymphoma. t-MDS/AML generally occurs within the first 6 years post transplant and has a very poor prognosis. A particular impact of fludarabine-cyclophosphamide pretreatment could not be detected.
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