Efficacy of Nonmyeloablative Hematopoietic Cell Transplant (HCT) in Secondary Myelodysplastic Syndrome (MDS) and Its Impact on the Primary Disease.

Allogeneic HCT is currently the only treatment option with curative potential for secondary MDS. The efficacy of nonmyeloablative HCT in patients (pts) with secondary MDS and its impact on the primary disease is unknown. We analyzed data from 25 patients, 38–74 (median 58) years of age, with secondary MDS who were not candidates for myeloablative HCT. The primary diseases included non-Hodgkin’s lymphoma (NHL) (n=11), chronic lymphocytic leukemia (CLL) (n=5), multiple myeloma (n=2), breast cancer (n=2), acute myelogenous leukemia (n=1), Hodgkin lymphoma (n=1), and other carcinomas (n=3). At the time of HCT, 19 pts (76%), including all with non-hematologic primary malignancies, were in complete remission of the primary underlying malignancy, while 4 patients with CLL and 2 patients with follicular NHL had active disease. Twenty-four patients had received 1–6 (median 2) treatments for the primary disease 0.8–10.8 (median 6.2) years before developing MDS, including autologous HCT in 12 (48%). One patient developed MDS after local treatment for squamous cell carcinoma. The secondary MDS status at HCT was RA(RS) (n=10), RAEB/RAEB-t (n=6) or AML (n=9). The interval from MDS diagnosis to HCT was 0.2–1.5 (median 0.5) years. All pts were conditioned with fludarabine, 90mg/m² and 2 Gy TBI and received unmodified G-CSF mobilized peripheral blood progenitor cells containing a median 6.2 x10⁶ CD34+ and 2.2 x 10⁸ CD3+ cells/kg from HLA-matched related (n=13) or unrelated (n=12) donors. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. All pts had initial donor engraftment at day 28 after HCT, but 2 pts experienced subsequent graft rejections followed by MDS relapse. The incidences of grades II, III and IV acute GVHD were 28%, 12% and 4%, respectively. Fourteen pts (54%) achieved complete remissions of their MDS. Fourteen (56%) patients died; 3 from non-relapse causes and 11 from relapse/progression of MDS. The 1 year estimates of non-relapse mortality, overall and progression free survivals were 17%, 56% and 36%, respectively. The 3-year overall survival was 35% for pts with RA(RS) (n=10) and 29% for patients with more advanced disease. All pts in complete remission of the primary disease at the time of HCT remained in remission of the primary disease after the HCT. Among four pts with active CLL at the time of HCT, one achieved CR after HCT but died from MDS progression, whereas the other 3 had stable disease at the last follow-up. Among 2 pts with active follicular NHL, one achieved CR after HCT but died from progression of MDS and the other pt died on day 7 from multi-organ failure. In summary, nonmyeloablative HCT allowed for development of graft versus tumor effects for MDS. Encouragingly, none of the patients had relapse or progression of their primary malignancy following nonmyeloablative conditioning and post-grafting immunossupression. Additionally, HCT may control the primary disease (CLL and indolent NHL) if active at the time of HCT.