Immunotransplantation for Hematologic Malignancies Using Allogeneic Peripheral Blood Stem Cell Transplantation.

Abstract

Background: Allogeneic (allo-) transplantation offers a therapeutic option for patients diagnosed with hematological malignancies such as multiple myeloma (MM), chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma (NHL), and high-risk myelodysplastic syndrome (MDS). Although this approach has shown graft-versus-leukemia effect and potentially being curative, high rate toxicity and treatment-related mortality (TRM) have limited its use other than in the context of clinical trials. The goal of this study was to decrease toxicity of allo- hematopoeitic cell transplantation (HCT) as treatment for patients who had chemosensitive hematological malignancies while allowing the benefit of “graft-versus-tumor” effect by using a non-myeloablative HCT (NM-HCT) approach.Methods: Patients included were newly diagnosed or previously treated MM patients of any stage, NHL patients who failed of ≥ 2 chemotherapies regimens (CHOP and at least one salvage treatment), CLL refractory to standard chemotherapy, and MDS with high-risk cytogenetics. Conditioning regimen consisted of fludarabine at 30 mg/m2/day on days −5, −4, −3 and melphalan at 80 mg/m2 x 2 on days −2 and −1. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine 3 mg/kg intravenous on day −2 and methotrexate at 10 mg/m2 intravenously on days 3, 6, and 11.Results: A total of 17 patients were assessable: 11 MM patients (7 IgG, 1 IgA, 2 light chain restriction, 1 non-secretory MM), 3 NHL patients (1 FL, 1 MCL, 1 LGL-NK cell), 2 CLL, and 1 MDS (with trisomy 8, 5q−) with a median age of 50.4 years old (range, 34 to 60 years). Three patients received more than two regimens prior to NM-HCT. The initial responses to therapy prior to NM-HCT were: 5 CR, 2 nCR, and 10 PR. All patients received identical 6/6 HLA sibling donor stem cells. All patients but one attained CR (94%) after NM-HCT. The median time for ANC engraftment was 15.4 days (range, 10–36 days). Eight patients developed acute GVHD grade I–III (5 skin, 3 gastrointestinal); all of them responded well to methylprednisolone treatment. Nine patients developed chronic GVHD (grade I–II). The 100-day mortality rate was 5.9% (1 patient died at day + 96 without evidence of MM). Post-transplant, all patients have reported a Karnofsky's scale performance status between 80%–100%. Three patients (all MM) relapsed after 4, 6, and 32 months post-transplantation. Only one patient received auto-HCT, but continues to have progressive disease, and is on thalidomide/dexamethasone. Only 3 patients had relapsed at 5−, 6−, and 25 months (all MM patients). After a median follow-up of 42.5 months (range, 1–78 months), median survival has not been reached.Conclusions: NM-HCT is a feasible treatment option with manageable toxicity profile. TRM was less than those reported for myeloablative HCT, and results suggest a graft-versus-tumor effect on these types of hematological malignancies using a NM-HCT approach based on CR rate observed as well as median time to progression. These encouraging results warrant further investigation.