ALBERT

Description: Background: Although busulfan (Bu) in combination with cyclosphosphamide (Cy) is a commonly used conditioning regimen for the treatment of patients with hematologic diseases, its toxicity profile when administered intravenously (IV) as well as efficacy remains unclear, especially in the setting of autologous transplant for lymphoma. Objective: To determine toxicity and the efficacy of the IV Bu/Cy conditioning regimen in patients who underwent autologous peripheral stem cell transplantation (APSCT) for the treatment of lymphoma. Methods: A retrospective analysis was performed in 37 patients (21 male; 16 female) who underwent APSCT and received IV Bu/Cy regimen between January 2000 and May 2004. Results: The median age was 50 years old (range: 20–68). Forty-seven percent of the patients were heavily pretreated (≥ 3 previous treatment, range 2–5). The distribution of lymphoma was: diffuse large B-cell lymphoma (DLBCL, 23), follicular lymphoma (8), mantle cell lymphoma (MCL, 5), and T-cell lymphoma (1). All patients received IV busulfan 3.2 mg/kg and cyclophosphamide 120 mg/kg, and were evaluable for toxicity. The patients engrafted (ANC ≥ 500 μ/l) at a median of 11 days (range: 9–14), and sustained platelet count (≥ 20,000 μ/l) at a median of 11 days (range: 8–42). The most common toxicities encountered were grade 1–2 including nausea, vomiting, stomatitis, esophagitis, and diarrhea. Grade 3–4 toxicities included hepatic veno-occlusive disease (HVOD, n=2), SIADH (n=1), and atrial fibrillation (n=2). Treatment related mortality (TRM) was seen in 3 patients due to HVOD (n=2) and septic shock (n=1). Twenty patients are still alive and 18 have no evidence of disease progression, with a median follow up of 17 months (range: 2–54 months). Kaplan-Meir actuarial OS at 24 months was 55.3% with a 47.3% DFS. Median event-free survival was 24 months (range 2–52). Conclusions: IV Bu/Cy is a well-tolerated conditioning regimen with acceptable TRM, when compared with other regimens in heavily pretreated patients. The risk for HVOD is low. Further prospective trials are necessary to evaluate the role of Bu/Cy regimen in autologous stem cell transplant for lymphoma.

Description: 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.