Risk-Adapted Approach to HLA-Matched Sibling Hematopoietic Cell Allografting: Impact of Adjusting Conditioning Intensity and Integrating Post-Transplant Therapeutic Interventions

Abstract

Background: Optimizing conditioning and post-transplant intervention may reduce non-relapse mortality and relapse, improving survival after allogeneic hematopoietic cell transplantation (allo-HCT).

Materials and methods: We used a risk-adapted intensity of busulfan at 130 mg/m(2)/day for either 2, 3, or 4 days, with a fixed dose of fludarabine (30 mg/m(2)/day for 5 days), and thymoglobulin (2.5 mg/kg/day for 2 days). Our algorithm was based on age, comorbiditie(s), and disease risk.

Results: Fifty-three patients with hematological malignancies (median age, 37 years; range, 16-65 years), received an allograft from human leukocyte antigen identical siblings. Post-transplant therapy was initiated between days 30 and 60 after allo-HCT. Twenty-five of 26 patients who were planned for post allo-HCT therapy received it (10 with myeloid malignancies received 5-azacytidine, 5 with FLT-3 ITD acute myeloid leukemia received sorafenib, 4 with Philadelphia-positive acute lymphoblastic leukemia or chronic myelogenous leukemia in blast crisis received dasatinib, or dasatinib followed by imatinib, and 5 with acute lymphoblastic leukemia received intrathecal cytarabine). The remaining 27 patients (51%) did not receive post-transplant therapy because of lack of approval by third-party payers. After a median follow-up of 13 months (range, 2-57 months), 1-year non-relapse-mortality was 2%, and cumulative incidences of grade 2 to 4 acute graft-versus-host disease and all grades chronic graft-versus-host disease were 23% and 9%, respectively. The 2-year overall survival (95% vs. 61%; P = .04) and progression-free survival (81% vs. 53%; P = .05) were significantly better for patients in the post-transplant therapy group.

Conclusion: This risk-adapted combined approach of selecting conditioning intensity and integrating post-transplant therapies results in lower non-relapse-mortality and encouraging improvement in survival. Our findings warrant confirmation in a large prospective multicenter trial.

Keywords: 5-Azacytidine; Allogeneic stem cell transplantation; Dasatinib; Personalized conditioning; Sorafenib.