1.
Fludarabine and Total Body Irradiation Conditioning Prior to Ablative Haploidentical Transplantation: Long-term Safety and Efficacy
Solomon, S. R., Solh, M., Zhang, X., Morris, L. E., Holland, H. K., Bashey, A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Although myeloablative conditioning (MAC) prior to haploidentical donor transplant (HIDT) with post-transplant cyclophosphamide is beig increasingly utilized, the optimal preparative regimen remains unclear. In our initial trial, the feasibility of HIDT following a MAC preparative regimen using fludarabine and 12Gy of total body irradiation was demonstrated in 30 patients. We now present long-term outcome results including an additional 52 patients, now with 47 months (16-96) median follow-up. Median patient age was 42 (19-61) years. The most common diagnoses were AML (51%) and ALL (33%), and 39% were high/very high disease risk index (DRI). Engraftment was universal with no cases of primary or secondary graft failure. Grade 3-4 acute graft-versus-host disease (GVHD) and moderate-to-severe chronic GVHD occurred in 17% and 23%, respectively. Non-relapse mortality (NRM) was 7% at 1 year and 13% at 4 years. Estimated 4-yr OS, DFS and cumulative incidence of relapse (CIR) was 67%, 60% and 27% respectively. CIR was significantly higher in patients with high/very high vs. low/intermediate risk DRI (38% vs. 20%, p=0.032), which led to inferior 4-yr OS (50% vs. 77%, p=0.001). Median time to systemic immunosuppressive therapy (IST) discontinuation was 7.8 months, with 84% of patients off IST at 2 years post-transplant. Current GHVD-, relapse-free survival (CGRFS) at 2, 3, and 4 years was 60%, 57% and 60% respectively. This approach to MAC HIDT results in universal engraftment, low rates of NRM, infection and clinically significant GVHD, relatively rapid IST discontinuation resulting in high rates of CGRFS and survival.
2.
Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia
Hamilton, B. K., Rybicki, L., Abounader, D., Adekola, K., Advani, A., Aldoss, I., Bachanova, V., Bashey, A., Brown, S., DeLima, M., et al
Biology of Blood & Marrow Transplantation. 2017;23(7):1117-1121
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P=.021), age >35 years (HR, 1.55; P=.025), and disease status at HCT (HR, 1.98; P=.005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.