CD34-selected hematopoietic stem cell transplants conditioned with myeloablative regimens and anti-thymocyte globulin for advanced myelodysplastic syndrome: limited graft-versus-host disease without increased relapse

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for patients with myelodysplastic syndrome (MDS). Donor T cells are critical for graft-versus-tumor effect (GVT) but carry the risk of graft-versus-host disease (GVHD). CD34 selection with immunomagnetic beads has been an effective method of depleting alloreactive donor T cells from the peripheral blood graft and has been shown to result in significant reduction in acute and chronic GVHD. We analyzed the outcomes of 102 adults (median age 57.6 years) with advanced MDS who received a CD34 selected allo-HSCT between January 1997 and April 2012 at Memorial Sloan Kettering Cancer Center. The cumulative incidence (CI) of grade II-IV acute GVHD at day 100 was 9.8% (95% CI: 5.0-16.5%) and at day 180, 15.7% (95% CI: 9.4-23.4%). The CI of chronic GVHD at 1 year was 3.9% (95% CI: 1.3-9.0%). The CI of relapse at 1 year was 11.8% (95% CI: 6.4-18.9%) and at 2 years 15.7% (95% CI: 9.4-23.4%). Forty-eight patients were alive with a median follow-up of 71.7 months. The overall survival (OS) at 2 years was 56.9% (95% CI: 48-67.3%) and at 5 years, 49.3% (95% CI: 40.4-60.2%). Relapse-free survival (RFS) at 2 years was 52.0% (95% CI: 41.9-61.1%) and at 5 years, 47.6% (95% CI: 37.5-56.9%). The CI of non-relapse mortality was 7.8% (95% CI: 3.7-14.1%) at day 100, 22.5% (95% CI 15.0-31.1%) at 1 year and 33.4% (95% CI:24.2-42.6%) at 5 years post-transplant. Chronic GVHD/relapse-free survival (CRFS) overlapped with RFS. These findings demonstrate that ex-vivo T- cell depleted (TCD) allo-HSCT by CD34 selection offers long term OS and RFS with low incidences of acute and chronic GVHD and without an increased risk of relapse.