Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts

Abstract

We compared outcomes of adult patients receiving T-cell depleted (TCD) hematopoietic stem cell transplantation (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52) with patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for acute lymphoblastic leukemia in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received ATG at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (p=0.001, 17.3% vs. 42.6% at 100 days) and chronic GVHD (p=0.006, 13.5% vs. 33.4% at 3 years) were significantly lower in the TCD group. The NRM at day 100, 1 and 3 years was 15.4%, 25.0% and 35.9% in the TCD group and 9.6%, 23.6% and 28.6% in the unmodified group (p=0.368). There was no difference in relapse (p=0.107, 21.3% vs. 35.5% at 3 years), OS (p=0.854, 42.6% vs. 43.0% at 3 years), or RFS (p=0.653, 42.8% vs. 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (HR=2.16, p=0.003, HR=1.77, p =0.022, HR=2.47, p<0.001), while graft type was not significant (HR=0.90, p=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.

Ex Vivo CD34+–Selected T Cell–Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

“…Additionally, the lack of a control group of patients receiving unmodified grafts during the same period, precludes the comparisons of the results of this approach with a more widely used approach with unmodified grafts. Notwithstanding, other studies with a control group have also shown a low incidence of GVHD without an increase in disease relapse when compared with unmodified graft recipients 27,41,42 .…”

“…Management of early toxicities, engraftment, and infections was performed according to standard clinical practice as previously described 25–27 .…”

Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant

“…[15,29] Positive selection of CD34+ cells was performed by using Isolex 300i Magnetic Cell Separator (Baxter, Deerfield, IL) and subsequent sheep RBC rosette depletion,[13] or using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Gladbach, Germany). [21,30] In addition, 32 patients received combined T cell depleted BM and PBSC allografts, on a protocol in which both products were being administered. Equine anti-thymocyte globulin (ATG, 15 mg/kg/dose × 2 equine) or rabbit ATG (2.5 mg/kg/dose × 2) provided graft rejection prophylaxis.…”

Hematopoietic Cell Transplantation Comorbidity Index Predicts Outcomes in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Receiving CD34 + Selected Grafts for Allogeneic Hematopoietic Cell Transplantation

“…(1, 2, 20) Positive selection of CD34+ cells was performed by using Isolex 300i Magnetic Cell Separator (Baxter, Deerfield, IL) and subsequent sheep RBC rosette depletion,(2) or using the CliniMACS CD34 Reagent System (Miltenyi Biotech, Gladbach, Germany). (8, 21) Equine or rabbit anti-thymocyte globulin (ATG) was used to promote engraftment in the majority of cases. Patients did not receive any other post-transplant immunosuppressive prophylaxis.…”