Comparative Effectiveness Analysis Of CD34 + Selected, T-Cell Depleted (TCD) HLA-Matched Sibling Grafts On Allogeneic Hematopoietic Cell Transplantation For Patients With Acute Myeloid Leukemia (AML) In Complete Remission
Year: 2010
Type: article
Abstract: Numerous single institution studies have demonstrated that TCD significantly reduces the incidence of graft-versus-host-disease (GVHD). However, concerns about leukemia relapse, graft rejection, and variability in technique have limited the widespread application of this approach. Promising results of TCD in patients with AML prompted the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to study a single uniform technique of CD 34+ selection using the Miltenyi CliniMacs device in a Phase II clinical trial (BMT CTN 0303) of adult AML patients in first or second complete remission (CR1/CR2) receiving peripheral blood stem cell (PBSC), HLA-matched sibling donor transplants. We compared outcomes of the 44 patients transplanted on the BMT CTN 0303 trial to a contemporary cohort of 102 patients with AML enrolled on the BMT CTN 0101 – Phase III clinical trial of anti-fungal prophylaxis after myeloablative HCT with pharmacologic immune suppression post-transplant (IST). This analysis compared TCD (BMT CTN #0303) versus IST (BMT CTN 0101) with respect to the endpoints of: neutrophil engraftment (ENG), rates of acute and chronic GVHD, transplant-related mortality (TRM), relapse, disease-free survival (DFS), and overall survival (OS). Groups were similar for patient-, disease- and transplant specific characteristics except for the proportion of patients in CR2 (TCD 7% vs. IST 27%), unfavorable risk cytogenetics (TCD 32% vs. IST 18%), the use of mobilized PBSC (TCD 100% vs. IST 81%) and graft composition (TCD ≤1 x105 CD3+ cells/kg). The results revealed lower rates of grades II-IV acute (p=0.046) and chronic GVHD (p=0.01) in the TCD group with no difference in ENG, leukemia relapse and TRM. DFS and OS were similar between the two groups in the univariate setting and also after adjustment for potential prognostic factors using a Cox proportional hazards model. Reduction of GVHD rates without an increase in relapse rates and no requirement for post-transplant immunosuppression are distinct advantages of this method of TCD. These results support the extension of this approach to the unrelated donor setting and additional larger, prospective studies to definitively address the role of rigorous TCD in HCT.Tabled 1TCD vs IST OutcomesOutcomeTCD % (95% Confidence Interval) N=44IST % (95% Confidence Interval) N=102DFS at 6 mo81 (66-90)75 (68-87)Relapse at 12 mo19 (6-32)19 (11-26)TRM at 12 mo19 (6-31)22 (14-30)ENG at 28 d100 (86-100)90 (79-100)Acute GVHD II-IV at 100 d20 (9-32)37 (28-47)Acute GVHD III-IV at 100 d5 (0-11)10 (4-16)Chronic GVHD at 12 mo19 (7-32)47 (35-58)Overall Survival at 12 mo74 (57-85)69 (59-77) Open table in a new tab
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2054138796