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

Abstract

Ex vivo CD34+ selected T-cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (a-) and chronic (c-) GVHD after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+ selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grade II–IV and III–IV aGVHD at 180 days were 16% (95% CI:12–21) and 5% (95% CI:3–9), respectively. The skin was the most frequent organ involved, followed by the GI tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (Budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. Cumulative incidence of any cGVHD at 3 years was 5% (95% CI:3–9), with a median time of onset of 256 days (range 95–1645). The 3-year transplant-related mortality, relapse, overall survival and disease-free survival were 24% (95%CI: 18–30), 22% (95% CI:17–27), 57% (95% CI:50–64) and 54% (95% CI:47–61), respectively. The 1-year and 3-years probability of cGVHD-free/relapse-free survival (CRFS) were 65% (95% CI:59–71) and 52% (95% CI:45–59), respectively. Our findings support the use of ex vivo CD34+ selected TCD allograft as a calcineurin inhibitor-free intervention for the prevention of GVHD in patients with acute leukemia and MDS.

Establishing a standardized system for review and adjudication of chronic graft‐vs‐host disease data in accordance with the National Institutes Consensus criteria

“…The additional step of capturing data within a GVHD specific database has significantly enhanced our ability to monitor GVHD incidence, response to therapy, and has decreased the time and effort required providing physicians with GVHD data to support projects and manuscripts. The adjudicated GVHD data has been used in several manuscripts within our institution . Improved monitoring of GVHD incidence has also enhanced our ability to assess feasibility of clinical trials in development.…”

Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome: Comparison of Outcomes between CD34+ Selected and Unmodified Hematopoietic Stem Cell Transplantation

“…Cause of death was determined using a NMDP algorithm 29 . CRFS was defined as the combined outcome of being alive and free of chronic extensive GVHD and relapse state 22 .…”

“…However, retrospective comparison studies have been published in patients with acute myelogenous leukemia (AML) in first complete remission 20 and acute lymphoblastic leukemia (ALL) 21 in first or second complete remission and have shown similar survival although with much less GVHD in the CD34 + selected transplants. This study compares the standard transplant outcomes and also the composite end point of chronic GVHD free and relapse free survival (CRFS) 22 which is currently being studied in a prospective manner through a BMT CTN study (BMT CTN 1301, NCT02345850) in patients with advanced MDS who underwent CD34 + selected allo-HSCT at MSKCC with those who received unmodified allo-HSCT at MDACC between 2001–2012.…”

Advances in ex vivo T cell depletion - where do we stand?

“…Earlier positive selection techniques employed the ISOLEX 300i magnetic cell selection system (Baxter; Deerfield, IL) followed by E‐rosetting . Current studies use the more efficient CliniMACS CD34 Reagent System (Miltenyi Biotec; Bergisch Gladbach, Germany), which uses super‐paramagnetic particle conjugated antibodies . The CliniMACS system is able to achieve a 5‐log T cell depletion while retaining a median viability of 98%, and in direct comparison with ISOLEX 300i the CliniMACS system yielded a product with higher CD34+ purity (90% vs 78%, P = 0.004), and lower median T‐cell content (0.06% vs 0.44%; P = 0.003) .…”