Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation

Abstract

The outcomes of 293 patients with leukemia undergoing HLA-identical sibling (n ‫؍‬ 158) or related HLA-mismatched (n ‫؍‬ 135) hematopoietic cell transplantation (HCT) performed during the same time period were compared. Patients received BUCY2 in HLA-identical sibling HCT or BUCY2 ؉ ATG in mismatched HCT as conditioning regimens, followed by unmanipulated marrow and/or peripheral blood (PB) transplantation. All patients achieved full engraftment. The cumulative incidences of grades II to IV acute graft-versus-host disease (aGVHD) in the matched and mismatched cohorts were 32% (CI, 25%-39%) versus 40% (CI, 32%-48%, P ‫؍‬ .13), respectively, with the relative risk (RR) ‫؍‬ 0.64 (95% CI, 0.43-0.94), P ‫؍‬ .02. The incidence of chronic GVHD did not differ significantly between the cohorts (P ‫؍‬ .97). Two-year incidences of treatment-related mortality and relapse for matched versus mismatched were 14% (range, 9%-20%) versus 22% (range, 15%-29%) with P ‫؍‬ .10 and 13% (range, 8%-19%) versus 18% (range, 10%-27%) with P ‫؍‬ .40, respectively. Two-year adjusted leukemia-free survival (LFS) and overall survival were 71% (range, 63%-78%) versus 64% (range, 54%-73%) with P ‫؍‬ .27 and 72% (range, 64%-79%) versus 71% (range, 62%-77%) with P ‫؍‬ .72, respectively. Multivariate analyses showed that only advanced disease stage and a diagnosis of acute leukemia had increased risk of relapse, treatment failure, and overall mortality. In summary, HCT performed with related HLA-mismatched donors is a feasible approach with acceptable outcomes. (Blood. 2006;107:3065-3073)

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

“…GBM was collected on the 4th day of treatment by aspiration, and GPB was obtained on the 5th day by leukapheresis using a continuous‐flow blood cell separator (Gambro BCT, Lakewood, CO, USA; or Baxter, Chicago, IL, USA). The reason for using this protocol was that patients in our institute receive transplants composed of GBM plus GPB, which are harvested on days 4 and 5, respectively 31, 32…”

“…In HLA‐haploidentical donor transplants, patients received a regimen similar to HLA‐matched patients, except for the addition of 4 g/m 2 /d cytarabine on days 10 to 9 and 2.5 mg/kg/d antithymocyte globulin (SangStat) intravenously on days 5 to 2 pre‐transplantation. GVHD prophylaxis included cyclosporine A (CSA) and short‐term methotrexate (MTX) with mycophenolate mofetil (MMF) 31, 32…”

Effect of HLA mismatch on acute graft-versus-host disease

“…A number of approaches have been developed to further expand donor availability and overcome the ''HLA barrier''. The use of ex vivo T-cell depletion, in vivo T-cell depletion, or post-transplant cyclophosphamide administration enables transplantation from a related donor with multiple HLA mismatches [19][20][21][22][23][24][25]. Although the risks of relapse and infection are a major problem following HSCT using these methods, transplantation using these methods seems to have overcome the HLA barrier and results in a good clinical outcome for patients who require transplantation, but lack an HLAidentical sibling.…”

Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia

“…Haploidentical HSCT has been successfully used in the management of hematological malignancies, with comparable disease-free survival and acceptable transplant-related mortalities (TRMs). 2 Haploidentical transplants have been carried out in patients with SAA failing IST and lacking HLA-matched related or unrelated donors. But the outcomes of haploidentical HSCT in SAA were not consistent for the small cohorts and different conditioning regimens and GVHD prophylaxis regimens.…”