1.
Improved survival for young acute leukemia patients following a new donor hierarchy for allogeneic hematopoietic stem cell transplantation: a phase III randomized controlled study
Zhang, M., Xiao, H., Shi, J., Tan, Y., Zhao, Y., Yu, J., Lai, X., Hu, Y., Zheng, W., Luo, Y., et al
American journal of hematology. 2021
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Abstract
The aim of our study was to evaluate the most optimal donor for young acute leukemia (AL) patients with multiple donors available for allogeneic hematopoietic stem cell transplantation (allo-HSCT), including HLA-matched sibling donors (MSDs), HLA-matched unrelated donors (URDs), haploidentical parental donors (HPDs), and haploidentical sibling donors (HSDs). From March 2008 to December 2016, 430 AL patients = 35?years of age were included in the discovery, retrospective study. Patients who received transplantation from a MSD or a HSD had better 5-year OS rates compared with patients who received transplantation from a URD or a HPD. A superior graft-versus-leukemia effect was observed for high-risk patients undergoing HSD-HSCT with a lower relapse rate (P = .014) and a higher disease-free survival (DFS) rate (P = .029) compared with those undergoing MSD-HSCT. Outcomes of high-risk patients receiving an URD or HPD were equivalent. For intermediate/standard-risk patients, either a MSD or HSD may be the front-line donor selection with comparable outcomes. URDs were preferred over HPDs with reduced non-relapse mortality and higher overall survival (OS) and DFS rates. We further conducted an independent prospective randomized study to evaluate the survival advantage with the new donor hierarchy. Two hundred and fifty patients were randomly assigned to follow our new donor hierarchy or the traditional donor hierarchy at a 2:1 ratio. The new donor hierarchy contributed to significantly superior 2-year OS and DFS rates (OS: 76.2% vs. 67.8%, P = .046; DFS: 71.8% vs. 64.5%, P = .039). This article is protected by copyright. All rights reserved.
PICO Summary
Population
Patients with acute leukaemia aged </=35 years undergoing allogeneic transplantation in a single centre in China, with multiple donors available (Retrospective cohort: n=430; RCT cohort: n=250)
Intervention
New donor hierarchy based on results from retrospective cohort (n=166): haploidentical sibling donor (HSD, n=91) then matched sibling donor (MSD, n=38); then matched unrelated donor (URD, n=9) or haploidentical donor (HPD, n=28)
Comparison
Traditional donor hierarchy (n=84): HLA-matched sibling donors (n=16) followed by matched unrelated donors (n=29), then other donors (haploidentical donors or unrelated cord blood, n=39)
Outcome
In the discovery, retrospective study, patients who received transplantation from a MSD or a HSD had better 5-year OS rates compared with patients who received transplantation from a URD or a HPD. In the RCT, a superior graft-versus-leukemia effect was observed for high-risk patients undergoing HSD-HSCT with a lower relapse rate and a higher disease-free survival (DFS) rate compared with those undergoing MSD-HSCT. Outcomes of high-risk patients receiving an URD or HPD were equivalent. In the RCT cohort, the new donor hierarchy contributed to significantly superior 2-year OS and DFS rates (OS: 76.2% vs. 67.8%; DFS: 71.8% vs. 64.5%).
2.
Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study
Chang, Y. J., Wu, D. P., Lai, Y. R., Liu, Q. F., Sun, Y. Q., Hu, J., Hu, Y., Zhou, J. F., Li, J., Wang, S. Q., et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020;:Jco2000150
Abstract
PURPOSE The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.
3.
Plerixafor and granulocyte-colony-stimulating factor for mobilization of hematopoietic stem cells for autologous transplantation in Chinese patients with non-Hodgkin's lymphoma: a randomized Phase 3 study
Zhu, J., Huang, H., Chen, H., Zhang, X., Li, Z., Wu, D., Zhou, D., Song, Y., Hu, Y., Liang, Y., et al
Transfusion. 2017
Abstract
BACKGROUND This Phase 3 randomized, double-blind study evaluated the efficacy and safety of plerixafor plus granulocyte-colony-stimulating factor for the mobilization of hematopoietic stem cells in Chinese patients with non-Hodgkin's lymphoma. STUDY DESIGN AND METHODS Adults (ages 18-75 years) with non-Hodgkin's lymphoma in first or second complete or partial remission, without previous hematopoietic stem cell mobilization or autologous transplant, were included. Patients received granulocyte-colony-stimulating factor 10 micro g/kg/day from Days 1 through 4 before they were randomized (1:1) to receive either plerixafor 0.24 mg/kg/day or placebo subcutaneously on Days 4 through 7 plus continued granulocyte-colony-stimulating factor on Days 5 through 8. Apheresis began on Day 5 and continued for no more than 4 days. The primary endpoint was collection of 5 x 106 CD34+ cells/kg or greater over no more than 4 days of apheresis. Other endpoints included the collection of 2 x 106 CD34+ cells/kg or greater and safety. RESULTS Overall, 101 patients were enrolled, and 50 were randomized to each group. More patients in the plerixafor group achieved 5 x 106 CD34+ cells/kg or greater (62 vs. 20%; p<0.0001) or 2 x 106 CD34+ cells/kg or greater (88 vs. 66%) and underwent transplantation (88 vs. 68%) compared with those in the placebo group. The most common plerixafor-related adverse events were nausea (7.8%) and diarrhea (3.9%). CONCLUSION Plerixafor plus granulocyte-colony-stimulating factor is superior to placebo plus granulocyte-colony-stimulating factor for the mobilization of CD34+ cells for autologous transplantation and is generally well tolerated in Chinese patients with non-Hodgkin's lymphoma.