Journal Article

Superior GVHD-free, relapse-free survival for G-BM to G-PBSC grafts is associated with higher MDSCs content in allografting for patients with acute leukemia

Xu, Xiaojun, Huang, Fen, Xu, Na, Ling, Yiwen, Liang, Xinquan, Liao, Xin, Ye, Jieyu, Fan, Zhiping, Xuan, Li, Fan, Qian, Liu, Hui, Yang, Ting, Liu, Qifa

2017

Overview

Background Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (G-PBSC) has largely replaced unstimulated bone marrow (un-BM) for allografting because of accelerated engraftment, but with a higher morbidity and mortality of graft-versus-host-disease (GVHD). Recent studies suggested that G-CSF-primed BM (G-BM) had similar engraftment but lower morbidity and mortality of GVHD comparing to G-PBSC. A prospective, randomized, multicenter study was conducted to compare G-BM with G-PBSC as the grafts in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia in first complete remission (CR1). Methods Totally 101 adult leukemia in CR1 undergoing HLA-identical sibling transplants were randomized into G-BM or G-PBSC group. The primary study endpoint was GVHD-free/relapse-free survival (GRFS). Results Both the engraftment of neutrophil and platelet were 2 days later in G-BM than in G-PBSC group ( P  = 0.412, P  = 0.39). G-BM group showed significantly lower II–IV acute GVHD (aGVHD) and similar III–IV aGVHD compared with G-PBSC group (12.2% vs 28.8% for II–IV, P  = 0.048; 4.1% vs 9.6% for III–IV aGVHD, P  = 0.267, respectively). The overall cumulative incidence of chronic GVHD (cGVHD) at 3 years were 22.3% ± 6.3% and 44.8% ± 7.6% ( P  = 0.026), respectively, and extensive cGHVD were 4.5% ± 3.1% and 15% ± 5.3% ( P  = 0.08), respectively, in G-BM and G-PBSC groups. Two groups had similar 3-year relapse, transplant-related mortality (TRM), overall survival (OS), and disease-free survival (DFS) (all P  > 0.05). G-BM group showed significantly higher probability of GRFS than G-PBSC group (73.5% ± 6.3% vs 55.8% ± 6.9% at 1 year, P  = 0.049; 69.0% ± 6.7% vs 49.7% ± 7.0% at 2 and 3 years, P  = 0.03, respectively). Graft content analysis revealed statistically higher frequency of myeloid-derived suppressor cells (MDSCs) in the G-BM than in G-PBSC grafts ( P  < 0.01), and recipients received statistically higher numbers of MDSCs in G-BM than in G-PBSC group ( P  = 0.045). Numbers of MDSCs infused to patients were negatively correlated with the severity of aGVHD ( P  = 0.032, r  = −0.214). Multivariate analysis showed that MDSC cell dose below the median (HR = 3.49, P  < 0.001), recipient age (HR = 2.02, P  = 0.039), and high risk of disease (HR = 2.14, P  = 0.018) were independent risk factors for GRFS. Conclusions G-BM grafts lead a better GRFS and less GVHD associated with a higher MDSCs content compared with G-PBSC grafts.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Acute leukemia / Adolescent / Adult / Bone marrow / Bone marrow transplantation / Bone Marrow Transplantation - adverse effects / Bone Marrow Transplantation - methods / Cancer Research / Care and treatment / Colony-stimulating factor / Cytokines / Cytomegalovirus / Disease-Free Survival / Female / Flow cytometry / Graft vs Host Disease - immunology / Graft vs Host Disease - prevention & control / Graft vs. host disease / Graft-versus-host disease / Graft-versus-host reaction / Granulocyte colony-stimulating factor / Granulocyte colony-stimulating factor (G-CSF)-primed bone marrow / Granulocyte Colony-Stimulating Factor - therapeutic use / Granulocytes / GVHD-free/relapse-free survival / Hematology / Hematopoietic Stem Cell Mobilization - methods / Hematopoietic stem cell transplantation / Hematopoietic Stem Cell Transplantation - adverse effects / Hematopoietic Stem Cell Transplantation - methods / Histocompatibility antigen HLA / Humans / Infections / Leukemia / Leukemia, Myeloid, Acute - immunology / Leukemia, Myeloid, Acute - therapy / Leukocytes (granulocytic) / Lymphocytes / Male / Medicine / Medicine & Public Health / Middle Aged / Morbidity / Mortality / Multivariate analysis / Myeloid-derived suppressor cells / Myeloid-Derived Suppressor Cells - cytology / Myeloid-Derived Suppressor Cells - drug effects / Myeloid-Derived Suppressor Cells - immunology / Neoplasm Recurrence, Local - immunology / Neoplasm Recurrence, Local - prevention & control / Oncology / Patient outcomes / Peripheral blood / Peripheral Blood Stem Cell Transplantation - adverse effects / Peripheral Blood Stem Cell Transplantation - methods / Physiological aspects / Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology / Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy / Remission / Risk assessment / Risk factors / Stem cell transplantation / Stem cells / Studies / Suppressor cells / Survival / Survival Analysis / Transplantation / Transplantation Conditioning - methods / Transplantation, Homologous - adverse effects / Transplantation, Homologous - methods / Transplants & implants / Young Adult