Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis

PLOS ONE, Nov 2019

Purpose Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLA-identical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis. Methods Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis. Results Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70–3.93, P < 0.00001). The risk of acute graft-versus-host disease (GVHD) is significantly higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42–2.49, P < 0.00001), but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55–0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08–1.62, P = 0.006; OR = 1.25, 95% CI = 1.03–1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT. Conclusion After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available.

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Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis

January Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis Dangui Chen 0 1 Di Zhou 1 Dan Guo 0 1 Peipei Xu 1 Bing Chen 0 1 0 Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University , Nanjing , People's Republic of China, 2 Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School , Gulou district, Nanjing , People's Republic of China 1 Editor: Senthilnathan Palaniyandi, University of Kentucky , UNITED STATES Haploidentical and human leukocyte antigen (HLA)-identical sibling hematopoietic stem transplantation are two main ways used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable progress has been made in haploidentical allo-HSCT (HID-SCT), and some institutions found HID-SCT had similar outcomes as HLAidentical sibling allo-HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic malignancies, we performed this meta-analysis. Relevant articles published prior to February 2017 were searched on PubMed. Two reviewers assessed the quality of the included studies and extracted data independently. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis. - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work is supported by Peak of Six Talent in Jiangsu Province (2015-WSN-075). Competing interests: The authors have declared that no competing interests exist. Purpose Methods Results Seven studies including 1919 patients were included. The rate of platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70±3.93, P < 0.00001). The risk of acute graft-versushost disease (GVHD) is significantly higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42±2.49, P < 0.00001), but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55±0.90, P = 0.005). The incidence rates of overall survival (OS) and disease-free-survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISDSCT are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08±1.62, P = 0.006; OR = 1.25, 95% CI = 1.03±1.52, P = 0.02). There is no significant difference in transplantation related mortality (TRM) rate after HID-SCT and ISD-SCT. Conclusion After myeloablative conditioning, patients receiving ISD-SCT have a faster engraftment, lower acute GVHD and longer life expectancy compared to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA-identical sibling donor available. Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with human leukocyte antigen (HLA)-identical sibling or unrelated donor is the main way for treatment for high-risk hematological malignancies. For patients without a suitable donor, especially those in urgent need of transplantation, haploidentical allo-HSCT (HID-SCT) is an option [ 1 ]. HID-SCT was unsuccessful for many years because of graft rejection and high incidence of acute graft-versus-host disease (GVHD), but the progress in GVHD prophylaxis and conditioning regimen has made HID-SCT possible [ 2,3 ]. A multicenter phase-2 study from the Chinese Bone Marrow Transplant Cooperative Group (CBMTCG) showed that the combination of cyclosporine A, methotrexate, mycophenolate mofetil (CsA + MTX + MMF) for GVHD prophylaxis signifi cantly decreased the incidence of acute GVHD without an increase in relapse or any adverse impact on survival in standard-risk patients compared with historical controls in ISD-SCT [ 4 ]. Similarly, ATG deletes T lymphocytes chronically in vivo, and prevents GVHD without increasing the risks of relapse [ 5,6 ]. Some institutions demonstrated HID-SCT using conditioning regimen including ATG yielded similar outcomes to ISD-SCT for hematological malignancies [ 7,8 ]. Some studies also indicated similar outcomes after HID-SCT compared to HLA-identical allo-HSCT [ 9,10 ]. At present, HID-SCT has been accepted by many transplantation centers. Over the past decades, much progress has been made to improve the outcomes of transplantation, including in the conditioning regimen; prophylaxis; lower cumulative incidence rates of GVHD, transplantation-related mortality/ no-relapse mortality (TRM/NRM) and relapse; higher rates of OS and DFS/LFS/PFS. However, there haven't been well-controlled studies to compare the efficacy of HID-SCT and ISD-SCT. Therefore, our meta-analysis aims to investigate whether HID-SCT has similar outcomes compared with I (...truncated)


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Dangui Chen, Di Zhou, Dan Guo, Peipei Xu, Bing Chen. Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: A meta-analysis, PLOS ONE, 2018, Volume 13, Issue 1, DOI: 10.1371/journal.pone.0191955