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Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

ABSTRACT: Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study including 58 patients who underwent CBT with MAC or MMAC from 2000 to 2011. Neutrophil and platelet engraftment rate, overall survival (OS) and disease free survival (DFS) were significantly higher in the MMAC group (adjusted hazard ratio [HR], 2.58, 2.43, 0.36 and 0.37; p < 0.01, p = 0.01, p = 0.02 and p = 0.02, separately). Nonrelapse mortality (NRM) was comparable (p = 0.183). To validate the outcomes noted in the MMAC group, we conducted a prospective single-arm clinical trial including 188 patients who underwent CBT with MMAC from 2011 to 2015. Engraftment rate, survival and NRM of the MMAC group in the prospective trail (MMAC-P) were similar to the MMAC group in the retrospective study (MMAC-R). This study is the first to demonstrate the superiority of MMAC to MAC in CBT for hematological malignancies.

SUBMITTER: Sun Z

PROVIDER: S-EPMC6033117 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

Sun Zimin Z Liu Huilan H Luo Chenhui C Geng Liangquan L Zheng Changcheng C Tang Baolin B Zhu Xiaoyu X Tong Juan J Wang Xingbing X Ding Kaiyang K Wan Xiang X Zhang Lei L Yao Wen W Song Kaiding K Zhang Xuhan X Wu Yue Y Yang Huizhi H Han Yongsheng Y Liu Xin X Zhu Weibo W Wu Jingsheng J Wang Zuyi Z

International journal of cancer 20180312 3

Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) was added to Bu/Cy and cytarabine (CA) to TBI/Cy for a modified myeloablative conditioning (MMAC). To compare the prognosis of MMAC with MAC, we conducted a retrospective study inclu ...[more]

PMID: 29473150

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Project description:PurposeHaploidentical 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.MethodsRelevant 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.ResultsSeven 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.ConclusionAfter 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.

Project description:BackgroundThe effects of ABO incompatibility on cord blood transplantation (CBT) have not been confirmed. We retrospectively investigated the effect of ABO incompatibility on the clinical outcomes and changes of isoagglutinin titres of 261 consecutive patients who underwent CBT in a single centre.Material and methodsWe studied patients with haematological malignancies undergoing unrelated CBT following myeloablative conditioning. There were 80 matched, 72 major mismatched, 72 minor mismatched, and 37 bidirectional mismatched transplants. Risk factors that could potentially influence the patients' outcomes were evaluated. Immunoglobulin M (IgM) isohaemagglutinin antibody (IHA) titres were determined 1 day before and 2, 4, 6 and 8 weeks after the transplant.ResultsABO mismatches did not influence engraftment, transfusion requirements, event-free survival or overall survival following CBT. The anti-donor IgM serum IHA titres fell to ≤1:8 at week 8 after CBT in all patients with ABO major and bidirectional mismatches. The percentages of patients requiring platelet and red blood cell transfusions in the period 31-61 days after CBT were markedly lower than in the period 0-30 days after CBT, being 15 vs 99% for platelets and 23 vs 78% for red blood cells, respectively. Of the 69 recipients of minor mismatched CBT tested, only three with AB blood type developed low titres of anti-recipient IHA after 5 months.DiscussionIn this study ABO incompatibility did not affect clinical outcomes after CBT. A higher number of CD34+ cells infused was correlated with earlier engraftment. Severe acute graft-versus-host disease was associated with poor overall survival. As the IHA titre decreased, so did the number of patients requiring blood transfusion. Rapidly decreasing anti-donor IHA titres and the non-production of donor anti-recipient A and/or B antibodies might contribute to a good outcome of ABO-incompatible CBT with myeloablative conditioning for haematological malignancies.

Dataset Information

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

Publications

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study.

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