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BACKGROUND: Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases, and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival; however, there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE: To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS: Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed. A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at +2 days were categorized into the recombinant human thrombopoietin group; a total of 27 patients who started to orally take Herombopag Olamine at +2 days were categorized into the Herombopag Olamine group; and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group. The implantation status, incidence of acute graft-versus-host disease of degree II-IV within 100 days, 1-year survival rate, 1-year recurrence rate, and safety were analyzed in the three groups. RESULTS AND CONCLUSION: (1) The average follow-up time was 52(12-87) months. The implantation time of neutrophils in the blank control group, recombinant human thrombopoietin group, and Herombopag Olamine group was (12.95±3.88) days, (14.04±3.71) days, and (13.89±2.74) days, respectively, with no statistically significant difference (P=0.352); the implantation time of platelets was (15.16±6.27) days, (17.67±6.52) days, and (17.00±4.75) days, with no statistically significant difference (P=0.287). (2) The complete platelet implantation rate on day 60 was 64.06%, 90.28%, and 92.59%, respectively, and the difference was statistically significant (P < 0.001). The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant (P < 0.001), and the difference between the blank control group and the Herombopag Olamine group was statistically significant (P=0.004). The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group (P=0.535). (3) 100-day II-IV degree acute graft-versus-host disease incidence in the blank control group, recombinant human thrombopoietin group, and Herombopag Olamine group were 25.00%, 30.56%, and 25.93%, respectively, and the difference was not statistically significant (P=0.752). (4) The incidence of cytomegalovirus anemia, cytomegalovirus pneumonia, and hepatic function injury had no statistical difference among the three groups (P > 0.05). (5) During the follow-up period, there was no thrombotic event in any of the three groups of patients. (6) The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation, with comparable efficacy and good safety [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies. In recent years, the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing. At present, the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China, but this model requires the collection of donor bone marrow fluid, which increases the pain and risk of the donor. OBJECTIVE: To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases. METHODS: Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3. Among them, 19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation, and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells. The study was approved by the Ethics Committee of Henan Provincial People’s Hospital. The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells (1×106 /kg) on the day of transplantation, followed by peripheral blood hematopoietic stem cells 6 hours later. In the bone marrow group, donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation. After transplantation, rabbit anti-human thymocyte immunoglobulin, cyclosporine A, mycophenolate mofetil, and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients. RESULTS AND CONCLUSION: No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells. There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate [100% (19/19) vs. 96.8%(30/31), P > 0.05], median duration for neutrophil engraftment (14 days vs.15 days, P > 0.05) and median duration for platelet engraftment (20 days vs.19 days, P > 0.05). The incidence of grade IIIV acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group [21.1% (4/19) vs. 58.1% (18/31), P = 0.01]. There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease [21.1% (4/19) vs. 25.8% (8/31), P > 0.05], the relapse rates [15.8% (3/19) vs. 16.1% (5/31), P > 0.05] and the incidence of early cytomegalovirus viremia [42.1% (8/19) vs. 35.5% (11/31), P > 0.05], and the 2-year overall survival rate [68.4% (10/19) vs. 70.9% (16/31), P > 0.05]. It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases, which reduced the incidence of acute graft-versus-host disease after transplantation, did not increase the incidence of chronic graft-versus-host disease, recurrence rate and early cytomegalovirus viremia, and reduced the pain and risk of donor pulp extraction. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of anti-HLA donor-specific antibodies (DSA) and desensitization for DSA+patients on engraftment of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods The patients who underwent haplo-HSCT and examinations for HLA antibodies and DSA in our department from March 2017 to July 2023 were recruited in this study.The effects of desensitization measure on engraftment in the DSA+patients after haplo-HSCT were analyzed. Results Among the 70 patients who underwent haplo-HSCT and test for HLA antibodies, 15(21.4%) patients were DSA positive, including 7(46.7%) cases of strong positive, 3(20.0%) cases of moderate positive, and 5(33.3%) cases of weak positive.The median duration for neutrophil implantation was significantly extended in the DSA+patients than the negative patients (P=0.027).For the 6 patients developed graft failure (GF), 4 were DSA+which was statistically higher than the DSA-patients (P=0.025).Multivariate regression analysis showed that DSA was an independent factor affecting GF (HR=9.273, 95%CI: 1.505~57.124, P=0.016).Among the 10 patients (7 strong positive and 3 moderate positive DSA) received desensitization therapy, 4 patients received combination desensitization, with a 100% rate of successful transplantation, and 6 received single desensitization, with 4(66.7%) experiencing GF, so the GF rate was obviously lower in the combination than the single desensitization (P=0.008). Conclusion In haplo-HSCT patients, DSA is an important factor leading to implantation delay and GF.While, single desensitization treatment has limited efficacy.In combined DSA desensitization therapy, the decrease of antibody titer should be dynamically monitored to ensure the successful implantation of stem cells and reduce GF rate.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose, but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE: To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS: 135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center, Department of Hematology, First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included. Combining the results of previous studies and our center’s experience, the cohort was divided into two groups using a CD34+ cell count of 5.0×106 /kg as the cut-off point. Clinical outcomes related to graft implantation, relapse incidence, non-relapse mortality, overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION: (1) CD34+ cell dose correlated with platelet engraftment, with platelets implanted earlier in the high-dose group than in the lowdose group (14 days vs. 16 days, P=0.013). (2) There was no significant difference in 3-year overall survival between the two groups (67.5% vs. 53.8%, P=0.257); nor was there a significant difference in progression-free survival between the two groups (65.6% vs. 44.2%, P=0.106), but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients (72.0% vs. 49.3%, P=0.036). (3) The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group (16.0% vs. 33.5%, P=0.05). (4) The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group, but there was no significant difference (17.3% vs. 6.7%, P=0.070); stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group (20.0% vs. 3.3%, P=0.046). (5) In conclusion, CD34+ cell doses >5.0×106 /kg promote early platelet implantation, improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence. However, in high-risk patients, high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation, which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period. Therefore, it is considered that graft versus host disease monitoring should be enhanced in patients who transfused highdose CD34+ cells. [ABSTRACT FROM AUTHOR]

Objective To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). Results Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P

Severe aplastic anemia (SAA) is a severe bone marrow failure syndrome caused by multiple causes, which is clinically manifested with severe anemia, infection and bleeding. The complex pathogenesis of SAA has not been fully understood. SAA is characterized with acute onset, severe disease condition and rapid progression. At present, with the in-depth study of SAA and the improvement of diagnosis and treatment, the therapeutic strategy for SAA has been evolved from classical immunosuppressive therapy based on antithymocyte globulin and cyclosporine to the application of thrombopoietin receptor agonist and combined treatment based on allogeneic hematopoietic stem cell transplantation, which may promote the reconstruction of hematopoietic function of SAA patients to varying degree and significantly improve survival and clinical prognosis, becoming the research hotspot of SAA treatment. In this article, new advances in the treatment of SAA at home and abroad were reviewed. [ABSTRACT FROM AUTHOR]

Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106 /kg and 1.99×106 /kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106 /kg and 5.75×106 /kg per donor, respectively. A reducedintensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical characteristics of cytokine release syndrome (CRS) in children with thalassemia major (TM) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and their prognosis., Methods: A retrospective analysis was performed for the clinical data of 280 children with TM who underwent haplo-HSCT in the Department of Hematology and Oncology, Shenzhen Children's Hospital, from January 2019 to December 2021. According to the CRS criteria, they were divided into two groups: CRS grade <3 (260 children) and CRS grade ≥3 (20 children). The children with TM were analyzed in terms of clinical characteristics of CRS after haplo-HSCT and their prognosis., Results: There were significant differences between the two groups in neutrophil engraftment time, clinical manifestations of CRS, and the rate of use of glucocorticoids within 4 days after haplo-HSCT ( P =0.012, 0.040, and <0.001 respectively). For the CRS grade <3 group, the incidence rate of acute graft-versus-host disease (aGVHD) was 9.6% within 3 months after transplantation, while no aGVHD was observed in the CRS grade ≥3 group within 3 months after transplantation, but there was no significant difference in the incidence of aGVHD between the two groups within 3 months after transplantation ( P =0.146). No transplantation-related death was observed in either group within 3 months after haplo-HSCT., Conclusions: The children with CRS grade≥3 have an early neutrophil engraftment time, severe and diverse clinical manifestations of CRS, and a high rate of use of glucocorticoids within 4 days after haplo-HSCT. For these children, early use of low-dose glucocorticoids after transplantation may alleviate CRS response and reduce the incidence of aGVHD, thereby bringing more benefits to the children. CRS after haplo-HSCT has no significant impact on the prognosis of the children.

Copyright of Chinese Journal of Contemporary Pediatrics is the property of Xiangya Medical Periodical Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: A great progress has been achieved in the allogeneic hematopoietic stem cell transplantation for aplastic anemia. However, graft-versus-host disease and graft failure after transplantation are still the main causes of non-relapse death, which seriously affect the survival of patients. OBJECTIVE: To summarize the current status and progress of allogeneic hematopoietic cell transplantation in the treatment of aplastic anemia. METHODS: The first author retrieved PubMed, CNKI, WanFang and VIP databases for the articles concerning allogeneic hematopoietic stem cell transplantation for aplastic anemia published from January 1990 to September 2019. The keywords were "aplastic anemia, matched sibling donor hematopoietic stem cell transplantation, unrelated donor hematopoietic stem cell transplantation, haploidentical hematopoietic stem cell transplantation, cord blood transplantation" in Chinese and English, respectively. Finally 55 eligible articles were included for result analysis. RESULTS AND CONCLUSION: HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation is the first choice. Unrelated donor hematopoietic stem cell transplantation may be an effective and feasible first-line therapy in pediatric severe aplastic anemia patients with no matched sibling donors. Haploidentical hematopoietic stem cell transplantation and cord blood transplantation can also be important transplantation methods for severe aplastic anemia when lack of HLA-matched donors. [ABSTRACT FROM AUTHOR]

Severe aplastic anemia (SAA) is a rare type of bone marrow hematopoietic failure, which is associated with toxic T lymphocyte-based immune dysfunction, abnormal hematopoietic microenvironment and damage of hematopoietic stem cells in patients. SAA characterized by acute onset, rapid progression and high mortality rate, which requires rapid and stable recovery of the patients' hematopoietic function. In this article, the therapeutic progresses on immunosuppressive therapy (IST), sibling human leukocyte antigen (HLA)-matched allogenetic hematopoietic stem cell transplantation (allo-HSCT), replacement of donor hematopoietic stem cell transplantation and unrelated umbilical cord blood hematopoietic stem cell transplantation (UCBT) for SAA were reviewed. [ABSTRACT FROM AUTHOR]

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: ①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively ( P =0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively ( P =0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% ( P =0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% ( P =0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% ( P =0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) ( P =0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively ( P =0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively ( P =0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively ( P =0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively ( P =0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively ( P =0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively ( P =0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively ( P =0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation is currently the mainstream mode of transplantation in China, but its widespread development is restricted by the higher incidence of graft-versus-host disease and implantation failure as compared with HLA identical hematopoietic stem cell transplantation. In order to solve these two problems, co-transplantation of mesenchymal stem cells and hematopoietic stem cells is used in some transplant centers to promote hematopoietic stem cell transplantation, and to reduce the incidence of graft-versus-host disease. Studies have shown that mesenchymal stem cells can promote the repair of liver cells in liver cirrhosis and hepatitis patients. It is unclear whether co-transplantation of mesenchymal stem cells and hematopoietic stem cells can prevent acute drug-induced liver injury. OBJECTIVE: To investigate the preventive and protective effects of infusion of umbilical cord blood mesenchymal stem cells on acute drug-induced liver injury after conditioning in haploidentical hematopoietic stem cell transplantation. METHODS: Clinical data of patients who underwent haploidentical hematopoietic stem cell transplantation from January 2010 to August 2017 was retrospectively analyzed. Eight cases were transfused with umbilical cord blood mesenchymal stem cells 1×106/kg within 4-6 hours before transfusion of hematopoietic stem cells. Seventeen-seven cases in the control group were not given umbilical cord blood mesenchymal stem cells. The changes of liver function indicators and treatment outcomes at 1 day, 2 weeks and 4 weeks after transplantation conditioning were observed. The study protocol was approved by the ethics committee of the First Affiliated Hospital of Xi’an Jiao Tong University with the approval No. 2016(20). Written informed consent was obtained prior to the initiation of the study. RESULTS AND CONCLUSION: (1) Patients in both groups had abnormalities in the biomedical indicators of liver function to different extent. These indicators peaked at 2 weeks post preconditioning, and then became normal after 4 weeks. (2) The levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, transglutaminase, and direct bilirubin were significantly lower in the observation group than the control group at 1 day and 2 weeks after transplantation conditioning (P < 0.05). (3) There were no adverse reactions such as fever, blood pressure increase/decrease, arrhythmia and hemolysis in the two groups during the infusion of hematopoietic stem cells and umbilical cord blood mesenchymal stem cells. These findings reveal that co-transfusion of umbilical cord blood mesenchymal stem cells during haploidentical hematopoietic stem cell transplantation may reduce acute drug-induced liver injury after transplantation conditioning, and it needs to be further investigated duo to limit numbers of patients. [ABSTRACT FROM AUTHOR]

Objective To explore the secondary transplantation strategy for graft failure of the primary haploidentical hematopoietic stem cell transplantation (haplo-SCT) associated with fatal complications in a patient with acute T-cell lymphocytic leukemia. Methods One male patient was diagnosed with acute T-cell lymphocytic leukemia. In November 2015, he received haplo-SCT from his sister as the donor. But graft failure was developed and complicated by Escherichia coli sepsis, serum disease, hepatic venous occlusion and multiple organ failure. At 32nd d after the first transplantation, secondary haplo-SCT from his father as the donor was performed. Prior to secondary transplantation, chemotherapy pretreatment was not conducted. Post-transplantation cyclophosphamide (PTCy)-based prevention measure against the graft-versus-host disease (GVHD) was adopted after transplantation. Results White blood cells were implanted on the 12nd d and platelet implantation was performed on the 67th d after haplo-SCT. Serum disease, septicemia and hepatic venous occlusion were cured and organ function was improved. However, the patient died from the recurrence of leukemia at 18th months after transplantation (June 2017). Conclusions Prior to secondary haplo-SCT, PTCy prevention measures against the GVHD rather than pretreated chemotherapy probably contributes to the success of transplantation. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant ( P =0.018 and P =0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

Objective: The purpose of this study is to determine the efficacy of haploidentical donor hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. Methods: The clinical data of 76 patients with severe aplastic anemia (SAA) patients who underwent haplo-HSCT from December 2014 to October 2020 were selectively analyzed. There were 50 males and 26 females with a median age of 16 (3-52) years old. There were 49 SAA-Ⅰ patients, 18 SAA-Ⅱ patients, and 9 patients with hepatitis-associated aplastic anemia. There were 15 cases of bone marrow put together with peripheral blood stem cell transplantation and 61 cases of peripheral blood stem-cell transplantation. Conditioning regimens were Cyclophosphamide (CY) + Fludarabine (Flu) + ATG for 46 patients and Busulfan (Bu) + CY+Flu+ATG for 30 patients. Results: Three patients died during the myelosuppressive phase following transplantation, and 73 patients had a median time of neutrophil engraftment of 12 (9-21) days; in addition to 3 patients who died early, 8 patients did not obtain platelet reconstruction after transplantation, and 65 patients had platelet engraftment with a medium time of 14 (9-90) d. The incidence of primary graft failure was 10.9% and the incidence of secondary graft failure was 5.5%. The incidence of Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) was 38.4%, the incidence of Ⅲ-Ⅳ aGVHD was 16.4%, the incidence of chronic graft anti-host disease (cGVHD) was 35.8%, and the incidence of extensive cGVHD was 22.4%. The medium follow-up time was 19.5 (1-75) months, the prospective overall survival (OS) for 2 years was (78.6±5.0) %, the failure-free survival (FFS) was (75.9±5.1) %, and the transplant-related mortality was (20.2±4.9) %. Multi-factor analysis revealed that the patient older than 35 years old, Ⅲ/Ⅳ aGVHD, HCT-CI≥3, the pre-transplant ferritin ≥1 500 μg/L, the number of neutrophils >1×10(9)/L at the time of onset were risk factors affecting OS ( P =0.008, 0.008, 0.014, 0.004, 0.027) . Patients with graft failure had lower OS and FFS than other patients ( P <0.001) . Conclusion: Haplo-HSCT is an effective method for treating SAA in children, adolescents, and young patients, and the occurrence of severe aGVHD and severe infection, as well as graft failure, are the main causes of survival rate. The prevention and treatment of severe aGVHD and infection are essential to improve efficacy.

Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups ( P =0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups ( P >0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs . (94.77±1.75) % , P =0.004; (91.45±2.63) % vs . (95.54±2.05) % , P =0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs . (95.08±1.41) % , P =0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively ( P =0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs . 27.41% , respectively, among those over 35 (40.07±6.65) % vs . (27.41±4.54) % ( P =0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs . (95.08±0.95) % , P =0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs . (94.49±1.45) % , P =0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs . (95.62±1.26) % , P =0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.

Objective: To investigate the efficacy and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in combination of ATG and post-transplant cyclophosphamide (PTCy) -induced immune tolerance after transplantation in treatment of childhood myelodysplastic syndromes(MDS）., Methods: From July 2016 to November 2020, a total of 8 children with MDS receiving the haploidentical allo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation in our hospital were enrolled, whose clinical data were retrospected and analyzed., Results: Median age at diagnosis of the 8 children (1 male and 7 females) was 6.4 (range, 10 months to 15 years) years old. The median medical history of MDS was 2.7 years (range, 3 months to 8 years). Among the 8 patients, 7 cases were diagnosed with refractory cytopenia of childhood and one with refractory anemia with excess of blasts. The HSC donors were father, mother or brother of patients and HLA matching in 6-9/12 loci were identical. All the donors were healthy and didn't carry the same pathogenic genes as the recipients. The median age of donors was 36.4 (range, 25 to 49) years old. The median mononuclear cell (MNC) number of the graft was 19.8, ranging in (13.2-47.3)×10 8 /kg, and the median CD34 + cell number was 11.8×10 6 /kg, ranging in (5.0-18.3)×10 6 /kg. Graft-versus-host disease prophylactic regimen was started on day 3 and 4 after transplantation, in which cyclophosphamide (50 mg/kg·d) was administered by intravenous infusion. From day 5 after transplantation, low-dose tacrolimus was administered by intravenous infusion and mycophenolate mofetil was administered orally. The median time of neutrophil and platelet engraftment was 12.6 (rang, 11 to 15) days and 13.3 (rang, 11 to 18) days, respectively. All the patients achieved full donor chimerism on neutrophil engraftment after transplantation. The median follow-up time was 1 032 (rang, 747 to 1 536) days. Both overall survival rate and disease-free survival rate were 100%., Conclusion: Haplo-HSCT combined with ATG and PTCy-induced immune tolerance after transplantation is a safe and effective treatment for children with MDS.

Haploidentical hematopoietic stem cell transplantation is a recommended alternative therapy for children with severe aplastic anemia who lack a human leukocyte antigen (HLA)-identical sibling donor and do not respond well to immunosuppressive therapy; however, due to non-identical HLA, the patients may have donor-specific anti-HLA antibody, which may lead to a relatively high incidence rate of poor graft function. Compared with HLA-identical transplantation, conditioning regimen for haploidentical transplantation still needs to be explored. This article reviews the detection and treatment of donor-specific anti-HLA antibody, the selection of conditioning regimen, and the mechanism and treatment of poor graft function in haploidentical hematopoietic stem cell transplantation.

Objective: To investigate the efficacy of haplotype hematopoietic stem cell transplantation in the treatment of acquired severe aplastic anemia (SAA) in children. Methods: The clinical characteristics of 59 pediatric patients with SAA, including 26 cases VSAA, 37males and 22 females, 47 cases typeⅠ and 12 cases typeⅡ, undrerwent haplo-HSCT in our hospital between December 1 st , 2011 and December 1 st , 2017 were retrospectively analyzed. Among 59 patients, 56 patients with a median age of 4.5 (1.2-14.8) years and median weight of 43 (12-80) kg underwent their first HSCT and 3 patients underwent their second HSCT. All patients received the following conditioning regimen: busulfan, cyclophosphamide, and rabbit ATG or Bu (-, CTX) , fludarabineand rabbit ATG. The prophylaxis of acute graft versus host disease (aGVHD) was cyclosporine (CsA) , MMF and methotrexate. All patients received bone marrow transfusion on day 01 and peripheral stem cell transfusion on day 02 from haploid donor. The median dose of donor mononuclear cell counts was 15.60 (7.74-21.04) ×10 8 /kg of recipient weight and CD34 + cell counts was 4.86 (3.74-7.14) ×10 6 /kg of recipient weight. Results: Neutrophils and platelets of all 59 children were implanted. The median implantation time of granulocytes and platelets were 13 (10-19) d, 19 (9-62) d, respectively. The incidence of grade Ⅰ-Ⅱ aGVHD was 45.76% (27 cases) and grade Ⅲ/Ⅳ 13.56% (8 cases) , The incidence of chronic GVHD was 8.47% (5 cases) , The incidences of CMV and EBV viremia were 59.32% (35 cases) and 28.81% (17 cases) , respectively. The median follow-up was 30 (8-80) months, 57 patients survived with disease free, 2 patients died of GVHD. Both of the estimated 5-year OS and DFS rates were (96.4±2.5) %. Conclusion: Haplo-HSCT could improve the outcomes of SAA children.

Objective: To investigate the prognosis of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). Method: The data of 102 patients with high-risk AML in the first complete remission phase (CR1) who received haplo-HSCT from January 2009 to July 2015 in Peking University People's Hospital were retrospectively analyzed. Results: These 102 cases included 17 AML-MRC cases (AML-MRC group) and 85 other types of AML cases (control group). There were 8 males and 9 females in the AML-MRC group, and the median age was 35 (17-61) years. There were 52 males and 33 females in other high-risk AML group, and the median age was 31 (11-60) years. No difference was observed between the two groups after haploidentical stem cell transplantation in the rates of cytomegalovirus, EBV (Epstein-Barr virus), blood flow infection rate and hematopoietic reconstitution ( P >0.05). The overall 2-year survival rate after transplantation was 80.8% (95% CI 51.6%-93.4%) and 72.5% (95% CI 62.8%-80.1%) ( P =0.650), the disease-free survival rate was 79.4% (95% CI 48.8%-92.9%) and 65.9% (95% CI 54.3%-75.2%) ( P =0.573), cumulative recurrence rate was 13.0%(95% CI 1.9%-34.7%) and 13.3%(95% CI 7.0%-21.5%) ( P =0.623), and non-relapse mortality was 6.7% (95% CI 0.3%-27.0%) and 20.0% (95% CI 12.0%-29.4%) ( P =0.436). Conclusion: The prognosis of haplo-HSCT in patients with AML-MRC in CR(1) is similar to that of other types of high-risk AML patients. Haplo-HSCT is an ideal choice for patients with AML-MRC in CR(1).

Objective: To determine the influence of donor-recipient sex matching on outcome of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute leukemia in the setting of T-cell-replete transplants. Methods: The retrospective study is based on 1 160 consecutive patients who received their first haplo-HSCT for acute leukemia between April 2002 and December 2014 at Peking University Institute of Hematology. The patients were divided into the sex-matched group and sex-mismatched group in terms of the recipient and donor sex. Then we conducted an analysis in four subgroups, male patients with male donors (M→M), male patients with female donors (F→M), female patients with female donors (F→F), and female patients with male donors (M→F). Transplant outcomes were measured in terms of hematopoietic recovery, acute graft versus host disease (aGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in the above four subgroups. Then univariate and multivariate analysis were conducted. Results: There was a higher 3-year and 5-year NRM but no difference in other transplant outcomes in sex-mismatched group when compared with the sex-matched group. F→M was compared with M→M, and the former group had higher 3-year and 5-year cumulative incidences of NRM (25.5% vs 16.1%, P =0.002; 27.1% vs 17.3%, P =0.002), decreased 5-year DFS (56.9% vs 64.4%, P =0.044), decreased 3-year OS (62.6% vs 69.8%, P =0.045). There was no significant difference in 3-year DFS and 5-year OS. There was no significant difference in grade Ⅱ-Ⅳ aGVHD and cGVHD incidence. When F→F group was compared with M→F group, only a higher grade Ⅱ-Ⅳ aGVHD incidence (43.9% vs 34.6%, P =0.047) existed. F→M was proved to be the independent risk factor influencing NRM and OS in multivariate analysis. Conclusion: In haplo-HSCT for acute leukemia, the donor-recipient sex combination of male patients with female donors was of a poorer prognosis, so a male donor was a better choice for a male patient.

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ 2 =8.433, P =0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [ OR =12.0(95% CI 1.39-103.5), P =0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion: DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.