Screening and clinical significance of intestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) in patients before haploidentical hematopoietic stem cell transplantation / 中国输血杂志

【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<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

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.

Treatment of severe aplastic anemia and hematopoietic stem cell transplantation / 器官移植

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.

Successful treatment of acute leukemia by secondary transplantation after the first haploidentical hematopoietic stem cell transplantation failure / 器官移植

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 reduced-intensity 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.

Impact of immunosuppression intensified conditioning regimen for patients with strong positive pre-transplantation donor-specific anti-HLA antibodies (DSAs) undergoing haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

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.

Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Clinical Efficacy of Haplo-HSCT of ATG Combined with PTCy for Children with Myelodysplastic Syndrome / 中国实验血液学杂志

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)×108/kg, and the median CD34+ cell number was 11.8×106/kg, ranging in (5.0-18.3)×106/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.

Research advances on haploidentical hematopoietic stem cell transplantation in the treatment of severe aplastic anemia in children / 中国当代儿科杂志

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.

Clinical study on haploidentical hematopoietic stem cell transplantation for children with bone marrow failure syndromes / 中华实用儿科临床杂志

Objective:To explore the efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSC) combined with tpCB in the treatment of children with bone marrow failure syndromes (BMFs).Methods:The clinical chara-cteristics of 78 BMFs pediatric patients, including inherited BMFs (4 cases) and acquired BMFs (74 cases) under-went haplo-HSC combined with the third-party cord blood (tpCB) in Chinese People′s Liberation Army General Hospital-Sixth Medical Center between July 2012 and July 2019 and were retrospectively analyzed, with 41 males and 37 females.Among them, 73 cases experienced first transplantation and 5 cases accepted second transplantation, with the median age of 5.6 years.The conditioning regimen was based on Busulfan, with 74 acquired BMFs cases using non-myeloablative and the remaining 4 cases using myeloablative.The prophylaxis of acute graft versus host disease (aGVHD) includes Cyclosporine, Mycophenolate mofetil (MMF) and Methotrexate.All patients received bone marrow from haploid donor and tpCB on day 1 and peripheral stem cell from haploid donor on day 2.The median dose of the total donor nucleated cells was 12.19×10 8/kg of recipient weight and CD 34+ cell dose was 6.13×10 6/kg of recipient weight. Results:The median time of granulocytes over 0.5×10 9/L and platelets over 20×10 9/L were + 13 d and + 17 d, respectively.All patients displayed complete donor-type chimerism at + 30 d. No primary graft failure occurred in any patient and second graft failure occurred in two cases.The incidence rate of grade ⅡtoⅣ and grade Ⅲ to Ⅳ aGVHD were 39.0% and 13.9%, respectively.The incidence of chronic GVHD with limited type and extensive type were 7.8% (95% CI: 7.1%-8.5%) and 2.6% (95% CI: 2.1%-3.1%), respectively.the median follow-up was 1 550 days, and 76 patients survived with free disease.The rate of transplant related mortality was 2.8%, and both of the estimated 5-year overall survival and failure-free survival rate were 97.2%(95% CI: 96.8%-97.6%). Conclusions:Haplo-HSC and umbilical cord blood can quickly provide hematopoietic stem cells.The results of haplo-HSC combined with the tpCB in pediatric patients with life-threatening BMFs are promising.

Treatment progress of severe aplastic anemia / 器官移植

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.

Current status of hematopoietic stem cell transplantation in the treatment of aplastic anemia / 中国组织工程研究

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.

A clinical study of haploidentical hematopoietic stem cell transplantation in the treatment of pediatric patients with acquired severe aplastic anemia: single center experience / 中华血液学杂志

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 1st, 2011 and December 1st, 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) ×108/kg of recipient weight and CD34+ cell counts was 4.86 (3.74-7.14) ×106/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.

Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation / 医学前沿

Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice. This review will focus on how the new era in which "everyone has a donor" will become a reality in China.

A clinical study of haploidentical hematopoietic stem cell transplantation in the treatment of pediatric patients with acquired severe aplastic anemia: single center experience / 中华血液学杂志

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 1st, 2011 and December 1st, 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) ×108/kg of recipient weight and CD34+ cell counts was 4.86 (3.74-7.14) ×106/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.

The clinical analysis of haploidentical stem cell transplantation in myelodysplastic syndrome-associated acute myeloid leukemia / 中华血液学杂志

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 CR1 is similar to that of other types of high-risk AML patients. Haplo-HSCT is an ideal choice for patients with AML-MRC in CR1.

Influence of donor-recipient sex matching on outcomes of haploidentical hematopoietic stem cell transplantation for acute leukemia / 中华血液学杂志

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.

Effects of preexisting donor-specific HLA antibodies for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

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), χ2=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.

The clinical analysis of haploidentical stem cell transplantation in myelodysplastic syndrome-associated acute myeloid leukemia / 中华血液学杂志

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).

Influence of donor-recipient sex matching on outcomes of haploidentical hematopoietic stem cell transplantation for acute leukemia / 中华血液学杂志

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.

Effects of preexisting donor-specific HLA antibodies for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

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), χ2=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.