Haploidentical hematopoietic stem-cell transplantation for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy

Objective To investigate the therapeutic effects of haploidentical hematopoietic stem - cell transplantation ( Haplo - PBSCT) for acute myeloid leukemia in first relapse after complete remission by standard induction chemotherapy. Methods Eighty - nine cases of AML in first relapse after complete remission by standard DA

Overview of the progress on haploidentical hematopoietic transplantation

Allogeneic hematopoietic stem cell transplant(HSCT) remains the only potentially curative option for variety of hematologic disorders. Lack of a suitable fully HLAmatched donor limits this option for many patients. Without a suitable related or unrelated HLA-matched donor,umbilical cord blood and haploidentical family members provide a potential source of stem cells. Timely donor availability makes haploidentical donors an attractive alternative donor source. Initial attempts at haploidentical HSCT was associated with significantly increased mortality owing to high rates of graft rejection and severe graftversus-host disease caused by major donor-recipient HLAdisparity. However, over the past decade, outcomes of haploidentical HSCT have improved significantly. Here, we review the advantages and challenges of haploidentical transplantation. We also discuss new developments to attempt to overcome the challenges to a successful haploidentical transplantation.

Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation

We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.

Hematopoiesis reconstitution and anti-tumor effectiveness of Pai-Neng-Da capsule in acute leukemia patients with haploidentical hematopoietic stem cell transplantation

BACKGROUND With the rapid development of haploidentical hematopoietic stem cell transplantation(haplo-HSCT),primary poor graft function(PGF)has become a lifethreatening complication.Effective therapies for PGF are inconclusive.New Chinese patent medicine Pai-Neng-Da(PND)Capsule exerts dual effect in promoting hematopoiesis recovery and regulating immunity.Still,the application of PND capsule in hematopoietic stem cell transplantation,especially in the haplo-HSCT setting,has not yet been reported.AIM To evaluate the role of PND capsule in acute leukemia patients with haplo-HSCT.METHODS We retrospectively collected data of acute leukemia patients who underwent haplo-HSCT at the Affiliated People’s Hospital of Ningbo University between April 1,2015 and June 30,2020.Twenty-nine consecutive patients received oral PND capsule from the sixth day to the first month after haplo-HSCT were included in the PND group.In addition,31 patients who did not receive PND capsule during haplo-HSCT were included in the non-PND group.Subsequently,we compared the therapeutic efficacy according to the western medical evaluation indexes and Chinese medical symptom scores,and the survival between the PND group and the non-PND group,using the chi-square test,Fisher’s exact test,and the Kaplan-Meier method.RESULTS The duration of platelet engraftment was shorter in the PND group than in the non-PND group(P=0.039).The PND group received a lower frequency of red blood cells and platelet transfusions than the non-PND group(P=0.033 and P=0.035,respectively).In addition,PND capsule marginally reduced the rate of PGF(P=0.027)and relapse(P=0.043).After 33(range,4-106)months of follow-up,the 3-year relapse-free survival(P=0.046)and progression-free survival(P=0.049)were improved in the PND group than in the non-PND group.Also,the therapeutic efficacy of the PND group according to Chinese medical symptom scores was significantly better than that of the non-PND group(P=0.022).Moreover,the adverse events caused by PND capsule were mild.Nevertheless,there were no significant differences in the duration of neutrophil engraftment,the risk of infection within 100 days after haplo-HSCT,the acute graft-versus-host disease,or the 3-year overall survival between the two groups.CONCLUSION PND capsule could promote hematopoiesis reconstitution,improve the therapeutic efficacy of Chinese medical symptom scores,present anti-tumor effectiveness,and prolong the survival of acute leukemia patients with haplo-HSCT.

Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Thymoma-associated Severe Aplastic Anemia: a Case Report

THYMOMA, a relatively rare epithelial neoplasm with unique clinical and pathologic features, is the most usual diagnosis for a mass located in the mediastinum. It is often associated withautoimmune disorders. The myastnema gravls ano pure red cell aplasia are the most common disorders, with the incidences of 40% and 5%, respectively, while the incidence of aplastic anemia is only about 0-1.4%. 1 Thymectomy is hard to perform on patients with severe aplastic anemia（SAA） due to severe pancytopenia.

Efficacy of rituximab-containing regimens on post-transplantation lymphoproliferative disorder following haploidentical hematopoietic stem cell transplantation:a report of 3 cases

Objective To evaluate the efficacy of rituximab-containing regimens on post - transplantation lympho-proliferative disorder ( PTLD ) following haploidentical hematopoietic stem cell transplantation ( HSCT) . Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time

Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico

BACKGROUND The impact of social determinants of health in allogeneic transplant recipients in low-and middle-income countries is poorly described.This observational study analyzes the impact of place of residence,referring institution,and transplant cost coverage(out-of-pocket vs government-funded vs private insurance)on outcomes after allogeneic hematopoietic stem cell transplantation(alloHSCT)in two of Mexico's largest public and private institutions.AIM To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico.METHODS In this retrospective cohort study,we included adolescents and adults≥16 years who received a matched sibling or haploidentical transplant from 2015-2022.Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico.Three payment groups were compared:Out-of-pocket(OOP),private insurance,and a federal Universal healthcare program“Seguro Popular”.Outcomes were compared between referred and institution-diagnosed patients,and between residents of Nuevo Leon and out-of-state.Primary outcomes included overall survival(OS),categorized by residence,referral,and payment source.Secondary outcomes encompassed early mortality,event-free-survival,graft-versus-host-relapse-free survival,and non-relapse-mortality(NRM).Statistical analyses employed appropriate tests,Kaplan-Meier method,and Cox proportional hazard regression modeling.Statistical software included SPSS and R with tidycmprsk library.RESULTS Our primary outcome was overall survival.We included 287 patients,n=164 who lived out of state(57.1%),and n=129 referred from another institution(44.9%).The most frequent payment source was OOP(n=139,48.4%),followed by private insurance(n=75,26.1%)and universal coverage(n=73,25.4%).No differences in OS,event-free-survival,NRM,or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution,nor patients who lived in-state vs out-of-state.Patients who covered transplant costs through private insurance had the best outcomes with improved OS(median not reached)and 2-year cumulative incidence of NRM of 14%than patients who covered costs OOP(Median OS and 2-year NRM of 32%)or through a universal healthcare program active during the study period(OS and 2-year NRM of 19%)(P=0.024 and P=0.002,respectively).In a multivariate analysis,payment source and disease risk index were the only factors associated with overall survival.CONCLUSION In this Latin-American multicenter study,the site of residence or referral for alloHSCT did not impact outcomes.However,access to healthcare coverage for alloHSCT was associated with improved OS and reduced NRM.

WJSC 6^(th) Anniversary Special Issues(1):Hematopoietic stem cell transplantation Allogeneic hematopoietic cell transplant for acute myeloid leukemia:Current state in 2013 and future directions

Acute myeloid leukemia(AML)represents a heterogeneous group of high-grade myeloid neoplasms of the elderly with variable outcomes.Though remissioninduction is an important first step in the management of AML,additional treatment strategies are essential to ensure long-term disease-free survival.Recent pivotal advances in understanding the genetics and molecular biology of AML have allowed for a risk-adapted approach in its management based on relapse-risk.Allogeneic hematopoietic cell transplantation(allo-HCT)represents an effective therapeutic strategy in AML providing the possibility of cure with potent graft-versus-leukemia reactions,with a demonstrable survival advantage in younger patients with intermediate-or poor-risk cytogenetics.Herein we review the published data regarding the role of allo-HCT in adults with AML.We searched MEDLINE/PubMed and EMBASE/Ovid.In addition,we searched reference lists of relevant articles,conference proceedings and ongoing trial databases.We discuss the role of allo-HCT in AML patients stratified by cytogenetic-and molecular-risk in first complete remission,as well as allo-HCT as an option in relapsed/refractory AML.Besides the conventional sibling and unrelated donor allografts,we review the available data and recent advances for alternative donor sources such as haploidentical grafts and umbilical cord blood.We also discuss conditioning regimens,including reduced intensity conditioning which has broadened the applicability of allo-HCT.Finally we explore recent advances and future possibilities and directions of allo-HCT in AML.Practical therapeutic recommendations have been made where possible based on available data and expert opinion.

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR LYMPHOMA: AN EVALUATION OF GRAFTS SOURCE AND MINIMAL RESIDUAL DISEASE

Objective： To determine whether the source of autologous hematopoietic stem cells altered the clinical outcomes of patients undergoing high dose chemotherapy and autologous hematopoietic stem cell transplantation （AHSCT） for aggressive lymphoma and to study the problem of minimal residual disease （MRD）. Methods： 14 lymphoma patients who had lymphoma with high risk factors, relapsed lymphoma or refractory lymphoma received autologous bone marrow transplantation （ABMT）. 14 lymphoma patients who were similar to ABMT group received autologous peripheral blood stem cells transplantation （APBSCT）. Regimen of CBV （cyclophos phamide 50-60 mg/kg/d×2 d, carmustine 15 mg/kg/d×1 d, etoposide 45-60 mg/kg/d×1 d） was received by all the patients as conditioning regimen in the transplant pretreatment followed by ABMT or APBSCT. Autologous peripheral blood stem cell （APBSC） was mobilized by CTX 2g-3g/m^2/d×2 d iv and G-CSF 5 μg/kg/d for five to seven days. MRD was continually supervised by PCR in bone marrow before and after transplantation. Cellular immunocyte function, such as natural killer cell （NK）, CD3, CD4, CD8 and slL-2R was tested before and twenty days after transplantation. Results： In ABMT group, the median time for hematopoietic recovery of absolute neutrophilia counts ≥0.5×10^9/L and platelet counts ≥20×10^9/L. was ＋18 days and ＋20 days respectively. In contrast, the APBSCT group was both at 12 days. Patients who have undergone ABMT all got complete remission （CR）, while 81.8% patients in APBSCT group got CR. The 3-year disease free survival （DFS） in APBSCT and ABMT group was 75% and 72.7% respectively （P〉0.05）. The mean days of immunity recovering in APBSCT was ＋20 days. After transplantation, MRD in 11 patients were positive, in whom 6 patients died. Conclusion： Aggressive lymphoma patients＇ hemapoiesis recovered more rapidly in APBSCT group than that in ABMT group, but 3-year DFS had no statistical difference. Patients positive for IgH/TCR-γ by molecular PCR analysis had poor DFS. Molecur monitoring of MRD using PCR techniques seems to represent a reliable prognostic indicator. Immunotherapy in the patients whose bone morrow was positive for MRD post-AHSCT may intensify remission and reduce relapse rates.

The role of collateral related donors in haploidentical hematopoietic stem cell transplantation

A key issue in the haploiedntical hematopoietic stem cell transplantation(haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors(CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs(n = 60) and maternal donors(MDs, n = 296), which were the last choice of donor selection in immediate related donors(IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0%(95% CI, 11.3%–32.7%) versus 17.4%(95% CI, 13.0%–21.8%)(P = 0.455) and 25.0%(95% CI, 13.9%–36.1%) versus 23.1%(95% CI, 18.2%–28.0%)(P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2%(95% CI, 40.4%–66.0%) versus 59.5%(95% CI, 53.8%–65.2%)(P = 0.406) and 56.5%(95% CI,43.8%–69.2%) versus 61.8%(95% CI, 56.1%–67.5%)(P = 0.458) for the CRDs and MDs, respectively.Female donor/male recipient(FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs.

HLA-mismatched/haploidentical hematopoietic stem cell transplantation： a field in which Chinese doctors are making great contributions

Allogeneic hematopoietic stem cell transplantation .（allo-HSCT） is one of the best, or even the only,option for the cure of leukemia, especially for patients with high risk factors . However, it is limited by the shortage of suitable donors, because only 25%-30% patients can find a human leukocyte antigen （HLA）-identical sibling donor. Although much progress has been made in finding a suitable unrelated donor or unrelated cord blood （uCB） due to the expansion of the worldwide unrelated donor program,

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

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.

Haploidentical hematopoietic stem cell transplantation for pediatric patients with chronic active Epstein-Barr virus infection:a retrospective analysis of a single center

Background This study aimed to evaluate the feasibility and clinical effect of haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for the treatment of pediatric patients with chronic active Epstein-Barr virus infection(CAEBV).Methods Children with CAEBV who did not have matched donors and underwent haplo-HSCT in Beijing Children's Hospital,Capital Medical University,from October 2016 to June 2020 were analyzed retrospectively.Data relating to the clinical manifestations,engraftment,and prognosis of the children were extracted from medical records.Results Twenty-five patients,including 16 males and 9 females,with an onset age of 5.0±2.6 years and a transplantation age of 6.9±2.9 years,were enrolled irnhis study.The mean time from diagnosis to transplantation was 3.8(2.0-40.2)months.The mean observation time was 19.0±12.0 months.Three patients received the reduced intensity conditioning regimen,and the remaining patients all received the modified myeloablative conditioning regimen.By the end of the follow-up,23 patients were characterized by disease-free survival(DFS),22 were characterized by event-free survival(EFS).and two died.One of the patients died of thrombotic microangiopathy(TMA),and another died of graft versus host disease(GVHD);this patient discontinued the treatment for economic reasons.The 3-year overall survival(OS)rate was estimated to be 92.0%±5.4%,and the 3-year EFS rate was estimated to be 87.4%±6.8%.All active patients survived after HSCT event-free.Acute GVHD degrees 1-3 were observed in ten patients(40.0%),and degree IV was observed in six(24.0%),who were all cured except for one patient.Chronic GVHD was observed in nine(36.0%),and most of these cases were mild.The incidence of TMA and veno-occlusive disease(VOD)was 28.0%and 4.0%.Conclusions Haploidentical hematopoietic stem cell transplantation is safe and effective in the treatment of pediatric CAEBV and can be used as an alternative therapy without matched donors or emergency transplantation.Patients with active disease before HSCT also benefited from haplo-HSCT.Haplo-HSCT requires careful monitoring for complications,such as GVHD and TMA.Early detection of TMA and timely treatment can reduce mortality and can improve the survival rate.

Haploidentical hematopoietic cell transplantation for severe acquired aplastic anemia: a case-control study of post-transplant cyclophosphamide included regimen vs. anti-thymocyte globulin & colony-stimulating factor-based regimen

Dear Editor,Haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT),a curative therapy for severe aplastic anemia(SAA)patients,has been used clinically for decades.Two models,not involving ex vitro T-cell depletion,have been adopted for haplo-HSCT in patients with SAA.The first is referred to as the"Beijing protocol"(Xu et al.,2017),and comprises a conditioning regimen using busulfex(BU),cyclophosphamide(CY).

Haploidentical hematopoietic stem cell transplantation may improve long-term survival for children with high-risk T-cell acute lymphoblastic leukemia in first complete remission

Background: The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods: A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results: Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5%vs. 100%,P = 0.003;5-year event-free survival [EFS]: 54.1%vs. 83.4%,P = 0.010;5-year cumulative incidence of relapse [CIR]: 45.2%vs. 6.3%,P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1%vs. 54.1%,P = 0.041;5-year CIR: 11.6%vs. 45.2%,P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0%vs. 58.5%,P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR;age ≥10 years was an independent risk factor for OS and EFS;and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion: Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

Haploidentical hematopoietic stem cell transplantation using reduced-intensity conditioning for pediatric patients with familial hemophagocytic lymphohistiocytosis

Importance: Allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only curative treatment for familial hemophagocytic lymphohistiocytosis (FHLH). Treatment of pediatric FHLH with reduced-intensity conditioning (RIC)-based haploidentical donor (HID) HSCT has been rarely reported. Objective: To investigate outcomes and adverse events in patients with FHLH who received HID-HSCT. Methods: We conducted a retrospective study of five patients, including three with mutations in PRF1 and two with XIAP deficiency. Four of the five donors were heterozygous for these mutations. The conditioning regimen included fludarabine, cyclophosphamide, and antithymocyte globulin, with or without low-dose irradiation. Unmanipulated mobilized bone marrow and peripheral blood stem cells were used as the grafts. results: All five patients were successfully engrafted. Four patients survived, and one patient died. All exhibited complete response (CR) after HSCT. All of the patients who survived exhibited CR to FHLH without severe regimen-related complications at a median of 29.5 months (range: 23–34 months) after HSCT. Four of the five patients had mixed donor chimerism. Three patients had 17% to 87% mixed donor chimerism but remained free of disease. Four patients received donor lymphocyte infusion (DLI), which improved the level of mixed donor chimerism. One patient experienced a decrease in donor chimerism to 1% and relapsed;Four patients developed acute graft-versus-host disease (GvHD) (grade I or II), and one patient developed grade IV GvHD. Interpretation: HID-HSCT with RIC can be considered for treatment for patients with FHLH, but the conditions and DLI regimens need to be optimized for long-term use, and more prospective studies should be conducted.

Positive stool culture could predict the clinical outcomes of haploidentical hematopoietic stem cell transplantation

We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT)(n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group;19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens .

急性粒-单核细胞白血病患者造血干细胞移植后微血栓形成凝血指标监测及治疗1例报告

本文报道1例急性粒-单核细胞白血病(急性髓系白血病M4型)(CBFB基因阳性)患者,经亲缘半相合造血干细胞移植后并发下肢微血栓形成,并总结其诊治经验。该患者经常规化疗后获完全缓解,但又于2年后复发,遂予行亲缘半相合造血干细胞移植。在患者接受移植后的常规治疗期间,动态观察其凝血相关指标[包括D-二聚体(D-dimer, D-D)、抗凝血酶Ⅲ(antithrombinⅢ,AT-Ⅲ)、血管性血友病因子(von Willebrand factor, vWF)、纤维蛋白原降解产物(fibrinogen degradation products, FDP)、纤维蛋白单体(fibrin monomer, FM)]。在移植后100 d左右,患者出现黄疸及转氨酶升高,采用经右下肢股静脉置管行血浆置换治疗3次。在去除静脉置管1周后,患者出现左踝部指凹性水肿,血管B超检查提示其左下肢腓肠肌浅静脉丛有微血栓形成;凝血指标检测显示,D-D、vWF、FDP、FM等指标升高,AT-Ⅲ水平降低。予口服拜瑞妥5 mg/d抗栓治疗2周后,患者上述凝血指标渐趋正常,左下肢肌间静脉丛血栓和肢肿消失。在造血干细胞移植后,除密切检查血管B超,动态监测D-D、AT-Ⅲ、vWF、FDP、FM等凝血指标可预测移植相关微血栓和高凝状态,并为临床开展有效抗的凝治疗提供实验依据。

供者特异性HLA抗体及去敏治疗对单倍体造血干细胞移植植入效果的影响

目的 分析供者特异性HLA抗体(anti-HLA donor-specific antibodies, DSA)及DSA阳性患者的去敏治疗对单倍体造血干细胞移植(haploidentical hematopoietic stem cell transplantation, haplo-HSCT)植入效果的影响。方法 收集2017年3月至2023年7月重庆医科大学附属第二医院血液内科行haplo-HSCT,并完成HLA抗体及DSA检测的患者70例,分析DSA阳性和DSA阳性患者去敏治疗对造血干细胞移植植入效果的影响。结果 70例haplo-HSCT患者完成抗体检测,DSA阳性患者15例(21.4%),其中7例(46.7%)强阳性,3例(20.0%)中度阳性,5例(33.3%)弱阳性。DSA阳性患者移植后粒系植入中位时间较DSA阴性患者明显延迟(P=0.027)。植入失败(graft failure, GF)患者6例,DSA阳性4例(26.7%),明显高于DSA阴性(P=0.025)。多因素分析结果显示,DSA是发生GF的独立影响因素(HR=9.273, 95%CI=1.505~57.124,P=0.016)。10例DSA中度和强阳性患者进行去敏治疗,4例采用联合去敏治疗,患者均成功植入(100.0%),6例采用单一去敏治疗,有4例(66.7%)发生GF,联合去敏治疗的GF发生率显著低于单一去敏治疗(P=0.008)。结论 DSA是导致haplo-HSCT患者植入延迟和GF的重要因素,对DSA中度及强阳性患者的单一去敏治疗效果有限,而多联合的去敏治疗时,动态监测抗体滴度水平下降,可保证干细胞的成功植入,降低GF发生。

CD34^(+)细胞数对单倍体造血干细胞移植治疗恶性血液病的影响

背景:单倍体造血干细胞移植与较高的植入功能不良相关,因此经常要求更高的CD34^(+)细胞数量,但现有研究关于异基因造血干细胞移植CD34+细胞剂量和研究终点关系的结论是有争议的。目的:探究CD34^(+)细胞数对单倍体造血干细胞移植治疗恶性血液疾病临床结果的影响。方法:纳入2019年1月至2021年12月期间于郑州大学第一附属医院造血干细胞移植中心行单倍体造血干细胞移植的恶性血液病患者,总计135例。结合既往研究结果及移植中心经验,以CD34+细胞数5.0×10^(6)/kg为截止点,将队列分为2组。评估两组的移植物植入情况、复发率及非复发死亡率、总生存期和无进展生存期等相关临床指标。结果与结论:①CD34+细胞剂量与血小板的植入相关,高剂量组血小板的植入时间早于低剂量组(14 d vs.16 d,P=0.013)。②两组患者3年总生存期无显著差异(67.5%vs.53.8%,P=0.257);两组间的无进展生存期也无显著性差异(65.6%vs.44.2%,P=0.106),但根据疾病风险指数(DRI)进行分层分析后发现低危患者高剂量组的3年无进展生存期较低剂量组升高(72.0%vs.49.3%,P=0.036)。③高剂量组3年累积复发率小于低剂量组(16.0%vs.33.5%,P=0.05)。④两组100 d内非复发死亡率高剂量组大于低剂量组,但无显著差异(17.3%vs.6.7%,P=0.070);进行分层分析发现,高危患者中高剂量组100 d内非复发死亡率明显高于低剂量组(20.0%vs.3.3%,P=0.046)。⑤综上所述,输注>5.0×10^(6)/kg的CD34^(+)细胞可促进血小板早期植入,可改善移植中低危风险患者的3年无进展生存期,并且降低移植后累积复发率;但在高危患者中,高剂量CD34+细胞导致移植后100 d内的非复发死亡率增高,考虑可能与移植后早期重度急性移植物抗宿主病的发生增多相关,因此考虑对回输高剂量CD34+细胞的患者应加强移植物抗宿主病的监测。