Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To evaluate the efficacy of purified donor CD34 positive hematopoietic stem cell (CD34 + cell) infusion in patients with poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods:The clinical data of 25 patients with PGF who underwent donor CD34 + cell sorting and infusion at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between September 2019 and March 2023, were retrospectively analyzed. The cohort included 19 haploidentical and 6 HLA-matched cases. CD34 + cells were purified using immunomagnetic beads for therapeutic infusion. The purification efficiency was evaluated based on the purity and recovery rate of CD34 + cells. Clinical outcomes were assessed by hematopoietic recovery, overall survival (OS) rate, and the incidence of graft-versus-host disease (GVHD) . Results:The median total number of CD34 + cells was 2.64 (0.82-6.53) × 10 8 before purification and 2.22 (0.48-5.68) ×10 8 after purification, with a median recovery rate of 78.37% (58.48%-115.72%) . After infusion of purified CD34 + cells, 8 of 10 patients (80.0%) with poor neutrophil engraftment achieved recovery (absolute neutrophil count ≥ 0.5×10 9/L) , with a median time to recovery of 21 (10-40) days. And 15 of 21 patients (71.4%) with poor platelet engraftment achieved recovery (platelet count ≥ 20×10 9/L) , with a median time to recovery of 15 (13-38) days. Only 3 patients (12.0%) developed GVHD after the infusion of purified CD34 + cells, including 2 cases of grade I acute GVHD and 1 case of limited chronic GVHD. With a median follow-up of 14.47 (0.23-41.63) months, the overall OS rate after CD34 + cell infusion was (65.63± 8.28) %. Seventeen patients survived, with a median survival time of 19.07 (0.23-41.63) months. Conclusion:Purification of CD34 + cells using immunomagnetic beads is effective, and the infusion of these purified donor CD34 + cells can safely and effectively improve PGF after allo-HSCT.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective:To evaluate the efficacy of purified donor CD34 positive hematopoietic stem cell (CD34 + cell) infusion in patients with poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods:The clinical data of 25 patients with PGF who underwent donor CD34 + cell sorting and infusion at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between September 2019 and March 2023, were retrospectively analyzed. The cohort included 19 haploidentical and 6 HLA-matched cases. CD34 + cells were purified using immunomagnetic beads for therapeutic infusion. The purification efficiency was evaluated based on the purity and recovery rate of CD34 + cells. Clinical outcomes were assessed by hematopoietic recovery, overall survival (OS) rate, and the incidence of graft-versus-host disease (GVHD) . Results:The median total number of CD34 + cells was 2.64 (0.82-6.53) × 10 8 before purification and 2.22 (0.48-5.68) ×10 8 after purification, with a median recovery rate of 78.37% (58.48%-115.72%) . After infusion of purified CD34 + cells, 8 of 10 patients (80.0%) with poor neutrophil engraftment achieved recovery (absolute neutrophil count ≥ 0.5×10 9/L) , with a median time to recovery of 21 (10-40) days. And 15 of 21 patients (71.4%) with poor platelet engraftment achieved recovery (platelet count ≥ 20×10 9/L) , with a median time to recovery of 15 (13-38) days. Only 3 patients (12.0%) developed GVHD after the infusion of purified CD34 + cells, including 2 cases of grade I acute GVHD and 1 case of limited chronic GVHD. With a median follow-up of 14.47 (0.23-41.63) months, the overall OS rate after CD34 + cell infusion was (65.63± 8.28) %. Seventeen patients survived, with a median survival time of 19.07 (0.23-41.63) months. Conclusion:Purification of CD34 + cells using immunomagnetic beads is effective, and the infusion of these purified donor CD34 + cells can safely and effectively improve PGF after allo-HSCT.

Objective:To investigate the therapeutic effect and safety of recombinant human thrombopoietin (rhTPO) combined with low-dose eltrombopag in the treatment of persistent thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A retrospective case series study was conducted. The retrospective analysis was conducted on the clinical data of 20 patients diagnosed with post-allo-HSCT thrombocytopenia at Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2018 to June 2021. All patients didn't meet the platelet implantation criteria [without the platelet count (Plt) ≥20×10 9/L for a consecutive period of 7 days and discontinuation of platelet transfusion] after transplantation, and they received subcutaneous injections of rhTPO (15 000 U) once daily and oral administration of eltrombopag (50 mg) once. Treatment efficacy was defined as maintaining Plt≥20×10 9/L for a consecutive period of 7 days after treatment and discontinuation of platelet transfusion; treatment inefficacy was defined as Plt<20×10 9/L after treatment or continuation of platelet transfusion. The therapeutic effect of rhTPO combined with low-dose eltrombopag was analyzed; the adverse reactions were evaluated; the clinical characteristics were compared between the effective treatment group and ineffective treatment group; the overall survival (OS) and disease-free survival (DFS) were analyzed using Kaplan-Meier method between the effective treatment group and ineffective treatment group. Results:Among the 20 patients, 9 were diagnosed with acute myeloid leukemia (AML), 5 with acute lymphoblastic leukemia (ALL), 4 with myelodysplastic syndromes (MDS), and 2 with severe aplastic anemia (SAA); 10 cases were primary failure of platelet recovery (PFPR), and 10 cases were secondary failure of platelet recovery (SFPR). The median time [ M ( Q1, Q3)] from transplantation to initiation of treatment was 79 days (50 days, 89 days), and the median duration of treatment was 19.5 days (15 days, 30 days). Of the total cohort, treatment was effective in 13 cases (65.0%, 8 cases of PFPR, 5 cases of SFPR), while 7 patients (35.0%) showed no response to treatment. The median time to achieve the therapeutic response among responders was 10 days (7 days, 19 days). During the combination treatment, 5 patients experienced elevated transaminase levels exceeding more than 2.5 times the upper limit of normal or bilirubin levels surpassing twice that limit. No instances of adverse reaction-related arterial thrombosis, myelofibrosis, or primary disease relapse occurred within this patient cohort. Megakaryocyte counts in the effective treatment group before combination treatment were higher than that in the ineffective treatment group, and the difference was statistically significant [14 (10, 20) vs. 2.5 (2, 4); Z = -2.33, P = 0.017]; Notably, no statistically significant differences were identified when comparing the compositions of gender, type of underlying diseases, human leukocyte antigen matching degree, blood type of donor and recipient, conditioning regimen use of antithymocyte globulin, quantity of CD34 + cells transfused, type of thrombocytopenia, acute graft-versus-host disease, fungal or bacterial infections, and viral infections between the two groups (all P > 0.05). The 1-year OS rates for the effective and ineffective treatment groups were 100.0% and 42.9%, respectively, and the difference in OS between the two groups was statistically significant ( P = 0.001). The 1-year DFS rates for the effective and ineffective treatment groups were 92.3% and 28.6%, respectively, and the difference in DFS between the two groups was statistically significant ( P = 0.003). Conclusions:The combination of rhTPO and low-dose eltrombopag has demonstrated certain therapeutic efficacy and good safety in the treatment of persistent thrombocytopenia after allo-HSCT.

In recent years,interest in exploring the potential of Blinatumomab for treatment of B-cell acute lymphoblastic leukemia(B-ALL)at earlier stages has grown.This is because Blinatumomab has shown promising results in the management of refractory/relapsed(R/R)B-ALL and minimal residual disease(MRD).Blinatumomab has shown comparable efficacy to that of conventional chemotherapy as an altern-ative to consolidation or intensive chemotherapy in pediatric B-ALL patients.Moreover,its use as consolidation therapy or in combination with chemotherapy/targeted therapy,especially in combination with third-generation tyrosine kinase inhibitors(TKIs),shows significant promise for improving prognosis for adult B-ALL patients.This may potentially reduce reliance on allogeneic hematopoietic stem cell trans-plantation(allo-HSCT)in Philadelphia chromosome-positive(Ph+)B-ALL patients.Moreover,Blinatumomab is safer,gentler,and more effect-ive than chemotherapy for older adult patients.Effective therapy options are not yet available for infants with KMT2A rearrangement B-ALL;however,preliminary research indicates that Blinatumomab may offer a breakthrough for this subgroup.In this article,we review progress in investigations of Blinatumomab use in newly diagnosed B-ALL patients.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis.Methods:In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022.Results:There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%–100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion:allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.

Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10 8/kg, and the number of CD34 + cells was 3.29 (2.53-6.10) ×10 6/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.