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.

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 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.

B-cell acute lymphoblastic leukemia(ALL)is a hematological malignancy.Blinatumomab,as a therapeutic target,targeting CD19,has demonstrated notable efficacy as a safe bridge to allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with re-lapsed/refractory acute lymphoblastic leukemia(R/R B-ALL).In the treatment of newly diagnosed ALL,blinatumomab,when combined with chemotherapy or other immunotherapies,reduces toxicity while ensuring efficacy.Similarly,combining blinatumomab with second-or third-generation tyrosine kinase inhibitors(TKIs)for the treatment of Philadelphia chromosome--positive(Ph+)ALL holds promise for eliminating the need for subsequent allo-HSCT in patients.Disease relapse and long-term survival of patients are closely related to minimal residual dis-ease(MRD)at the conclusion of treatment,and blinatumomab contributes to enhancing the MRD conversion rate in patients with ALL,thus improving the long-term prognosis.This article comprehensively reviews the clinical trials and current progress of blinatumomab in various B-ALL patient groups.

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:TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied.Methods:42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed.Results:There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion:Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

Objective:To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion.Methods:The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up.Results:The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %.Conclusions:TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.