[Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation].

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.

[Efficacy and safety of allogeneic hematopoietic stem cell transplantation for the treatment of primary myelofibrosis].

Objective: To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients. Methods: A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [M(Q1, Q3)]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months. Results: All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. Ⅱ-Ⅳ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection. Conclusion: Allo-HSCT can be used as a safe and effective approach to treat PMF.

[Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia].

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.

[Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome].

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

[Clinical analysis of 76 patients with severe aplastic anemia treated with haploid hematopoietic stem cell transplantation].

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.

[Survival efficacy of MDS/AML patients with TP53 abnormal received allogeneic hematopoietic stem cell transplantation].

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.

[Clinical characteristics and CT findings of Pneumocystis Jirovecii pneumonia in 46 cases with hematological diseases].

Objective: To summarize the original CT features of Pneumocystis Jirovecii pneumonia in patients with hematological diseases. Methods: A retrospective analysis was carried out in 46 patients with proven pneumocystis pneumonia (PJP) in the Hospital of Hematology, Chinese Academy of Medical Sciences between January 2014 and December 2021. All patients had multiple chests CT and related laboratory examinations, imaging typing were conducted based on the initial CT presentation, and the distinct imaging types were analyzed against the clinical data. Results: In the analysis, there were 46 patients with proven pathogenesis, 33 males, and 13 females, with a median age of 37.5 (2-65) years. The diagnosis was validated by bronchoalveolar lavage fluid (BALF) hexamine silver staining in 11 patients and clinically diagnosed in 35 cases. Of the 35 clinically diagnosed patients, 16 were diagnosed by alveolar lavage fluid macrogenomic sequencing (BALF-mNGS) and 19 by peripheral blood macrogenomic sequencing (PB-mNGS) . The initial chest CT presentation was categorized into 4 types, including ground glass (GGO) type in 25 cases (56.5%) , nodular type in 10 cases (21.7%) , fibrosis type in 4 cases (8.7%) , and mixed type in 5 cases (13.0%) . There was no substantial discrepancy in CT types among confirmed patients, BALF-mNGS diagnosed patients and PB-mNGS diagnosed patients (χ(2)=11.039, P=0.087) . The CT manifestations of confirmed patients and PB-mNGS diagnosed patients were primarily GGO type (67.6%, 73.7%) , while that of BALF-mNGS diagnosed patients were nodular type (37.5%) . Of the 46 patients, 63.0% (29/46) had lymphocytopenia in the peripheral blood, 25.6% (10/39) with positive serum G test, and 77.1% (27/35) with elevated serum lactate dehydrogenase (LDH) . There were no great discrepancies in the rates of lymphopenia in peripheral blood, positive G-test, and increased LDH among different CT types (all P>0.05) . Conclusion: The initial chest CT findings of PJP in patients with hematological diseases were relatively prevalent with multiple GGO in both lungs. Nodular and fibrosis types were also the initial imaging findings for PJP.

[Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion].

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.

[Role of preoperative ultrasound-guided inferior parathyroid gland localization and new classification to assist intraoperative search and protection of parathyroid glands].

Objective: To investigate the role and significance of ultrasound-guided inferior parathyroid gland (IPTG) localization in searching and protecting parathyroid glands before thyroid surgery. Methods: A randomized controlled trial study was conducted. A total of 306 patients (433 cases of lateral parathyroidectomy) who underwent primary thyroidectomy and central lymph node dissection in Beijing Tongren Hosipital from March to October 2021 were enrolled. In order to locate IPTG more quickly and effectively, new IPTG classification and the definition of quadrant position were carried out. The patients were divided into the study group (n=228) and the control group (n=205). The study group underwent ultrasound-guided IPTG examination before operation and measured the distance between the IPTG and the lower pole of the thyroid and the midline of the trachea. During the operation, the IPTG was found and protected depending on the localization. The control group did not use any auxiliary preoperative positioning method. The distribution ratio of IPTG and the coincidence rate between intraoperative validation and ultrasound localization were calculated. Results: There were 306 patients enrolled in the final analysis (95 males and 211 females), with a median age of 41 years old (18-70). Type Ⅱ and Ⅲ IPTG accounted for 77.2% (176/228) of the total cases. The total coincidence rate ranged from 72.8% to 79.4% in different IPTG groups. Type Ⅲ and quadrant 2 IPTG had the highest coincidence rate [92.4% (73/79) and 92.9% (79/85), respectively]. The study group had better in situ retention rate [82.0% (187/228) vs 73.2% (150/205), χ2=4.896, P=0.027] and less implantation rate [8.8% (20/228) vs 16.1% (33/205), χ2=5.393, P=0.020] than those of the control group. The in situ retention rate were better in type Ⅲ IPTG group, compared with those of the control group [94.9% (74/78) vs 77.4% (48/62), χ2=7.898, P=0.005]. There was no permanent hypoparathyroidism in two groups and the temporary hypoparathyroidism rate was 32.0% (24/75) and 34.6% (18/52), respectively (χ2=0.095, P=0.758). Conclusion: Ultrasound-guided IPTG localization examination has important implications for searching and protecting IPTG during operation, which can significantly increase in situ retention rate of IPTG and decrease the implantation rate.

[Risk factors for recurrence and survival analysis in locally advanced T4a papillary thyroid carcinoma after R0 resection].

Objective: To investigate the treatment outcomes and risk factors of postoperative recurrence in T4a papillary thyroid carcinoma (PTC). Methods: A total of 185 patients with locally advanced T4a PTC treated in Beijing Tongren Hospital, Capital Medical University from January 2006 to December 2019 were retrospectively analyzed, including 127 females and 58 males, aged between 18 and 80 years, with 74 patients aged over 55 years. According to AJCC thyroid tumor staging, 111 cases were stage I (T4aN0M0 26 cases, T4aN1aM0 35 cases, and T4aN1bM0 50 cases) and 74 cases were stage Ⅲ (T4aN0M0 29 cases, T4aN1aM0 19 cases, and T4aN1bM0 26 cases). Kaplan-Meier method was used to calculate the overall survival and the recurrence-free rate, and univariate and multivariate logistic regression analyses on the clinical data were performed. Results: Recurrent laryngeal nerve invasion was observed in 150 cases, trachea invasion in 61 cases, esophagus invasion in 30 cases, and laryngeal structure invasion in 10 cases. Postoperative follow-up periods were 24-144 months, with an average of 68.29 months. Of the 185 patients, 18 (9.73%) had recurrences or metastases, including 9 cases (4.86%) died of recurrences or metastases. The 5-year and 10-year overall survival rates were respectively 95.21% and 93.10%. The 5-year and 10-year disease-free survival rates were respectively 89.65% and 86.85%. Univariate analysis showed that age of onset, tumor diameter, preoperative recurrent laryngeal nerve palsy, esophageal invasion and cervical lymph node metastasis were the risk factors for postoperative recurrence of T4a PTC(all P<0.05). Multivariate analysis showed that preoperative recurrent laryngeal nerve palsy (OR=3.27, 95%CI: 1.11-9.61, P=0.032) and lateral cervical lymph node metastasis (OR=4.71, 95%CI: 1.19-18.71, P=0.027) were independent risk factors for T4a PTC recurrence. Survival rate of patients with T4a PTC involving only the recurrent laryngeal nerve or the outer tracheal membrane was significantly better than that of patients with tracheal invasion (P<0.05). Conclusions: T4a PTC patients with R0 resection can still achieve good efficacy. Preoperative recurrent laryngeal nerve palsy and lateral cervical lymph node metastasis are independent risk factor for postoperative recurrence in the patients.

[Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma].

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

[Efficacy of basiliximab in the treatment of 87 cases of steroid-refractory or steroid-dependent acute graft-versus-host disease].

Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.

[Efficacy and safety of Venetoclax in the treatment of 25 patients with recurrent hematologic malignancies after an allogeneic hematopoietic stem cell transplantation].

Objegtive: To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group) . The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs. Results: ①In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18-52) years; There were 13 cases of acute myeloid leukemia (AML) , 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF) ; the median time from MRD positive to the application of VEN was 2.5 (0-12.5) months. The median course of treatment was 2 (1-4) . On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688-5383) µg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses) , MRD in 4 patients decreased by 50% compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80% (12/15) . On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 µg/L or >3 000 µg/L turned negative for MRD (33.3%) , and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 µg/L turned negative for MRD (83.3%) . Grade 3/4 neutropenia occurred in 5 patients (33%) and grade 3/4 thrombocytopenia occurred in 5 patients (33%) , there were no new cases of severe infection and death. ②In the salvage group, there were 7 males and 3 females, with a median age of 44 (28-59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML) , 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD) ; the median time from relapse to application of VEN was 0 (0-1) months. The median treatment was 1 (1-2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200-6 155) µg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR) , 4 cases were ineffective and the ORR was 60% (6/10) . On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 µg/L achieved CR (25%) , and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 µg/L achieved CR (33.3%) . Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100%) . One patient died of severe pulmonary infection. ③The median follow-up was 4.5 (1-8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7) % and (50.0± 15.8) %, respectively (χ(2)=1.873, P=0.171) . The OS of patients with and without primary response to one course of VEN were (90.9±8.7) % and (36.2±14.7) % respectively (χ(2)=6.843, P=0.009) . Three patients with TP53 mutation achieved the major responses after VEN treatment. Conclusion: Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.

[Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis].

Objective: To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes (AML-MRC) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed. Methods: The clinical data of 75 patients with AML-MRC who underwent allo-HACT from 2006 to 2020 were retrospectively analyzed for clinical characteristics, survival, relapse-related indicators, and risk factors affecting transplantation prognosis. Additionally, the clinical characteristics and prognosis of multilineage dysplasia (M) group, history of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myelodysplastic proliferative tumor (MDS/MPN) (H) group, and MDS related cytogenetic abnormalities (C) group were compared. The bone marrow of 43 patients underwent targeting second-generation sequencing (137 genes) . Results: ①There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95%CI 30-49) months, and a median survival time (OS) of 78 (95%CI 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95%CI 45.6%-71.4%) and 52.0% (95%CI 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95%CI 16.6%-30.0%) and 22.7% (95%CI 13.2%-33.8%) , respectively. Furthermore, multivariate analysis revealed that pre-transplant non-CR1 status was an independent risk factor for OS and EFS. Other independent risk factors for OS included abnormal karyotype of -5/5q- chromosome and the absence of chronic graft-versus-host disease (cGVHD) after transplantation. ②Among the 75 patients, 59 (78.7%) were in group H, 20 had received demethylation drugs before turning to AML and nine cases (12.0%) in group C and seven cases (9.3%) in group M. There was no significant difference in the three-year OS and EFS among the three groups[group M vs H vs C: OS: 71.4% (95%CI 44.7%-100.0%) vs 55.0% (95%CI 41.8%-72.5%) vs 55.6% (95%CI 31.0%-99.7%) , P=0.700; EFS: 71.4% (95%CI 44.7%-100.0%) vs 46.5% (95%CI 34.0%-63.8%) vs 55.6% (95%CI 31.0%-99.7%) , P=0.600]. Compared with primary and secondary AML-MRC, there was no statistically significant difference in the three-year OS and EFS[61.9% (95%CI 41.9%-91.4%) vs 55.0% (95%CI 41.8%-72.5%) , P=0.600; 61.9% (95%CI 41.9%-91.4%) vs 46.5% (95%CI 34.0%-63.8%) , P=0.400]. Furthermore, there was no significant difference in the time to AML between patients who received demethylation treatment before (20 cases) and those who did not (39 cases) [195 (16-937) d vs 162 (9-3167) d, P=0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups (P=0.400, P=0.700) . ③ NGS test was performed on bone marrow samples of 43 patients (57.3%) , and 73 mutation types were found. Additionally, U2AF1 had the highest mutation incidence (11 cases, 25.6%) , and more than 10% were found: RUNX1 (ten cases, 23.3%) , NRAS (ten cases, 23.3%) , ASXL1 (six cases, 14.0%) , PTPN11 (five cases, 11.6%) , TET2 (five cases, 11.6%) . Univariate analysis showed U2AF1[P=0.875, HR=1.110 (95%CI 0.295-4.195) ], RUNX1[P=0.685, HR=0.728 (95%CI 0.157-3.375) ], NRAS[P=0.919, HR=0.923 (95%CI 0.196-4.334) ] mutation did not affect OS. Conclusion: Chromosome abnormality of -5/5q-, cGVHD, and non-CR1 status before transplantation were independent risk factors for OS in patients with allo-HSCT and AML-MRC. Additionally, the MHC subgroup classification was not a factor affecting the prognosis of transplantation. Treatment with demethylated drugs may not delay MDS turning to AML and prolong the OS after transplantation.

[The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation].

Objective: To investigates the relationship between CYP3A5 gene polymorphism, tacrolimus concentration, and acute graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A retrospective analysis of the clinical data of 35 Chinese adult patients who received allo-HSCT from July 2019 to February 2020 was conducted. Also, bone marrow samples were collected before transplantation for CYP3A5 genotyping, and intravenous infusion of tacrolimus and a short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15 ng/ml) . Results: In 16 allo-HSCT patients with CYP3A5 *3/*3 gene, the initial concentration of tacrolimus (9.82 ng/ml vs 8.53 ng/ml) , the initial concentration/dose (C/D) ratio (5.72 ng·ml(-1)·mg(-1) vs 4.26 ng·ml(-1)·mg(-1)) , and the median C/D ratio in the first two weeks after HSCT (5.29 ng·ml(-1)·mg(-1) vs 4.61 ng·ml(-1)·mg(-1), 5.65 ng·ml(-1)·mg(-1) vs 4.56 ng·ml(-1)·mg(-1)) were significantly higher than in 19 patients with at least one CYP3A5 * 1 allele (P=0.028, 0.001, 0.037, 0.045) . The incidence of Ⅲ-Ⅳ aGVHD in patients with CYP3A5*1 alleles was higher than in patients with CYP3A5*3/*3 gene[ (26.3±10.1) %vs (6.2±6.1) %, P=0.187]. Conclusion: CYP3A5 genotype-directed administration may help achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD, and improve the efficacy of transplantation.

[The immunoregulatory functions of exosome derived from mesenchymal stem cells that are genetically modified by adeno-associated virus].

Objectives: To verify the effects and mechanisms of natural MSC-exosome in treating acute GVHD in mice, explore and establish a method for targeted modification of MSC-exosome, and verify the functions of the modified MSC-exosome. Methods: In different doses of MSC-exosome groups and MSC group, weight loss in acute GVHD mice was observed; then the proliferation levels of activated T cells were measured through T cell activation experiment in vitro and OVA antigen-specific T cell activation experiment in vivo. AAV2YF3 mutants carrying PD-L1 and PD-L1-ITGB1 were obtained after the construction of recombinant expression vectors and were then applied to infect human MSC to modify their exosome. The immunoregulatory functions of the modified MSC-exosome were measured with the abovementioned methods. Results: ①Mouse MSC-exosome (300 µg×3 times) and MSC (1×10(6)×3 times) effectively alleviated the weight loss in acute GVHD mice. ②Compared with IL-2, 10, 25 and 50 µg human MSC-exosome inhibited the proliferation of activated T cells in vitro, respectively, 86.0% (IL-2) , 40.0%, 39.6%, and 42.8%; compared with PBS, 50, 100 and 200 µg mouse MSC-exosome inhibited the proliferation of antigen-specific activated OT-1 cells in vivo, respectively, 42.6%, 33.1%, 14.2%, and 10.6%. ③After the infection of AAV2YF3 mutant carrying PD-L1 or PD-L1-ITGB1, the positive proportion of MSC-exosome exceeds 40% and 60%, respectively. ④Compared with the natural state, MSC-exosome modified by PD-L1 or PD-L1-ITGB1 showed better proliferation inhibitory effect in vivo and increased the proportion of Treg cells in vitro. Conclusions: MSC-exosome exhibited similar immunomodulatory effects with MSC. MSC-exosome after PD-L1 and PD-L1-ITGB1-targeted modification effectively inhibited the proliferation of activated T cells and increased the proportion of Treg cells.

[Syngeneic hematopoietic stem cell transplantation for aplastic anemia].

Objective: To evaluate the efficacy of syngeneic hematopoietic stem cell transplantation in the treatment of aplastic anemia. Methods: The clinic data of 11 patients with aplastic anemia undergoing syngeneic HSCT were retrospectively analyzed. Results: Among all of the 11 patients with AA, 4 males and 7 females were determined, with a median age of 22 (7-44) years old. All of the 11 patients achieved engraftment after the first transplantation: neutrophils engraftment occurred after a median of 10 days (range 8-23) , and platelet engraftment occurred after a median of 11 days (range 8-28) . Eight patients achieved long-term stable engraftment: three patients had graft failure, and two of them underwent secondary transplantation (1 case achieved long-term stable engraftment, but graft failure occurred again after hematopoietic reconstruction in another case) . The median follow-up time was 53 (5-135) months. All of the 11 patients survived, and the blood routine of 9 patients was normal for a long time. Conclusion: Syngeneic hematopoietic stem cell transplantation has a good long-term survival rate in the treatment of aplastic anemia, and graft failure is still the most significant problem.

[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10(6)/kg. Results: ①All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. ②Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively. Conclusion: The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419.