The one-year survival rate for patients experiencing a relapse of B-cell acute lymphocytic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT) is approximately 30%. Patients experiencing a relapse after allogeneic HSCT frequently encounter difficulties in obtaining autologous CAR-T products. We conducted a study involving 14 patients who received donor-derived CAR-T therapy for relapsed B-ALL following HSCT between August 2019 and May 2023 in our center. The results revealed a CR/CRi rate of 78.6% (11/14), a GVHD rate of 21.4% (3/14), and a 1-year overall survival (OS) rate of 56%. Decreased bone marrow donor cell chimerism in 9 patients recovered after CAR-T therapy. The main causes of death were disease progression and infection. Further analysis showed that GVHD (HR 7.224, 95% CI 1.42-36.82, P=0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61-28.83, P=0.009) are significantly associated with OS after CAR-T therapy. Based on the findings, we conclude that donor-derived CAR-T cells are effective in treating relapsed B-ALL patients following HSCT. Additionally, GVHD and poor platelet recovery impact OS, but further verification with a larger sample size is needed.

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

IntroductionChimerism is closely correlated with disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, chimerism rate is dynamic changes, and the sensitivity of different chimerism requires further research.MethodsTo investigate the predictive value of distinct chimerism for relapse, we measured bone marrow (BM), peripheral blood (PB), and T-cell (isolated from BM) chimerism in 178 patients after allo-HSCT.ResultsReceiver operating characteristic (ROC) curve showed that T-cell chimerism was more suitable to predict relapse after allo-HSCT compared with PB and BM chimerism. The cutoff value of T-cell chimerism for predicting relapse was 99.45%. Leukemia and myelodysplastic syndrome (MDS) relapse patients’ T-cell chimerism was a gradual decline from 2 months to 9 months after allo-HSCT. Higher risk of relapse and death within 1 year after allo-HSCT. The T-cell chimerism rates in remission and relapse patients were 99.43% and 94.28% at 3 months after allo-HSCT (P = 0.009), 99.31% and 95.27% at 6 months after allo-HSCT (P = 0.013), and 99.26% and 91.32% at 9 months after allo-HSCT (P = 0.024), respectively. There was a significant difference (P = 0.036) for T-cell chimerism between early relapse (relapse within 9 months after allo-HSCT) and late relapse (relapse after 9 months after allo-HSCT) at 2 months after allo-HSCT. Every 1% increase in T-cell chimerism, the hazard ratio for disease relapse was 0.967 (95% CI: 0.948–0.987, P<0.001).DiscussionWe recommend constant monitoring T-cell chimerism at 2, 3, 6, and 9 months after allo-HSCT to predict relapse.

目的:探讨靶向B细胞成熟抗原（BCMA）的嵌合抗原受体T细胞（CAR-T）治疗自体造血干细胞移植后复发多发性骨髓瘤（MM）患者的疗效及安全性。方法:回顾性分析2019年7月至2022年1月解放军联勤保障部队第九六〇医院收治的接受靶向BCMA的CAR-T治疗自体造血干细胞移植后复发MM的3例患者临床资料，并复习相关文献。结果:3例MM患者移植后复发时骨髓浆细胞分别为23.5%、6.5%、34.5%。经过靶向BCMA的CAR-T治疗，3例均达到完全缓解（CR），均出现细胞因子释放综合征（CRS），其中1例为1级CRS，2例为2级CRS。3例患者输注CAR-T后，CAR-T均出现扩增及细胞因子的变化。1例在CAR-T治疗后30个月时疾病再次复发，2例仍处于持续CR状态。结论:靶向BCMA的CAR-T对自体造血干细胞移植后复发的MM患者具有较好疗效和安全性。

Objective:To evaluate the safety and efficacy of bortezomib plus highdose melphalan (L-phenylalanine nitrogen mustard) (Bor-HDM) pretreatment regimen for multiple myeloma (MM) with autologous hematopoietic stem cell transplantation (ASCT).Methods:From August 2008 to December 2021, the relevant clinical data were retrospectively reviewed for 58 MM patients undergoing MM transplantation.The conditioning regimens were Bor-HDM (n=36) and HDM (n=22). Non-hematopoietic adverse reactions, hematopoietic reconstruction time, remission rate post-ASCT and minimal negative rate of residual disease (MRD) on flow cytometry within 3 months post-ASCT and survivals were analyzed.Results:In Bor-HDM and HDM groups, median time of neutrophil engraftment was 12(8-30) and 11(8-29) day and median time of platelet reconstitution 16(8-33) and 16(7-32) day respectively.There was no significant inter-group difference ( P=0.890, P=0.638). In Bor-HDM group, the most common non-hematological adverse reactions were nausea (n=21, 58.0%) and diarrhea (n=11, 30.6%). There was no transplant-related death.Complete remission (CR) rate was (25/36, 69.4%) versus (9/22, 40.9%). The inter-group difference was statistically significant ( P=0.032). Median follow-up period was 29.0(2.0-91.0) vs. 20.5(5.0-114.0) month, 3-year progression-free survival(PFS)62.1% vs. 39.7% and 3-year overall survival(OS) 83.8% vs. 62.5%.There were relapse (n=10 vs.10) and death (n=6 vs. 7). Median PFS in Bor-HDM and HDM groups was non-attained and 27 months( P=0.047) and median OS time non-attained and 40 months respectively ( P=0.282). Multivariate analysis revealed that CR was an independent risk factor for PFS ( HR=28.896, 95% CI: 6.130-136.198, P<0.001). Non-CR was an independent risk factor for OS ( HR=3.843, 95% CI: 1.334-11.071, P=0.013; HR=28.595, 95% CI: 6.273-130.355, P<0.001). Conclusions:Bor-HDM pretreatment regimen of ASCT is both safe and efficacious for MM patients.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood malignancy. The cure rate has reached 90% after conventional chemotherapy and hematopoietic stem cell transplantation (HSCT), but the prognosis of patients with relapsed and refractory (R/R) leukemia is still poor after conventional treatment. Since FDA approved CD19 CAR-T cell (Kymriah) for the treatment of R/R B-ALL, increasing studies have been conducted on CAR-T cells for R/R ALL. Herein, we report the treatment of a patient with ALL who relapsed after allogeneic HSCT, had a complete remission (CR) to murine scFv CD19 CAR-T but relapsed 15 months later. Partial response was achieved after humanized CD19 CAR-T treatment, and the patient finally achieved disease-free survival after sequential CD22 CAR-T treatment. By comparing the treatment results of different CAR-T cells in the same patient, this case suggests that multiple CAR-T therapies are effective and safe in intramedullary and extramedullary recurrence in the same patient, and the expansion of CAR-T cells and the release of inflammatory cytokines are positively correlated with their efficacy. However, further clinical studies with large sample sizes are still needed for further clarification.