0
selected
-
1.
Intensified conditioning regimens with total marrow irradiation/etoposide/cyclophosphamide and busulfan/etoposide/cyclophosphamide overcome the impact of pre-transplant minimal residual disease on outcomes in high-risk acute lymphoblastic leukemia patients in complete remission
Zhao, X., Xu, Z., Li, Z., Zhou, X., Hu, Y., Wang, H.
Cancer medicine. 2024
Abstract
PURPOSE Among high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), those with positive minimal residual disease (MRD) are susceptible to poor outcomes. Therefore, it is necessary to determine the most suitable preparatory regimen for these patients. METHODS Data were analyzed from 141 patients who received allo-HSCT and were diagnosed with high-risk ALL. These patients underwent intensified conditioning regimens, including either total marrow and lymphoid irradiation (TMLI)-etoposide (VP16)-cyclophosphamide (CY) or busulfan (BU)-VP16-CY between October 2016 and November 2022. A total of 141 individuals were in complete remission (CR) before transplantation and, among all patients, 90 individuals exhibited a negative MRD status and 51 patients had a positive MRD status. RESULTS In patients who tested negative for MRD, the incidence of relapse within a 2-year timeframe was 25.0% (24.8%-25.5%), compared with 32.2% (31.2%-33.2%) in MRD-positive patients; however, this difference was not statistically significant. There were no significant differences in the 2-year disease-free survival (DFS) and 2-year overall survival (OS) rates between the MRD-negative and MRD-positive groups (DFS: 67.2% (57.9%-78.1%) vs. 55.5% (42.6%-72.3%); OS: 69.0% (61.9%-88.2%) vs. 66.7% (53.9%-82.5%)). Furthermore, no notable variations were observed in the occurrence of transplant-related mortality (TRM) and graft-versus-host disease (GVHD) across the two groups. CONCLUSION This study reveals the benefits of TMLI-VP16-CY and BU-VP16-CY conditioning regimens in high-risk ALL patients with CR and MRD-positive status. A large-scale prospective clinical trial is warranted in the future.
-
2.
Cytoplasmic CD79a is a promising biomarker for B lymphoblastic leukemia follow up post CD19 CAR-T therapy
Chen, M., Fu, M., Wang, A., Wu, X., Zhen, J., Gong, M., Zhang, X., Yue, G., Du, Q., Zhao, W., et al
Leukemia & lymphoma. 2022;63(2):426-434
Abstract
Minimal residual disease (MRD) detection is an important prognostic parameter in patients with refractory or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). CD79a has been reported to exhibit a high degree of linage-specificity for B-cell differentiation, with a specificity of 88% and a sensitivity of 100%. In this study, we investigated the efficiency and prognostic role of cytoplasmic CD79a (cCD79a) antibody-gated multicolor flow cytometry (MFC) in MRD detection in patients with B-ALL who received CD19-targeted chimeric antigen receptor (CAR) T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The retrospective analysis was carried on to 59 patients who accepted allo-HSCT after CD19-CAR-T infusion from June 2016 to May 2017. The MFC MRD statuses before and after allo-HSCT were both strongly correlated with the transplantation prognosis, the MFC panel with cCD79a gating can effectively monitor MRD after CD19 CAR T-cell therapy and predict the prognosis after allo-HSCT. Trial registration: ClinicalTrials#: ChiCTR-IIh-16008711.gov: NCT03173417. Registered 30 May 2017 - retrospectively registered, https://www.clinicaltrials.gov/.
-
3.
[Effect of Philadelphia Chromosome Karyotype and Allogeneic Hematopoietic Stem Cell Transplantation on Patients with Acute Lymphoblastic Leukemia]
Wang, Y., Xu, X. M., Zhang, M., Wang, H.
Zhongguo shi yan xue ye xue za zhi. 2022;30(5):1397-1406
Abstract
AbstractObjective: To explore the effect of Philadelphia chromosome karyotype (Ph) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the treatment of acute lymphoblastic leukemia (ALL). METHODS The data of 429 patients with all from January 2012 to December 2020 were retrospectively analyzed. According to the results of cytogenetic karyotype analysis, they were divided into Ph(+) group (n=64), Ph(-) monomeric karyotype (MK) group (n=53) and Ph(-) NMK group (n=312). According to the treatment plan, they were divided into allo-HSCT group (n=236) and non-allo-HSCT group (n=193). The effects of karyotype and allo-HSCT on the short-term and long-term outcomes of all patients were analyzed. RESULTS Among the 429 patients, 6 (1.40%) died during induction therapy, 60 (13.99%) had no response, 363 (84.62%) achieved complete remission (CR) and 287 (66.90%) achieved minimal residual disease negative (MRD-). There was no significant difference in short-term efficacy (CR%, CR1%, MRD-%) among Ph(+) group, Ph(-) MK group and Ph(-) non-MK group (P>0.05). The median OS was 6.9 months (95% CI: 4.6-8.2 months) for 60 unresponsive patients and 39.8 months (95% CI: 28.6-45.9 months) for 363 CR patients. There was no significant difference in the long-term efficacy [5-year cumulative recurrence rate (CIR%), disease-free survival rate (DFS%) and overall survival rate (OS%) among Ph(-) group, Ph(-) MK group and Ph(-) non-MK group (P>0.05). Among 429 patients, 55.01% (236/429) underwent allo-HSCT. The short-term efficacy (CR%, MRD-%) and long-term efficacy (CIR%, DFS%, OS%)] of patients with allo-HSCT after more than 2 consolidation cycles were better than those of patients with non-allo-HSCT (P<0.05). For the three subgroups of Ph(+) group, Ph(-) MK group and Ph(-) non-MK group, the short-term and long-term efficacy of allo-HSCT patients was better than that of non-allo-HSCT patients. Multivariate logistic regression analysis showed that liver/spleen/lymph node enlargement was a risk factor for CIR, DFS and OS, with adjusted or of 1.23 (95% CI: 1.08-2.78, P=0.032), 1.21 (95% CI: 1.03-2.34, P=0.038) and 1.25 (95% CI: 1.08-2.97, P=0.028), respectively. No transplantation was a risk fator for CIR, DFS, OS. The adjusted or were 2.34 (95% CI: 1.18-5.39, P<0.001), 2.15 (95% CI: 1.10-4.34, P<0.001) and 2.28 (95% CI: 1.09-4.11, P<0.001), respectively. CONCLUSION Karyotype (Ph(+/-) and MK/non-MK) seems to have no effect on the short-term and long-term efficacy of all patients; allo-HSCT can affect the short-term and long-term efficacy of all patients and improve their prognosis; liver/spleen/lymph node enlargement and non-implementation of allo-HSCT treatment strategy are the risk factors for poor prognosis of all patients.
-
4.
Comparing the outcomes between TMLI and non-TMLI conditioning regimens for adult high-risk acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a single-center experience
Zhao, X., Lu, X., Tang, L., Yan, H., Chen, W., Shi, W., Zhong, Z., You, Y., Xia, L., Hu, Y., et al
Leukemia & lymphoma. 2020;:1-9
Abstract
This study aimed to retrospectively evaluate the outcomes of adult patients with high-risk acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either total marrow and lymphoid irradiation (TMLI)-containing or non-TMLI conditioning regimen. Seventy adult patients with high-risk ALL who received allo-HSCT were enrolled in this study and divided into two groups based on the conditioning regimen type (TMLI group: n = 29 and non-TMLI group: n = 41). We noted significant statistical differences in the 1-year estimated cumulative incidence of relapse (25% vs. 46.5%, p = 0.018), the 1-year estimated overall survival (73.1% vs. 52.6%, p = 0.033) and disease-free survival (65.2% vs. 48.2%, p = 0.026) but found no considerable difference in transplant-related mortality (12% vs. 13.4%, p = 0.619) between patients in the TMLI and non-TMLI groups. The TMLI-containing regimen is safe and alternative for patients with high-risk ALL undergoing allo-HSCT.
-
5.
Efficacy and safety of anti-CD19 CAR T-cell therapy in 110 patients with B-cell acute lymphoblastic leukemia with high-risk features
Zhang, X., Lu, X. A., Yang, J., Zhang, G., Li, J., Song, L., Su, Y., Shi, Y., Zhang, M., He, J., et al
Blood advances. 2020;4(10):2325-2338
-
-
Free full text
-
Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is effective in patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, efficacy data is sparse in subgroups of patients with high-risk features such as BCR-ABL+, TP53 mutation, extramedullary disease (including central nervous system leukemia) or posttransplant relapse. It is also uncertain whether there is an added benefit of transplantation after anti-CD19 CAR T-cell therapy. We conducted a phase 1/2 study of 115 enrolled patients with CD19+ B-ALL. A total of 110 patients were successfully infused with anti-CD19 CAR T cells. In all, 93% of patients achieved a morphologic complete remission, and 87% became negative for minimal residual disease. Efficacy was seen across all subgroups. One-year leukemia-free survival (LFS) was 58%, and 1-year overall survival (OS) was 64% for the 110 patients. Seventy-five nonrandomly selected patients (73.5%) subsequently received an allogeneic hematopoietic stem cell transplant (allo-HSCT). LFS (76.9% vs 11.6%; P < .0001; 95% confidence interval [CI], 11.6-108.4) and OS (79.1% vs 32.0%; P < .0001; 95% CI, 0.02-0.22) were significantly better among patients who subsequently received allo-HSCT compared with those receiving CAR T-cell therapy alone. This was confirmed in multivariable analyses (hazard ratio, 16.546; 95% CI, 5.499-49.786). Another variate that correlated with worse outcomes was TP53 mutation (hazard ratio, 0.235; 95% CI, 0.089-0.619). There were no differences in complete remission rate, OS, or LFS between groups of patients age 2 to 14 years or age older than 14 years. Most patients had only mild cytokine release syndrome and neurotoxicity. Our data indicate that anti-CD19 CAR T-cell therapy is safe and effective in all B-ALL subgroups that have high-risk features. The benefit of a subsequent allo-HSCT requires confirmation because of nonrandom allocation. This trial was registered at www.clinicaltrials.gov as #NCT03173417.
-
6.
Anti-CD19 CAR-T Therapy Bridging to Allo-HSCT for Relapsed/refractory B-cell Acute Lymphoblastic Leukemia: An Open-Label Pragmatic Clinical Trial
Jiang, H., Li, C., Yin, P., Guo, T., Liu, L., Xia, L., Wu, Y., Zhou, F., Ai, L., Shi, W., et al
American journal of hematology. 2019
Abstract
Chimeric antigen receptor-modified T-cell (CAR-T) therapy is effective and safe for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), but its value has been limited in terms of long-term leukemia-free survival. New strategies that can help CAR-T therapy achieve lasting effect are urgently warranted. This non-randomized interventional pragmatic clinical trial aimed to explore whether consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) could improve the long-term prognosis of the minimal residual disease-negative complete remission (MRD(-) CR) patients after CAR-T therapy. In the first stage, 58 r/r B-ALL patients received split doses of CAR-T cells after lymphodepleting chemotherapy, and 51 (87.9%) achieved CR. In the second stage, 21/47 MRD(-) CR patients without previous allo-HSCT and contraindications or other restrictions, on their own accord, received consolidative allo-HSCT within three months after CAR-T therapy. There was no difference in overall survival (OS) between the MRD(-) CR patients who received allo-HSCT and those who didn't, but event-free survival (EFS) and relapse-free survival (RFS) were significantly prolonged by allo-HSCT in the subgroups with either high (≥ 5%) pre-infusion bone marrow MRD assessed by flow cytometry (BM-FCM-MRD) or poor prognostic markers (P < 0.05). However, no difference was found in EFS and RFS for patients with pre-infusion BM-FCM-MRD < 5% and without poor prognostic markers (P > 0.05). To conclude, CAR-T therapy bridging to allo-HSCT is a safe and effective therapeutic strategy for r/r B-ALL patients, and may prolong their EFS and RFS, especially when they have high pre-infusion BM-FCM-MRD or poor prognostic markers. This article is protected by copyright. All rights reserved.