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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.
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A prognostic score system in adult T-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation
Xiao, M., Zhou, J., Zhu, X., He, Y., Wang, F., Zhang, Y., Mo, X., Han, W., Wang, J., Wang, Y., et al
Bone marrow transplantation. 2024
Abstract
Adult T-cell acute lymphoblastic leukemia (T-ALL) is highly aggressive with poor prognoses, while hematopoietic stem cell transplantation (HSCT) is a curable option. However, no transplant-specific prognostic model for adult T-ALL is available. We identified 301 adult T-ALL patients who received HSCT at our hospital between 2010 and 2022. These patients were randomly assigned at a 7:3 ratio to a derivation group of 210 patients and a validation group of 91 patients. Next, we developed a prognostic risk score system for adult T-ALL with HSCT, which we named COMM, including 4 predictors (central nervous system involvement, Non-CR1 (CR2+ or NR) at HSCT, minimal residual disease (MRD) ≥ 0.01% after first induction therapy, and MRD ≥ 0.01% before HSCT). Patients were categorized into three risk groups, low-risk (0), intermediate-risk (1-4), and high-risk (5-12), and their 3-year overall survival (OS) were 87.5% (95%CI, 78-93%), 65.7% (95%CI, 53-76%) and 20% (95%CI, 10-20%; P < 0.001), respectively. The area under the subject operating characteristic curve for 2-, 3- or 5-year OS in the derivation cohort and in the validation cohort were all greater than 0.75. Based on internal validation, COMM score system proved to be a reliable prognostic model that could discriminate and calibrate well. We expect that the first prognostic model in adults T-ALL after HSCT can provide a reference of prognostic consultation for patients and families, and also contribute to future research to develop risk adapted interventions for high-risk populations.
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Hyper-CVAD-Based Stem Cell Microtransplant as Post-Remission Therapy in Acute Lymphoblastic Leukemia
Cai, B., Wang, Y., Lei, Y., Shi, Y., Sun, Q., Qiao, J., Hu, K., Lei, Y., Li, B., Liu, T., et al
Stem cells translational medicine. 2022
Abstract
Post-remission strategies for patients with acute lymphoblastic leukemia (ALL) are limited to the multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT), and cellular therapies are seldom involved. Although chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) has been studied in patients with acute myeloid leukemia, its efficacy in ALL is still undetermined. We enrolled 48 patients receiving hyper-CVAD-based MST between July 1, 2009, and January 31, 2018. No acute or chronic graft-versus-host disease occurred in patients receiving MST. Four-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, and the 4-year relapse rate was 65%. No patient experienced non-relapse mortality. Subgroup analysis showed that OS rates were comparable between groups with different age, risk stratification, minimal residual disease status prior to MST and immunophenotype. Adult patients tended to achieve better 4-year LFS (62% vs. 26%, P = .058) and lower hematologic relapse rate (38% vs. 74%, P = .058) compared with adolescent and young adult patients. Donor chimerism/microchimerism was detectable ranging from 0.002% to 42.78% in 78% (42/54) available samples within 14 days after each infusion and at 3 months or one year after the last cell infusion. Multivariate analyses demonstrated that white blood cells <30 × 109/L at diagnosis and sufficient hyper-CVAD cycles were prognostic factors for better 4-year OS and LFS, while the B-cell phenotype and higher number of infused CD34+ cells in the first cycle were predictors for favorable 4-year LFS. The hyper-CVAD-based MST was a feasible strategy for treating ALL patients with mild toxicity.
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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.
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Comparative Analysis of Flow Cytometry and RQ-PCR for the Detection of Minimal Residual Disease in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia after Hematopoietic Stem Cell Transplantation
Zhao, X., Zhao, X., Chen, H., Qin, Y., Xu, L., Zhang, X., Liu, K., Huang, X., Chang, Y.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The aim of this study was to examine the value of MRD detection by multiparameter flow cytometry (MFC) and RQ-PCR at the early stage after hematopoietic stem cell transplantation (HSCT) for predicting relapse and leukemia-free survival (LFS) in Philadelphia chromosome-positive ALL (Ph+-ALL). Patients who maintained complete molecular remission (CMR, BCR/ABL<0.01%) status at 1 and 3 months were associated with a lower relapse rate (P=0.02 and <0.001) and better LFS (P=0.014 and 0.013) than those without a CMR. Negative MFC at 1, 2 and 3 months was associated with a lower relapse rate (P=0.01, 0.004, and 0.04 respectively) and better LFS (P=0.044, <0.0001 and 0.013, respectively). Multivariate analysis showed that MRD positivity identified by MFC or RQ-PCR at 3 month was an independent risk factor for relapse (HR 6.042 (95% CI 2.283-15.988), P<0.001), LFS (HR 3.614 (95% CI 1.610-8.111), P=0.002) as well as OS (HR 2.547, 95%CI 1.008-6.443), P=0.048). In summary, MRD detection by MFC and RQ-PCR detection of BCR-ABL at the early stage were important predictors of outcome in patients with Ph+-ALL, and these tests played complementary roles in predicting prognosis.