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Auto-hematopoietic stem cell transplantation or chemotherapy? Meta-analysis of clinical choice for AML
Ge, S., Wang, J., He, Q., Zhu, J., Liu, P., Wang, H., Zhang, F.
Annals of hematology. 2024
Abstract
For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41-0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02-1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28-6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85-1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis.
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Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data
Zhou, J., Wang, Z., Wang, H., Cao, Y., Wang, G.
Frontiers in pharmacology. 2023;14:1331844
Abstract
Background: Central nervous system lymphoma (CNSL) is considered an aggressive lymphoma with a poor prognosis. Studies investigating CNSL have shown that chimeric antigen receptor (CAR) T-cell therapy has demonstrated an effective response in limited sample sizes. Therefore, we conducted this systematic review and meta-analysis to clarify the sustained efficacy and factors associated with the sustained efficacy of CAR T-cell therapy in the treatment of CNSL. Methods: We searched studies from PubMed, Embase, Medline, and the Cochrane Center Register of Controlled Trials up to July 2023. Studies that included individual data on the duration of response (DoR) after receiving CAR T-cell therapy were enrolled. Pooled response rates were calculated using fixed-effects or random-effects models. Subgroup analysis was performed to analyze the heterogeneity, and a Cox regression model was performed to identify the factors associated with sustained efficacy. Results: In total, 12 studies including 69 patients were identified and included in this meta-analysis. The pooled relapse rate was 45% [95% CI 35, 56]. Subgroup analyses of relapse rates revealed that CAR T-cells using the CD28/4-1BB domain (CD28/4-1BB vs. CD28 vs. 4-1BB, p = 0.0151), parenchymal or leptomeningeal involvement (parenchymal or leptomeningeal vs. both parenchymal and leptomeningeal, p < 0.0001), and combined treatment with CAR T-cell therapy [Autologous stem cell transplantation (ASCT) plus CAR T-cell therapy vs. CAR T cells with maintenance therapy vs. CAR T-cell therapy alone, p = 0.003] were associated with lower relapse rates in patients. Time-to-event endpoints were assessed using reconstructed individual patient survival data to explore key modulators of DoR. Partial response status at CAR-T infusion and the use of ASCT plus CAR T-cell therapy were associated with longer DoR at the multivariate level, with hazard ratios of 0.25 and 0.26, respectively. Conclusion: CAR T-cell therapy shows promising and sustained efficacy in CNSL patients. However, further prospective large-scale studies are needed to assess these effect modifiers to optimize patient selection and improve the sustained efficacy of CAR T-cell therapy in the treatment of CNSL. Systematic review registration: https://clinicaltrials.gov/, identifier PROSPERO CRD42023451856.
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Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and Relapse Settings: A Retrospective Study in China
Liu, J., Wang, H., Li, X., Wu, Y., Ma, Y., Gu, Z., Li, F., Li, M., Guo, J., Zhao, Y., et al
Annals of transplantation. 2023;28:e938467
Abstract
BACKGROUND Myeloablative chemotherapy supported by autologous stem cell transplantation (ASCT) is an option for primary central nervous system lymphoma (PCNSL) in both the relapse setting and as postremission consolidation, but the level of evidence in this field is still low. MATERIAL AND METHODS We retrospectively analyzed 47 HIV-negative PCNSL patients from 2010 to 2021. To assess the outcomes in patients undergoing ASCT. RESULTS Of the 47 patients, the median age was 51 (range, 21-77) years, and 28 (59.6%) were male. After induction, 33 (70.2%) patients achieved complete remission, and 6 (12.8%) patients achieved partial remission. At a median follow-up of 21.4 months (95% CI 8.86-33.95), the median progression-free survival (PFS) was 23.3 months (95% CI 14.87-31.73), and the 4-year PFS rate was 14.6%. The median overall survival (OS) time was 62.4 months (95% CI 41.93-82.87), and the 4-year OS rate was 71.5%. Among 20 patients who received ASCT (10 consolidation, 10 salvage), the 4-year PFS and 4-year OS rates were 57.3% and 71.2%, respectively. In the multivariate analysis, ASCT therapy (hazard ratio [HR] 0.16, P=0.016) and early remission (HR 0.12, p=0.003) were found to be independent prognostic factors for a longer PFS. Two treatment-related deaths occurred in patients with multiple relapses before ASCT. Pancytopenia and diarrhea were the most common adverse events. CONCLUSIONS ASCT offers potential long-term PFS with good tolerability for patients with PCNSL. Our retrospective cohort adds to the currently available literature and identifies disease status after induction as a significant factor affecting survival.
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4.
[Study on Application of RVD Regimen Sequential Auto-HSCT in the Treatment of Multiple Myeloma Evaluated by Propensity Score Matching]
Wang, Y., Xue, Y., Fu, C. M., Feng, K., Li, X. L., Duan, Y. Y., Zhang, C. X., Yang, Y. J., Shi, H., Fu, J., et al
Zhongguo shi yan xue ye xue za zhi. 2022;30(4):1150-1155
Abstract
OBJECTIVE To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
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5.
Immunoparesis recovery 1 year after ASCT is independently associated with favorable survival in patients with symptomatic multiple myeloma who undergo autologous stem cell transplantation
Gao, W., Li, J., Wu, Y., Li, Y., Leng, Y., Liu, A., Yang, G., Tian, Y., Wang, H., Wang, G., et al
Annals of hematology. 2019
Abstract
Immunoparesis is defined as a reduction in the levels of one, two, or three uninvolved immunoglobulins. However, there are very limited data on the incidence and prognostic significance of immunoparesis recovery 1 year after autologous stem cell transplantation (ASCT) in MM. We reviewed medical records of de novo MM patients who received ASCT at Beijing Chao Yang hospital. One hundred eight MM patients were included in the study. Conventional chemotherapy was administered as induction regimen in 16 patients (14.8%), whereas novel agents were used in 92 patients (85.2%). Most patients had immunoparesis at diagnosis (89.1%) and at the moment of ASCT as well (75%). After a median follow-up of 49 months, in the group with immunoglobulin recovery 1 year after ASCT, there was a trend towards longer progression-free survival (PFS) than in the group with immunoparesis (P = 0.054). And overall survival (OS) was significantly longer in patients with immunoparesis recovery (P = 0.004). In multivariate analysis, immunoparesis recovery 1 year after ASCT was independently associated with improved OS (P = 0.016). In conclusion, lack of immunoparesis recovery 1 year after ASCT in MM patients is associated with significantly shorter OS and this group of patients needs new treatment strategy to improve the prognosis.
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Prognostic analysis of DLBCL patients and the role of upfront ASCT in high-intermediate and high-risk patients
Zhao, Y., Wang, H., Jin, S., Zheng, J., Huang, M., Tang, Y., Jin, Z., Qiu, H., Tang, X., Fu, C., et al
Oncotarget. 2017;8(42):73168-73176
Abstract
The role of autologous stem cell transplantation (ASCT) as a frontline treatment in patients with diffuse large B cell lymphoma (DLBCL) who are in their first remission has not been fully elucidated in the rituximab era. We analyzed 272 DLBCL patients who received 4-6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or R-CHOP followed by ASCT, from January 2005 to June 2013 in our institution. Multivariate analysis showed the none germinal center B cell (non-GCB) subtype (P=0.014, P=0.012) and International Prognostic Index (IPI) (3-5) (P=0.004, P=0.016) were independent unfavorable predictors of overall survival (OS) and progression-free survival (PFS), respectively. To investigate the treatment effect of upfront ASCT, we selected 94 high-intermediate and high-risk DLBCL patients who achieved complete remission after R-CHOP, with 41 in the ASCT and 53 in the non-ASCT groups. Survival analysis revealed patients who received upfront ASCT compared with those who did not had better OS (3-year OS: 74.5% vs. 50.4%, P=0.029) or PFS (3-year PFS: 59.6% vs. 32.1%, P=0.004), suggesting up-front ASCT following R-CHOP could improve the outcome of high-intermediate and high-risk DLBCL patients. CONFLICTS OF INTEREST The authors declare no conflicts of interest.
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7.
Autologous transplant remains the preferred therapy for relapsed APL in CR2
Ganzel, C., Mathews, V., Alimoghaddam, K., Ghavamzadeh, A., Kuk, D., Devlin, S., Wang, H., Zhang, M. J., Weisdorf, D., Douer, D., et al
Bone Marrow Transplantation. 2016;51(9):1180-3
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Abstract
Despite their favorable prognosis, 10-20% of acute promyelocytic leukemia (APL) patients relapse. Reinduction therapy is often followed by autologous hematopoietic cell transplantation (auto-HCT). Arsenic trioxide (ATO) has become part of standard reinduction and is often followed by auto-HCT. Data on patients in CR2 were collected from two large transplant registries (Center for International Blood and Marrow Transplant Research (CIBMTR) and European Group for Blood and Marrow Transplant (EBMT)) and two specialty referral centers. The outcome of patients in CR2 who received only ATO-based therapy as reinduction was retrospectively compared with those who got an auto-HCT, with or without ATO. Prognostic factors included age, disease risk, extramedullary disease and duration of CR1. Of 207 evaluable patients, the median age was 31.5 years, 15.3% had extramedullary disease and median WBC at diagnosis was 4.8 x 10(9)/L. Sixty-seven patients received ATO alone and 140 underwent auto-HCT. The groups were comparable for age, gender, extramedullary disease, risk group and duration of CR1. At 5 years, overall survival (OS) was 42% and 78% for the ATO-only and auto-HCT groups, respectively (P<0.001). In addition, OS was associated with longer duration of CR1 (P=0.002), but not with disease risk at diagnosis. These data suggest that auto-HCT for APL patients in CR2 results in better OS than ATO-based therapy alone. The authors declare no conflict of interest.