-
1.
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.
-
2.
Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML
Cao, X. Y., Chen, J. Q., Wang, H., Ma, W., Liu, W. W., Zhang, F. F., Xue, S., Dong, L., Liu, T., Zhao, X. Z., et al
Annals of medicine. 2023;55(1):388-400
Abstract
BACKGROUND Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated. OBJECTIVE To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML. STUDY DESIGN From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed. RESULTS At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52-632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2-36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9-26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5-81.4%) and 3.2% (95%CI, 0.4-22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5-93.6%) and 81.3% (95%CI, 64.2-93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8-26.3%) and 11.7% (95%CI, 3.9-35.0%). CONCLUSION Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.
-
3.
Efficacy of azacitidine in preventing relapse after hematopoietic stem cell transplantation for advanced myeloid malignancies: a systematic review and meta-analysis
Pan, T., Han, S., Zhou, M., Qi, J., Wang, H., Xu, X., Li, X., Yao, Y., Han, Y.
Expert review of hematology. 2022;:1-8
Abstract
BACKGROUND Relapse is the leading cause of death from myeloid malignancies after allogeneic hematopoietic stem cell transplantation (HSCT). Azacitidine has gained attention in recent years in the prophylaxis of relapsed refractory hematologic malignancies. This study evaluated the efficacy of AZA in preventing relapse after HSCT in patients with myeloid malignancies. METHODS A systematic review and meta-analysis of all available cohort studies were performed regarding the application of AZA for prophylaxis of relapse after HSCT for advanced MDS and AML. Databases were searched for relevant studies. Endpoints included 2-year relapse rate, survival, relapse-related mortality, as well as the incidence of graft-versus-host disease (GVHD). RESULTS A total of 444 patients from 13 studies were included in this analysis. The pooled estimate of the cumulative incidence of relapse after two years in enrolled patients was 25% (95% confidence interval [CI], 18%-33%). The pooled estimates of 2-year survival probabilities were 65% (95% CI, 50%-79%). The pooled cumulative incidence of relapse-related mortality was 28% (95% CI, 22%-34%). The pooled estimated incidence of acute and chronic GVHD, respectively, were 28% (95% CI, 22%-34%) and 38% (95% CI, 27%-49%). CONCLUSION AZA administration is efficacious for relapse prevention after HSCT in myeloid malignancies.
-
4.
Decitabine-Intensified Modified Busulfan/Cyclophosphamide Conditioning Regimen Improves Survival in Acute Myeloid Leukemia Patients Undergoing Related Donor Hematopoietic Stem Cell Transplantation: A Propensity Score Matched Analysis
Li, Z., Shi, W., Lu, X., Lu, H., Cao, X., Tang, L., Yan, H., Zhong, Z., You, Y., Xia, L., et al
Frontiers in oncology. 2022;12:844937
Abstract
To identify the benefit of decitabine (Dec)-intensified myeloablative conditioning on the outcomes of patients with acute myeloid leukemia (AML) after related donor hematopoietic stem cell transplantation (HSCT), we performed a retrospective matched-pair study from a pool of 156 patients to evaluate Dec [20 mg/m(2)/day intravenously (i.v.) on days -11 to -7]-intensified modified busulfan/cyclophosphamide (mBuCy) conditioning regimen vs. mBuCy regimen in 92 AML patients, with 46 patients in each cohort. The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was lower in the Dec group (15.2% ± 0.3% vs. 32.6% ± 0.5%, P = 0.033). Compared with mBuCy group (15.5% ± 0.3%), a significantly higher proportion of limited chronic GVHD (cGVHD) in Dec group (35% ± 0.6%) was observed (P = 0.025). Dec-intensified mBuCy conditioning was associated with better 2-year overall survival (OS) and GVHD-free relapse-free survival (GRFS) (81% ± 6.2% vs. 59.4% ± 7.5%, P = 0.03; 58.7% ± 8.1% vs. 40.9% ± 7.3%, P = 0.042; respectively). Our results also elucidated that the Dec group had better 2-year OS and lower 2-year cumulative incidence of relapse (CIR) in patients acquiring haploidentical HSCT than that of the mBuCy group (84.8% ± 7.1% vs. 58.2% ± 10.3%, P = 0.047; 17.9% ± 0.8% vs. 40.0% ± 1.0%, P = 0.036; respectively), which did not increase the treatment-related mortality and regimen-associated toxicities. Dec-intensified myeloablative regimen and high-risk stratification were the variables associated with OS, leukemia-free survival (LFS), and GRFS in multivariate analysis. In high-risk patients, no differences were found in CIR, OS, LFS, and GRFS between the two groups. These data indicated that Dec-intensified mBuCy conditioning regimen was associated with better survival than mBuCy regimen in AML patients, especially in patients undergoing haploidentical HSCT.
-
5.
[The Prognostic Value of FOSB Gene in Acute Myeloid Leukemia]
Luan, S. H., Ma, Y. Q., Yang, J. J., Wang, H., Liu, D. H., Dou, L. P.
Zhongguo shi yan xue ye xue za zhi. 2022;30(4):1063-1070
Abstract
AbstractObjective: To analyze the expression of FOSB in acute myeloid leukemia (AML) and its correlation with prognosis of the patient based on the large sample data. METHODS The genome, transcriptome, gene chip and clinical information from multiple public databases were statistical analyzed. RESULTS The expression of FOSB gene in AML patients was significantly higher than that in normal people. The prognostic analysis of the 163 patients showed that the patients with high FOSB expression showed longer OS and EFS than those with FOSB low expression. The patients were further divided into chemotherapy group and allogeneic hematopoietic stem cell transplantation (allo-HSCT) group according to the treatment method, and then each group was divided into two subgroups (FOSBhigh, FOSBlow) according to the median expression level of FOSB. In the allo-HSCT group, the patients with FOSB high expression was longer event-free survival (EFS: P=0.017) and overall survival (OS: P=0029). At the same time, allo-HSCT in patients with high FOSB expression could improve the prognosis of the patients (Chemotherapy vs Allo-HSCT, OS: P<0.001, EFS: P=0.007). Multivariate analysis showed that the high expression of FOSB was an independent favorable prognostic factor for EFS and OS (EFS: HR=0.501, P=0.019; OS: HR=0.461, P=0.009) of the patients. CONCLUSION The high expression of FOSB indicated a good prognosis for acute myeloid leukemia.
-
6.
Clinical significance of FLT3-ITD/CEBPA mutations and minimal residual disease in cytogenetically normal acute myeloid leukemia after hematopoietic stem cell transplantation
Wang, H., Li, X. Q., Chu, T. T., Han, S. Y., Qi, J. Q., Tang, Y. Q., Qiu, H. Y., Fu, C. C., Tang, X. W., Ruan, C. G., et al
Journal of cancer research and clinical oncology. 2021
Abstract
PURPOSE Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. RESULTS A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITD(mut) and CEBPA(wt) were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPA(mut)/FLT3-ITD(wt) had the best prognosis, and patients with CEBPA(wt)/FLT3-ITD(mut) had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.
-
7.
Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myeloid Leukemia and Myelodysplastic Syndromes with Low/Intermediate, but not High Disease Risk Index: A CIBMTR Study: Superior DFS with MAC compared to RIC HCT in AML/MDS with low/intermediate risk DRI
Bejanyan, N., Zhang, M., Bo-Subait, K., Brunstein, C., Wang, H., Warlick, E. D., Giralt, S., Nishihori, T., Martino, R., Passweg, J., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
-
-
-
Free full text
-
Editor's Choice
Abstract
Myeloablative (MAC) as compared to reduced-intensity conditioning (RIC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, disease specific risk factors in AML/MDS can further inform when MAC vs. RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the disease risk index (DRI) in 4387 adults (age 40-65 years) to identify the impact of conditioning intensity. In the low/intermediate risk DRI cohort, RIC was associated with lower non-relapse mortality (NRM) (HR=0.74, 95% CI 0.62-0.88; p<0.001), but significantly higher relapse risk (HR=1.54, 95% CI 1.35-1.76; p<0.001) and thus inferior disease-free survival (DFS) (HR=1.19, 95% CI 1.07-1.33; p=0.001). In the high/very high risk DRI cohort, RIC resulted in marginally lower NRM (HR=0.83, 95% CI 0.68-1.00; p=0.051), and significantly higher relapse risk (HR=1.23, 95% CI 1.08-1.41; p=0.002) leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for AML/MDS with low/intermediate risk DRI, but similar benefit to RIC in high/very high risk DRI. Novel MAC regimens with less toxicity could benefit all, but more potent anti-neoplastic approaches are needed for the high/very high risk DRI group.
PICO Summary
Population
Adult patients aged 40-65 years with acute myeloid leukaemia or myelodysplastic syndrome (AML/MDS) (n=4387)
Intervention
Reduced intensity conditioning (RIC) and low/intermediate risk (n=999), RIC and high/very high risk (n=728)
Comparison
Myeloablative conditioning (MAC) and low/intermediate risk (n=1539), MAC and high/very high risk (n=1121)
Outcome
In the low/intermediate risk disease risk index (DRI) cohort, RIC was associated with lower non-relapse mortality (NRM) , but significantly higher relapse risk and thus inferior disease-free survival (DFS). In the high/very high risk DRI cohort, RIC resulted in marginally lower NRM, and significantly higher relapse risk leading to similar DFS using either RIC or MAC.
-
8.
[Efficacy of Haploidentical Hematopoietic Stem Cell Transplantation in Treatment of Intermediate Risk Acute Myeloid Leukemia with Negative for FLT3-ITD, NPM1 or Biallelic CEBPA Mutation]
Chen, C., Qi, J. Q., Chu, T. T., Wang, H., Wu, D. P., Ruan, C. G., Han, Y.
Zhongguo shi yan xue ye xue za zhi. 2020;28(3):731-736
Abstract
OBJECTIVE To compare the efficacy of haploidentical hematopoietic stem cell transplantation (hi-HSCT) HLA-matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) and post-remission chemotherapy (PR-CT) in treatment of intermediate risk acute myeloid leukemia with negative for FLT3-ITD, NPM1 or biallelic CEBPA mutation. METHODS The clinical data of patients with intermediate risk NPM1(wt)/non-CEBPA(dm)/FLT3-ITD(neg) AML from October 2009 to May 2016 were retrospectively analyzed. RESULTS The overall survival rate of the patients treated with PR-CT, MSD-HSCT or hi-HSCT was 63.7%, 71.7%, 75.5%, respectively (P0.05); the disease-free survival (DFS) rate was 52.8%, 67.1%, 71.3% respectively (P0.001); the cumulative incidence of relapse was 24.7%, 16.9%, 14.4% respectively (P0.05); the non-relapse mortality was 26.2%, 17.3%, 14.4% reapectively (P0.05). The analysis of transplantation, related adverse events showed that II-IV grade of aGVHD in the MSD-HSCT group and hi-HSCT group was 48.9% and 45.6% respectively (P0.05); the extensive cGVHD event was 21.6% and 8.8% (P0.05) respectively. CONCLUSION The efficiency of hi-HSCT and MSD-HSCT is superior to that of PR-CT for treatment of patients with intermediate risk NPM1(wt)/non-CEBPA(dm)/FLT3-ITD(neg) AML after CR1, there is no statistically significant difference in the efficiency of consolidatorg treatment and the transplantation-related mortality between hi-HSCT and MSD-HSCT.
-
9.
Reduced-intensity versus Myeloablative Conditioning Regimens for Younger Adults with Acute Myeloid Leukemia and Myelodysplastic Syndrome: A systematic review and meta-analysis
Ma, S., Shi, W., Li, Z., Tang, L., Wang, H., Xia, L., Hu, Y.
Journal of Cancer. 2020;11(17):5223-5235
Abstract
Background: Historically, reduced-intensity conditioning (RIC) was recommended to be performed for older patients who were considered ineligible for myeloablative conditioning (MAC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the evidence regarding the optimal conditioning intensity in younger patients with AML or MDS is weak and contradictory. Methods: PubMed, Medline, Embase, and other online sources were searched from the initial period to February 25, 2020. Odds ratios and 95% confidence intervals were calculated to estimate pooling effects. Results: Four randomized controlled trials (RCTs) about conditioning intensity involving 633 patients were included. There were no significant differences of 1/2/4/5 years progression-free survival (PFS) and relapse incidence (RI) between two conditioning intensities. Overall survival (OS) was similar at 1/2/4 years, but patients receiving RIC had a higher OS at 5 years. Additionally, RIC were associated with lower non-relapse mortality, less grade II-IV and grade III-IV acute graft-versus-host disease (GVHD), and lower incidence of chronic GVHD compared with MAC regimens. Subgroup analysis showed similar OS and RI for AML patients, and there was a trend towards lower NRM and grade II-IV aGVHD in RIC group. Available data for MDS indicated that OS, PFS, and RI were comparable. For intermediate-risk patients, there was no evidence that RIC is inferior to MAC. However, for high-risk patients, MAC tends to perform better. Conclusions: Based on the above results, it might be concluded that RIC is a feasible treatment option for adults with AML or MDS younger than 66 years, particularly those with intermediate-risk disease. Future RCTs incorporating of risk stratifications are warranted to guide the optimal decision under certain conditions.
-
10.
ADAMTS-13 activity reduction in plasma of acute myeloid leukemia predicts poor prognosis after bone marrow transplantation
Liu, C., Han, M., Zhao, L., Zhu, M., Xu, Q., Song, Y., Wang, H.
Hematology (Amsterdam, Netherlands). 2018;:1-5
Abstract
OBJECTIVE This research aimed to explore the significance of low activity of ADAMTS-13 in acute myeloid leukemia (AML) after bone morrow transplantation (BMT), and to evaluate the disease progress and prognosis of the patients with low or normal activity of ADAMTS-13 after BMT. METHODS 46 AML patients were included in our research. ADAMTS-13 activity was measured before BMT. Their medical indicators were recorded one month after BMT. All the patients were followed up and their disease progression was evaluated afterwards. The medical indicators and prognosis situation were compared between Low ADAMTS13 Group (<481 ng/ml) and Normal Group (481-785 ng/ml) according to the reference range of local laboratory. ROC curves were used to evaluate the predictive value of ADAMTS13 for infection complications and survival. RESULTS Low ADAMTS13 Group show extended APTT, PT and elevated CRP and D-Dimer levels, compared with Normal Group. Low ADAMTS13 Group suffered more BMT-related complications than Normal Group. In addition, Low ADAMTS13 Group underwent higher mortality than Normal Group in the one-year follow up after BMT and two-year follow up after onset of AML. ADAMTS13 has AUC of 0.7675, 0.7254, 0.8019 for lung infection, CMV infection and death within one year after BMT, suggesting that ADAMTS13 has predictive value for prognosis of AML patients after BMT. DISCUSSION For patients with low ADAMTS13 activity, the prognosis was worse and the probability of serious complications and mortality was significantly higher than AML patients with normal ADAMTS13 activity, which suggest predictive role of ADAMTS13 activity for the prognosis of AML after BMT. CONCLUSION AML patients with low activity of ADAMTS-13 had worse prognosis after BMT.