scholarly journals Autologous Stem Cell Transplantation Is a Viable Postremission Therapy for Intermediate-Risk Acute Myeloid Leukemia in First Complete Remission in the Absence of a Matched Identical Sibling: A Meta-Analysis

2019 ◽  
Vol 141 (3) ◽  
pp. 164-175 ◽  
Author(s):  
Zhichao Li ◽  
Yinmei Liu ◽  
Qing Wang ◽  
Linjun Chen ◽  
Liyuan Ma ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Intermediate Risk ◽  
Wild Type ◽  
Postremission Therapy ◽  
First Complete Remission ◽  
Acute Myeloid

Background: The preferred type of postremission therapy (PRT) for intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate. Although allogeneic stem cell transplantation (alloSCT) is regarded as a curative strategy for AML, the efficacy of autologous stem cell transplantation (autoSCT) for patients without a matched sibling donor (MSD) has remained controversial. Methods: To compare survival outcomes after alloSCT versus autoSCT for patients with intermediate-risk AML in CR1, we performed a meta-analysis of 11 clinical studies. The outcomes included relapse-free survival (RFS), overall survival (OS), relapse rate (RR), and treatment-related mortality (TRM). Results: Compared with autoSCT, alloSCT showed better RFS, OS, and RR benefits, but higher TRM. Subgroup analysis based on donor category (MSD and matched unrelated donor [MUD]) of alloSCT showed alloSCT from MSD rather than from MUD had better OS benefits compared to autoSCT. For fms-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) wild-type patients, alloSCT and autoSCT had comparable RFS and OS outcomes. Conclusion: Our results suggest that, in the absence of an available MSD, autoSCT remains a viable PRT alternative for intermediate-risk AML in CR1, especially for FLT3-ITD wild-type patients.

scholarly journals Maintenance with Hypomethylating Agents after Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Smith Kungwankiattichai ◽  
◽  
Ben Ponvilawa ◽  
Claudie Roy ◽  
Pattaraporn Tunsing ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Hypomethylating Agents ◽  
Eligibility Criteria ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Review question / Objective: P: Patients with AML or MDS after allo-SCT; I: Hypomethylating agents after allo-SCT; C: Observation after allo-SCT; O: Overall survival rates. Condition being studied: Hypomethylating agents (HMAs) seem to have a range of properties favorable to post-allogeneic hematopoietic stem cell transplantation (allo-SCT) maintenance in acute myeloid leukemia (AML) patients. This meta-analysis was performed to review all relevant studies to compare the outcomes of patients undergoing allo-SCT for AML or MDS receiving HMA maintenance therapy with observation only. Information sources: The systematic search of the Embase and MEDLINE databases identified 4,416 articles, from which 512 duplicates were removed. This resulted in 3,904 articles available for title and abstract review. Subsequently, 3,875 articles were excluded as the article type and study design did not fulfill the inclusion criteria, or there was no report on a primary outcome of interest. The remaining 29 articles underwent full-length review and 18 of those were excluded for the aforementioned reasons. Ultimately, the eligibility criteria for our meta-analysis were met by 11 studies: 2 RCTs, 1 prospective cohort study, and 8 retrospective cohort studies.

scholarly journals FLAMSA-RIC for Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (9) ◽  
pp. 1437 ◽  
Author(s):  
Weerapat Owattanapanich ◽  
Patompong Ungprasert ◽  
Verena Wais ◽  
Smith Kungwankiattichai ◽  
Donald Bunjes ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Reduced-intensity conditioning (RIC) regimens are established options for hematopoietic stem cell transplantation (HSCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the efficacy of RIC regimens for patients with high-risk disease is limited. The addition of a fludarabine, amsacrine, and cytarabine (FLAMSA)-sequential conditioning regimen was introduced for patients with high-risk MDS and AML to combine a high anti-leukemic activity with the advantages of RIC. The current systematic literature review and meta-analysis was conducted with the aim of identifying all cohort studies of patients with AML and/or MDS who received FLAMSA-RIC to determine its efficacy and toxicity. Out of 3044 retrieved articles, 12 published studies with 2395 overall patients (18.1–76.0 years; 96.8% AML and 3.2% MDS; follow-up duration of 0.7–145 months; 50.3% had active AML disease before HSCT) met the eligibility criteria and were included in the meta-analysis. In the pooled analysis, the 1- and 3-year overall survival (OS) rates were 59.6% (95% confidence interval (CI), 47.9–70.2%) and 40.2% (95% CI, 28.0–53.7%), respectively. The pooled 3-year OS rate of the patients who achieved CR1 or CR2 prior to HSCT was 60.1% (95% CI, 55.1–64.8%) and the percentage of those with relapse or refractory disease was 27.8% (95% CI, 23.3–32.8%). The pooled 3-year leukemia-free survival (LFS) rate was 39.3% (95% CI, 26.4–53.9%). Approximately 29% of the patients suffered from grades 2–4 acute graft-versus-host disease (GVHD), while 35.6% had chronic GVHD. The pooled 1- and 3-year non-relapse mortality (NRM) rates were 17.9% (95% CI, 16.1–19.8%) and 21.1% (95% CI, 18.8–23.7%), respectively. Our data indicates that the FLAMSA-RIC regimen is an effective and well-tolerated regimen for HSCT in patients with high-risk AML and MDS.

Molecular Markers Predicting Clinical Outcome in Patients with Intermediate-Risk Acute Myeloid Leukemia Receiving Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 604-604
Author(s):  
Jordi Esteve ◽  
Susana Kalko ◽  
Montserrat Torrebadell ◽  
Mireia Camos ◽  
Pedro Jares ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Intermediate Risk ◽  
Npm1 Mutation ◽  
Acute Myeloid

Abstract Post-remission therapy in patients with acute myeloid leukemia (AML) is assigned according to the predictable biological risk of the disease, mainly based on cytogenetics. Nonetheless, optimal post-remission strategy for the intermediate-risk subtype, given the prognostic heterogeneity of this category, is currently undefined. Analysis of potentially relevant molecular features within this subgroup might contribute to clarify the role of autologous stem cell transplantation (autoHSCT) in these patients. Thirty seven patients (age: 53, 15–66; 51% female) diagnosed with intermediate-risk de novo AML during the period 1994–2006 who received an autoHSCT in first complete response were included in the study. Pre-transplant therapy was similar in all patients, consisting of standard induction chemotherapy (ICE, n=8, IDICE, n=29) and one cycle of high-dose ara-C-based consolidation chemotherapy. Internal tandem duplication of flt-3 (flt-3 ITD) and exon 12 NPM1 mutations were studied by either PCR or RT-PCR following standard methods. Gene expression profiling was examined in 28 patients with oligonucleotide HGU133 Plus 2.0 arrays (Affymetrix). Gene expression measures were normalized using RMA methodology (Affy package), and dChip v1.3 and Limma software (Bioconductor) were used for unsupervised and supervised analyses. In order to identify genes with prognostic value, a supervised analysis based on patients’ outcome (relapsed patients vs. long-term responders, i.e. >2-year duration) was performed. The combined results of NPM mutation and flt-3 ITD defined three subgroups of patients with different outcome: group 1 (n=12), constituted by patients with mutated NPM1 without flt-3 ITD; group 2 (n=20), which included patients with neither NPM1 mutation or flt-3 ITD; and group 3 (n=5), defined by flt-3 ITD regardless NPM1 mutational status. Thus, 5-year survival of these 3 subgroups of patients was 91%±9%, 52%±12%, and 20%±18%, respectively (p=0.02; see figure). Preliminary results of multiple gene profile comparisons between subgroups of patients with different outcome disclosed a cluster of genes with differential expression. Thus, in the most significant balanced comparison, 1238 genes were found to vary significantly in the unsupervised analysis, and 109 differentially expressed genes were identified in the supervised analysis. Interestingly, overexpression of genes such as TNF, RETN, CFLAR, SLC16A7, ENG, CD48, PLCR1, and SULTB1 correlated with a high relapse risk, whereas increased expression of YY1, FBXL12 and EXOSC6 were associated with a favorable outcome. In conclusion, presence of NPM1 mutation and flt-3 ITD are strong predictors of the outcome after autoHSCT in patients with intermediate-risk AML. Furthermore, genome-wide analysis may contribute to further define gene clusters with prognostic significance in patients with cytogenetically intermediate-risk AML receiving autoHSCT as consolidation therapy. Figure Figure

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