Clinical Relevance of IDH1 and IDH2 Mutations and Single Nucleotide Polymorphism (SNP) rs11554137 in Patients with Acute Myeloid Leukemia Treated with Stem Cell Transplant in First Complete Remission

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4643-4643
Author(s):  
Hala Abalkhail ◽  
Naeem A. Chaudhri ◽  
Claudia Ulrike Walter ◽  
Hazzaa Al Zahrani ◽  
Randa Nounou ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Snp Polymorphism ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 4643 Background: Mutations in the genes encoding for the cytosolic isocitrate dehydrogenase 1 (IDH1) and the mitochondrial version of this enzyme (IDH2) have been reported in acute myeloid leukemia (AML) and other types of cancer. Presence of these mutations in AML correlated with more aggressive disease in some studies, but other studies did not find significant correlation with outcome when patients were treated with intensive chemotherapy. The polymorphism at rs11554137 in IDH1 was reported to correlate with inferior outcome in cytogenetically normal AML patients. Most of the studies evaluating the prognostic relevance of IDH1, IDH2 and the rs11554137 polymorphism were reported in patients treated with standard chemotherapy. The prognostic significance of these markers is not fully studied when AML patients are treated with intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the prognostic value of the IDH1, IDH2, and rs11554137 polymorphism in patients with AML treated with HSCT in first complete remission (CR1). Methods: Samples from 69 patients with AML were analyzed for mutations in IDH1, IDH2, and the SNP rs11554137 by direct sequencing. All patients were diagnosed with AML, treated with chemotherapy followed by HSCT in CR1. They included intermediate (N=42) and adverse (N=27) cytogenetic risk groups. Results: The R132H and the SNP C to T change at rs11554137 (silent G105) in IDH1 were detected in 5 (7%) and 6 (9%) of 69 AML patients. The IDH2 mutations (N=5; 7%) included R140Q, 172K, and T169A. Patients with IDH1 or IDH2 mutations did not differ significantly in their overall survival, event free survival, or time to relapse from those without mutation. In addition, the rs11554137 SNP polymorphism did not correlate with outcome in this group of AML patients. We also looked at the combination of mutations as compared with cytogenetic risk and found no difference in survival or event free survival based on IDH1 or IDH2 mutations or rs11554137 polymorphism in the intermediate cytogenetic risk group. Conclusion: The data suggests that HSCT after intensive chemotherapy in CR1 may neutralize the negative prognostic impact of IDH1 and IDH2 or the rs11554137 SNP polymorphism. However, the number of cases is relatively small and further studies with larger number of cases are needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India

2017 ◽  
Vol 3 (6) ◽  
pp. 773-781 ◽  
Author(s):  
Abhijeet Ganapule ◽  
Sandeep Nemani ◽  
Anu Korula ◽  
Kavitha M. Lakshmi ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Cost Effectiveness ◽  
Myeloid Leukemia ◽  
Cost Effective ◽  
Effective Strategy ◽  
Event Free Survival ◽  
Myeloablative Conditioning ◽  
Free Survival ◽  
Acute Myeloid

Purpose There are limited data from developing countries on the role and cost-effectiveness of allogeneic stem cell transplantation (allo-SCT) for patients with acute myeloid leukemia (AML). Patients and Methods We undertook a retrospective descriptive study of all patients with AML who underwent allo-SCT from 1994 to 2013 at our center to evaluate the clinical outcomes and cost-effectiveness of this therapeutic modality. Results Two hundred fifty-four consecutive patients, median age 34 years, who underwent allo-SCT at our center were included in this study. There were 161 males (63.4%). The 5-year overall survival (OS) and event-free survival for the entire cohort was 40.1 ± 3.5% and 38.7 ± 3.4%, respectively. The 5-year OS for patients in first (CR1), second, and third complete remission and with disease/refractory AML was 53.1 ± 5.2%, 48.2 ± 8.3%, 31.2 ± 17.8%, and 16.0 ± 4.4%, respectively ( P < .001). From 2007, reduced intensity conditioning (RIC) with fludarabine and melphalan (Flu/Mel) was used in a majority of patients in CR1 (n = 67). Clinical outcomes were compared with historical conventional myeloablative conditioning regimens (n = 38). Use of Flu/Mel was associated with lower treatment-related mortality at 1 year, higher incidence of chronic graft-versus-host-disease, and comparable relapse rates. The 5-year OS and event-free survival for Flu/Mel and myeloablative conditioning group was 67.2 ± 6.6% versus 38.1 ± 8.1% ( P = .003) and 63.8 ± 6.4% versus 32.3 ± 7.9% ( P = .002), respectively. Preliminary cost analysis suggests that in our medical cost payment system, RIC allo-SCT in CR1 was likely the most cost-effective strategy in the management of AML. Conclusion In a resource-constrained environment, Flu/Mel RIC allo-SCT for AML CR1 is likely the most efficacious and cost-effective approach in a subset of newly diagnosed young adult patients.

Allogeneic Stem Cell Transplantation Versus Conventional Postremission Therapy for Acute Myeloid Leukemia in First Complete Remission: A Matched Pairs Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1974-1974
Author(s):  
Matthias Stelljes ◽  
Utz Krug ◽  
Dietrich Beelen ◽  
Jan Braess ◽  
Maria Cristina Sauerland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
No Donor ◽  
Unrelated Donors ◽  
Related Donor ◽  
First Complete Remission ◽  
Acute Myeloid

Abstract Abstract 1974 Most available data on the relative value of allogeneic stem cell transplantation (allo-SCT) for acute myeloid leukemia (AML) in first complete remission (CR1) in the past, were generated from donor versus no-donor comparisons, focusing on documented tissue-typed patients and their siblings. The inclusion of patients who are not HLA-typed, for instance all those without siblings, causes bias of unknown magnitude. Additionally, concerns about the equivalence of related and unrelated donors should no longer be a problem in contemporary evaluation of allo-SCT. Using data of the prospective AMLCG 1999 trial, we performed a matched-pair analysis, to evaluate outcome in patients with AML according to post-remission allo-SCT or conventional postremission chemotherapy (PRT). 165 patients pairs in CR1 were identified, who matched for the following criteria: AML type (de novo AML, s-AML, t-AML, high-risk MDS); cytogenetic risk group [unfavorable (UNF-CG), intermediate (INT-CG), and favorable with the exclusion of t(15;17)]; age (± 5 years); and time in CR1 to account for the time to transplant in allo-SCT patients. If possible, patients were also matched for sex and assigned induction treatment (TAD-HAM versus HAM-HAM). 34 patient pairs had an UNF-CG, 122 pairs INT-CG, and 9 pairs had favorable cytogenetics. Median patients age at diagnosis was 45 years (range: 16–59). In the allo-SCT cohort, 105 patients had a related donor (matched related donor [MRD] 104, haploidentical 1) and 60 a matched unrelated donor (MUD). Median follow-up of surviving patients after first diagnosis of CR1 was 7.5 years. Projected 7-year relapse-free survival (RFS) was 56% in the allo-SCT group and 39% in the control group (p <.0001, log-rank test). Overall survival (OS) was 58% and 45% (p=.143), respectively. RFS was significantly improved by allo-SCT in patients with UNF-CG (23% vs. 12% at 7 years; p=.005) or INT-CG (58% vs. 37%; p=.001). OS was 31% in allo-SCT patients with UNF-CG versus 18% in matched controls (p=.052) and 64% in INT-CG patients with allo-SCT versus 54% in matched controls (p=.403). Dividing the 330 patients into age groups by decades, revealed an age dependent, increasing risk of relapse for patients receiving conventional post-remission therapy, with cumulative relapse incidences of 51% (<31 years), 47% (31–40 years), 60% (41–50%) and 87% (51–60 years) at 7 years, whereas allo-SCT patients had similar relapse incidences of 32%, 34%, 25% and 34% respectively. The higher relapse incidence in control patients >50 years of age, resulted in a significantly better OS of allo-SCT patients with 27% versus 58% (p=.022) in this age group. In the subset of patients with INT-CG, allo-SCT patients with non-normal karyotype had both a significant better OS and RFS after 7 years compared to control patients, whereas patients with normal karyotype had similar RFS and OS regardless of NPM1 and FLT3 mutational status. Of note, 48 of 99 patients with AML relapse in the control cohort, received an allo-SCT (18 from a MRD, 30 from a MUD) beyond CR1 (9 with UNF-CG, 38 with INT-CG, 1 with favorable CG). Median OS of 48 matched patients receiving an allo-SCT in CR1 was 54%, while it was 39% in paired patients with allo-SCT beyond CR1 (p=.289). We conclude that allo-SCT is the most potent post-remission therapy for AML with UNF-CG and INT-CG. Its impact on OS is difficult to assess, as about a third of patients initially treated with conventional PRT, underwent allo-SCT beyond CR1. In contrast to results from donor versus no-donor comparisons, our data highly suggest a benefit of allo-SCT in CR1, particularly for elderly patients, and in line with such comparisons, for patients with intermediate-II (according to the European LeukemiaNet [ELN] recommendation) or unfavorable ELN cytogenetic risk. Ultimately, the gold standard for the evaluation of allo-SCT in patients with INT-CG in CR1 is a randomized controlled trial, which is now feasible with unrelated donors becoming widely available and is conducted by the German Cooperative Transplant Study Group (ETAL-1 study). Disclosures: No relevant conflicts of interest to declare.

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