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Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome.

ABSTRACT: Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk-patients with low/intermediate DRI-R and HCT-CI/Age??3 (N?=?272); Intermediate-risk-patients with low/intermediate DRI-R and HCT-CI/Age?>3 (N?=?168); High-risk-patients with high/very high DRI-R and HCT-CI/Age??3 (N?=?284); and Very high-risk-patients with high/very high DRI-R and HCT-CI/Age?>3 (N?=?184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P?

SUBMITTER: Kongtim P

PROVIDER: S-EPMC7285649 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome.

Kongtim Piyanuch P Parmar Simrit S Milton Denái R DR Perez Jorge Miguel Ramos JMR Rondon Gabriela G Chen Julianne J Chilkulwar Abhishek R AR Al-Atrash Gheath G Alousi Amin A Andersson Borje S BS Im Jin S JS Hosing Chitra M CM Bashir Qaiser Q Khouri Issa I Kebriaei Partow P Oran Betul B Popat Uday U Champlin Richard R Ciurea Stefan O SO

Bone marrow transplantation 20180926 6

Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS ...[more]

PMID: 30258129

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Project description:BackgroundAllogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia.MethodsPatients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk.ResultsThe incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46-2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1-1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34-2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33-2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21-1.83, p < 0.0001) compared to MMUD. The risk of grade II-IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis.ConclusionsCBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.

Project description:IntroductionAzacitidine (AZA) either single-agent or with donor lymphocytes infusions (DLI) has been used as a salvage treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT). To date, the majority of data come from patients relapsed after HSCT from full-matched donors.MethodsWe report a multicenter, collaborative, retrospective analysis of 71 patients with hematologic (n = 40, 56%) and molecular relapse (n = 31, 44%) of myeloid neoplasms after HSCT from alternative donors (mismatched unrelated, n = 39, 55%; haploidentical, n = 29, 41%) consecutively treated at three European centers with AZA ± DLI.ResultsMedian time from HSCT to relapse was 9 months. Additional DLI were given to 33 patients (46%). After a median of four cycles, overall response rate (ORR) was 49% and complete response (CR) rate was 38%. CR lasted for a median of 17 months (range 5-89 months). Median follow-up in the entire cohort was 11 months (range 1-115 months). Event-free survival (EFS) and overall survival (OS) at 1 year were 26% and 53%, respectively. Treatment of molecular relapse granted higher CR rate (65% versus 15%; p = 0.0001), 1-year EFS (43% versus 13%; p = 0.006), and 1-year OS (79% versus 34%; p < 0.001) compared to hematologic relapses. Addition of DLI resulted in significantly higher responses and longer 1-year EFS and OS (Mantel-Byar test, p = 0.004 and p = 0.002, respectively). When applied to our cohort, the APSS-R score confirmed its ability to stratify patients into distinct prognostic groups with significantly different response rates (p = 0.0005) and survival (p < 0.0001). Treatment was well tolerated, with the incidence of late acute and chronic graft-versus-host disease of 27% and 18%, respectively.ConclusionAZA ± DLI proved feasible and effective in AML and MDS relapsing after HSCT from alternative donors. Despite modest efficacy among hematologic relapses, pre-emptive treatment with AZA ± DLI fared better in molecular relapse. Additional DLI contributed to improving efficacy and ensuring longer survival.

Dataset Information

Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome.

Publications

Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome.

Similar Datasets

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