Dataset Information

Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status.

ABSTRACT: Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients with therapy-related myelodysplastic syndrome (n=67) who underwent allogeneic transplantation, comparing these patients to similarly treated patients with de novo disease (n=199). The 5-year overall survival was not different between patients with therapy-related and de novo disease (49.9% versus 53.9%; P=0.61) despite a higher proportion of individuals with an Intermediate-2/High International Prognostic Scoring System classification (59.7% versus 43.7%; P=0.003) and high-risk karyotypes (61.2% versus 30.7%; P<0.01) among the patients with therapy-related disease. In mutational analysis, TP53 alteration was the most common abnormality in patients with therapy-related disease (n=18: 30%). Interestingly, the presence of mutations in TP53 or in any other of the high-risk genes (EZH2, ETV6, RUNX1, ASXL1: n=29: 48%) did not significantly affect either overall survival or relapse-free survival. Allogeneic stem-cell transplantation is, therefore, a curative treatment for patients with therapy-related myelodysplastic syndrome, conferring a similar long-term survival to that of patients with de novo disease despite higher-risk features. While TP53 alteration was the most common mutation in therapy-related myelodysplastic syndrome, the finding was not detrimental in our case-series.

SUBMITTER: Aldoss I

PROVIDER: S-EPMC5709102 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of <i>TP53</i> mutational status.

Aldoss Ibrahim I Pham Anh A Li Sierra Min SM Gendzekhadze Ketevan K Afkhami Michelle M Telatar Milhan M Hong Hao H Padeganeh Abbas A Bedell Victoria V Cao Thai T Khaled Samer K SK Malki Monzr M Al MMA Salhotra Amandeep A Ali Haris H Aribi Ahmed A Palmer Joycelynne J Aoun Patricia P Spielberger Ricardo R Stein Anthony S AS Snyder David D O'Donnell Margaret R MR Murata-Collins Joyce J Senitzer David D Weisenburger Dennis D Forman Stephen J SJ Pullarkat Vinod V Marcucci Guido G Pillai Raju R Nakamura Ryotaro R

Haematologica 20170929 12

Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients w ...[more]

PMID: 28971906

Similar Datasets

Project description:ObjectivesThis study aimed to describe the impact of allogeneic/haploidentical hematopoietic stem cell transplantation on nutritional status and intake in a group of children aged 2 to 18 years.MethodsIn an observational study, data were collected prospectively. Patients were prescribed individual nutritional support by hospital routines. Anthropometrics were measured pre-transplant at hospital admission and weekly from the day of transplant (day 0) until day +28. z scores for weight, height, and BMI were calculated using Norwegian growth references to assess nutritional status. Pre-transplant diet was assessed on the day of hospitalization. Nutrient provision from enteral nutrition (EN = oral and tube) and parenteral nutrition (PN) was assessed by daily records from day +1 until day +28, or previous discharge, and compared with recommendations (RI) from the Nordic Nutrition Recommendations and ESPGHAN guidelines. Total energy intake was presented as the percentage (%) of basal metabolic rate (BMR) calculated by the Schofield equation. Macro- and micronutrient provisions were presented as medians (interquartile range) and the % of RI.ResultsTwenty-eight patients, mean age 10.3 years (range 3.5-16.6), were included. Two-thirds (n = 18) had malignant diseases. At admission, mean weight Z-score was -0.3, height z scores -0.7, and BMI Z-score 0.1. Eighteen percent (n = 5) were stunted and 25% (n = 7) had overweight. At admission, 25% (n = 7) had established tube feeding, and 7% (n = 2) also had PN. No significant changes in weight z scores were detected during the studied weeks ( P = 0.454). The median daily energy provision was 115% (110-123) of BMR and proteins 1.5 (1.3-1.8) g/kg. EN was provided during a median of 93% of the studied days and provided 21% of the energy. PN was given on a median of 96% of the studied days and provided 79% of energy. RI for vitamins, magnesium, and zinc was met. Provision of copper, iodine, selenium, calcium, and phosphate was below RI.ConclusionsCombined EN and PN providing 115% of BMR and 1.5 g/kg protein ensured stable weight by day +28 and covered RI, except for trace elements and minerals.

Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders for which allogeneic hematopoietic cell transplantation (HCT) is currently the sole curative treatment. Epigenetic lesions are considered a major pathogenetic determinant in many cancers, and in MDS, epigenetic-based interventions have emerged as life-prolonging therapies. However, the impact of epigenomic aberrations on HCT outcomes among patients with MDS are not well understood. We hypothesized that epigenomic signatures in MDS patients before undergoing HCT serve as a novel prognostic indicator of the risk of post-HCT MDS relapse. To evaluate these epigenomic signatures in MDS patients, we analyzed reduced representation bisulfite sequencing profiles in a matched case-control population of 94 patients. Among these HCT recipients, 47 patients with MDS who relapsed post-HCT (cases) were matched 1:1 to patients with MDS who did not relapse (controls). Only patients with wild-type TP53, RAS pathway, and JAK2 mutations were included in this study to promote the discovery of novel factors. Cases were matched with controls based on conditioning regimen intensity, age, sex, Revised International Prognostic Scoring System, Karnofsky Performance Status, graft type, and donor type. Pre-HCT whole-blood samples from cases and matched controls were obtained from the Center for International Blood and Marrow Transplant Research repository. We comprehensively identified differentially methylated regions (DMRs) by comparing the methylation patterns among matched cases and controls. Our findings show that cases displayed more hyper-DMRs pretransplantation compared with controls, even after adjusting for pre-HCT use of hypomethylating agents. Hyper-DMRs specific to cases were mapped to the transcription start site of 218 unique genes enriched in 5 different signaling pathways that may serve as regions of interest and factors to consider as prognostic determinants of post-HCT relapse in MDS patients. Interestingly, although patients selected for this cohort were wild-type for the TP53 gene, cases showed significantly greater levels of methylation at TP53 compared with controls. These findings indicate that previously identified prognostic genes for MDS, such as TP53, may affect disease relapse not only through genetic mutation, but also through epigenetic methylation mechanisms.

Dataset Information

Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status.

Publications

Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of <i>TP53</i> mutational status.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets