Dataset Information

Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older with Severe Aplastic Anemia.

ABSTRACT: We report on 499 patients with severe aplastic anemia aged ? 50years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n?=?275, 55%) or HLA-matched (8/8) unrelated donors (n?=?187, 37%) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.03 to 1.92; P?=?.03) and after unrelated donor transplantation (HR, 1.47; 95% CI, 1 to 2.16; P?=?.05). The 3-year probabilities of survival for patients with performance scores of 90 to 100 and less than 90 after HLA-matched sibling transplant were 66% (range, 57% to 75%) and 57% (range, 47% to 76%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57% (range, 48% to 67%) and 48% (range, 36% to 59%). Age at transplantation was not associated with survival, but grades II to IV acute graft-versus-host disease (GVHD) risks were higher for patients aged 65years or older (subdistribution HR [sHR], 1.7; 95% confidence interval, 1.07 to 2.72; P?=?.026). Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor (CNI)?+?methotrexate (sHR, .52; 95% CI, .33 to .81; P?=?.004) and CNI alone or with other agents (sHR, .27; 95% CI, .14 to .53; P < .001) compared with CNI?+?mycophenolate. Although donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes.

SUBMITTER: Rice C

PROVIDER: S-EPMC6401340 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older with Severe Aplastic Anemia.

Rice Carmel C Eikema Dirk-Jan DJ Marsh Judith C W JCW Knol Cora C Hebert Kyle K Putter Hein H Peterson Eefke E Deeg H Joachim HJ Halkes Stijn S Pidala Joseph J Anderlini Paolo P Tischer Johanna J Kroger Nicolaus N McDonald Andrew A Antin Joseph H JH Schaap Nicolaas P NP Hallek Michael M Einsele Herman H Mathews Vikram V Kapoor Neena N Boelens Jaap-Jan JJ Mufti Ghulam J GJ Potter Victoria V Pefault de la Tour Régis R Eapen Mary M Dufour Carlo C

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20180905 3

We report on 499 patients with severe aplastic anemia aged ≥ 50years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n = 275, 55%) or HLA-matched (8/8) unrelated donors (n = 187, 37%) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.03 to 1.92; P = .0 ...[more]

PMID: 30194027

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Project description:IMPORTANCE:Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. OBJECTIVE:To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia. DESIGN, PARTICIPANTS, AND SETTING:The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013. EXPOSURES:Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution. MAIN OUTCOMES AND MEASURES:Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up. RESULTS:Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P?=?.009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence, 22% vs 28%; HR, 0.77; 95% CI, 0.48-1.23), or chronic graft-vs-host disease at 1-year (cumulative incidence, 28% vs 30%; HR, 0.81; 95% CI, 0.53-1.24) for long vs short, respectively. Pretransplant leukocyte telomere length in the recipients was not associated with posttransplant survival (HR, 0.91; 95% CI, 0.64-1.30). CONCLUSIONS AND RELEVANCE:Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term posttransplant survival.

Project description:We previously showed an association between donor leukocyte relative telomere length (RTL) and post-hematopoietic cell transplantation (HCT) survival in patients with severe aplastic anemia (SAA) who received bone marrow grafts at ages <40 years. Here, we tested the generalizability of the prior findings in an independent validation cohort and by recipient age and stem cell source in the combined discovery and validation cohorts. We used monoplex quantitative real-time PCR to measure RTL in: (1) a new SAA validation cohort of 428 patients (age range, .2 to 77 years) with available pretransplantation donor blood samples in the Center for International Blood and Marrow Transplant Research repository, and (2) 278 patients from the original cohort who had sufficient DNA to repeat RTL testing. We used Cox proportional hazard models to calculate hazard ratios (HRs), and 95% confidence intervals (CIs) across categories of donor RTL. Data from the validation cohort showed no association between donor RTL and patient survival, but further analysis identified differences by recipient age and stem cell source as the likely explanation. In patients <40 years, the HR comparing longest with shortest and middle RTL tertiles?=?.75; 95% CI, ?.44 to 1.30 versus HR?=?1.05; 95% CI, .59 to 1.89 for patients ?40 years, P interaction?=?.37. In bone marrow recipients, the HR?=?.68; 95% CI,?.72 to 1.10 versus HR?=?1.29; 95% CI, .64 to 2.62 for peripheral blood stem cell grafts; P interaction?=?.88. Analyses using data from the 2 cohorts showed a statistically significant survival benefit only in <40-year-old patients receiving bone marrow graft (HR comparing longest and middle RTL tertiles with shortest?=?.69; 95% CI, .50 to .95, P?=?.02). The study suggested that the association between donor RTL and post-HCT outcomes in recipients with SAA may vary by recipient age and stem cell source. A larger study is needed to account for multiple comparisons and to further test the generalizability of our findings.

Dataset Information

Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older with Severe Aplastic Anemia.

Publications

Allogeneic Hematopoietic Cell Transplantation in Patients Aged 50Years or Older with Severe Aplastic Anemia.

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