Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Latour, Régis Peffault de; Calado, Rodrigo T.; Busson, Marc; Abrams, Jeffrey S.; Adoui, Nadir; Robin, Marie; Larghero, Jérôme; Dhédin, Nathalie; Xhaard, Aliénor; Clave, Emmanuel; Charron, D.; Toubert, Antoine; Loiseau, Pascale; Socié, Gèrard; Young, Neal S.

doi:10.1182/blood-2012-01-403337

Cited by 29 publications

(33 citation statements)

References 36 publications

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“…Short telomeres after HCT were more common in females and those with cGVHD, 164 and pre-HCT short telomere length in recipients has been associated with transplant-related mortality. 165,166 Finally, in a longitudinal study including 287 lymphoma patients, accelerated telomere shortening was associated with MDS/AML risk after autologous HCT. 167 …”

Section: Non-transplant-related Risk Factorsmentioning

confidence: 98%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Morton

Saber

Baker

et al. 2017

Biology of Blood and Marrow Transplantation

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Subsequent neoplasms (SN) following hematopoietic cell transplantation (HCT) cause significant patient morbidity and mortality. Risks for specific SN types vary substantially, with particularly elevated risks for post-transplant lymphoproliferative disorders, myelodysplastic syndrome/acute myeloid leukemia, and squamous cell malignancies. This consensus document provides an overview of the current state of knowledge regarding SN after HCT and recommends priorities and approaches to overcome challenges and gaps in understanding. Numerous factors have been suggested to impact risk, including patient-related (e.g., age), primary disease-related (e.g., disease type, pre-HCT therapies), and HCT-related characteristics (e.g., type and intensity of conditioning regimen, stem cell source, development of graft-versus-host disease). However, gaps in understanding remain for each of these risk factors, particularly for patients receiving HCT in the current era due to substantial advances in clinical transplantation practices. Additionally, the influence of non-transplant-related risk factors (e.g., germline genetic susceptibility, oncogenic viruses, lifestyle factors) is poorly understood. Clarification of the magnitude of SN risks and identification of etiologic factors will require large-scale, long-term, systematic follow-up of HCT survivors with detailed clinical data. Most investigations of the mechanisms of SN pathogenesis after HCT have focused on immune drivers. Expansion of our understanding in this area will require interdisciplinary laboratory collaborations utilizing measures of immune function and availability of archival tissue from SN diagnoses. Consensus-based recommendations for optimal preventative, screening, and therapeutic approaches have been developed for certain SN after HCT, whereas for other SN, general population guidelines are recommended. Further evidence is needed to specifically tailor preventative, screening, and therapeutic guidelines for SN after HCT, particularly for unique patient populations. Accomplishment of this broad research agenda will require increased investment in systematic data collection with engagement from patients, clinicians, and interdisciplinary scientists in order to reduce the burden of SN in the rapidly growing population of HCT survivors.

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Section: Non-transplant-related Risk Factorsmentioning

confidence: 98%

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Morton

Saber

Baker

et al. 2017

Biology of Blood and Marrow Transplantation

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“…Ferritin was considered , or $2500 ng/mL 2 and CRP , or $9 mg/L, as previously reported. 9 Recipient and donor telomere lengths were determined in peripheral blood leukocytes by quantitative polymerase chain reaction, as previously described. 9 Age-adjusted patient telomere length was determined by subtracting linear predicted length from observed length.…”

Section: Methodsmentioning

confidence: 99%

“…More recently, we and others have reported on the correlation of recipient or donor telomere length with OS and TRM. 9,10 A number of clinical and biological factors may be used to inform transplantation-related decision making. However, clinical and biological data, including pretransplant telomere length and comorbidity index scores, are mostly assessed separately, making it difficult to gauge each factor's contribution to TRM.…”

Section: Introductionmentioning

confidence: 99%

Clinical profile, biological markers, and comorbidity index as predictors of transplant-related mortality after allo-HSCT

et al. 2017

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“…Conversely, young patients are also exposed to a risk of TRM: biological markers such as pre-transplant C-reactive protein, 11 ferritin levels 12 and more recently, the pre-transplantation recipient telomere length have been studied in this setting to identify and prevent this risk. 13 In this study, we compared the outcomes for all patients with AML aged 35 and over who received either a RIC or a myeloablative conditioning (MAC) regimen before allogeneic transplantation in our center between 2000 and 2010 in order to analyze the role of the conditioning regimen intensity in this setting.…”

Section: Introductionmentioning

confidence: 99%

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML

Sébert

Porcher

Robin

et al. 2014

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation provides the best chance of long-term survival for patients with AML, but is associated with an unpredictable risk of treatment-related mortality. From January 2000 to December 2010, we compared the outcomes for patients with AML aged 35 and over using reduced-intensity conditioning (RIC, N = 60) or conventional myeloablative conditioning (MAC) regimen (N = 72) transplantation. The median follow-up was 47 months (10-134). The 4-year cumulative incidence of non-relapse mortality was 21%. After adjusting for cytogenetic risk, gender donor/recipient mismatch and CD34+ cells, non-relapse mortality was significantly lower with the RIC regimen (P = 0.027). The 4-year cumulative incidence of relapse was 38% and no difference was observed in the adjusted relapse rate between the two groups. The 4-year OS rate was 46%. Using both Cox regression and inverse probability-of-treatment weighted (IPTW) method, a similar OS rate was found with both regimens (adjusted hazard ratios for conventional vs reduced of 1.14 (95% CI 0.67-1.93, P = 0.64) with Cox regression, and 1.14 (95% CI 0.55-2.34, P = 0.73) with IPTW). Until prospective trials are completed, this study supports the use of a reduced-intensity regimen prior to transplantation for patients with AML aged 35 and over. INTRODUCTIONAllogeneic hematopoietic stem cell transplantation (HSCT) provides the best chance for long-term survival and offers the lowest risk of relapse for patients with high-risk AML. 1 Advances in genomic technologies have identified AML as a genetically heterogenous disease: many patients can now be classified into prognostic subgroups on the basis of their underlying molecular genetic defects, 2 although the indication for HSCT in all intermediate-risk patients in first remission of AML is still debated. 3 The major limitation of HSCT is the risk of treatment-related mortality (TRM), especially among older candidates with comorbidities. 4 As the incidence of AML is highest in people older than 60, reduced-intensity conditioning (RIC) regimens have been developed for over a decade in order to decrease TRM. 5 These regimens are now increasingly used to facilitate HSCT in patients with advanced age or medical comorbidities, primarily because RIC regimens are well tolerated and are associated with less toxicity. 6,7 Previously published retrospective analyses suggested similar survival rates, but with a significantly higher risk of relapse after RIC regimen for patients aged 50 and over with AML 8 or for patients with myelodysplastic syndromes. 9 Using unrelated donors (URDs), another retrospective study reported a higher relapse rate in AML patients younger than 50 years after RIC regimen, with a similar leukemia-free survival between the two regimens. 10

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Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation

Abstract: Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatmentrelated mortality (TRM) after hematopoietic stem cell transplantation (HSCT).

Cited by 29 publications

References 36 publications

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Subsequent Neoplasms Working Group Report

Clinical profile, biological markers, and comorbidity index as predictors of transplant-related mortality after allo-HSCT

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML

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