Leukocyte Telomere Shortening in Recipients after Hematopoietic Cell Transplant and Its Association with Factors That Affect Recipient Outcomes: An Analysis of BMT CTN Protocol 1202

IF 3.6 3区医学 Q2 HEMATOLOGY

Transplantation and Cellular Therapy Pub Date : 2025-02-01 DOI:10.1016/j.jtct.2025.01.072

Kyra J.W. Mendez PhD, MPH, RN , Hormuzd A. Katki PhD , Caitrin Bupp MPH , Stephen R. Spellman MBS , Dr. Valerie Stewart MS, PhD , Sharon A. Savage MD , John E. Levine MD , Wael Saber , Abraham Aviv MD , Shahinaz M. Gadalla MD, PhD

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Abstract

Introduction

Leukocyte telomere length (LTL) significantly shortens after hematopoietic cell transplant (HCT) because of hematopoietic cell proliferation to achieve engraftment and immune reconstitution. The magnitude of LTL shortening is associated with patient outcomes after HCT. Limited LTL shortening is associated with increased relapse risk, and excess LTL shortening is associated with higher risk of non-relapse mortality.

Objective

This study aimed to identify factors associated with LTL shortening in the first three-months after HCT.

Methods

We studied 916 HCT recipients from the Blood & Marrow Transplant Clinical Trial Network 1202 Protocol who had donor blood samples available in the CIBMTR Biorepository. Southern blotting was used to measure LTL in donor pre-HCT and recipient post-HCT samples (average of 90 days). LTL shortening was calculated as donor mean LTL – recipient mean LTL. We examined LTL as a continuous outcome and in categories (limited LTL shortening: <25^th percentile vs ≥25^th percentile; excess LTL shortening: >75^th percentile vs ≤75^th percentile). We explored bivariate associations between LTL and donor, recipient, and clinical and transplant characteristics and included variables with P<0.1 in final multivariable linear and logistic regression models.

Results

Multiple linear regression models found an association between less LTL shortening and older donor age (P<0.001) and peripheral blood (PB) vs bone marrow (BM) graft (P=0.001). In logistic regression models, older donor age (P<0.001); PB vs BM graft (P=0.003); female vs male donors (P=0.019); and lymphoid vs myeloid disease (P=0.039) were significantly associated with a higher likelihood of limited LTL shortening. Older recipient age (P=0.001); receiving Busulfan-Cyclophosphamide (Bu/Cy; P=0.046) and total body irradiation (TBI; P<0.001) conditioning regimens vs Busulfan-Fludarabine (Bu/Flu); and receiving antithymocyte globulin (ATG) or Campath (P=0.01) vs not receiving ATG or Campath were associated with a lower likelihood of limited LTL shortening (Figure 1).

More LTL shortening was associated with older recipient age (P= 0.01) and conditioning regimens with Bu/Cy (P=0.02) and TBI (P<0.001) vs Bu/Flu regimens. Having African American (AA) vs non-Hispanic white (NHW) donors (P=0.045); receiving T-cell depletion vs calcineurin-inhibitor/methotrexate (MTX)-based GVHD prophylaxis regimens (P=0.028); and TBI-based vs Bu/Flu conditioning regimens (P<0.001) were associated with higher likelihood of excess LTL shortening (Figure 2).