ABSTRACT
Venous thromboembolism (VTE) is a well-documented complication of both solid and hematologic malignancies, but there are fewer data on allogeneic hematopoietic cell transplant (HCT) recipients. Therefore, we studied the incidence, risk factors, and impact of VTE on post-HCT outcomes in a contemporary cohort. We retrospectively reviewed patients who underwent allogeneic HCT between 1/2014 and 8/2019 to identify patients with post-HCT VTE. Patient, disease, and transplant-related risk factors for VTE were investigated using competing risk analysis. A total of 431 patients were included in this study. Median (IQR) age in years was 59 (46-65) at transplant. The most common indication for transplant was acute myelogenous leukemia (49.4%). Within our cohort, 64 patients (14.8%) developed post-HCT VTE with a median (IQR) follow up time of 24.6 (8.4- 47.1) months. The cumulative incidence of VTE was 4.2% at 6-month, 9.0% at 12-month, 12.6% at 24-month and 13.8% at 36-months. In multivariable analysis, older age (HR per 10-year increase, 95% CI: 1.36, 1.09-1.70) history of VTE (HR, 95% CI : 1.95, 1.09-3.49), and grade 2-4 acute GVHD (HR, 95% CI: 1.75, 1.05-2.94) were independently associated with VTE. VTE was significantly associated with an increased risk of non-relapse mortality (NRM) (HR4.09, 95% CI 2.47-6.74) and decreased overall survival (OS) (HR 2.19, 95% CI 1.48-3.24). VTE is an important complication after allogeneic HCT and is significantly associated with increased NRM and decreased OS. Older patients, those with prior VTE, and patients with acute GVHD are at increased risk for development of VTE after HCT.
ABSTRACT
Graft-versus-host disease (GVHD) causes severe morbidity and mortality in allogeneic haematopoietic stem cell transplantation (HSCT) because of destruction of recipient tissues by donor alloreactive T cells. We hypothesized that GVHD-specific T-cell clones are expanded within affected tissue of HSCT patients and can also be detected in blood at the time of active disease. A multiplex polymerase chain reaction (PCR) was used to amplify T-cell receptor (TCR) variable beta (VB) chain rearrangements in skin biopsies from eight allogeneic HSCT patients. Molecular analysis of the complementarity-determining region 3 (CDR3) of amplified products defined expanded, potentially disease-associated 'clonotypes' and enabled the design of clonotype-specific PCR assays. We detected immunodominant clones in seven of eight GVHD-positive skin biopsies. In serial skin biopsies from the same patient, the identical clone was found in each biopsy. In a patient who underwent two successive HSCTs from different donors, distinct clones were identified for each engraftment. Using clonotypic PCR assays, individual tissue-derived clones could be identified in peripheral blood samples obtained during active GVHD. We hypothesize that clonotypic sequences derived from target tissue can serve as markers for GVHD and may have utility in diagnosis and monitoring response to therapy, as well as enable future therapies targeted against pathogenic clones.
