Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study

Abstract

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.

Venous thromboembolism in children with central nervous system tumors: Comparison of an institutional cohort to a national administrative database

“…This may have been due to the small number of OCP‐treated patients in either cohort (Tables 1 and 3). An increased rate of VTE after HSCT, particularly after allogeneic transplants, has been reported 18 ; however, the association showed significance only in our univariate analysis of the PHIS cohort (Table 4). HSCT in patients with primary CNS tumors is universally autologous, which may explain the lack of association between HSCT and VTE in our study.…”

“…Data for this study were obtained from the PHIS, which is an administrative database that contains data from inpatient, ambulatory surgery, emergency department, and observation encounters at 52 tertiary care children's hospitals in the United States 16,17 . The PHIS database has been previously described 3,18 . This part of the study was deemed exempt by the NCH IRB; permission to use the PHIS data was granted by the Children's Hospital Association.…”

Thromboembolism Incidence and Risk Factors in Children with Cancer: A Population-Based Cohort Study

“…TEs are associated with increase in morbidity and mortality, as well as increased utilization of health resources, even after consideration of cancer type and stage. 6,22,35 TEs can also delay or truncate cancer treatment 18 and lead to CVC replacements. 4 Anti-thrombotic therapy for TE is associated with adverse effects, such as increased risk of major bleeding, reported to occur between 0.3 and 24% of patients.…”

“…Several potential risk factors for TEs such as sex, diagnostic era and presence of metastatic or intra-thoracic disease had variable impact in different settings. For example, Lipay et al had identified male sex as a risk factor of TEs in cancer, 11 while another study observed a non-statistically significant increase of TEs in female HSCT recipients 22 and some studies found no impact of sex on TEs. 17,18 Our study reaffirms the contribution of certain risk factors such as older age and underlying type of malignancy.…”

“…8,13 Haematopoietic stem cell transplant (HSCT) has been shown to create a state of acquired thrombophilia, 21 and a recent study has shown that TEs are a clinically relevant complication of HSCT in children and young adults. 22 Published data in children are mostly limited to singlecentre, single disease retrospective studies or prospective studies consisting of children with acute lymphoblastic leukaemia (ALL). 7,8,11,[13][14][15][16][17][18][19][22][23][24][25][26][27] A large multi-institutional study that includes all paediatric cancer types is important to improve our understanding of risk factors for TE, and to have a sufficiently large sample size allowing for robust modelling and improved precision in estimates.…”