July 26, 2018
2 min read

Childhood bone marrow transplant recipients at risk for late mortality

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Patients who underwent blood or marrow transplantation during childhood remained at greater risk for death up to 25 years later compared with the general population, according to a study published in JAMA Oncology.

Still, mortality rates following transplantation have decreased over the past 3 decades.

Allogeneic blood or marrow transplantation is now a curative option for many malignant and nonmalignant diseases of childhood,” Anna Sällfors Holmqvist, MD, PhD, researcher at Lund University in Sweden, and colleagues wrote. “Nonetheless, the high intensity of therapeutic exposures at a young age increases the risk of organ compromise and may lead to late mortality. Earlier studies of cohorts of adults who have undergone allogeneic bone marrow transplantation, as well as studies in mixed cohorts of both children and adults, have shown an increased risk of late mortality, primarily due to recurrent disease, subsequent malignant neoplasm, chronic graft-vs-host disease, infections, and cardiovascular and pulmonary disease.”

Homqvist and colleagues conducted a retrospective cohort study of 1,388 patients (59.7% male; 70.7% non-Hispanic white) who lived for at least 2 years after allogeneic bone marrow transplant performed during childhood. Median age at transplantation was 14.6 years (range, 0-21).

Primary diagnoses included acute lymphoblastic leukemia (25.1%), acute myeloid leukemia or myelodysplastic syndrome (23.5%), inborn errors of metabolism (13.8%) and severe aplastic anemia (10.6%).

Median follow-up was 14.9 years (range, 2-41.2).

Researchers observed 295 deaths, resulting in an OS rate of 79.3% at 20 years posttransplant.

The leading causes of death included infection and/or chronic GVHD (49.6%), primary disease (24.6%) and subsequent malignant neoplasms (18.4%).

Patients who underwent bone marrow transplantation during childhood had a 14.4-fold (95% CI, 12.8-16.1) increased risk for death compared with the general population.

At 25 years or more following transplant, relative mortality remained elevated (standardized mortality ratio, 2.9; 95% CI, 2-4.1).

Researchers observed an absolute excess risk for death from any cause of 12 per 1,000 person-years (95% CI, 10.5-13.5).

Ten-year cumulative incidence of late mortality decreased over time, from 18.9% before 1990 to 12.8% from 1990-1999 and to 10.9% from 2000-2010 (P = .002). This association remained significant after adjustment for demographic and clinical factors.

The limitations of the study included reliance on death certificates for cause of death and lack of data on pretransplant treatment.

“This study demonstrates that there has been a significant decrease in all-cause late mortality among children undergoing allogeneic bone marrow transplantation during the past 3 decades. Nevertheless, these individuals who lived 2 years or more after marrow transplantation remain at an elevated risk of late death even 25 years after marrow transplantation. Although the risk of relapse-related mortality plateaus with time, nonrelapse-related mortality continues to increase and is the major cause of late death in this population.” – by Cassie Homer

Disclosures: The researchers report no relevant financial disclosures.