Late mortality after autologous blood or marrow transplantation in childhood: a Blood or Marrow Transplant Survivor Study-2 report

Abstract

Autologous blood or marrow transplantation (BMT) is a curative option for several types of childhood cancer. However, there is little information regarding the risk of late mortality. We examined all-cause mortality, relapse-related mortality (RRM), and nonrelapse-related mortality (NRM) in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at 1 of 2 US transplant centers. Vital status information was collected using medical records, National Death Index, and Accurint databases. Overall survival was calculated using Kaplan-Meier techniques. Cumulative incidence of mortality used competing risk methods. Standardized mortality ratio (SMR) was calculated using age-, sex-, and calendar-specific mortality rates from Centers for Disease Control and Prevention. Cox regression analysis was used to determine predictors of all-cause late mortality. Among the 345 2-year survivors, 103 deaths were observed, yielding an overall survival of 70.3% 15 years post-BMT. The leading causes of death included primary disease (50.0%), subsequent neoplasm (21.4%), and infection (18.2%). Overall, the cohort was at a 22-fold increased risk of late mortality (SMR, 21.8; 95% CI, 17.9-26.3), compared with the general population. Mortality rates remained elevated among the 10-year survivors (SMR, 20.6; 95% CI, 9.9-37.2) but approached those of the general population ≥15 years post-BMT. The 10-year cumulative incidence of RRM (14.3%) exceeded that of NRM (10.4%). The 10-year cumulative mortality rate declined over time (<1990, 35.1%; 1990-1999, 25.6%; 2000-2010, 21.8%; = .05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared with the general population. The late mortality rates have declined over the past 3 decades.

Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report

“…Similar to other studies, 4,9-13 the leading causes of NRM included infection and SMNs. Risk of infection-related mortality was highest among older patients and those with PCD.…”

“…4,9-13,21,22 The composition of the cohorts has varied (disease-specific 7-10,12,21-23 or all-inclusive, 4,11,13 or restricted to pediatric populations 13 ); the time to entry into the cohort has varied (from BMT, 5,6,11,21,22 1 year after BMT, 12 or ≥ 2 years after BMT 4,7-10,13 ), transplant eras have varied, 4-13,21-23 and methods used to determine vital status have differed (registry data, 9,10,21 NDI, 4,11,13 or institutional database 12 ). Nonetheless, all studies 4,9,11-13 except one 10 demonstrate elevated mortality risk when compared with the general population. In our study, conditional on surviving ≥ 2 years, autologous BMT recipients were at a 2.1-fold higher risk of all-cause mortality when compared with the general population.…”

“…Several studies have described the risk of late mortality after autologous BMT. 4,[9][10][11][12][13]21,22 The composition of the cohorts has varied (disease-specific [7][8][9][10]12,[21][22][23] or all-inclusive, 4,11,13 or restricted to pediatric populations 13 ); the time to entry into the cohort has varied (from BMT, 5,6,11,21,22 1 year after BMT, 12 or $ 2 years after BMT 4,[7][8][9][10]13 ), transplant eras have varied, [4][5][6][7][8][9][10][11][12][13][21][22][23] and methods used to determine vital status have differed (registry data, 9,10,21 NDI, 4,11,13 or institutional database 12 ). Nonethel...…”

Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry (STELLAR) to Compare Long-term Outcomes After Hematopoietic Cell Transplantation to Those in Siblings Without Sickle Cell Disease and in Nontransplanted Individuals With Sickle Cell Disease: Design and Feasibility Study

“…This study was modeled on the extensively validated methodology of the Childhood Cancer Survivor Study and the BMTSS [ 24 , 49 , 50 ]. These studies have refined, validated, and implemented approaches to studying of late effects of treatment.…”

Living Long and Well After an Autograft

“…In the article that accompanies this editorial, the authors 1 representing the Bone Marrow Transplant Survivor Study (a collaboration between City of Hope and the University of Minnesota and, more recently, the University of Alabama) have extended their previous work in children 2 by including 4,702 patients of all ages (median age, 53 years; range, 0-78 years) after an autograft for hematologic malignancies in four eras: 1981-1999; 2000-2005; 2006-2010; and 2011-2014 (Fig 1). 1 The study focuses on outcomes in patients surviving at least 2 years, and comparison across the eras was restricted to 5 years of follow-up to ensure adequate follow-up from the most current era.…”