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Late mortality after autologous blood or marrow transplantation in childhood: a BMTSS-2 report

Anna Sällfors Holmqvist, Yanjun Chen, Jessica Wu, Kevin Battles, Ravi Bhatia, Liton Francisco, Lindsey Hageman, Michelle Kung, Emily Ness, Mariel Parman, Donna Salzman, Jeanette Falck Winther, Joseph Rosenthal, Stephen J. Forman, Daniel J. Weisdorf, Mukta Arora, Saro H. Armenian and Smita Bhatia

Key points

  • Two-year survivors of autologous BMT in childhood have a substantially increased risk of late mortality compared to the general population.

  • There has been a significant decline in all-cause mortality in children undergoing autologous BMT over the past three decades.

Abstract

Autologous BMT is a curative option for several types of childhood cancer. However, there is paucity of information regarding their risk of late mortality. We examined all-cause, relapse-related [RRM] and non-relapse-related [NRM] mortality in 2-year survivors of autologous BMT performed before age 22 between 1980 and 2010 at one of two U.S. 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%, p=0.05). In conclusion, childhood autologous BMT recipients have an increased risk of late mortality, compared to the general population. The late mortality rates have declined over the past three decades.

  • Submitted February 15, 2018.
  • Accepted April 7, 2018.