December 20, 2013 | by Roberta Nichols
Improvements in hematopoietic cell transplants have been credited with increasing survival among patients undergoing the procedure by an estimated 10 percent per decade.
Yet, childhood survivors of the transplants, which are often referred to as bone marrow transplants (BMT), also are at a substantial risk of developing chronic and sometimes life-threatening medical conditions after transplantation.
In fact, nearly one in four will develop a severe or debilitating health condition (such as stroke or heart disease, another type of cancer or musculoskeletal problems) 15 years after transplantation.
At the American Society of Hematology (ASH) Meeting and Exposition in New Orleans in December, Saro Armenian, D.O., M.P.H., medical director of City of Hope's Pediatric Survivorship Clinic, presented a report from the Bone Marrow Transplant Survivor Study (BMTSS).
“This study identified subgroups of survivors who may be at an especially high risk for these complications,” said Armenian, first author of the study. “This can inform current treatment strategies as well as screening practices for late effects in survivors seen in our clinics.”
The original BMT Long-term Follow-up Study cohort, begun in 2000, consisted of more than 2,500 children and adults who had received blood stem cell or bone marrow transplantation at City of Hope or the University of Minnesota between 1974 and 1998 and who had survived two or more years. The principal investigator for this National Cancer Institute-funded study was Smita Bhatia, M.D., M.P.H., director of the Center for Cancer Survivorship at City of Hope and the Ruth Ziegler Chair in Population Sciences.
In the new study presented at ASH, participants included 317 BMTSS patients who underwent hematopoietic cell transplantation (HCT) in childhood between 1976 and 1998 at one of the institutions. Their median age at transplant was 7.9 years, and at study participation was 19.9 years.
Forty-two percent of participants were female, 86.7 were non-Hispanic white, and 79 percent underwent allogeneic HCT (in which they received hematopoietic stem cells from a related or unrelated donor).
Two issues were identified as potentially chronic and or life-threatening for some of these survivors.
“Exposure to TBI was associated with a 1.3-fold risk of a chronic health condition, and a 2.6-fold risk of a severe/life-threatening/fatal condition compared to chemotherapy only,” Armenian said. Total body irradiation (TBI) was used in 61 percent of two-year survivors.
Chronic graft-versus-host disease (cGvHD) was reported in 26 percent of patients. Among allogeneic HCT recipients, cGvHD was associated with a two-fold risk of severe/life-threatening/fatal conditions compared to survivors without cGvHD.
Overall survival in this group was 80 percent at 10 years after HCT, Armenian reported. The main cause of death included primary disease (61 percent), secondary cancer (8 percent), cGvHD (6 percent), cardiopulmonary compromise (5 percent) and other causes, including infections and other organ toxicity (21 percent). Researchers also found that the cohort was at a 22-fold increased risk of premature death compared to age-and sex-matched general population.
Female participants, those treated with TBI, and autologous HCT survivors had the highest risk of premature death.
“This represents a broad assessment of multiple outcomes,” said Armenian. “It is important that the next generation of studies explore the reasons why certain complications occur in some individuals but not in others. Understanding this can set the stage for personalized care and long-term management,” Armenian said.
Smita Bhatia, the study's senior author, agreed.
“Childhood HCT survivors carry a substantial burden of morbidity, years following completion of therapy, providing clear evidence for their close monitoring in a specialized setting targeting these high-risk complications,” said Bhatia.
Other City of Hope researchers participating in this study included Can-Lan Sun, M.D., Ph.D., director of survey research; Liton Francisco, staff scientist in outcomes research; Joseph Rosenthal, M.D., the Barron Hilton Chair in Pediatrics; and Stephen J. Forman, the Francis & Kathleen McNamara Distinguished Chair of Hematology and Hematopoietic Cell Transplantation.