Young survivors of acute leukemia at high risk for late mortality
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SALT LAKE CITY — Pediatric and young adult survivors of acute leukemia who underwent allogeneic hematopoietic stem cell transplantation appeared to be at increased risk for late mortality, according to study results.
The results — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — suggest more research is needed to address causes of late mortality, such as graft-versus-host disease, in this patient population.
Rationale and methods
OS rates have improved gradually for children and young adults who undergo allogeneic HSCT for acute leukemia.
“This is likely owing to improvements in transplantation practices, namely high-resolution HLA typing and improved supportive care strategies,” Larisa Broglie, MD, MS, assistant professor of pediatrics in the division of blood and marrow transplantation, and clinical director of the bone marrow transplant and cellular therapy immune deficiency and dysregulation team at Children’s Hospital of Wisconsin, told Healio.
“These interventions most often affect outcomes early after transplant. Therefore, we hypothesized that early mortality rates have improved but late mortality, which can reflect deaths from late effects, has not improved,” Broglie added. “We hoped to highlight areas where future research could focus to help to continue to improve survival outcomes for our patients.”
Researchers sought to examine late mortality — defined as OS at 5 years and 7 years after allogeneic HSCT — among children, adolescents and young adults who survived and were disease free 2 years after transplantation. Investigators compared mortality rates between 2000 and 2006 vs. 2007 and 2013.
Key findings
Researchers reported 5-year OS rates of 89.7% (95% CI, 88.7-90.8) between 2000 and 2006, and 91.5% (95% CI, 90.7-92.3) between 2007 and 2013.
They reported 7-year OS rates of 86.7% (95% CI, 85.5-87.8) in 2000-2006, and 87.8% (95% CI, 86.8-88.8) between 2007-2013.
Multivariable Cox regression analyses showed a lower risk for mortality within 5 years of transplant during 2007-2013 (HR = 0.74; 95% CI, 0.63-0.86); however, researchers reported a similar risk for death after 5 years between the two time periods (HR = 1.19; 95% CI, 0.96-1.47).
Researchers then examined why late mortality had not improved over time. They also assessed transplant complications, late effects and causes of death for the two eras.
Chronic GVHD (54% vs. 46%) and extensive GVHD (39% vs. 31%) occurred more frequently in the 2007-2013 cohort than the 2000-2006 cohort.
In addition, GVHD-associated deaths occurred more frequently in the 2007-2013 cohort (21% vs. 17%).
Renal disease and diabetes also occurred more frequently in the 2007-2013 cohort.
Implications
“Our findings highlight that late mortality has not improved throughout time, despite improvements in transplantation practices,” Broglie said. “Future research is needed to address causes of late mortality — such as GVHD — among children, adolescents and young adults. In addition, it solidifies the importance of continued long-term follow-up of children and young adult survivors of allogeneic HSCT.”
This analysis included children and young adults as a single cohort; however, there are differences in transplant approaches and outcomes based on age, Broglie added.
“We are currently finalizing our analysis of data to look at pediatric patients aged younger than 15 years and compare them with young adults aged between 15 years and 39 years,” Broglie said.
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Broglie L, et al. Abstract 56. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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