Survival Differences between Adolescents/Young Adults and Children with B Precursor Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplantation

Abstract

Risk adapted therapy has been the cornerstone of treatment for pediatric B-precursor acute lymphoblastic leukemia (B-ALL). Recently, age (>13 years at diagnosis) has been identified as a very high-risk feature for chemotherapy treated pediatric B-ALL patients. Whether age at time of transplant is associated with poor outcomes in adolescents and young adults (AYA) is unknown. We hypothesized AYA receiving allogeneic hematopoietic cell transplantation (allo-HCT) would have greater relapse and inferior survival. We reviewed the outcomes in 136 consecutive patients (ages 0 to 30 years) with B-ALL who received myeloablative allo-HCT at our institution. Fifty-eight percent (n=79) were children <13 years of age and 42% (n=57) were AYA 13 to 30 years of age. Overall survival at 5-years was significantly lower in the AYA group [HR 1.74, 95% CI: 1.04–2.95; p=0.03]. In addition, AYA patients had a greater risk of transplant related mortality (TRM) at 1-year [HR 2.23, 95% CI: 1.01–4.90, p=0.05] but no difference in relapse [RR 0.85, 95% CI 0.41–1.76; p=0.66]. Based on this analysis, AYA patients undergoing allo-HCT for B-ALL have significantly inferior survival and greater TRM compared to children <13 years but no difference in relapse suggesting allo-HCT may overcome relapse in AYA. Further improvements in peri-transplant care are needed to limit complications in AYA patients.

Similar outcomes between adolescent/young adults and children with AML following allogeneic hematopoietic cell transplantation

“…3,4 Given these findings, as well as our recent study showing inferior outcomes after allo-HCT for AYA patients with ALL, 10 we hypothesized that similar results would be present in AYA AML patients undergoing allo-HCT. In this analysis of 168 patients, including children and AYA with AML who received a myeloablative allo-HCT between 1995 and 2010, we identified no differences in survival or relapse between children and AYA patients.…”

“…These findings are in contrast to our AYA ALL patient outcomes treated in a similar period, where higher TRM was reported that negatively affected DFS. 10 The reasons for these differences are not entirely clear but may reflect the fact that patients with ALL receive considerably more chemotherapy compared with AML patients. The typical duration of treatment for patients with ALL is 2-3 years, compared with 5-6 months for patients with AML, which may contribute to greater overall organ toxicity and TRM reported in patients receiving allo-HCT for ALL.…”

“…7,9 We recently investigated survival differences between AYA patients and younger-aged children (o13 years of age) with B-cell ALL who received allogeneic hematopoietic cell transplantation (allo-HCT) at our institution and found significantly inferior survival in the AYA group. 10 These findings were primarily because of greater TRM in AYA patients. Based on these results and the higher mortality recently reported in chemotherapy-treated AYA AML patients, 3,4 we hypothesized that AML AYA patients undergoing allo-HCT would have inferior outcomes as compared with younger patients.…”

Survival Improvements in Adolescents and Young Adults after Myeloablative Allogeneic Transplantation for Acute Lymphoblastic Leukemia

“…However, few studies specifically addressed outcomes among AYAs undergoing HCT (Burke MJ, BBMT 2013), and it is unclear whether the benefits of improvements in supportive care have been realized equally in the vulnerable AYA population. For these reasons, we sought to determine whether outcomes for AYAs following myeloablative allogeneic HCT for ALL have improved to a similar degree as those among older and younger patients.…”

Closing the gap: Novel therapies in treating acute lymphoblastic leukemia in adolescents and young adults

“…As opposed to the infrequent use of allogeneic HSCT in pediatric populations, this procedure is often favored in AYAs with ALL. Yet the cumulative incidence of non-relapse mortality in patients aged greater thirteen years or older who have undergone allogeneic HSCT is as high as 28% [29]. Conversely, a meta-analysis that compared studies that treated AYA patients with ALL with either a pediatric-inspired regimen or a conventional adult chemotherapy regimen found that the cumulative rate of non-relapse mortality among patients that received a pediatric regimen was only 7% [30].…”