Allogeneic Hematopoietic Stem Cell Transplantation for Adolescents and Young Adults with Acute Myeloid Leukemia

Abstract

Few reports have focused on adolescent and young adult (AYA) patients with acute myeloid leukemia (AML) treated with hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis based on data obtained from a Japanese nationwide registration database to compare HSCT outcomes in AYA patients with AML with those in children with AML. An analysis of the 2973 patients with de novo AML who received allogeneic HSCT from 1990 to 2013 showed inferior 5-year overall survival (OS) (54% versus 58%, P <.01) and increased treatment-related mortality (TRM) (16% versus 13%, P = .02) in AYA patients. Multivariate analysis for both OS and TRM showed a significant negative impact on AYAs. However, the negative impact of older age lost its significance in an additional analysis focusing on 1407 recent transplant recipients with high-resolution HLA typing (2000 to 2013). Finally, we analyzed the impact of transplantation center type on HSCT outcomes in 317 adolescent patients (15 to 18 years old) and found no difference in outcomes between patients treated at a pediatric or an adult hospital. Higher age was a strong predictive factor for inferior OS resulting from increased TRM, which can be eliminated with better donor selection using high-resolution HLA typing.

Identifying risk factors associated with worse outcomes in adolescents and young adults undergoing hematopoietic stem cell transplantation

“…Both OS and TRM for AYAs undergoing allogeneic HSCT were poor in our study, consistent with past reports demonstrating inferior outcomes for this population, primarily due to higher rates of TRM . These dismal outcomes may reflect the nearly one‐third of patients identified as having high‐risk disease by the DRI, and represent a similar proportion as compared to other studies conducted at large, adult transplant centers .…”

“…Every year, across the United States, nearly 2000 adolescents and young adults (AYAs), defined as those aged 15‐39 years old, undergo allogeneic hematopoietic stem cell transplantation (HSCT) . While this patient population is relatively healthy, AYAs have significantly poorer outcomes following allogeneic HSCT when compared to children less than 15 years old, but there have been few studies examining their specific risk factors. Several models in adults have been developed to help predict outcomes in patients undergoing allogeneic HSCT, including the hematopoietic stem cell transplantation‐comorbidity index (HCT‐CI) .…”

“…While allogeneic HSCT is thought to be more tolerable in younger patients, resulting in better outcomes when compared to adults, this has not been the case for AYAs. These patients have significantly worse outcomes than those of younger pediatric patients, with most deaths being the result of TRM . Even with these poor outcomes, there have been limited studies examining the risk factors of AYAs, including one small, retrospective study that demonstrated that only four of the 15 variables included in the HCT‐CI had significant prevalence in this population .…”

“…These patients have significantly worse outcomes than those of younger pediatric patients, with most deaths being the result of TRM. 2,3,9 Even with these poor outcomes, there have been limited studies examining the risk factors of AYAs, including one small, retrospective study that demonstrated that only four of the 15 variables included in the HCT-CI had significant prevalence in this population. 5 Additionally, this population faces unique challenges both psychologically and from the health system itself.…”

Acute myelogenous leukemia in adolescents and young adults

“…Patients require acute management and supportive care during all treatment phases, especially the first few days to weeks of intensive induction therapy. As noted, TRM rates are higher in AYA than in younger children receiving chemotherapy or HSCT, but AYA can usually tolerate more intensive regimens than elderly adults can . With recent improvements in the results of AML treatment, the balance between treatment intensity and toxicity and their interrelation with the disease's genetic background has become increasingly important, and trials need to use risk‐ and genotype‐adapted therapy.…”