Haematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukaemia: Special Considerations and Challenges

Abstract

Adolescents and young adults (AYAs) represent a challenging group of acute lymphoblastic leukaemia (ALL) patients with specific needs. While there is growing evidence from comparative studies that this age group profits from intensified paediatric-based chemotherapy, the impact and optimal implementation of haematopoietic stem cell transplantation (HSCT) in the overall treatment strategy is less clear. Over recent years, improved survival rates after myeloablative allogeneic HSCT for ALL have been reported similarly for AYAs and children despite differences in transplantation practise. Still, AYAs appear to have inferior outcomes and an increased risk of treatment-related morbidity and mortality in comparison with children. To further improve HSCT outcomes and reduce toxicities in AYAs, accurate stratification and evaluation of additional or alternative targeted treatment options are crucial, based on specific molecular and immunological characterisation of ALL and minimal residual disease (MRD) assessment during therapy. Age-specific factors such as increased acute toxicities and poorer adherence to treatment as well as late sequelae might influence treatment decisions. In addition, educational, social, work, emotional, and sexual aspects during this very crucial period of life need to be considered. In this review, we summarise the key findings of recent studies on treatment approach and outcomes in this vulnerable patient group after HSCT, turning our attention to the different approaches applied in paediatric and adult centres. We focus on the specific needs of AYAs with ALL regarding social aspects and supportive care to handle complications as well as fertility issues. Finally, we comment on potential areas of future research and concisely debate the capacity of currently available immunotherapies to reduce toxicity and further improve survival in this challenging patient group.

Real-world evidence on treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with B-cell acute lymphoblastic leukemia

“…Only 15 (29%) transplanted patients were Ph+ , suggesting that blinatumomab and TKI treatment led to a lasting remission, potentially causing the transplant-sparing effect. This is crucial clinically, as transplantation, a complex procedure, is linked to potential complications [ 28 ]. Blinatumomab might serve as a potential transplantation alternative in Ph+ B-ALL, but further studies are needed to validate our findings.…”

The current approach and the treatment of adolescents and young adults with acute lymphoblastic leukemia

“…Pediatric protocols, as a rule, include late intensification and early and intensive central nervous system (CNS) prophylaxis. Conversely, adult protocols use more myelosuppressive drugs (like anthracyclines, cyclophosphamides…) and more patients (about 30% of AYA) are transplanted in the first complete remission (CR1), in contrast to less than 5-10% of children in CR1 [5]. Considering this, numerous retrospective, as well as prospective clinical trials were conducted and confirmed the eligibility and improved outcome with the use of pediatric regimens in treating AYA patients [6].…”

“…The risk adapted treatment approach is generally accepted and the risk stratification is based primarily on cytogenetics and minimal/measurable residual disease (MRD). New immunotherapeutic drugs (blinatumomab and inotuzumab ozogamicin), with a proven efficacy in relapsed/refractory patients with ALL, are currently investigated as a part of frontline protocols in order to induce deeper remissions [5].…”

Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data

“…Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with hematologic malignancies, including various leukemias and lymphomas, as well as is used in children with high-risk solid tumors [ 1 ]. HSCT is only beneficial for children who have a high risk of relapse from conventional chemotherapy [ 2 ]. Therefore, therapy plans that precisely identify these high-risk patients and perform HSCT when suitable allogeneic donors are available are the preferred treatment for various disorders.…”