ASH Releases New Guidelines for AYA Acute Lymphoblastic Leukemia Care

The American Society of Hematology (ASH) has issued new guidelines containing key recommendations for the treatment of adolescent and young adults (AYAs) with frontline and relapsed/refractory acute lymphoblastic leukemia (ALL), which were published in Blood Advances.^1,2

Frontline ALL Therapy

One of the publications focused on providing evidence-based recommendations for patients, clinicians, and other healthcare professionals regarding the frontline treatment of AYAs with ALL. An expert panel issued a total of 15 recommendations along with various good practice statements.

Some key recommendations include the following:

• AYAs with B-cell ALL (B-ALL) or T-cell ALL (T-ALL) should receive pediatric-inspired or asparaginase-based regimens;
• Empiric dose capping and dose reductions may be reasonable to mitigate the risk of asparaginase-related toxicities in AYAs;
• Prophylactic premedication is recommended to prevent hypersensitivity reactions among AYAs receiving asparaginase-based treatment;
• Providers should not routinely use cryoprecipitate replacement or fibrinogen concentrate outside of active bleeding;
• Clinicians should not routinely use unfractionated heparin as prophylaxis for venous thromboembolism (VTE);
• AYAs who develop asparagine-related allergies or hypersensitivity reactions on pegaspargase should switch to an Erwinia-based asparaginase formulation rather than discontinue asparaginase-based therapy.

Additionally, the panel identified insufficient evidence on whether to resume asparaginase-based therapy in AYAs who experience non-hypersensitivity asparaginase-associated toxicity.

“These guidelines address many of the challenging nuances to treating ALL in AYAs, including management of chemotherapy effects, psychosocial support, and survivorship, including fertility concerns,” Wendy Stock, MD, Anjuli Seth Nayak Professor of Medicine at the University of Chicago and co-chair of the ASH Guidelines for Frontline Management of ALL in AYAs, stated in a press release regarding the guidelines.³ “Additionally, they highlight that we’re in a period of great progress in terms of new approaches to treating and monitoring this disease.”

Beyond affirming asparaginase as a cornerstone of frontline AYA therapy, the guidelines for frontline management of ALL contained various recommendations related to allogenic transplant, psychosocial support, and future clinical trials. These suggestions included the following:

• Regarding AYAs in first complete remission (CR1), clinicians should avoid routinely proceeding with allogenic hematopoietic stem cell transplantation (allo-HSCT) consolidation;
• Rituximab (Rituxan) plus standard chemotherapy is suggested for AYAs with CD20-positive B-ALL;
• Clinicians are suggested to add blinatumomab (Blincyto) to treatment for AYAs with B-ALL who achieve morphologic remission, regardless of minimal residual disease (MRD) status;
• Providers are suggested not to add nelarabine (Arranon) to treatment for AYAs with T-cell lymphoblastic lymphoma based on insufficient evidence highlighting its efficacy in this population;
• The guidelines suggest against adding bortezomib (Velcade) to treatment for AYAs with T-ALL;
• AYAs are suggested to undergo reduced intensity therapy with tyrosine kinase inhibitors (TKIs) for remission induction over intensive chemotherapy with TKI for Philadelphia chromosome-positive ALL;
• Clinicians are suggested to employ intrathecal methotrexate or triple intrathecal therapy for central nervous system (CNS) prophylaxis;
• It is suggested not to routinely use cranial radiation as CNS prophylaxis for patients receiving asparaginase-based backbones;
• It is recommended to change therapeutic approaches for patients with ALL and persistent MRD after at least 3 months of frontline treatment.

The guideline authors acknowledged the need to address knowledge gaps associated with certain outcomes such as the late effects of therapy and psychosocial effects, which include fertility and health-related quality of life. Given the rapidly evolving landscape of ALL therapy with respect to immunotherapies and other targeted agents, the authors noted that modifying current regimens may help improve survival rates and change toxicity profiles, thereby potentially benefitting patients.

Relapsed/Refractory ALL Therapy

Panel members also issued 8 treatment recommendations related to AYAs with relapsed/refractory ALL. The updated guidelines suggest a major shift in the treatment of this population, with novel immunotherapeutic approaches recommended over traditional chemotherapy strategies despite limited direct comparisons between these agents.

Specifically, the panel emphasized the following:

• AYAs with relapsed/refractory B-ALL are recommended to receive blinatumomab or inotuzumab (Besponsa) rather than chemotherapy;
• Among AYAs with relapsed B-ALL and no prior HSCT who achieve a second or greater remission on CD19 CAR T-cell therapies, the panel suggests additional consolidation with allo-HSCT;
• For AYAs with relapsed B-ALL and a second or greater remission, it is suggested to use allo-HSCT over chemotherapy alone as definitive consolidation treatment;
• It is suggested to use myeloablative conditioning regimens encompassing total body irradiation over chemotherapy alone among AYAs with relapsed/refractory ALL who are proceeding to allo-HSCT;
• Clinicians should use CNS-directed therapy via intrathecal chemotherapy for AYAs with isolated CNS relapse of ALL;
• It is recommended not to use CNS radiation alone for AYAs with isolated CNS relapse of ALL;
• AYAs with relapsed/refractory T-ALL are suggested to undergo nelarabine-based therapy based on low certainty of available evidence.

“There are 2 huge challenges for treating this population: the speed at which the field is evolving and the need to bridge pediatric and adult oncology approaches to treatment. These guidelines meet both challenges, and our hope is that they will spur additional collaboration between adult and pediatric oncologists to effectively treat these patients,” Sumit Gupta, MD, PhD, professor in the Department of Pediatrics at the University of Toronto, head of the Leukemia/Lymphoma Section at the Hospital for Sick Children, and co-chair of the ASH Guidelines for Management of Relapsed and Refractory Disease in AYAs with ALL, noted in the press release.³

References

1. DuVall AS, McNeer J, Cheung MC, et al. American Society of Hematology 2026 guidelines for frontline management of acute lymphoblastic leukemia in adolescents and young adults (ALL in AYAs). Blood Adv. Published online February 11, 2026. doi:10.1182/bloodadvances.2021006469.
2. O'Dwyer KM, Winestone LE, Cheung MC, et al. ASH 2026 guidelines for management of relapsed/refractory disease in adolescents and young adults with ALL. Blood Adv. Published online February 11, 2026. doi:10.1182/bloodadvances.2021006479
3. ASH publishes clinical practice guidelines on frontline and relapsed/refractory management of ALL in adolescents and young adults. News release. American Society of Hematology. February 11, 2026. Accessed February 12, 2026. https://tinyurl.com/bdfuxtz4