ASH Releases New Guidelines for ALL Care in Adolescents and Young Adults

The American Society of Hematology (ASH) has published new clinical practice guidelines for the management of acute lymphocytic leukemia (ALL) in adolescents and young adults (AYAs).¹

Appearing in Blood Advances, the comprehensive, evidence-based guidelines provide a framework for ALL management for patients aged 15 to 39 in both frontline and relapsed/refractory (R/R) settings. The guidelines have been jointly developed by pediatric and adult medical experts with input from patient representatives.

Guidelines for Frontline Management

The first set of guidelines for ALL management in the frontline setting was determined by an evidence review panel at Brown University. Consisting of 15 recommendations and good practice statements, the panel strongly emphasized asparaginase as a cornerstone of therapy.²

Among key highlights include:

• Pediatric-Inspired Regimens: The panel strongly recommends pediatric-inspired protocols over traditional adult regimens for Philadelphia chromosome-negative (Ph–) B-cell ALL. These intensified schedules, incorporating higher cumulative doses of vincristine (Oncovin), corticosteroids, and pegaspargase (Oncaspar), have demonstrated superior event-free survival (EFS) in the AYA population.
• Minimal Residual Disease (MRD) Prioritization: MRD is established as a critical prognostic factor. Guidelines mandate MRD assessment at the end of induction and during consolidation to guide subsequent intensification or the decision to proceed to hematopoietic stem cell transplant (HSCT).
• Ph+ ALL Targeted Therapy: For Philadelphia chromosome-positive (Ph+) ALL, the integration of a tyrosine kinase inhibitor, such as imatinib (Gleevec) or dasatinib (Sprycel), with chemotherapy is recommended. Emerging data also support the frontline use of ponatinib (Iclusig) in combination with reduced-intensity chemotherapy to improve deep molecular responses.
• Asparaginase Toxicity Mitigation: While asparaginase is a cornerstone of pediatric-inspired therapy, the guidelines advise rigorous monitoring for hepatotoxicity, pancreatitis, and thrombosis in AYAs, as these patients experience higher toxicity rates than younger children.
• Site of Care: The guidelines emphasize that AYAs should ideally receive treatment at specialized centers capable of administering complex pediatric-inspired protocols and providing AYA-specific supportive care, including fertility preservation.

Additionally, the panel does not recommend routine allogeneic HSCT in first complete remission; however, they note that it may serve more benefit in higher risk subsets, such as those with persistent or recurrent MRD despite optimal therapy or those with suboptimal early treatment response.

The panel also identified knowledge gaps and areas for which evidence remains limited, including:

• Optimal integration and sequencing of immunotherapies such as blinatumomab (Blincyto) or inotuzumab ozogamicin (Besponsa) in frontline treatment
• The role of chimeric antigen receptor (CAR) T-cell therapy earlier in the disease course
• Best strategies for toxicity mitigation specific to AYAs
• Fertility preservation outcomes following pediatric-inspired regimens

For these cases, while no formal recommendations were made, the panel identifies several research priorities, emphasizing the need for prospective, AYA-focused clinical trials and improved inclusion of AYAs in cooperative group studies to address these critical gaps.

Guidelines for Relapsed/Refractory Management

For management of R/R disease, the panel issued 8 recommendations along with 1 research-only recommendation.³ In this setting, the guidelines suggest a paradigm shift away from traditional chemotherapy approaches in favor of novel immunotherapies to achieve a second remission and bridge patients to allogeneic HSCT.

Specifically, the guidelines revolved around the following:

• Bispecific T-Cell Engagers: Blinatumomab is recommended for patients with R/R B-cell ALL, particularly those with low-level marrow blasts or MRD-positive disease.
• Antibody-Drug Conjugates: For patients with high disease burden, inotuzumab ozogamicin is a preferred salvage option. Clinicians are cautioned to monitor for sinusoidal obstruction syndrome, especially if the patient is proceeding to HSCT.
• CAR T-Cell Therapy: The guidelines highlight the role and utility of CAR T-cell therapy, particularly following relapse.
• Bridging to Transplantation: For the majority of R/R AYA patients, the primary goal of salvage therapy remains the achievement of an MRD-negative remission to allow for a consolidative allogeneic HSCT, which offers the best chance for long-term cure.

Fallen Through the Cracks: The Need for Specialized Care

Across both sets of guidelines, the panel emphasized that AYAs have unique psychosocial and biological needs that are often unmet in traditional adult oncology settings. At the same time, the population has historically faced worse outcomes compared with pediatric patients, necessitating specialized, age-appropriate treatment models and multidisciplinary support.

“Caring for these individuals is complex given the unique challenges associated with their age group, which doesn’t align neatly with standard pediatric or adult treatment regimens,” said Robert Negrin, MD, president of ASH, in a news release.¹ “These guidelines aim to address this gap by outlining best treatment practices and providing vital standardization to clinical approaches to improve patient care.”

REFERENCES

1. 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/4hdu566e

2. DuVall AS, McNeer J, Cheung MC, et al. ASH 2026 guidelines for frontline management of acute lymphoblastic leukemia in adolescents and young adults. Blood Advances. Published online February 11, 2026. doi:10.1182/bloodadvances.2021006469

3. 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 Advances. Published online February 11, 2026. doi:10.1182/bloodadvances.2021006479