Clinical practice guidelines on frontline and relapsed/refractory management published

The American Society of Hematology (ASH) released guidelines on frontline management of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs), as well as the management of relapsed or refractory disease in this population. Both guidelines, grounded in evidence-based practice, were developed by pediatric and adult experts in collaboration with patient representatives to improve outcomes for this vulnerable patient population. They were published in the journal Blood Advances.

“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, ASH President. “These guidelines aim to address this gap by outlining best treatment practices and providing vital standardization to clinical approaches to improve patient care.”

Both guidelines call for additional research on treating this patient population for ALL, including clinical trials directly comparing immunotherapies and studies to determine whether additional patients can forego transplant without compromising outcomes.

Frontline Management Guidelines

The guidelines for frontline management consist of 15 recommendations and several good practice statements. Recommendations include endorsement of:

• Pediatric-inspired regimens over traditional adult-inspired protocols
• Asparaginase as a cornerstone of therapy, including recommendations addressing administration and supportive care
• Re-evaluation of allogeneic transplant in first remission given insufficient evidence to support its routine use

“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,” said 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. “Additionally, they highlight that we’re in a period of great progress in terms of new approaches to treating and monitoring this disease.”

Relapsed/Refractory Guidelines

The guidelines for management of relapsed or refractory disease consist of eight recommendations and one research-only recommendation. Recommendations include support of:

• Immunotherapy over traditional chemotherapy approaches
• Allogeneic transplant in patients who achieve remission but with individualized assessment and shared decision-making to determine benefits and risks
• Intrathecal chemotherapy for isolated central nervous system relapse

“There are two 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,” said Sumit Gupta, MD, Ph.D., 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.

“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.”

About ALL in AYAs

ALL is a fast-growing cancer of the blood and bone marrow, arising when the body overproduces abnormal, immature white blood cells called lymphoblasts. These abnormal cells are unable to fight infection and disrupt the production of red blood cells, which transport oxygen and nutrients, as well as platelets, which promote clotting.

Approximately 20% of total ALL cases occur in AYAs (15 to 39 years of age), yet this age group has historically experienced inferior outcomes, especially when compared to pediatric patients diagnosed with ALL, who are less likely to relapse and have substantially higher survival rates. This difference can be attributed in part to a greater likelihood of high-risk leukemia biology for AYAs, more treatment-related toxicities, and wide variance in approaches to therapy.