The National Comprehensive Cancer Network® (NCCN®) has issued its first ever NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia (ALL). The new guidelines were presented by the co-chairs of the NCCN ALL Panel, Joseph C. Alvarnas, MD, Director of Medical Quality and Associate Director in the Division of Hematology and Hemapoietic Cell Transplantation at the City of Hope Comprehensive Cancer Center and Patrick A. Brown, MD, Associate Professor of Oncology and Pediatrics/Director of the Pediatric Leukemia Program, at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
"We felt that it was very important to develop a clear standard of treatment for adult acute lymphoblastic leukemia (ALL)," said Dr. Brown. "We now have consistent data demonstrating that young adults - those between the ages of 15 and 39 - with ALL benefit significantly from treatments inspired by those used for children with ALL. The main reason for this is that younger adult patients can tolerate the intensive therapies that we use for our pediatric patients, and this translates into better outcomes. We hope that these new NCCN Guidelines will give oncologists the information they need to ensure that young adult ALL patients receive these intensive therapies."
Dr. Brown noted that there had been considerable cross-over and discussion between his group and the panel which just released the new NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology headed by Peter F. Coccia, MD, of the UNMC Eppley Cancer Center at The Nebraska Medical Center. Both the NCCN ALL and AYA Guidelines emphasize the importance of providing expert, comprehensive supportive care and the importance of increasing the enrollment of young adult patients into clinical trials.
The NCCN Guidelines also address treatment for older ALL patients, a group that Dr. Brown said is often more difficult to treat successfully than the younger patients. This is in large part due to the higher frequency of poor-risk cytogenetic abnormalities observed among older adults with ALL. One such abnormality is a translocation that results in the Philadelphia chromosome (Ph), which leads to the formation of the BCR-ABL fusion gene. Given the poor prognosis associated with Ph-positive ALL, the NCCN Guidelines initially stratify patients (both in AYA and adults) based on the presence of this abnormality. Regardless of age group, patients with Ph-positive ALL benefit from treatment regimens that incorporate BCR-ABL-targeting tyrosine kinase inhibitors.
The role of allogeneic stem cell transplantation (SCT) in treating ALL was also discussed. The NCCN Guidelines recommend allogeneic SCT as a consolidation option in patients with Ph-positive ALL, although the optimal role of SCT in this setting is yet to be defined. In addition, consolidation with allogeneic SCT is strongly recommended in patients with Ph-negative ALL with high-risk features. Evaluation of minimal residual disease can provide further risk stratification following initial induction therapy, and may help to identify patients who could potentially benefit from allogeneic SCT. Older adult patients, however, may not be appropriate candidates for SCT or intensive therapy options. Dr. Alvarnas discussed that in older adults, presence of comorbid factors such as organ dysfunction, limits the use of intensive regimens, which significantly impacts on the outcomes for this population. Dr. Brown pointed to the emergence of novel immune based therapies as new hope for increased remission rates and longer disease-free survival in older ALL patients.
Both Dr. Brown and Dr. Alvarnas emphasized the need for adequate central nervous system (CNS)-directed treatment to prevent CNS relapse for all patients with ALL, and the importance of comprehensive supportive care measures tailored to the needs of each patient.
"ALL is the rarest form of leukemia in adults," Dr. Brown said. "Its treatment poses many challenges and requires expertise and experience in a number of medical disciplines and supportive care areas. We recommend that ALL patients be referred to specialized treatment centers, and if possible, enrolled on clinical trials."
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