REFILE-Low research participation, shorter therapy tied to ALL relapse in young adults

10/10/18

(Changes "anemia" to "leukemia" in para 1.)

By Marilynn Larkin

NEW YORK (Reuters Health) - Acute lymphoblastic leukemia (ALL) is more likely to relapse in adolescents and young adults (AYAs; ages 15-39) than in children, and lower clinical trial enrollment and shorter therapy course are associated factors, researchers say.

Dr. Julie Wolfson of the University of Alabama at Birmingham and colleagues retrospectively studied 93 AYA ALL patients (median age 23, 67.7% female) and 91 children with ALL (median age, four years, 61.5% male) treated at City of Hope between 1990 and 2010. In both groups, about one-third were non-Hispanic white; about half were Hispanic; and about 6.5% were Asian-Pacific Islander.

Further, about 18% of AYAs were treated with pediatric-inspired regimens in a pediatric oncology service; about 70% were treated in an adult oncology service with adult-inspired regimens; and 11% were in a mixed pediatric/adult oncology service on mixed therapeutic regimens.

As reported online September 27 in Cancer Epidemiology, Biomarkers and Prevention, 48% of AYAs relapsed while on therapy versus 17% of children. After adjustment for clinical prognosticators, health care delivery and treatment, this resulted in a 10.5-fold higher risk of relapse for AYAs.

Independent predictors of AYA relapse included lack of clinical trial enrollment (HR, 2.6) and nonwhite race/ethnicity (HR, 2.2).

When compared with children, AYAs also had an increased risk of relapse after completing therapy (HR, 7.7). Longer therapy (months of maintenance: HR, 0.7; months of consolidation: HR, 0.8) protected against AYA relapse.

"These findings highlight the importance of clinical trial enrollment and therapy duration...in ensuring durable remissions in AYA ALL," the authors conclude.

"During the two decades included in this study period, there were technological advances made in how we monitor the disease response to therapy (i.e., are we looking at disease response under a microscope or with more nuanced testing, such as minimal residual disease)," Dr. Wolfson said in an email to Reuters Health.

"Also," she noted, "a relatively new subtype of ALL was identified (Ph-like ALL) that is both more difficult to treat, and is seen more often in AYAs than in children."

"Although we were not able to specifically control for either of these in the study," she said, "we were able to control for how quickly patients responded to treatment...and for how high a patient's white blood count was at diagnosis, which indicates a higher-risk disease group."

"In the future, however, it will be important to look at all of these factors together," she said.

"These findings reinforce the importance of considering enrolling AYA patients in a clinical trial, and also considering the psychosocial factors that may need to be addressed in order to support a patient continuing through the full duration of therapy."

Dr. Bijal Shah, a hematology and oncology specialist at Moffitt Cancer Center in Tampa, Florida, agrees with the findings. "There are very few AYA- specific trials," he told Reuters Health by email. "Usually such trials are 'pediatric' (with age range of 0-30 y), or 'adult' (with age range of 18-99 y). This makes it very difficult to really understand the impact of treatment changes in this population."

"AYA patients with ALL, in particular, may have higher-risk disease, which may also explain inferior outcomes," he noted. "That said, this underscores the need to think about this age group differently."

Clinicians should also consider "the competing needs of an AYA patient (e.g., graduating high school/college, new job, new family, etc.) and how (these) will impact compliance with treatment," he said.

Further, he added, "How do we reconcile the long-term side effects that come with 'cure'? For example, if we take a pediatric-guided treatment approach for ALL in this age group, we can anticipate far more chronic neuropathy and arthritis - frequently (requiring) joint replacement and/or spinal surgery - due the increase in vincristine and steroid exposure, respectively."

"So, while this treatment approach 'may' come with higher cure rate," he said, "what is the price we pay?"

SOURCE: http://bit.ly/2IyHPNL

Cancer Epidemiol Biomarkers Prev 2018.

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