Community Experience with Pediatric Inspired Treatment of Acute Lymphoblastic Leukemia in the Adolescent and Young Adult Population in Kaiser Permanente Northern and Southern California Regions

Background:

Pediatric inspired treatment for Acute Lymphoblastic Leukemia has been increasingly used for treatment of adolescents and young adults in the United States and Europe. In 2019 Dr. Stock published results of CALGB 10403 which showed that a pediatric inspired regimen was tolerable and efficacious in a population of ALL patients up to the age 40. Prior to that publication the use of pediatric inspired treatment was quite variable and mostly used in academic hospital systems. There was concern about tolerability, utilization and efficacy of pediatric inspired protocols. Kaiser Permanente is a vertically integrated care delivery system. The Northern and Southern California regions are the two largest regions each caring for approximately 4.5 million members and cared for in a network of medical offices and hospitals.

Methods:

We reviewed the Cancer Registries of the Kaiser Permanente Northern and Southern California regions for patients aged 15-39 diagnosed with acute lymphoblastic leukemia between 2010 - 2018. In our patient cohort, 60% of patients were under 26 and 40% were older than 26. We examined the initial induction plan selected and determined if the induction used steroids, vincristine, an anthracycline and asparaginase and if so was classified as pediatric inspired. If not induction was classified as an adult protocol. Patients were characterized as pediatric inspired or adult then followed based on the initial induction plan selected. Neither the sub type of ALL, the molecular characteristics or the MRD status at the end of induction was reviewed. The selection of chemotherapy agents after the initial induction plan was not reviewed. The use of pediatric inspired induction over the time of the study was reviewed. The patients clinical course was reviewed for the next 6 months and utilization including hospital days, ICU days was reviewed. Patients were followed for toxicities of treatments including sepsis, lab abnormalities, and documented side effects of chemotherapy. The pattern of BMT referral was reviewed. The vital status known at the end of the evaluation was also reviewed.

Results

A total of 222 patients were evaluated. In our patient cohort, 60% of patients were under 26 and 40% were older than 26. Over the study period 66.7 % of the patients received a pediatric inspired induction. The use of pediatric inspired treatments increased over the study period with 38% use in 2010 to 90% in 2018. For patients over age 21 in 2010 the use was 10% in 2018 84%. There was a significantly greater number of inpt days for patients initiated on adult protocols at months, 1, 3 and 6. There was no difference in ICU days. For outpatient utilization there was a significantly higher use of the ED at months 1,3,6 for patients initiated on adult treatments. For patients over 21 there was a significantly increased number of BMT consults during the first 6 months after diagnosis. There was no statistical difference in documented bacteremia, mucositis, pancreatitis, neuropathy or sepsis between the 2 groups. For patients over 26 there was a significant increase in peripheral neuropathy in the adult treated group. There was a significantly elevated risk of mortality at 2 years after diagnosis for the adult treated group. For patients over the age 26 the risk of mortality was similar at 2 years.

Conclusion

We saw a rapid increase of utilization of pediatric inspired inductions over the study period within the Kaiser Permanente California regions. Patients who initiated treatment on adult protocols had over the first 6 months more inpatient days, were more likely to utilize the ED, were more likely to have a BMT consult. Patients who received adult protocol treatments had higher mortality at 2 years after diagnosis. We conclude that adult oncologists now favor pediatric inspired treatment approaches and there do not seem to be any safety concerns with this approach and in fact pediatric inspired treatments may lead to lower utilization and decreased mortality.