COPENHAGEN (FRONTLINE MEDICAL NEWS) – A study from seven Nordic and Baltic countries adds to the growing body of evidence that young adults with acute lymphoblastic leukemia do better when they are treated like children – that is, with a standard pediatric chemotherapy regimen.

In a study of 221 patients from the age of 18 to 45 with acute lymphoblastic leukemia (ALL) treated with a pediatric regimen and followed for a median of 4 years, the event-free survival rate was 73%, compared with 42% for historical controls, reported Dr. Nina Toft from Herlev (Denmark) University Hospital.

“We have improved the survival for ALL patients 18 to 45 years, and we show that the cure rates are close to those of children. If you compare an adult in the standard-risk group with a child in the standard-risk group, there’s no difference,” she said at a briefing at the annual congress of the European Hematology Association (EHA).

The findings support those from an earlier study reported at the 2014 annual meeting of the American Society of Hematology. That study, conducted by Dr. Wendy Stock of the University of Chicago Medical Center and her colleagues showed that among 296 adolescents and young adults with ALL treated with an intensive pediatric chemotherapy combination regimen rather than a less-intensive adult regimen, the rate of overall survival (OS) at 2 years was 78%, and the event-free survival (EFS) rate was 66%.

In the current study, Dr. Toft and her colleagues looked at event-free survival among 1,509 children and adults (up to age 45) diagnosed with Philadelphia chromosome-negative ALL from July 2008 through December 2014.

The patients were treated in Sweden, Norway, Iceland, Finland Denmark, Lithuania, and Estonia, and all received the Nordic Society for Pediatric Hematology and Oncology (NOPHO)–ALL 2008 protocol , consisting of induction with prednisolone, vincristine, doxorubicin, and pegylated (PEG) asparaginase; consolidation for patients with standard- and intermediate-risk disease, with mercaptopurine, vincristine, PEG asparaginase, and methotrexate; and additional intensive combination chemotherapy for patients with high-risk disease, followed by maintenance with mercaptopurine and/or methotrexate, PEG asparaginase, vincristine, and dexamethasone.

Of the 1,509 patients, 1,022 were children from 1 to 9 years, 266 were preteens/adolescents (10-17 years), and 221 were adults up to age 45.

All patients were stratified by clinical, cytogenetic, and other factors into one of four risk groups: standard, intermediate, high risk, or high risk in first remission after a hematopoietic stem cell transplant, and all were treated with the NOPHO-ALL 2008 protocol.

The investigators found that in general older patients had higher-risk disease. Nonetheless, treatment intervals and severe toxicities, with the exception of osteonecrosis and thrombosis, were “almost identical” between adults and children, Dr. Toft said.

After a median of 4 years of follow-up, 16 patients, 3 of whom were adults, had died during the induction phase, and 50 patients (12 adults) had died in first remission.

There were a total of 123 relapses (36 among adults), and 1 adult and 12 children were diagnosed with a second malignancy.

Overall 5-year EFS rates were 88% for patients aged 1-9 years, 79% for those 10-17 years, and 73% for those 18-45, and these differences were significant (P less than .001). However, when EFS was stratified by risk group, EFS rates were lower only for adults with intermediate-risk disease (78% vs. 90% for 1- to 9-year-olds and 82% for 10- to 17-year-olds, P = .002).

Although the investigators did not formally report overall survival data, it was approximately 95% among all children in the cohort, and approximately 76% among the adults, Dr. Toft said in response to a reporter.

“What we need now is further cooperation, because we need to unite and get more patients so that we can show new developments faster. We also need to find new risk criteria, because of the intermediate-risk group; something is missing for the adults. We need more cytogenetics, we need something to define the patients as high risk or not,” Dr. Toft said.

“We also need new drugs, because with this method we’ve reached the limit of toxicity,” she added.

The study was sponsored by health authorities in the participating countries. Dr. Toft reported no relevant financial disclosures.


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