Patients with high-risk acute lymphoblastic leukemia who received stronger postinduction intensification (PII) experienced improved outcomes that were sustained for 10 years, according to a study published in Leukemia.

The Children’s Cancer Group reported a 10-year follow-up (CCG-1961; ClinicalTrials.gov Identifier: NCT00002812) to a previous study (CCG-1882; ClinicalTrials.gov Identifier: NCT00898469) in patients with high-risk acute lymphoblastic leukemia. In this follow-up, the researchers reported data from patients with rapid early response (RER) and slow early response (SER) to induction therapy. The primary endpoints were event-free survival (EFS) and overall survival (OS).

A total of 2057 patients, aged 10 to 21 years or older than 1 year with a white blood cell count of at least 50,000/uL, were enrolled between September 1996 and May 2002. Patients with RER (1299 patients) were randomly assigned to 1 of 4 PII regimens:  standard or augmented strength combined with standard or increased length. Following interim maintenance, patients with SER (447 patients) were randomly assigned to receive either idarubicin and cyclophosphamide or weekly doxorubicin in the delayed intensification phases.

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The 10-year EFS for the RER treatment groups were 79.4% ± 2.4% and 70.9% ± 2.6% (hazard ratio [HR], 0.65; 95% CI: 0.52-0.82; P  <.001) for augmented and standard strength PII, respectively. The 10-year OS rates were 87.2% ± 2.0% and 81.0% ± 2.2% (HR 0.64; 95% CI: 0.48-0.86; P =.003) for augmented and standard strength PII, respectively. The outcomes for standard compared with augmented length PII in patients with RER (P =.66 for EFS; P =.54 for OS) were similar, as were the outcomes for idarubicin and cyclophosphamide compared with weekly doxorubicin treatments in patients with SER (P =.22 for EFS; P =.16 for OS); the researchers concluded that no advantage was conferred.

Patients with SER had a higher rate of both marrow relapse (P <.001) and remission death (P =.047) compared with patients with RER. The rates of grade 3 or 4 infections in patients receiving idarubicin and cyclophosphamide compared with patients receiving doxorubicin were 18.1% and 7.9%, respectively, during delayed intensification phase 1 and 14.1% and 9.2%, respectively, during delayed intensification phase 2.

The authors concluded that “the previously reported advantage for augmented intensification is sustained at 10 years” and noted that “this study provides the platform for subsequent studies.”

Reference

  1. Steinherz PG, Seibel NL, Sather H, et al. Treatment of higher risk acute lymphoblastic leukemia in young people (CCG-1961), long-term follow-up: a report from the Children’s Oncology Group. Leukemia. 2019:1. doi: 10.1038/s41375-019-0422-z