Chemotherapeutic Conditioning Associated With Lower Rates of Complications in Young Children With ALL

For patients younger than 4 years of age with acute lymphoblastic leukemia (ALL), the use of chemotherapeutic conditioning was associated with low rates of complications and mortality in an analysis of the international FORUM study. Findings were reported in the journal Blood Advances.

This phase 3 study (ClinicalTrials.gov Identifier: NCT01949129) includes a randomized portion and a nonrandomized portion, with the nonrandomized portion being the subject of the current report. The nonrandomized portion included children younger than 4 years of age with high-risk ALL, assigned to receive chemotherapeutic conditioning for allogeneic hematopoietic stem cell transplantation (HSCT). 

Conditioning regimens in this analysis included the use of fludarabine (Flu) and thiotepa (Thio) plus either intravenous busulfan (Bu) or treosulfan (Treo). The study’s primary endpoint was overall survival (OS), and numerous secondary endpoints were also examined for this analysis. 

There were 191 children included in this analysis who underwent allogeneic HSCT between April 2013 and July 2021. Of these patients, 100 received Flu/Thio/Bu conditioning while 91 received Flu/Thio/Treo. Patients overall had a median age of 2.2 years (range, 0.5-4 years) at the time of HSCT. 

The overall 3-year OS probability in this population was 0.69 (95% CI, 0.61-0.76). Based on conditioning regimen, the 3-year OS probability for patients given Flu/Thio/Bu was 0.63 (95% CI, 0.52-0.72), in comparison with 0.76 (95% CI, 0.64-0.84) for those given Flu/Thio/Treo (P =.075).

The 3-year event-free survival (EFS) probability in the overall population was 0.52 (95% CI, 0.44-0.59). By conditioning regimen, 3-year EFS probabilities were 0.52 (95% CI, 0.41-0.61) with Flu/Thio/Bu and 0.51 (95% CI, 0.39-0.62) with Flu/Thio/Treo (P =.794). 

Multivariable analysis of EFS indicated that having an age below 1 year at diagnosis was associated with a worse outcome (for age ≥1 year: hazard ratio [HR], 0.49; 95% CI, 0.25-0.99; P =.046). In a multivariable analysis of OS, presence of an KMT2A–AFF1 aberration was linked to a worse outcome (HR, 1.96; 95% CI, 1.05-3.68; P =.036). 

By conditioning regimen, the 3-year cumulative incidences of nonrelapse mortality were 0.06 (95% CI, 0.02-0.12) with Flu/Thio/Bu and 0.03 (95% CI, <0.01-0.09) with Flu/Thio/Treo (P =.406). Additionally, the 3-year cumulative incidences of relapse were 0.42 (95% CI, 0.31-0.52) with Flu/Thio/Bu and 0.45 (95% CI, 0.34-0.56) with Flu/Thio/Treo (P =.920). 

Acute graft vs host disease (GVHD) of grade 2 to 4 was reported at rates of 29% in the Flu/Thio/Bu group and 17% in the Flu/Thio/Treo group by day 100. Rates of grade 3 or 4 acute GvHD events were reported to be 10% and 9%, respectively (P =.813). Chronic GvHD incidence at 3 years was 0.07 (95% CI, 0.03-0.13) for patients receiving Flu/Thio/Bu and 0.05 (95% CI, 0.02-0.11) for patients receiving Flu/Thio/Treo (P =.518). 

“In conclusion, this nonrandomized part of the international, multicenter FORUM trial showed that chemotherapeutic conditioning with either Flu/Thio/Bu or Flu/Thio/Treo allows for HSCT for children with high-risk ALL aged <4 years with a low complication rate,” the study investigators wrote in their report.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

This article originally appeared on Hematology Advisor