Researchers Develop a Validated Pediatric Disease Risk Index for AML and ALL

A pediatric disease risk index (DRI) reported in Blood was capable of stratifying children with acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) into clinically distinct risk groups based on pre-transplant clinical characteristics, including age, cytogenetics, and disease status.

“The ability to assign a risk group for any patient prior to hematopoietic cell transplantation is invaluable as it helps in counseling the patient and family,” said corresponding study author Mary Eapen, MRCPI, MBBS, of the Medical College of Wisconsin. She added that it “facilitates discussion on whether a patient at higher risk may benefit from an alternative novel therapy prior to transplantation, or in some cases, may benefit from a planned novel treatment targeted toward leukemia control after transplant.”

In the study, Dr. Eapen and colleagues analyzed patient and disease characteristics and outcomes for 2,569 patients younger than 18 years with AML (n=1,224) or ALL (n=1,345) who were undergoing hematopoietic cell transplant at select transplant centers. Patients were randomized to a training subset and a validation subset to develop a prognostic scoring system and to assess the prognostic ability of the scoring system, respectively.
The primary endpoint was leukemia-free survival (LFS), defined as survival in remission, and overall survival (OS) was considered a secondary endpoint.

In the AML group, most patients were at least 3 years old at time of transplantation (75% in the training cohort and 73% in the validation cohort). In the ALL group, 95% of patients each in the training and validation cohorts were 2 years of age or older.

During the development of the prognostic scoring system, the researchers identified three independent predictors for shorter LFS in patients with AML:

  • age <3 years at transplant
  • disease status at the time of transplantation
  • cytogenetic risk

In the ALL cohort, the investigators identified two independent predictors for lower LFS in ALL:

  • age <2 years at time of transplant
  • disease status at transplantation

By assigning these independent predictive factors a point value ranging from 0 to 5, the researchers developed four risk categories for patients with AML and three risk categories for those with ALL. The five-year LFS rates for each category are presented in the TABLES.

Use of the risk score in the validation subset confirmed that risk stratification with the DRI can also predict OS. For example, compared with patients with AML who had a low risk score, OS was lower for those with AML and an intermediate risk score (HR=2.71; 95% CI 1.10-6.65; p=0.0298), high risk score (HR=4.36; 95% CI 1.76-10.84; p=0.0015), and very high risk score (HR=7.65; 95% CI 3.07-19.07; p<0.0001). In ALL, survival was lower for patients with intermediate-risk (HR=1.54; 95% CI 1.13-2.11; p=0.0068) and high risk (HR=3.30; 95% CI 1.92-5.68; p<0.0001) compared with patients with low risk.

Dr. Eapen added that the risk tool described in this study “is independent of donor type and may be used to stratify heterogeneous populations of children and adolescents in hematopoietic cell transplant trials based on their risk group.”

These trials could include those looking at graft-versus-host disease prophylaxis and treatment or treatment for other transplant-specific complications. “This stratification can also be used for uniform assignment of patients to facilitate comparison across transplant centers as in the annual report of center-specific analysis that compares survival across transplant centers in the United States,” she said.

In terms of limitations, Dr. Eapen noted that she and her research colleagues do not envision the DRI as a fixed tool. Instead, they recommend refinement of the tool as new information becomes available, including information from “further assessment of leukemia burden using more sensitive techniques for residual disease detection and by quantification of burden.”

Study authors report no relevant conflicts of interest.


Qayed M, Ahn KW, Kitko CL, et al. A validated pediatric disease risk index for allogeneic hematopoietic cell transplantation. Blood. 2020 November 18. [Epub ahead of print]