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Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) are still a difficult-to-treat patient population. High mortality (80% of ALL deaths occur within this patient subset) and lack of representation in clinical research highlights a need to better understand optimal treatment approaches and relevant prognostic factors for this age group.1 Previous literature has illustrated superior overall survival (OS) in AYA patients when using pediatric protocols compared with adult regimens. Nevertheless, further research on pediatric regimens is required, with more concise AYA age definition, greater representation, and toxicity data. Previously, the ALL Hub published a study comparing a pediatric and an adult therapy regimen in AYA patients with ALL. An overview on the main differences in pediatric and AYA treatment approaches is summarized on the ALL Hub here.
For prognosis, measurable residual disease (MRD) has previously demonstrated to be effective for predicting survival outcomes. However, the optimal time for MRD assessment, to assist treatment decisions as well as prognostic assessment, is still in debate. Listen also to our podcast with Janine Stutterheim discussing the value of MRD in infants with ALL.
A single-center, retrospective analysis was recently published by Akhil Rajendra and colleagues in Blood Advances, assessing the efficacy and toxicity of a modified pediatric regimen, Berlin-Frankfurt-Münster 90 (BFM-90), in a defined and well-represented AYA group (aged 15–25). The authors also investigated the association of different baseline disease characteristics, including MRD, with OS and event-free survival (EFS).1 The key findings are summarized below.
Figure 1. Study design for the BFM-90 protocol and drugs given during each stage*
TKI, tyrosine kinase inhibitors (imatinib or dasatinib); 6-MP, 6-mercaptopurine; 6-TG, 6-thioguanine; IT, intrathecal.
*Data from Rajendra et al.1
A total of 463 patients with ALL, aged 15–25 years, were enrolled. Of these, 349 received the BFM-90 protocol. Baseline patient characteristics are presented in Table 1.
Table 1. Baseline patient characteristics*
Characteristic |
Patients |
---|---|
Median age, years (range) |
18 (15–25) |
Sex (male), % |
78.2 |
Diagnosis, % |
|
CNS involvement, % |
5.7 |
High-risk, %† |
34 |
Hypodiploidy, % |
10.3 |
High-risk WBC baseline count, % |
|
ALL, acute lymphoblastic leukemia; T-ALL; T-cell ALL; B-ALL, B-cell ALL; CNS, central nervous system; ETP, early T-cell precursor ALL; WBC, white blood cell. |
3-year OS and EFS with the BFM-90 protocol were 61.8% and 59.4%, respectively.
A univariate cox-regression analysis was performed for the association of diagnosis (T-ALL, B-ALL), baseline CNS involvement, MRD positivity post induction, MRD positivity beyond induction, WBC-based risk, cytogenetic risk, and infections with EFS and OS.
A multivariate analysis was performed for baseline CNS involvement, MRD positivity post induction, MRD positivity beyond induction, and infections.
Also of note, following the median 41-month follow-up, 79 (22.6%) patients had relapsed and 18 (23%) were classified as having experienced CNS relapse. Only 15 (4.3%) patients underwent allogeneic hematopoietic stem cell transplantation.
This retrospective study demonstrates the feasibility and safety of using the BFM-90 protocol for a well-defined AYA cohort with ALL. Although rates of toxicity were low, the authors highlight a need for preventative measures against fungal and bacterial infections during induction. Furthermore, the data provides further evidence for the association of postinduction MRD negativity with superior survival outcomes, while patients with high-risk ETP ALL were identified has having inferior survival outcomes.
Limitations outlined by the research team were that the study was neither risk- or response-adapted, it was a single-center experience, and newer, high-risk molecular factors that may influence survival outcomes were excluded.
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