Prognostic Factors in Childhood Anaplastic Large Cell Lymphoma: Long Term Results of the International ALCL99 Trial

Simple Summary The long-term follow-up and the results of the analysis of clinical, pathological and molecular prognostic factors for 420 children, adolescents and young adults affected by anaplastic large cell lymphoma (ALCL), enrolled in the international ALCL99 trial, were reported. The 10-year follow-up highlighted a progression free survival of 70% and an overall survival of 90%; rare late relapses occurred and no secondary malignancies were registered. Among clinical and pathological characteristics, only morphology including the small cell/lymphohistiocytic (SC/LH) pattern was independently associated with the risk of disease progression or relapse. When available minimal disseminated disease (MDD) data (n = 162) were included, both SC/LH pattern and MDD positivity resulted significantly associated with a poorer outcome when assessed by multivariate analysis. Considering MDD and SC/LH results, three biological/pathological risk groups with significantly different prognoses were identified. These results should be considered in the design of future ALCL trials to tailor individual treatments. Abstract With the aim of describing the long-term follow-up and to define the prognostic role of the clinical/pathological/molecular characteristics at diagnosis for childhood, adolescent and young adults affected by anaplastic large cell lymphoma (ALCL), we analyzed 420 patients aged up to 22 years homogeneously treated within the international ALCL99 trial. The 10-year progression free survival (PFS) was 70% and overall survival was 90%, rare late relapses occurred but no secondary malignancies were reported. Among clinical/pathological characteristics, only patients presenting a small cell/lymphohistiocytic (SC/LH) pattern were independently associated with risk of failure (hazard ratio = 2.49). Analysis of minimal disseminated disease (MDD), available for 162 patients, showed that both SC/LH pattern (hazard ratio = 2.4) and MDD positivity (hazard ratio = 2.15) were significantly associated with risk of failure in multivariate analysis. Considering MDD and SC/LH results, patients were separated into three biological/pathological (bp) risk groups: a high-risk group (bpHR) including MDD-positive patients with SC/LH pattern; a low-risk group (bpLR) including MDD-negative patients without SC/LH pattern; and an intermediate-risk group (bpIR) including remaining patients. The 10-year PFS was 40%, 75% and 86% for bpHR, bpIR and bpLR, respectively (p < 0.0001). These results should be considered in the design of future ALCL trials to tailor individual treatments.