Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts

Abstract

The outcome of children and adults with acute lymphoblastic leukemia is markedly different. Since there is limited information on the distribution of clinico-biological variables in different age cohorts, we analyzed 5202 patients with acute lymphoblastic leukemia enrolled in the Italian multicenter AIEOP and GIMEMA protocols and stratified them in nine age cohorts. The highest prevalence of acute lymphoblastic leukemia was observed in children, although a second peak was recorded from the 4(th) decade onwards. Interestingly, the lowest incidence was found in females between 14-40 years. Immunophenotypic characterization showed a B-lineage in 85.8% of patients: a pro-B stage, associated with MLL/AF4 positivity, was more frequent in patients between 10-50 years. T-lineage leukemia (14.2%) was rare among small children and increased in patients aged 10-40 years. The prevalence of the BCR/ABL1 rearrangement increased progressively with age starting from the cohort of patients 10-14 years old and was present in 52.7% of cases in the 6th decade. Similarly, the MLL/AF4 rearrangement constantly increased up to the 5(th) decade, while the ETV6/RUNX1 rearrangement disappeared from the age of 30 onwards. This study shows that acute lymphoblastic leukemia in adolescents and young adults is characterized by a male prevalence, higher percentage of T-lineage cases, an increase of poor prognostic molecular markers with aging compared to cases in children, and conclusively quantified the progressive increase of BCR/ABL(+) cases with age, which are potentially manageable by targeted therapies.

Figure 1.

(A) Percentage of the distribution of ALL among various age groups; (B) Lineage derivation in the various age cohorts. BALL: gray line; T-ALL: black line.

Figure 2.

Gender distribution. (A) Gender distribution analysis among age cohorts. The analysis reveals a decreased incidence of females between 14 and 50 years. The gray line represents females, the black line males. (B) Gender distribution and lineage derivation among different age groups. The gray continuous line represents B-ALL females, the gray dotted line B-ALL males, the black continuous line T-ALL males and the black dotted line T-ALL females.

Figure 3.

Organ involvement among age cohorts in the whole cohort (continuous line) and stratified according to the lineage derivation (B-ALL: dashed line, T-ALL: dotted line). (A) Mediastinal involvement; (B) spleen involvement; (C) liver involvement; (D) CNS involvement.

Figure 4.

Incidence of the molecular aberrations in different age cohorts of B-ALL patients. A significant decrease of ETV6/RUNX1 is observed with age progression, while BCR/ABL and MLL1/AF4 rearrangements are more frequent in adults.

Figure 5.

Hyperleukocytosis and stage of differentiation of B-ALL analyzed on the basis of the molecular aberrations. (A) Percentage of cases with hyperleukocytosis (WBC count >50×10⁹/L) in cases with ETV6/RUNX1+ (black bars), E2A/PBX1+ (dark gray bars), MLL1/AF4+ (light gray bars) and BCR/ABL+ (white bars). (B–E) Stage of differentiation within the different molecular aberrations [(B) ETV6/RUNX1; (C) E2A/PBX1+; (D) MLL1/AF4; (E) BCR/ABL+]; the black bars indicate a pro-B ALL, the light gray bars a common ALL and the dark gray bars a pre-B ALL. Detailed P-values are provided in Online Supplementary Tables S2–S9.