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Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials

From the Services d’Hématologie Pédiatrique et Adulte, Laboratoire Central d’Hématologie, Hôpital Saint-Louis; Service d’Onco-Hématologie, Hôpital Trousseau, Paris; Service d’Hématologie, Hôpital Edouard Herriot, Lyon; Unité d’Onco-Hématologie Pédiatrique, Hôpital des Enfants, Bordeaux; Laboratoire de Biochimie et de Biologie Moléculaire, Faculté de Médecine Nord, Marseille; Service d’Hématologie, Hôpital Lapeyronie, Montpellier; Service d’Hématologie, Hôpital Dupuytren, Limoges; Service d’Hématologie, Hôpital Purpan, Toulouse; Service d’Hématologie, Hôpital Morvan, Brest; Service d’Hématologie, Hôpital Haut-Levêque, Lyon; Service d’Hématologie, Hôpital Henri Mondor, Créteil; Hématologie Pédiatrique, Hôpital d’Enfants La Timone, Marseille, France.

Address reprint requests to André Baruchel, MD, Service d’Hématologie Pédiatrique, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France; email: andre.baruchel{at}sls.ap-hop-paris.fr.

Purpose: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents.

Patients and Methods: From June 1993 to September 1994, 77 and 100 adolescents (15 to 20 years of age) were enrolled in the pediatric FRALLE-93 and adult LALA-94 protocols, respectively. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving complete remission (CR) and event-free survival (EFS).

Results: Patients were younger in the FRALLE-93 than in the LALA-94 protocol (median age, 15.9 v 17.9 years, respectively), but other characteristics were similar, including median WBC count (18 x 10⁹ cells/L v 16 x 10⁹ cells/L), B/T-lineage (54 of 23 v 72 of 28 patients), CD10-negative ALL (13% v 15%), and poor-risk cytogenetics (t(9;22), t(4;11), or hypodiploidy less than 45 chromosomes: 6% v 5%). The CR rate depended on WBC count (P = .005) and trial (94% v 83% in FRALLE-93 and LALA-94, respectively; P = .04). Univariate analysis showed that unfavorable prognostic factors for EFS were as follows: the trial (estimated 5-year EFS, 67% v 41% for FRALLE-93 and LALA-94, respectively; P < .0001), an increasing WBC count (P < .0001), poor-risk cytogenetics (P = .005), and T-lineage (P = .01). The trial and WBC count remained significant parameters for EFS in multivariate analysis (P < .0001 and P = .0004). Lineage subgroup analysis showed an advantage for the FRALLE-93 trial for CR achievement (98% v 81%; P = .002) and EFS (P = .0002) in B-lineage ALL and for EFS (P = .05) in T-lineage ALL. Age was not a significant prognostic factor in this population of adolescents.

Conclusion: This study’s findings indicate that adolescents should be included in intensive pediatric protocols and that new trials should be designed, inspired by pediatric protocols, for the treatment of young adults with ALL.

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