Pediatric-Like Intensified Therapy In Adult Acute Lymphoblastic Leukemia: A Single Centre Experience

Acute lymphoblastic leukemia (ALL) shows different outcome in children and adults, with event-free-survival (EFS) rates of 70–80% and 30–40% at 5 years, respectively. Results improved in young adults/adolescents with de novo ALL, when treated with pediatric intensive regimens rather than with adult regimens. Clinical studies are ongoing in older patients, toxicity related-therapy seeming the limiting issue.

We report a single centre experience on adult ALL patients treated with an intensive pediatric-inspired schedule, aiming to assess its tolerability and efficacy.

From 11/07 to 03/11 we treated 24 ALL patients (M/F=17/7) according to modified AIEOP-LAL2000 regimen. Treatment consisted of 7 days steroid pre-treatment, and four drugs 78-days induction (phase IA and IB) after which high risk (HR) patients were treated with three polychemotherapy blocks, while intermediate (IR) and standard risk (SR) patients went on 8-weeks consolidation and subsequent intensification. A 2 cycle consolidation therapy with nelarabine was planned for T-ALL patients. Patients with HLA-matched donor underwent allo-SCT; 2-years maintenance therapy was given to the others. Median age was 30 years (17–47).

22/24 patients completed the phase IA, 2 being out for grade IV toxicity (intestinal occlusion and sepsis). 17 (70.8%) obtained a complete remission (CR), 5 (21%) were refractory. One of the resistant patients achieved CR after polychemotherapy blocks, two after phase IB. Median induction duration (IA+IB) was 95 days (82–136); delays were mostly experienced after phase IB, hematologic toxicity being an important cause of delay, with median time to neutrophil count recovery of 28 days (18–34) and 39 days (16–62) for phase IA and IB respectively. A higher absolute number of adverse events during phase IA than during IB was registered (infections and gastrointestinal), without a significant prolongation of phase IA. After induction, 3 of the 19 CR patients received consolidation therapy, then 2/3 underwent allo-SCT. 6 patients received blocks: 3/6 undewent allo-SCT, 2/6 dropped out after the first and the second block for reversible grade II-III renal toxicity and one relapsed. 5 patients were treated with nelarabine, then 2/5 underwent allo-SCT. 3/19 directly underwent allo-SCT, while 1 patient completed the whole therapeutic program because no suitable donors for allo-SCT were found. One patient died after phase IB for pulmonary infection. With a median follow up of 12 months (3–50), 14/24 (58,3%) patients are alive, 8 in CR (5 underwent allo-SCT). 10 patients died, 5 for relapsed/refractory disease, 5 in CR (3 after allo-SCT).

A pediatric-inspired therapeutic regimen demonstrated a significant hematologic and a subsequent infective toxicity in adult ALL patients, this causing a lack in dose-intensity maintenance. The overall outcome seemed to be comparable to the one reached in other studies conducted on larger population but a longer follow-up and a larger population are needed to draw definitive conclusions.

BolognAIL, European LeukemiaNet, AIRC, Fondazione Del Monte di Bologna e Ravenna, FIRB 2006, PRIN 2008, Ateneo RFO, Project of Integrated Program (PIO), Programma di Ricerca Regione - Università 2007–2009.

No relevant conflicts of interest to declare.