Adult ALL Patients Treated with Pediatric Inspired Trials Have Inacceptable Early Death but Better Relapse Free Survival Compared to Adult Trials: A Tunisian Single Center Experience

In Tunisia children with acute lymphoblastic leukemia (ALL) are treated according to the EORTC 58951 protocol with complete remission rate (CR) of 84% and long-term survivals reaching 80% at 5 years. Survivals of adult ALL remain disappointing mainly because of the high rate of early deaths, the limited number of allografted patients performed only for those aged < 40y, and lack of access to the international bone marrow donors registry. Are the improvements made in the last decades in developed countries in the treatment of adult ALL transposable for patients diagnosed in developing countries? The aim of the present study is to report the experience of a Tunisian hematology center in the management of adult ALL.

Fifty one adult ALL patients were treated with three consecutive trials in the hematology department of Aziza Othmana university hospital of Tunis between January 2005 and July 2011.18 patients were treated with Tunisian LALA03 protocol (pediatric –inspired induction) between 2005 and 2007: BFM-like HR induction (PND 60mg/m²x22d, VCRx4, DNR 30mg/m²x4, ASPx8). HR patients receive 6 consolidations blocs (GRAALL03 blocs) + CNS RT+ maintenance therapy. SR patients receive EORTC AR2 consolidations (IB, interval therapy, IIAIIB) +CNS RT +maintenance therapy. This protocol led to an inacceptable rate of induction death of 38.8%. 24 and 9 patients were respectively treated with Hyper-CVAD regimen from 2008 to 2010 and GRAALL05 since 2010.

Male/female ratio was is 2.6. Median age was 37.5 years (21–59). Immunophenotyping revealed B-cell precursor and T-lineage ALL in respectively 60% and 35% of patients. 1 patient had biphenotypic leukemia and the immunophenotype was not precised in one case. Median baseline WBC count was 18.2 × 10⁹/L (0.3–265 ×10⁹/L). Three patients presented with central nervous system (CNS) disease at diagnosis. 21.5% of patients have Philadelphia positive ALL. Only 14 patients had SCT from a matched sibling donor. Complete remission rate after induction was 74.5%. Eight patients (15.6%) had early death during induction from septic shock and pneumonia in 5 and 3 cases respectively. Median overall survival (OS) was 18 months. 3 years OS was 30%. By univariate analysis, age less than 32 years (p=0.01) and bone marrow transplantation (p=0.04) had positive impact on OS. For the whole study population 3 year relapse free survival (RFS) was 20%. Despite a lower RFS with Hyper CVAD there was no significant difference between the three trials but a trend to better outcome with pediatric inspired trials i.e. LALA03 and GRAALL05.

Pediatric-inspired protocols are associated with increased early death but prolonged remission duration compared to Hyper-CVAD. Hyper-CVAD is well tolerated but is associated to a high rate of relapse in our patients mainly because of the small number of SCT. The outcome of adult ALL in Tunisia is still unsatisfactory and can be improved with pediatric-like regimens. Effective therapy for adult ALL is feasible in our country. Controlling death induction by supportive measures and better management of myelosuppression and offering a stem cell transplant to a greater number of patients could be an option to improve on the RFS and OS.

No relevant conflicts of interest to declare.