Improved Outcome of Adult Acute Lymphoblastic Leukemia Treated with Individualized Protocol Adjusted to the Status of Minimal Residual Disease and Age. Interim Analysis of PALG ALL 5–2007 Study
Authors: Giebel Sebastian , Holowiecki Jerzy , Krawczyk-Kulis Malgorzata , Jagoda Krystyna , Piszcz Jaroslaw , Paluszewska Monika , Adamczyk-Cioch Maria , Ejduk Anna , Czyz Anna , Piatkowska-Jakubas Beata , Lech-Maranda Ewa , Stella-Holowiecka Beata , Szarejko Monika , Kyrcz-Krzemien Slawomira , Kloczko Janusz , Jedrzejczak Wieslaw Wiktor , Dmoszynska Anna , Warzocha Krzysztof , Komarnicki Mieczyslaw , Skotnicki Aleksander , Robak Tadeusz , Hellmann Andrzej , Zdziarska Barbara , Sulek Kazimierz , Domagala Maria , Razny Malgorzata , Zawilska Krystyna M , Starzak-Gwozdz Jolanta 
Published: October 2019

Abstract
Abstract 2138
In a previous study by the Polish Adult Leukemia Group (PALG 4–2002) we demonstrated that status of minimal residual disease (MRD) during induction-consolidation is the most important factor predicting long-term outcome of adult ALL (Br J Haematol 2008). In a new PALG 5–2007 protocol the treatment was intensified for patients with MRD level >0.1% of bone marrow cells and adjusted to age. Induction consisted of Epirubicine(4×), Vincristine(4×), Prednisone and PEG-asparaginase. Patients with complete remission (CR) but MRD >0.1% obtained additional 2nd phase of induction: AraC+Cyclophosphamide(Ctx) + 6MP. Consolidation consisted of 2 courses of Methotrexate(Mtx) + Etoposide + Dexamethasone and subsequent 2 cycles of Ctx + high dose AraC, asparaginase, intrathecal prophylaxis and CNS irradiation. Doses of Mtx were 500 mg/m2 for patients with MRD<0.1%, aged >35y and 1500 mg/m2 for all remaining ones. For Ph+ ALL imatinib 600 mg/d was administered in parallel to chemotherapy. Patients with standard risk disease continued with 2 years maintenance while those with high-risk were referred for alloHSCT. High risk was defined as the presence of at least one of: initial WBC >30×10e9/L, age >35y, pro-B, early-T, mature-T, late CR, t(9;22), t(4;11) or MRD >0.1% at any time during induction-consolidation.
Results of PALG 5–2007 protocol (N=108, median age 32y, range 16–55y) were compared to PALG 4–2002 (N=253, age 28y, range 16–55y), in which MRD status was not taken into account for treatment decisions. CR rate was 92% for PALG 5–2007 compared to 89% for PALG 4–2002. The probability of the overall survival at 36 months was 56% vs. 33% (p=0.02), while leukemia-free survival was 53% vs. 28% (p=0.04), respectively. The probability of relapse decreased from 54% in PALG 4–2002 to 16% in PALG 5–2007 (p=0.002). In a multivariate analysis adjusted to age, initial WBC and the presence of t(9;22) treatment according to PLAG 5–2007 protocol was associated with decreased risk of mortality (HR=0.57, p=0.02), relapse (HR=0.37, p=0.006) and treatment failure (HR=0.64, p=0.049).
We conclude that individualized therapeutic approach with treatment intensity adjusted to MRD status and age may result in improved outcome of adults with ALL.
*This multi-institutional study was supported by Polish Ministry of Sciences Grant NN-402366433

Disclosures:
Off Label Use: Dasatinib as first line therapy in Ph ALL.