Evaluating outcomes of adult patients with acute lymphoblastic leukemia and lymphoblastic lymphoma treated on the GMALL 07/2003 protocol

• Published in: Annals of hematology 2022-03, Vol.101 (3), p.581-593
• Main Authors: Fredman, Danielle, Moshe, Yakir, Wolach, Ofir, Heering, Gabriel, Shichrur, Keren, Goldberg, Idan, Hofstetter, Liron, Neaman, Miriam, Scheib, Tomer, Marcu-Malina, Victoria, Avigdor, Abraham, Shimoni, Avichai, Nagler, Arnon, Canaani, Jonathan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Chromosomes; Female; Hematology; Humans; Israel - epidemiology; Leukemia; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neoplasm, Residual - diagnosis; Oncology; Original Article; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology; Prognosis; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-021-04738-y

Chemotherapy-based approaches still constitute an essential feature in the treatment paradigm of adult acute lymphoblastic leukemia (ALL). The German Multicenter Study Group (GMALL) is a well-established protocol for ALL. In this study, we assessed our recent experience with the GMALL 07/2003 protocol reviewing all adult ALL patients who were treated with GMALL in three major centers in Israel during 2007–2020. The analysis comprised 127 patients with a median age of 41 years (range 17–83). Sixty-two were B-ALL (49%), 20 (16%) patients were Philadelphia chromosome positive ALL, and 45 (35%) were T-ALL. The 2-year and 5-year overall survival rates were 71% and 57%, respectively. The 2-year relapse rate was 30% with 2-year and 5-year leukemia-free survival rates of 59% and 50%, respectively. Adolescents and young adults experienced significantly longer overall survival (84 months versus 51 months; p =0.047) as well as leukemia-free survival compared with older patients (66 months versus 54 months, p =0.003; hazard ratio=0.39, 95% confidence interval, 0.19–0.79; p =0.009). T-ALL patients had longer survival compared to B-ALL patients while survival was comparable among Philadelphia chromosome positive patients and Philadelphia chromosome negative patients. An increased number of cytogenetic clones at diagnosis were tightly associated with adverse prognosis (15-month survival for ≥2 clones versus 81 months for normal karyotype; p =0.003). Positive measurable residual disease studies following consolidation were predictive for increased risk of relapse (64% versus 22%; p =0.003) and shorter leukemia-free survival (11 months versus 42 months; p =0.0003). While GMALL is an effective adult regimen, a substantial patient segment still experiences relapse.