Background: More than 80% of children with acute lymphoblastic leukemia (ALL) can be cured, but subsets of patients have significantly worse outcomes. Improved supportive care and intensification of chemotherapy for the high-risk group of ALL have contributed to this improvement in survival rates.
Aims: In this study, we analyzed the clinical, biological features, and therapeutic results of patients treated with the high-risk group of the EORTC 58951 pediatric protocol.
Methods: From January 2000 to December 2021, 395 patients with ALL aged less than 30 years were treated by the EORTC 58951 pediatric protocol in the Hematologic department of Hedi Chaker Hospital. From those 37 patients were treated by the high-risk group (VHR). The VHR group includes patients with poor prednisone response at day 8 (more than 1000 blasts/mm3 on the blood smear), those with worse cytogenetic abnormalities (t (9,22), t (4,11), 11q23 deletion...), and those with complete remission after two courses of chemotherapy. From those patients, we analyzed the clinical and biological features (Age, sex, blood count, cytogenetic abnormalities, and blasts phenotypes) and therapeutic Results:
remission rate, rate relapse, overall survival (OS), event-free survival (EFS) at 10 years follow up.
Results: We enrolled 109 cases (27%) of ALL classified VHR groups. The median age of patients was 12 years old. Seventy-eight cases (72%) were aged under 15 years old. The sex ratio M/F was 1,8. Fifty-seven cases (52%) had T-ALL. A tumor syndrome was noted in 87 cases (83%). Hyperleukocytosis of more than 100 G/L was detected in 38 cases (35%). Oncologic karyotype revealed t(9,22) in 6 cases (6%), 11q23 deletion in 3 cases (3%), and t(4,11) in 3 cases (3%). On the 7th day of treatment with corticosteroids, 79% of cases were corticoresistant. The complete remission (CR) rate was 87% (95 cases). The rate of toxic death was 28%. Allogeneic bone marrow transplantation was performed in 30 of 95 patients with CR. Relapse occurred in 39 patients (38%). With a median follow-up of 140 months (11 years), OS and EFS at 10 years were both 41% versus 69% for other risk groups of ALL.
Summary/Conclusion: Although the CR rate was 87%, OS and EFS were only 41% lower than those reported in the literature (80%). This could be explained by the higher rate of toxic death (28%) and the higher rate of relapse (38% versus 15 to 20% in the literature). Incorporating novel therapies, particularly immunotherapy (Blinatumumab, CAR T-cells) could improve the survival rates by decreasing the intensity of conventional chemotherapy and thereby reducing associated toxicity.
Keywords: Children, High risk, Young adult, Acute lymphoblastic leukemia