Capizzi Vs HDMTX in the Intermediate Maintenance Phase in Patients with Intermediate-Risk ALL in a 3rd Level Hospital in Northeastern Mexico

Abstract

INTRODUCTION: Methotrexate is a fundamental drug in the treatment of acute lymphoblastic leukemia (ALL), playing an important role in CNS prophylaxis. Two strategies of methotrexate intensification have been studied: high-dose regimens (with leucovorin salvage) and Capizzi regimen (escalating doses, without salvage, with addition of L-asparaginase). Fifty-five percent of pediatric patients with ALL in Mexico are treated in general hospitals, with limited hospital bed availability, which may represent a deferral of treatment. We wanted to explore a feasible, economical and accessible ambulatory scheme, which may represent an option for those centers that do not have the infrastructure for maintenance with HDMTX. OBJECTIVE: Evaluate the efficacy of methotrexate/L-asparaginase combination therapy based on the Capizzi scheme versus standard high-dose methotrexate (HDMTX) in the intermediate maintenance phase of a cohort of patients diagnosed with intermediate-risk B- ALL. METHODS: From January 2017 to June 2023, all patients diagnosed with ALL between 0 and 15 years of age, at a single center in northeastern Mexico, were collected in a prospective hospital registry. Based on risk stratification, patients received an adjusted treatment protocol with variations in intensity and duration for the different phases, based on the BFM. The type of intermediate maintenance received (Capizzi vs HDMTX scheme), duration time of the intensive phase, patients' overall survival and relapse events were evaluated. Demographic data were reported by distribution analysis and the Kaplan-Meier method was used to analyze and predict OS and EFS. RESULTS: Forty-four pediatric patients with a diagnosis of B-ALL and intermediate risk were included, 32 patients from the Capizzi group (G1) and 12 from the HDMTX group (G2). The median age at diagnosis was 7.5 years, 60% of patients were male. No statistically significant differences were found with respect to the duration of the intensive phase of treatment between the groups (p=0.58). Two deaths were recorded (Capizzi 1, HDMTX 1), with no differences in the type of treatment used (p=0.90). The risk of relapse according to the type of scheme used was not statistically significant (Capizzi 3 vs HDMTX 2, p=0.46, OR 0.51, 95% CI 0.07-3.55) (Table 1). Overall survival of patients during the study time (intensive treatment phase) was 90.9%, being 90.6% in the Capizzi group and 91.7% in the HDMTX group (p=0.851) (Figure 1). CONCLUSIONS: According to our results, no difference was found regarding the temporality of the 2 schemes (p=0.58), risk of relapse (p=0.46) or mortality (p=0.90). It is useful in our center because it provides us with an ambulatory, feasible and economical option that equals the results of the standard risk treatment. Due to the limited number of patients included in the study, it is recommended to increase the population in order to corroborate these results.