A Phase II trial of intrathecal liposomal cytarabine and chemoimmunotherapy with high-dose methotrexate in children, adolescents and young adults with de-novo mature B-NHL

Background Children, adolescents, and young adults (CAYA) with advanced mature B non-Hodgkin lymphoma (MB-NHL) have achieved ≥ 90% overall survival with intensive chemoimmunotherapy and intrathecal chemotherapy (IT). However, patients receive multiple IT doses requiring sedation with general anesthesia which may be associated with long-term late effects in cognitive development. Liposomal cytarabine (LC) has a half-life of 100-263hours, potentially decreasing the number of IT doses required. LC has been associated with toxicities when used in combination with high-dose methotrexate (HD-MTX) and ARA-C in adults with MB-NHL. Methods This phase II study incorporated 2 doses of LC to the French-American-British backbone in central nervous system (CNS) negative patients and 4 doses in CNS positive patients. Results Of 41 patients, 33 (19 FAB Group B, LDH ≤ 2X ULN; 6 FAB Group B, LDH ≥ 2X ULN; 8 FAB Group C) received LC and only 1 (3%) had a transient Grade 3 adverse event, likely secondary to disease progression. We successfully reduced the number of IT in Group B patients from 9 to 5 and in Group C CNS negative patients from 10 to 7. CNS positive patients received 9 IT instead of 13. The 2-year event-free survival and overall survival were 94.5% and 97.2%, respectively. We demonstrated that IT LC in CAYA with MB-NHL was feasible and safe in the setting of HD- MTX and ARA-C when decadron was used as a premedication and the LC was given after MTX clearance. Conclusion We maintained event free survival at numbers consistent with previous reports using the standard increased number of IT injections. We safely decreased the total number of IT without compromising CNS control.