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 100–263 h, 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.