Proliferative kinetics of the leukemic cells in meningeal leukemia

Abstract

The proliferative kinetics of leukemic cells was investigated in the cerebrospinal fluid (CSF) and the leptomeninges of 5 patients with meningeal leukemia (ML) and 15 selected autopsies showing meningeal involvement. The 3H-thymidine labeling index (TLI), mitotic index (MI) and 3H-uridine labeling index (ULI) of leukemic cells in the CSF at the time of diagnosis were 0.7 k 0.2, less than 0.01 and 96.2 2 0.796, respectively. The TLI was found to be higher at the time of recurrence than at the initial diagnosis of meningeal leukemia. The grade of leukemic cell infiltration was classified according to Price's criteria. The mitotic index was also estimated on the histologic sections. An infiltration of Grade 2 or greater was observed in all 4 patients who had not received an intrathecal administration of methotrexate (MTX). The clinical course of 2 patients with a higher M I (0.88 and 0.32%) was shorter than the other 2 (0.03 and 0.01%). In the patients who did not show clinical manifestations of ML, the infiltration of leukemic cells in the leptomeninges was mild in degree, and the MI was less than 0.01%. Likewise, mild infiltration and low MI was observed in 8 cases treated with an intrathecal administration of methotrexate. These findings seem to support the general concept that the proliferation of leukemia cells infiltrating leptomeninges is remarkably slow at an incipient stage of ML; then it undergoes a gradual acceleration, possibly slowing down again at an advanced stage of the disease.

Central nervous system prophylaxis in adults with acute lymphoblastic leukemia

“…The liposomal preparation provides a prolonged exposure of free AraC in the cerebrospinal compartment. Exposure for an extended period is particularly important because of the proliferation kinetics of leukemic cells in the CNS 54, 72. Earlier phase 1/2 studies established that the administration of liposomal AraC resulted in the maintenance of elevated AraC levels in the CSF for ≥14 days, requiring fewer lumbar punctures or intraventricular administrations compared with conventional IT therapies like MTX and AraC 73, 74.…”

The Use of Ommaya Reservoirs to Deliver Central Nervous System-Directed Chemotherapy in Childhood Acute Lymphoblastic Leukaemia

“…An emphasis on prolonged leukaemic exposure to methotrexate to optimise cytotoxicity is supported by an abundance of pre-clinical work, which is discussed in detail by Ettinger and colleagues [47]. The optimal exposure time is thought to be 48-72 hours as the cell cycle takes approximately 3 days [48,49], however, it might be longer in the CNS due to slower proliferation kinetics in this microenvironment [50,51]. There has never been a randomised trial of Ommaya vs lumbar puncture delivery of methotrexate.…”