Comparison of Central Nervous System Prophylaxis With Cranial Radiation and Intrathecal Methotrexate Versus Intrathecal Methotrexate Alone in Acute Lymphoblastic Leukemia

• Published in: Blood Vol. 62; no. 2; pp. 241 - 250
• Main Authors: Muriel, Federico Sackmann, Svarch, Eva, Pavlovsky, Santiago, Eppinger-Helft, Mariana, Braier, Jorge, Vergara, Berta, Garay, Guy, Kvicala, Rita, Divito, Jorge M., Failace, Renato, Dibar, Eduardo, Jimenez, Elías
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.08.1983; The Americain Society of Hematology
• Subjects: Adult; Biological and medical sciences; Brain - diagnostic imaging; Brain - radiation effects; Brain Neoplasms - prevention & control; Brain Neoplasms - secondary; Child; Dexamethasone - therapeutic use; Hematologic and hematopoietic diseases; Humans; Injections, Spinal; Leukemia, Lymphoid - drug therapy; Leukemia, Lymphoid - pathology; Leukemia, Lymphoid - radiotherapy; Leukemia, Lymphoid - secondary; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocyte Count; Medical sciences; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Psychomotor Performance - radiation effects; Tomography, X-Ray Computed; Antineoplastic agent; Human; Intracranial; Chemotherapy; Nervous system diseases; Antimetabolic; Central nervous system; Tumor; Malignant hemopathy; Acute lymphocytic leukemia; Radiotherapy; Intrathecal administration
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V62.2.241.241

In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%–15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with a WBC count >50,000, it was 16% (6/37) in the treated group and 19% (6/31) in the control group. No difference was observed according to treatment in both prognostic groups. Patients in this study were retrospectively compared with a consecutive protocol in which patients received 3 doses of i.t. MTX-DMT alone during induction plus 3 doses weekly during the first month of remission and every 3 mo thereafter. The incidence of primary CNS leukemia at 60 mo in patients with a WBC count less than 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. This difference was not significant. However, the relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence of primary CNS relapse in patients with a WBC count more than 50,000 at 48 mo was 28% in the irradiated group and 42% in the nonirradiated group. The difference was not significant. The duration of complete remission was similar, remaining at 15% and 16% of patients disease-free at 48 mo, respectively. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT × 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) the use of i.t. MTX-DMT alone compares similarly with cranial irradiation plus i.t. MTX-DMT in the incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count less than 50,000 were significantly longer in those without cranial irradiation.