Radiation Therapy and Chemotherapy in Treating Children With CNS Relapse From Acute Lymphoblastic Leukemia

OBJECTIVES: I. Determine the efficacy and toxicity of intensified systemic treatment with delayed central nervous system (CNS) irradiation in children with acute lymphoblastic leukemia and isolated CNS disease. II. Determine the efficacy of systemic thiotepa in reducing or clearing blasts in the cerebrospinal fluid of these patients. III. Evaluate the toxicity of single dose thiotepa followed by dexamethasone, vincristine, daunorubicin, and triple intrathecal therapy in these patients. IV. Determine the response rate of intrathecal sustained release cytarabine (DTC101) in patients with first bone marrow remission with first isolated CNS relapse. V. Assess the safety and toxicity of DTC101 in these patients. OUTLINE: Patients with significant neurologic symptoms (e.g., seizures, cranial nerve palsy, paresis, mental status changes) are entered directly on the Induction regimen and do not receive the Therapeutic Window. The following acronyms are used: ARA-C Cytarabine, NSC-63878 ASP Asparaginase, NSC-109229 (E. coli) or 106977 (Erwinia) CF Leucovorin calcium, NSC-3590 CTX Cyclophosphamide, NSC-26271 DM Dexamethasone, NSC-34521 DNR Daunorubicin, NSC-82151 DTC101 Sustained release cytarabine G-CSF Granulocyte Colony-Stimulating Factor (Amgen), NSC-614629 HC Hydrocortisone, NSC-10483 Mesna Mercaptoethane sulfonate, NSC-113891 MP Mercaptopurine, NSC-755 MTX Methotrexate, NSC-740 TIT Triple Intrathecal Therapy, IT MTX/IT HC/IT ARA-C TMP-SMX Trimethoprim-sulfamethoxazole TSPA Thiotepa, NSC-6396 VCR Vincristine, NSC-67574 VP-16 Etoposide, NSC-141540 THERAPEUTIC WINDOW: Single Agent Chemotherapy. TSPA or DTC101. \*\* Thiotepa window closed as of 7/6/98 \*\* \*\* DTC101 window opened 11/15/99 \*\* INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. CONSOLIDATION: 2-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. ARA-C/ASP; plus TIT. INTENSIFICATION I: 4-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. CTX/MP/MTX/VP-16; with CF; plus TIT. RE-INDUCTION: 3-Drug Combination Chemotherapy plus Triple Intrathecal Therapy. DM/DNR/VCR; plus TIT. INTENSIFICATION II: 6-Drug Combination Chemotherapy with Leucovorin Rescue plus Triple Intrathecal Therapy. ARA-C/ASP/CTX/MP/MTX/VP-16; with CF; plus TIT. CHEMORADIOTHERAPY: Radiotherapy plus 3-Drug Combination Chemotherapy. Craniospinal irradiation using x-rays with energies of 4-6 MV (electrons acceptable for spinal cord irradiation); plus ASP/DM/VCR. MAINTENANCE: 2-Drug Combination Chemotherapy Alternating with 2-Drug Combination Chemotherapy. MP/MTX; alternating with CTX/VCR.