DECAL is an effective and tolerable salvage regimen for treating patients with recurrent NHL and HD.

Background. Intrathecal chemotherapy, radiation therapy, and systemic chemotherapy are used for both prophylaxis and treatment of central nervous system (CNS) disease in hematologic malignancies. Twenty‐three cases of myelopathy that occurred in patients who received intensive CNS‐directed therapy were evaluated to identify the determinants of this severe CNS toxicity. Methods. Nine cases treated by the authors and 14 collected from the literature are discussed. Twelve had Burkitt's leukemia/lymphoma. Patient ages ranged from 3 to 30 years (median, 15 years). The dose intensity of CNS‐directed therapies, including intrathecal cytosine arabinoside (ara‐C), intrathecal methotrexate (MTX), systemic high dose (HD) MTX, systemic HD ara‐C, systemic thiotepa, and CNS radiation, was evaluated by the determination of single drug doses and cumulative total drug or irradiation doses over elapsed treatment durations. Results. Central nervous system treatment was prophylactic in 10 cases; active CNS disease was being treated in 13 cases. One patient received only intrathecal ara‐C before toxicity occurred; others received intrathecal ara‐C and varying combinations of intrathecal MTX, HD ara‐C, HD MTX, CNS radiation, and systemic thiotepa. Eight patients died of toxicity, of whom 6 had autopsy‐proven cord necrosis; 3 were ventilator‐dependent; 10 had persistent paraplegia or paraparesis; and 2 recovered completely. Conclusion. Both highly intensive, short CNS treatment sequences and lower intensity, long term cumulative treatments may result in this rare but severe myelopathy. The cause is multifactorial, with systemic chemotherapy, intrathecal chemotherapy, and radiation therapy contributing to toxicity. Multiple intrathecal ara‐C and/or MTX doses given at frequent (daily) intervals should be avoided. Concurrent intrathecal ara‐C and systemic HD ara‐C also appear to be especially toxic. Intrathecal hydrocortisone given with intrathecal ara‐C does not protect against myelopathy. Multiple, frequently spaced courses of CNS‐directed therapies must be avoided, especially in patients who have received prior CNS radiation.

Long-term EFS in children with LB NHL can be achieved in the majority of patients. Disease progression, which includes recurrence at the primary tumor site, is a major cause of treatment failure in patients with mediastinal presentations. Addition of DAUN and L-ASP to the COMP regimen does not produce a more effective treatment than LSA2L2.

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOPbased induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass у one-third thoracic diameter at T5 and/or LDH у2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard-vs high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 ± 7% and 80 ± 7%, respectively. The 5-year EFS and OS were significantly better in the standard-vs high-risk subgroups (100% vs 61 ± 11%) (P Ͻ 0.003) and (100% vs 65 ± 11%) (P Ͻ 0.01), respectively. Lactate dehydrogenase (LDH) у2 × normal (NL) was associated with significantly poorer outcomes (LDH у2 × NL vs Ͻ2 × NL) (5-year EFS: 55 ± 12% vs 100%) (P Ͻ 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH Ͻ2 × NL) and Murphy stage III disease. Leukemia (2002) 16, 594-600.

Addition of daunomycin to standard COMP therapy did not improve outcome in pediatric disseminated NLB NHL. Patients with LC disease had a significantly reduced long-term EFS, but were retrieved at a higher rate than patients with SNCC disease, resulting in equivalent long-term survival.