Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine.

Abstract

To address the problem of historically poor results in the treatment of children with advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia (ALL), an intensive chemotherapy regimen was devised using the most effective single agents in high-dose short courses. Treatment commenced with a fractionated schedule of intravenous (IV) cyclophosphamide (300 mg/m2 every 12 hours for six doses) followed immediately by Adriamycin (50 mg/m2) and vincristine (1.5 mg/m2) with combined intrathecal (IT) methotrexate and cytarabine. Predictably, this treatment produced virtually complete disappearance of all tumor and profound myelosuppression. Immediately on hematologic recovery, IV high-dose methotrexate (1,000 mg/m2 over 24 hours) followed by IV cytarabine (400 mg/m2 over the next 48 hours) was administered with leucovorin rescue and repeated IT treatments. The treatment sequence described above is repeated four times, with the dose of cytarabine doubled in succeeding courses, up to 3,200 mg/m2. The entire planned therapy required approximately 24 weeks. Since 1981, we treated a total of 29 children with this approach, 19 of whom had massive unresectable intraabdominal tumor. According to initial extent of disease, 17 were classified as stage III, four as stage IV non-Hodgkin's lymphoma (NHL), and eight as B cell ALL. Eight of the 12 patients with stage IV NHL or B cell ALL had initial involvement of the CNS. Twenty-seven of 29 patients (93%) attained a complete remission. Fourteen of 17 stage III NHL patients remain disease free, for periods ranging from 3+ months to 4 1/2+ years. The actuarial estimate of the proportion of stage III patients remaining disease free at 2 years is 81%. Results in patients with initial involvement of the CNS and/or marrow are much less favorable, with only two of ten patients who attained remission apparently being cured. In addition to stage, the initial serum lactic dehydrogenase (LDH) level emerged as a prognostic indicator, higher levels (over 1,000 IU/L) being associated with the worst prognosis (P less than .05). Major toxicity consisted of severe hematopoietic suppression and febrile episodes associated with neutropenia. We conclude that this treatment is highly effective for advanced-stage Burkitt's tumors in children free of initial CNS involvement.

Intensive short‐term chemotherapy regimen induces high remission rate (over 90%) and event‐free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia

“…However, the authors observed that patients older than 60 years clearly had an inferior outcome, with a survival rate of only 17% [9]. The addition of Rituximab and the improvement in supportive care measures possibly contributed to the achievement of similar outcomes in older and younger adults [10].In 1997, we reported a monocentric experience of 21 patients (8 adults and 13 children) treated with the intensive short-term pediatric-derived chemotherapy regimen POG 8617 [11], demonstrating that the outcome in adults was not significantly different than in children [12]. Fourteen years after our original report, we present here the longterm results of the same chemotherapy regimen employed in a multicenter experience recruiting a larger cohort of 71 consecutive BL patients.…”

The hyper-CVAD regimen improves outcome in relapsed acute lymphoblastic leukemia

“…[3][4][5] Once a patient relapses or fails to achieve a complete remission, salvage chemotherapy regimens have been reported to have reinduction rates of 20-60%, but, nevertheless, median CR remission duration averages only 3.4 months. 6 Over a period of 44 months, 66 patients at our institution were given salvage chemotherapy with the 'hyper-CVAD' regimen, a dose-intensive regimen patterned after the childhood Burkitt ALL therapy designed by Murphy et al 7 We called the regimen 'hyper-CVAD' after the acronym for the initial induction combination. 8 Our findings are summarized in this report.…”

Secondary chromosomal abnormalities predict outcome in pediatric and adult high‐stage Burkitt lymphoma

“…11 With the current chemotherapy regimens, the overall cure rates are approximately 90% in children and 50% to 60% in adults. [12][13][14][15] However, patients with high-stage disease continue to have a less favorable prognosis, with cure rates of 80% to 85% in children 15 and 40% to 50% in adults 16 There are no known biological tumor features that reliably predict the behavior of BL. In addition, it is not entirely clear if the difference in outcome between children and adults is a result of a relatively poor tolerance to treatment in the latter or if it is at least partially attributable to differences in tumor biology.…”