Studies conducted in the 1960s in LBL used chemotherapy regimens developed for the treatment of less clinically aggressive types of NHL.4'5'22'25'26 These studies reported poor outcomes. For example, Nathwani et al. reported results in 95 patients (children and adults) treated on various protocols that did not include CNS prophylaxis.4 Patients with leukemic involvement were included in these series. The complete response rate was 24%, and the median survival was 17 months, with less than 10% of patients alive and disease free at 5 years. Similar results were reported for other similar chemotherapy regimens.

The use of intensive chemotherapy and radiation protocols in childhood LBL resulted in substantial improvements in outcome. Long-term disease-free survival rates between 60 and 80% were reported for children treated with regimens such as LSA2L2. A randomized trial in childhood LBL, comparing LSA2L2 with COMP (cyclophosphamide, vincristine, methotrexate, prednisone) demonstrated a 2-year actuarial failure-free survival of 76% for the LSA2L2 arm compared with only 26% for those receiving COMP (p = 0.0002).27

Subsequently, chemotherapy/radiotherapy regimens similar in design to LSA2L2, adapted from those in adult ALL, have been applied to adult patients with LBL.8'19'20'28-30 Most of these regimens are characterized by intensive remission induction chemotherapy, CNS prophylaxis, a phase of consolidation chemotherapy, and a prolonged maintenance phase, often lasting for 12-18 months.

Results from some of these regimens are summarized in Table 56.2. A recent study from MD Anderson Cancer Center has explored the use of hyperCVAD (fractionated cyclophosphamide, vincristine, doxoru-bicin, and dexamethasone, alternating with high-dose methotrexate and cytosine arabinoside) in 33 adult patients with LBL. Intrathecal CNS prophylaxis was given and mediastinal radiation was recommended (although not always given) to all patients with medi-astinal presentations. They reported a 91% complete remission rate, and 3-year actuarial progression-free and overall survival rates of 66 and 70%, respectively.31 Since all of these series are small, differences in reported outcomes are unlikely to be significant. Results from the unselected patient series reported by the Non-Hodgkin's Lymphoma Classification Project are inferior to this, with a reported 5-year actuarial overall survival of only approximately 20%.32 This may reflect selection bias in the clinical series.

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