Results of the LMT81 protocol, a modified LSA₂L₂ protocol with high dose methotrexate, on 84 children with non‐B‐cell (lymphoblastic) lymphoma

Abstract

From May 1981 to June 1989, 84 children with non-B-cell lymphoma (82 lymphoblastic, 1 T-cell immunoblastic, 1 unclassified diffuse lymphoma) were treated in the pediatric department of the Institut Gustave Roussy according to a protocol called LMT81, which was derived from the LSA2L2 protocol of Wollner and modified by the adjunction of 10 courses of high dose methotrexate to improve the CNS prophylaxis. No planned irradiation was performed except in cases of initial tests (2 patients) or CNS (5 patients) involvement and residual mass (2 patients). Sixty patients had mediastinal involvement; for the others, primaries were in the head and neck (7), nodes (2), (sub)cutaneous (4), bone (7), and elsewhere (2). According to Murphy's staging system, there were 2 stage I, 6 stage II, 33 stage III, and 43 stage IV. Among the stage IV patients, 41 had bone marrow involvement, 24 of them with more than 25% blast cells in bone marrow and 19 with blast cells in blood; 7 had CNS involvement. Three patients did not achieve complete remission, 4 died in remission (two measles, one post-transfusion AIDS, one unexplained definitive aplasia) and 13 relapsed at 2 to 29 months (median-13 months). Among the 77 patients without initial CNS involvement, there was only one isolated CNS relapse. With a median follow-up of 57 months (10-106 months), the event-free survival is 75% (SE 2.5) for the 84 patients with a plateau at 29 months, 73% (SE 8) for stage I and II patients, 79% (SE 4) for stage III, and 72% (SE 4) for stage IV patients. Survival was similar in each stage group. Reasons for failure of treatment, however, were different, being toxic deaths in stage II; initial therapy resistance, early relapses, and toxic deaths in stage III; and tumor failures in stage IV. In conclusion, this protocol is efficacious on T and non-T, non-B childhood lymphoma with a low incidence of CNS relapse. A future study will seek to diminish toxicity and long-term sequellae while at least maintaining the same cure rate of patients.

Accumulation of methotrexate polyglutamates in lymphoblasts is a determinant of antileukemic effects in vivo. A rationale for high-dose methotrexate.

“…It is possible that the MTXPG concentration required to elicit antileukemic effects may be different (i.e., higher) in T-lineage ALL blasts compared with B-lineage ALL blasts. Although improved results in T-lineage ALL have been credited to the use of HDMTX (3-5 grams/m 2 ) in two recently reported clinical trials (9,41), it remains to be determined whether MTX doses higher than those used in the present study (i.e., Ͼ 1,000 mg/m 2 ) would achieve higher MTXPG concentrations and hence greater antileukemic effects in patients with T-lineage ALL.…”

High survival rate with the LMT-89 regimen in lymphoblastic lymphoma (LL), but not in T-cell acute lymphoblastic leukemia (T-ALL)

“…All patients received a modified LMT-81 regimen (named LMT-89), which was derived from the LSA2 L2 protocol. 17 This new LMT-89 regimen differed from the previous LMT-81 protocol: the induction phase was intensified (Table 1) and preceded by a pre-phase COP regime followed by two identical courses of COPADM. Compared to the LMT-81 protocol, CCNU was removed and five courses of VP16 were added.…”

“…We treated 27 patients with newly diagnosed LL according to an LMT-89 protocol, which is a modified version of the LMT-81 protocol previously reported in pediatric patients. 17 LMT-89 starts with a new induction regimen comprising one course of COP (cyclophosphamide 300 mg/m 2 at D1, vincristine, and prednisone) and two courses of COPADM (cyclophosphamide, vincristine, prednisone, doxorubicin and high-dose methotrexate). The duration of treatment was 1 year plus another 1 year of maintenance therapy with MTX and 6-MP for patients with bone marrow or CNS involvement.…”

Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence

“…With current treatment regimens, event-free survival (EFS) rates of 75% to 85% are achieved. [1][2][3][4][5][6][7] Despite these acceptable EFS rates, concepts of risk-adjusted treatment could not be realized because of the lack of prognostic parameters. However, such parameters are highly needed, as survival rates in relapsed patients with T-LBL are only about 10%, 8 and therefore identification of high-risk patients for targeted treatment intensification is desired to prevent relapses.…”