After LMT81 and SFOP LMT89 protocols (both modified LSA2L2), the SFOP LMT96 was designed according to BFM 86 back bone (

Reiter and al, J Clin Oncol, 13:359.1995
). The aim of LMT96 protocol was to increase chemotherapy intensity early (day 8) and late (after the intensification phase). From February 1997 to December 2003, 83 unselected patients (pts) with newly diagnosed TLL were included in LMT96 protocol: classic corticosteroid prephase (d1 to d7); induction phase with Cyclophosphamide(CPM: 1g/m2) and high dose methotrexate (HDMTX: 3g/m2 infusion over 3h) at d8, followed by Vincristine, Daunorubicin (40mg/m2) d15, 22, 29; 8 injections of Asparaginase, 2 intrathecal injection MTX at d8 and d15 and prednisone for 4 weeks; two consolidation phases with HDMTX, Cyclophosphamide (CPM), Cytarabine and Asparaginase; one interphase with HDMTX and; an intensification phase similar to a phase II BFM study, a maintenance phase with Mercaptopurine/MTX including initially six intensified monthly pulse phases alternating either HDMTX/Asparaginase, or Cytarabine/prednisone. The total duration of treatment was 18 months for stage I, II and III and 24 months for stage IV. Cranial radiotherapy (18Gy) was only performed in pts with CNS disease. 66% were boys, median age was 10.5 y [1.9 – 17.2] and 88% had a mediastinal involvement. According to St Jude classification, 5 had a stage I or II (6%); 47 had a stage III (57%); 24 had a stage IV [ (63%), 18 bone marrow (BM) involvement, 4 CSF+ and 2 both]. 7 pts received corticosteroid before diagnosis and were classified as stage X and treated as stage IV. After induction phase and consolidation (d 65), the complete remission rate was 95%. 1 pt had a progressive disease and died and 2 pts in partial remission are alive after salvage treatment with local radiotherapy or intensification. Up to now, 8 pts relapsed between 3.7 months and 18 months (median=10.5 months) and 1 pt who developed a glioblastoma before relapsing at 69.2 months. All relapses were mediastinal, 3 were combined with BM and 1 with BM and CSF. The median of FU is 4 years. Five-year EFS is 87% [CI95%: 79–94] and OS is 89% [CI95%: 82–96]. In conclusion these results are as high as those of BFM experience. The intensified monthly pulse courses for 6 months did not seem decrease the relapses on therapy. Early intensification at d8 (with CPM and HDMTX) is feasible with a BFM regimen. Omission of prophylactic cranial irradiation while using a short duration (3 hours) of HDMTX infusion did not jeopardize the outcome. We suggest that our early intensification might be combined with a classic BFM regimen.

Topics:
6-mercaptopurine, adrenal corticosteroids, asparaginase, bone marrow, boys, brachial plexus neuritis, central nervous system dysfunction, chemotherapy regimen, child, colony-stimulating factors

Author notes

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2005, The American Society of Hematology
2005
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