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Efficacy of imatinib mesylate (STI571) in conjunction with alpha-interferon: long-term quantitative molecular remission in relapsed P-190BCR-ABL-positive acute lymphoblastic leukemia

Leukemia volume 16, pages 2159–2160 (2002)Cite this article

The problem of how to cure P190BCR-ABL+ as well as P210BCR-ABL+ acute lymphoblastic leukemia (ALL) patients still remains unsolved. Encouraging results have been reported with the use of imatinib mesylate (STI571) (Novartis, Basel, Switzerland) that has shown efficacy in both CML and Ph+ ALL.1,2 The duration of the response, however, has been short in the majority of acute phase CML as well as Ph+ ALL. A combination of imatinib mesylate with biological response modifiers could be a possibly successful option. In particular, α-IFN has shown efficacy in maintaining remission if administered to P190BCR-ABL+ ALL patients, with long-lasting control of the disease.3 Based on this, we tested the in vivo effect of imatinib mesylate and α-IFN in combination in a patient affected by P190BCR-ABL+ ALL, in a third relapse after previous successful reinductions of remission with α-IFN and imatinib mesylate as single treatments, tailoring the effects of the combination with qualitative RT-PCR and real time RT-PCR transcript quantification.

A 45-year-old woman was referred with acute lymphoblastic leukemia (ALL) in May 1990. Cytogenetic analysis was apparently normal. The patient received a remission induction chemotherapy cycle according to a modified L-20 regimen. Briefly, this consisted of vincristine 2.0 mg/m2 weekly (weeks 1 to 5), 6-methylprednisolone 60 mg/m2/d (days 1–32), cyclophosphamide 1000 mg/m2 (day 4) and 800 mg/m2 (day 32), adriamycin 30 mg/m2 (days 15–18 and day 32). Prophylactic central nervous system treatment with dexamethasone, cytosine-arabinoside and methotrexate was administered weekly. After a morphological complete remission (CR) was achieved in July 1990, the patient was submitted to a rotational consolidation regimen for 1 year (starting August 1990, ending August 1991), followed by a standard maintenance treatment with cycles of methotrexate/6-mercaptopurine (6 weeks duration) alternated with periodical L-20 reinduction (vincristine/6-methylprednisolone). This treatment was administered continuously for up to 2 years from the first demonstration of CR. In April 1997 the patient experienced a morphological relapse. Cytogenetic analysis was apparently normal, whereas the presence of a distinctive P190BCR-ABL fusion protein was detected with molecular biology. An identical L-20 reinduction cycle was administered, obtaining a second CR in May 1997. Autologous peripheral blood stem cell transplantation (ASCT) was performed in September 1997 with busulphan 4/mg/kg/day (4 days) and cyclophosphamide 60 mg/kg/day (2 days) as a conditioning regimen. The ASCT was followed by a maintenance treatment with cycles of α-IFN (Roferon-α; Roche, Milan, Italy) 3 MU, three times a week for 6 weeks (subcutaneous injection), alternating with metothrexate 70 mg/m2/day and 6-mercaptopurine 30 mg/m2/weekly for 6 weeks duration, administered continuously for 1 year. Afterwards, the patient was treated with α-IFN alone with the same schedule (6 weeks on, 6 weeks off) without interruption until morphological CR was maintained.3

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Acknowledgements

This work was supported in part by MURST 40%, COFIN 2001–2002 and AIRC.

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Authors and Affiliations

  1. Department of Hematology, H San Salvatore, Pesaro, Italy

    G Visani & B Guiducci

  2. Institute of Hematology and Medical Oncology ‘Seràgnoli’, University of Bologna, Bologna, Italy

    A Isidori, M Malagola, G Martinelli, PP Piccaluga, M Amabile, S Tura & M Baccarani

  3. Novartis Pharma, Origgio (Va), Italy

    D Alberti

  4. Novartis Pharma, Basel, Switzerland

    R Capdeville

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  1. G Visani
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Visani, G., Isidori, A., Malagola, M. et al. Efficacy of imatinib mesylate (STI571) in conjunction with alpha-interferon: long-term quantitative molecular remission in relapsed P-190BCR-ABL-positive acute lymphoblastic leukemia. Leukemia 16, 2159–2160 (2002). https://doi.org/10.1038/sj.leu.2402729

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