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Long-term molecular complete remission with IFN-α in Ph+ adult acute lymphoid leukemia patients

Leukemia volume 22, pages 1617–1618 (2008)Cite this article

Allogeneic stem cell transplantation (SCT) is currently considered the unique potentially curative therapeutic option for Philadelphia chromosome-positive acute lymphoid leukemia (Ph+ ALL).1, 2 However, SCT can be pursued only in a minority of cases. We previously described the ability of interferon-α (IFN-α) plus chemotherapy or autologous SCT (ASCT) to induce molecular complete remission (CR) in Ph+ ALL.3 We now show that such an approach can lead to sustained molecular remissions, by updating the follow-up of our original report.

From 1992 to 1998, 14 adult Ph+ ALL patients were referred to our institute and were candidates to receive either ASCT or chemotherapy (if age was over 55 years) followed by IFN-α within a pilot study. Allogeneic SCT was allowed/performed in patients with a suitable human leukocyte antigen-matched donor. Informed consent had been obtained from all the enrolled patients and the protocol was approved by the local ethical committee. All patients received standard induction chemotherapy (modified L-20)3, 4 consisting of vincristine 2.0 mg m−2 weekly (weeks 1–5); 6-methylprednisolone 60 mg m−2 day−1 (days 1–32); cyclophosphamide 1000 mg m−2 (day 4) and 800 mg m−2 (day 32); and adriamycin 30 mg m−2 (days 15–18 and day 32). Prophylactic central nervous system treatment was performed weekly, introducing the following drugs: dexamethasone 4 mg; cytosine–arabinoside 40 mg; and methotrexate 10 mg. Patients achieving morphological and cytogenetic CR were then submitted to a rotational consolidation regimen lasting 6 months,3 including cytarabine, cyclophosphamide, VM26, methotrexate, 6-mercaptopurine, vincristine and prednisone with monthly intrathecal therapy.4 Patients aged <55 years underwent ASCT or SCT; patients aged ⩾55 years received standard maintenance treatment for 6 months (alternating vincristine/prednisone with methotrexate/6-mercaptopurine). Subsequently, maintenance treatment (all ages) was based on cycles of IFN-α (3 MU three times a week for 6 weeks) alternated with methotrexate/6-mercaptopurine for up to 2 years. Thereafter, patients maintaining CR had the same schedule of IFN-α (6 weeks on, 6 weeks off). BCR-ABL1 transcript levels were detected at diagnosis and during the follow-up by real-time quantitative PCR, initially as reported by Amabile et al.5 and subsequently by using a standardized method that was established within the framework of the EU Concerted Action.6 The method independently measures, in each sample by real-time quantitative PCR, the copy number of mRNA encoding the p210 BCR-ABL protein or the p190 BCR-ABL protein and a control gene (ABL1) to verify sample-to-sample RNA quality variations. Real-time quantitative PCR was performed on an ABI PRISM 7700 Sequence Detector (Perkin Elmer, Foster City, CA, USA). The quantification principles and procedure using the TaqMan probe have been previously described. All real-time RT-PCR experiments were performed in duplicate. The copy number of BCR-ABL1 and ABL1 transcripts was derived by the interpolation of threshold cycle (ct) values to the appropriate standard curve, and the result, for each sample, was expressed as a ratio of BCR-ABL1 mRNA copies to ABL1 mRNA copies percent. The threshold was systematically set at 0.1 to avoid any particular problems of baseline creeping. The lowest level of detectability of the method is 0.001 (corresponding to a sensitivity of 10−4 in the clinical setting). Molecular CR was defined as a level of BCR-ABL1/ABL1 × 100 lower than 0.001 followed by nested-PCR negativity in three consecutive determinations.

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Acknowledgements

This work was supported by European LeukemiaNet, COFIN 2002-2003 (Professor M Baccarani and SA Pileri), FIRB/RFO (Professor M Baccarani and SA Pileri), AIRC, Progetto Strategico di Ateneo 2006 (Dr Piccaluga), Fondazione CARISBO Bologna, Fondazione del Monte di Bologna e Ravenna. AIL Pesaro Onlus and BolognAIL grants.

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Author notes

  1. P P Piccaluga and G Martinelli: These two authors equally contributed to this work.

Authors and Affiliations

  1. Department of Hematology and Oncological Science, Units of Hematology and Hematopathology, ‘L and A Seràgnoli’, S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

    P P Piccaluga, G Martinelli, S Paolini, M Amabile, I Iacobucci & M Baccarani

  2. Department of Hematology, S Salvatore Hospital, Pesaro, Italy

    A Isidori & G Visani

  3. Chair of Hematology, University of Brescia, Brescia, Italy

    M Malagola

  4. Department of Hematology, Ravenna Hospital, Ravenna, Italy

    M Rondoni

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  1. P P Piccaluga
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  2. G Martinelli
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  7. M Amabile
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Correspondence to P P Piccaluga.

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Piccaluga, P., Martinelli, G., Isidori, A. et al. Long-term molecular complete remission with IFN-α in Ph+ adult acute lymphoid leukemia patients. Leukemia 22, 1617–1618 (2008). https://doi.org/10.1038/leu.2008.10

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