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Management of Philadelphia chromosome-positive acute lymphoblastic leukemia

Leukemia Supplements volume 1, pages S7–S9 (2012)Cite this article

Abstract

Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during frontline therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) and result in hematologic remission rates exceeding 90%. Minimal residual disease levels are generally lower when TKIs are used in combination with chemotherapy rather than as monotherapy. Although outcome has improved substantially with TKI-based regimens compared with historic controls, allogeneic stem cell transplantation (SCT) in first remission provides the best chance of cure for the majority of patients eligible for SCT. Administration of imatinib after SCT further reduces molecular recurrence and is associated with greatly improved relapse-free and overall survival. The high relapse rate in non-transplanted patients is largely attributable to the emergence of leukemic clones with mutations in the tyrosine kinase domain of BCR-ABL. Ongoing studies with newer TKIs will determine whether these more potent agents are able to sustain remissions without SCT. Assessment of minimal residual disease has become an integral part of the management of Ph+ALL, as it has prognostic importance and is used to guide therapeutic intervention. Novel immunotherapeutic interventions and combinations of TKIs are currently being investigated in clinical trials and may further improve the prognosis of patients with Ph+ALL.

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Authors and Affiliations

  1. Department of Medicine, Hematology and Oncology, Johann-Wolfgang Goethe University, Frankfurt, Germany

    O G Ottmann

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  1. O G Ottmann
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Correspondence to O G Ottmann.

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Competing interests

The author received consulting fees for Advisory Board participation and lecture fees from Novartis and Bristol Myers Squibb.

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This article was published as part of a supplement that was supported by Novartis, MSD Italia, Roche, Celgene, GlaxoSmithKline, Sanofi, Gilead, Adienne, Italfarmaco, Pierre Fabre Pharmaceuticals with an unrestricted educational contribution to AREO—Associazione Ricerche Emato-Oncologiche (Genoa) and AMS—Associazione Malattie del Sangue (Milan) for the purpose of advancing research in acute and chronic leukemia.

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Ottmann, O. Management of Philadelphia chromosome-positive acute lymphoblastic leukemia. Leukemia Suppl 1 (Suppl 2), S7–S9 (2012). https://doi.org/10.1038/leusup.2012.7

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