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Does Early Imatinib-Induced Myelosuppression Predict Hematologic Responses in Patients With Advanced-Phase Chronic Myeloid Leukemia?

Division of Oncology, Section of Bone Marrow Transplant and Leukemia, Washington University School of Medicine, St Louis, MO

To the Editor: As summarized in a recently published excellent review,¹ initial trials of imatinib mesylate (Gleevec, STI571) for the treatment of chronic myelogenous leukemia (CML) have yielded very encouraging results at all stages of the disease.^1–4 Imatinib is also well tolerated, but myelosuppression (grades 3 to 4 neutropenia or thrombocytopenia) occur in approximately 60% of patients receiving higher doses of imatinib ( 600 mg daily) and during more advanced phases of the disease. The prognostic significance of myelosuppression remains speculative and largely unknown.¹ It has been suggested that patients who develop myelosuppression are at higher risk for relapses. We therefore sought to examine, in a single institution, the relationship between imatinib-induced myelosuppression and subsequent hematologic responses in patients with advanced-phase CML.

Among 11 patients with blast-phase CML treated with imatinib (600 mg daily) at our institution, seven developed grades 3 to 4 neutropenia (absolute neutrophil count < 1.0 x 10⁹/L; n = 6), thrombocytopenia (platelet count < 50 x 10⁹/L; n = 4), or both (n = 3) as early as 8 days (median, 27 days; range, 8 to 28 days) after initiation of imatinib. A summary of patient characteristics and outcomes is presented in Table 1. Median age was 48 years (range, 21 to 60 years), and four of the seven patients had prior induction chemotherapy for blast-phase CML. In contrast to the reported hematologic responses (53% to 56% for untreated patients and 17% to 44% for previously treated patients),^3,4 none of our patients with imatinib-induced myelosuppression achieved a hematologic response. Two patients had only transient improvement in their peripheral-blood counts. As a result of the myelosuppression, imatinib was permanently discontinued in two patients, and dose was reduced to 400 mg daily in one patient. The remaining four patients continued imatinib at 600 mg daily despite myelosuppression. Five of the seven patients died a median of 3 months (range, 2 to 9 months) after starting imatinib. One patient who was allografted 3 months after initiation of imatinib is, to date, alive and in complete remission with a follow-up of 19 months. The remaining patient discontinued imatinib after 1 month of therapy and was subsequently lost to follow-up.

In conclusion, we confirm that early imatinib-induced myelosuppression may identify patients who have a very low likelihood of achieving subsequent hematologic responses. The prognostic significance of early imatinib-induced myelosuppression in CML can only be defined through large collaborative studies.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The authors indicated no potential conflicts of interest.

REFERENCES

1. Deininger MW, O’Brien SG, Ford JM, et al: Practical management of patients with CML receiving Imatinib. J Clin Oncol 21:1637–1647, 2003[Abstract/Free Full Text]

2. Drucker BJ, Sawyers CL, Kantarjian H, et al: Activity of a specific inhibitor of the bcr-abl tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038–1042, 2001[Abstract/Free Full Text]

3. Kantarjian HM, Cortes J, O’Brien S, et al: Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood 99:3547–3553, 2002[Abstract/Free Full Text]

4. Sawyers CL, Hochhaus A, Feldman E, et al: Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: Results of a phase II study. Blood 99:3530–3539, 2002[Abstract/Free Full Text]

5. Sneed TB, Kantarjian HM, Talpaz M, et al: Significance of myelosuppression during the course of therapy with imatinib in patients with CML in chronic phase. Blood 100:787a, 2002

6. Marin D, Marktel S, Foot N, et al: G-CSF reverses cytopenia and may increase cytogenetic responses in patients with CML treated with imatinib mesylate. Blood 100:782a, 2002

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cashen, A. Articles by Khoury, H. Search for Related Content PubMed PubMed Citation Articles by Cashen, A. Articles by Khoury, H. Social Bookmarking                            What's this?