Re: Imatinib mesylate administration in the first 100 days after stem cell transplantation

Document Type

Letter to the Editor

Publication Date

1-1-2004

Journal

Biology of Blood and Marrow Transplantation

Volume

10

Issue

12

DOI

10.1016/j.bbmt.2004.09.004

Abstract

Indications:15 patients with Philadelphia chromosome-positive leukemia (chronic myeloid leukemia [CML, 8], acute lymphoblastic leukemia [6], and acute myeloid leukemia [AML, 1]) having undergone stem cell transplantation.Patients:15 patients aged 16 to 69 years (median age, 42 years).TypeofStudy:This letter to the editor described the outcome of Glivec therapy in the first 100 days after stem cell transplantation (SCT).DosageDuration:Initially 100-400 mg daily; average daily dose was 100 mg daily. Duration: at least 100 days.Results:Doses exceeding 200 mg daily were associated with significant myelosuppression, which required both Glivec dose reduction and initiation of transfusion and growth factor support to achieve graft recovery. At all doses, Glivec was associated with fully reversible hematologic toxicity; grade 3 and 4 neutropenia was observed in 6/15 and 4/15 patients, respectively. Significant thrombocytopenia was also noted; grade 3 and 4 toxicity was observed in 4/15 and 3/15 patients evaluated, respectively. Nonhematologic toxicities were uncommon. Periorbital edema/weight gain and transient increases in total bilirubin (1.0 to 2.3 mg/dL) were noted in 1/15 patient each. 2/15 patients relapsed while receiving Glivec during the first 100 days (AML [1] and CML in blastic phase [1]). The administration of Glivec was found to predictably increase tacrolimus serum levels by 25% to 33% within 72-hours of medication initiation.AdverseEffects:Adverse events observed include myelosuppression, hematologic toxicities (neutropenia grade III [6] and grade IV [4], and thrombocytopenia grade III [4] and grade IV [3]), periorbital edema/weight gain (1), and transient increases in total bilirubin (1).AuthorsConclusions:These preliminary observations suggest that imatinib can be safely administered in the first 100 days after SCT. Tolerated doses are usually lower than in non-SCT patients, and close monitoring (particularly hematologic) is required. Although a theoretical concern in this setting is the possibility that such reduced dosages may favor the selection of spontaneously arising resistant clones, in view of the potential benefits, we believe that this "adjuvant" approach is worth exploring, ideally in a randomized study.FreeText:All patients received a fully ablative preparative regimen and achieved full donor-derived engraftment. Tacrolimus and methotrexate were administered as graft-versus-host disease prophylaxis. The median day of Glivec initiation after transplantation was day +34 (range, 16-37). All patients were still receiving immunosuppressive therapy and had no cytogenetic or molecular evidence of disease. Concomitant treatments: tacrolimus, methotrexate, growth factor, and blood transfusion. Test: serum bilirubin.

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