Year: 2010
Type: article
Study design: Case Report
Abstract: Successful treatment using omacetaxine for a patient with CML and BCR-ABL1 35INSAn alternatively spliced BCR-ABL mRNA transcript with a 35-bp insertion (35INS) was recently described among patients with chronic myelogenous leukemia (CML), and has been associated with in vitro resistance to tyrosine kinase inhibitors. 1 We now describe a patient with CML and 35INS who had clinical resistance to imatinib and dasatinib, but a complete cytogenetic response to omacetaxine (previously known as homoharringtonine).The patient, a 19-year-old woman with CML in chronic phase, initially had a complete hematologic and partial cytogenetic response to imatinib (400 mg/d).After 6 months of imatinib, she became noncompliant and was lost to follow-up.She returned 3 months later with recurrent chronic-phase CML.She experienced a second hematologic response to imatinib, but did not achieve cytogenetic remission.After 4 months of this second course of imatinib, a significant increase in BCR-ABL transcripts was observed, and therapy was changed to dasatinib (100 mg/d).However, she experienced persistent headaches during the subsequent 2 months and demonstrated a persistent rise in white blood cell count, leading to discontinuation of dasatinib.Salvage therapy with interferon alpha (5 000 000 units/m 2 per day subcutaneously) and cytarabine (20 mg/m 2 daily, subcutaneously, 10 days/month) reduced her white blood cell count but did not cause a cytogenetic or molecular response.No HLA-matched donor was identified among her 3 siblings or the National Marrow Donor Program registry.ABL kinase mutation analysis demonstrated the presence of a 35 base-pair insertion between exons 8 and 9.Compassionate-use treatment with omacetaxine (1.25 mg/m 2 per dose subcutaneously twice daily ϫ 14 days in each 28-day period) was approved by the Institutional Review Board of the Albert Einstein College of Medicine, and was started after informed consent was obtained.She experienced a complete cytogenetic response after 3 months of treatment.At the time of this writing, 2 months later, the patient remains in cytogenetic remission, on maintenance dosing of omacetaxine (1.25 mg/m 2 twice daily ϫ 7 days in each 28-day period), with no nonhematologic toxicity.BCR-ABL transcripts, measured by quantitative reversetranscription-polymerase chain reaction, have decreased to 1.75%.CML is characterized by t(9;22)(q34;q11) translocation which leads to the production of the BCR-ABL fusion oncoprotein, which contains an activated tyrosine kinase domain.2 Acquisition of point
Source: Blood
Authors: Kris M. Mahadeo, Peter D. Cole
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1997142209