RESUMEN
Chronic myelogenous leukemia (CML) is a hematopoietic disorder caused by the BCR/ABL gene or Philadelphia chromosome. The first Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treatment of CML was imatinib in 2001. Since then, multiple therapies, such as nilotinib, dasatinib, bosutinib, and, more recently, ponatinib, have made their way as viable treatment options for first-line and secondary therapies. Most patients tend to respond to first-line treatment. Although there is a subset of patients who do not achieve complete molecular response with first line, newer options have proven beneficial. As we progress through therapies, there still remain some patients who do not adequately respond to current available therapies. The treatment options and guidelines become more difficult in such situations, not only with respect to cost but also patient quality of life and satisfaction. We discuss a 75-year-old white female with CML, who has had multiple therapies with hematological remission but has never achieved complete molecular remission, currently on bosutinib and tolerating it well.
RESUMEN
Imatinib has improved outcomes in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (all). Minimal residual disease (mrd) is a useful tool for predicting leukemia relapse. However, there is no consensus on how to treat children with elevation of BCR-ABL transcripts but no evidence of hematologic relapse during chemotherapy combined with imatinib. Here, we report the case of a child with Ph+ all who had persistent elevation of mrd, but no evidence of hematologic relapse while receiving imatinib plus intensive chemotherapy. Dasatinib was substituted for imatinib because no suitable donor for allogeneic hematopoietic stem-cell transplantation (hsct) was available. Less-intensive chemotherapy with methotrexate and 6-mercaptopurine was administered concomitantly. No serious adverse events were encountered. With continuous dasatinib combined with chemotherapy, but no allogeneic hsct, our patient reached complete molecular remission and has been in complete molecular remission for more than 13 months. This report is the first about the long-term use of dasatinib in patients with Ph+ all and mrd elevation but hematologic remission during imatinib chemotherapy. In a similar situation, chemotherapy combined with dasatinib instead of allogeneic hsct could be considered to avoid hsct-related mortality and morbidity. Clinical trials are needed.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirugía , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Trasplante de Células Madre/métodos , Tiazoles/uso terapéutico , Adolescente , Adulto , Terapia Combinada , Dasatinib , Femenino , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Inducción de Remisión , Trasplante Homólogo , Adulto JovenRESUMEN
Small clinical studies have found that patients with idealized response to imatinib can sustain long-lasting responses after treatment discontinuation, suggesting that these patients may be effectively "cured" of chronic myeloid leukemia (CML). Treatment discontinuation is not presently considered routine practice and is not recommended outside the context of clinical research. Many questions remain regarding "cure" in CML: how "cure" is defined, what factors predict successful treatment discontinuation, and what management strategies are the most appropriate post-discontinuation, especially when molecular relapse occurs. This review addresses these issues and discusses the current knowledge regarding treatment discontinuation and a potential for "cure" of CML.