RESUMO
BACKGROUND: Role of erythropoietin (EPO) in the treatment of late anemia in patients with Chronic Myeloid Leukemia (CML) is still undefined. METHODS: Fifty CML patients treated at 14 institutions with frontline imatinib for at least 12 months and in stable complete cytogenetic response who developed a late chronic anemia treated with EPO were retrospectively evaluated. RESULTS: Median time from imatinib start to EPO treatment was 42.2 months [interquartile range (IQR) 20.8-91.9]. Median Hb value at EPO starting time was 9.9 g/dL (IQR 8.9-10.3): Eleven patients (22.0%) were transfusion dependent. Alpha-EPO (40 000 UI weekly) was employed in 37 patients, beta-EPO (30 000 UI weekly) in 9 patients, zeta-EPO (40 000 UI weekly) in 2 patients, and darbepoetin (150 mcg/weekly) in the remaining 2 patients. On the whole, 41 patients (82.0%) achieved an erythroid response, defined as a stable (>3 months) improvement >1.5 g/dL of Hb level, and 9 patients (18.0%) indeed resulted resistant. Among responding patients, 10 relapsed after a median time from EPO start of 20.7 months (IQR 10.8-63.7). No EPO-related toxicity was observed. CONCLUSIONS: Results of EPO treatment for late chronic anemia during long-lasting imatinib therapy are encouraging, with a high rate of response.
Assuntos
Anemia/tratamento farmacológico , Anemia/etiologia , Antineoplásicos/efeitos adversos , Eritropoetina/uso terapêutico , Mesilato de Imatinib/efeitos adversos , Leucemia Mieloide de Fase Crônica/complicações , Inibidores de Proteínas Quinases/efeitos adversos , Idoso , Anemia/sangue , Anemia/diagnóstico , Antineoplásicos/uso terapêutico , Biomarcadores , Gerenciamento Clínico , Suscetibilidade a Doenças , Índices de Eritrócitos , Eritropoetina/administração & dosagem , Eritropoetina/efeitos adversos , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do TratamentoAssuntos
Leucemia Mieloide de Fase Crônica/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Humanos , Leucemia Mieloide de Fase Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Indução de Remissão/métodosRESUMO
Chronic myelogenous leukemia (CML) is a malignancy of the human hematopoietic stem cell (HSC) caused by the p210BCR/ABL oncoprotein. Although alternative splicing of pre-mRNA is a critical determinant of a cell's protein repertoire, it has not been associated with CML pathogenesis. We identified a BCR/ABL-dependent increase in expression of multiple genes involved in pre-mRNA splicing (eg SRPK1, RNA Helicase II/Gu, and hnRNPA2/B1) by subtractive hybridization of cDNA from p210BCR/ABL-eGFP vs eGFP-transduced umbilical cord blood CD34+ cells. beta1-integrin signaling is important to HSC maintenance and proliferation/differentiation, and is abnormal in CML. As an example of how changes in pre-mRNA processing might contribute to CML pathogenesis, we observed alternative splicing of a gene for a beta1-integrin-responsive nonreceptor tyrosine kinase (PYK2), resulting in increased expression of full-length Pyk2 in BCR/ABL-containing cells. Treatment of p210BCR/ABL-positive cells with the Abl-specific tyrosine kinase inhibitor STI571 reverted PYK2 splicing to a configuration more consistent with normal cells, and correlated with decreased expression of BCR/ABL-induced proteins involved in pre-mRNA processing. Whether altered PYK2 splicing contributes to CML pathogenesis remains undetermined; however, we propose that generic changes in pre-mRNA splicing as a result of p210BCR/ABL kinase activity may contribute to CML pathogenesis.
Assuntos
Proteínas de Fusão bcr-abl/fisiologia , Células-Tronco Hematopoéticas/patologia , Proteínas Tirosina Quinases/genética , Splicing de RNA , Antígenos CD34 , Quinase 2 de Adesão Focal , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide de Fase Crônica/etiologia , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Precursores de RNA/genéticaAssuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos Alquilantes/uso terapêutico , Bussulfano/uso terapêutico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/etiologiaRESUMO
We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.