Fertility and disease outcomes in patients with chronic myeloid leukemia / 中华血液学杂志

Objective@#To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) .@*Methods@#Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People’s Hospital.@*Results@#A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response4.5 (MR4.5) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal.@*Conclusions@#It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.

Fertility and disease outcomes in patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) . Methods: Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People's Hospital. Results: A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response(4.5) (MR(4.5)) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal. Conclusions: It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.

The correlation study of the glycogene ST8SIA4 in the multidrug resistance of human chronic myeloid leukemia / 重庆医学

Objective To investigate the differential expression of ST8SIA4 in the both chronic myeloid leukemia(CML) cell lines KCL22 and adriamycin resistant cell lines KCL22/ADR ,peripheral blood mononuclear cells (PBMC) of CML patients ,to clar-ify the correlation of ST8SIA4 and multidrug resistance of CML .Methods Using real-time PCR and Western blot for quantification of ST8SIA4 ,we compared the differential expression of ST8SIA4 in CML cell lines and PBMC of CML patients .The differentially expressed ST8SIA4 gene was silenced ,and the chemosensitivity to anti-tumor drugs was analyzed in vitro .Results ST8SIA4 was differentially expressed in CML cell lines and PBMC of CML patients(P< 0 .05) .The altered level of ST8SIA4 was increased drug-resistant phenotype of KCL22/ADR cells both in vitro and in vivo(P< 0 .05) .Conclusion The expression of ST8SIA4 was different in CML cell lines and PBMC of CML patients ,these characteristic alterations were associated with multidrug resistance in CML .

Korean Guidelines for Treating Chronic Myelogenous Leukemia - The Korean Society of Hematology Chronic Myelogenous Leukemia Working Party / 대한내과학회지

BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.

Aspectos diagnósticos, evolutivos y terapéuticos de la leucemia mieloide crónica / Diagnostic, evolutive and therapeutic aspects of chronic myeloid leukemia

Introducción: la leucemia mieloide crónica (LMC) es un síndrome mieloproliferativo crónico caracterizado por la presencia de una alteración citogenética en las células proliferantes, el cromosoma Filadelfia (Ph), que da lugar a la formación de un gen híbrido BCR-ABL, fundamental en la patogénesis de la enfermedad. Objetivo: describir el comportamiento de esta enfermedad en los pacientes tratados en el Instituto de Hematología e Inmunología. Métodos: se estudiaron las características de esta enfermedad en sus aspectos diagnósticos, evolutivos y terapéuticos, en los pacientes atendidos desde marzo de 1974 hasta junio de 2012. Resultados: el grupo de edad que predominó para ambos sexos fue de 30 a 39 años. El 21 por ciento de los pacientes se encontraban asintomáticos en el momento del diagnóstico. La esplenomegalia fue el signo predominante en el 64 por ciento de los pacientes. Los hallazgos iniciales más significativos del hemograma consistieron en leucocitosis, basofilia y anemia. El 81 por ciento de los casos se encontraba en fase crónica al inicio de la enfermedad. La mayoría de los pacientes debutaron con niveles de LDH elevados. Se observó el cromosoma Filadelfia en el 68 por ciento de los pacientes a quienes se les realizó estudio citogenético. El estudio del reordenamiento del gen BCR/ABL se realizó en el 70 por ciento de los casos, siendo positivo en su totalidad. La media de supervivencia en relación con el tratamiento fue mayor en los pacientes tratados con mesilato de imatinib desde el momento del diagnóstico (11.7 años). La media de supervivencia global es de 11.44 años y la mediana es de 8.18 años. Conclusiones: todos los parámetros demográficos, clínicos, de laboratorio y terapéuticos coincidieron con lo descrito en la literatura, excepto la edad de aparición de la LMC que evidenció una disminución

Introduction: Chronic myeloid leukemia (CML) is a chronic myeloproliferative syndrome characterized by the presence of a citogenetic alteration in proliferant cells, the Philadelphia chromosome (Ph), giving rise the formation of a hybrid gene BCR-ABL, with a fundamental role in the pathogenesis of the disease. Objective: To describe the clinical behavior of the illness in patients treated at the Institute of Hematology and Immunology. Methods: Characteristics according to diagnose, evolution and therapeutic aspects of the patients treated at from March 1974 to June 2012 were studied. Results: The age group that prevailed for both sexes was 30-39 years; 21 percent of the patients were asintomatic at diagnosis. Splenomegaly was the predominant sign in 64 percent of the patients. The most significant initial discoveries on blood film were leucocytosis, basophillia and anemia; at debut 81 percent of the patients were in chronic phase. Most patients debuted with high levels of LDH. Ph chromosome was observed in 68 percent of individuals with cytogenetc studies. The BCR/ABL gene was detected in every patient with molecular studies. The mean of survival in relation to treatment was higher in patients treated with imatinib mesilate at diagnosis (11.7 years). The mean of global survival was 11.44 years with the median of 8.18 years. Conclusion: All demographic, clinical, laboratory and therapeutic parameters coincided with the literature with the exception of a lower age at onset of CML

Importance of adherence to BCR-ABL tyrosine-kinase inhibitors in the treatment of chronic myeloid leukemia

Treatment of chronic myeloid leukemia with BCR-ABL tyrosine kinase inhibitors requires full adherence in order to maximize the likelihood of achieving optimal responses, and to minimize healthcare costs. In this article, we review some of the methods available for assessing compliance, the main consequences of nonadherence on treatment outcomes, major factors commonly associated with poor compliance, a few successful measures for improving adherence and the most accepted recommendations for proactively managing adverse events.

The Application of Bone Marrow MR Imaging in Mornitoring Chronic Myeloid Leukemia / 实用放射学杂志

Objective To study the value of bone marrow MR imaging in mornitoring chronic myeloid leukemia(CML).Methods 12 cases of CML underwent twice MR examination of pelvis and femur respectively at different time.MRI appearances were compared with the results of morphology and blood routine at the same time.The relation between MR findings and course was analysed.Results MR appearances of bone marrow were changed with the progression of disease.The condition of patients was improved in 2 cases and worse in 4 cases,the signal intensity of bone marrrow were increased and decreased respectively.The signal intensity of bone marrow showed no change in 6 patients whose condition kept stable.Conclusion The characteristics of MRI can reflect the progression of CML,it is of important value in mornitoring this disease.