DNA damage in acute myeloid leukemia patients of Northern Mexico.

The purpose of this study was to evaluate DNA damage in the whole genome of peripheral blood leukocytes from patients with acute myeloid leukemia (AML) compared with a control group using DNA breakage detection-fluorescent in situ hybridization (DBD-FISH). Our results suggest that the DNA damage detected in patients with newly diagnosed AML was similar to that observed for the controls; this might be explained by the stimulation of a repair pathway by the pathogenesis itself. These findings indicate that inhibiting the repair pathway could be proposed to enhance the efficacy of chemotherapy.

[Hematologic and molecular response with dasatinib as second-line treatment in chronic myeloid leukemia (CML) with treatment failure]. / Respuesta hematológica y molecular en leucemia mieloide crónica (LMC) con falla a tratamiento con dasatinib como fármaco de segunda línea.

BACKGROUND: Chronic myeloid leukemia is a myeloproliferative disease characterized by the Philadelphia chromosome and with this, the chimeric protein BCR-ABL. The first-line treatment is imatinib, a tyrosine kinase inhibitor, that has showed good results, but with a significant percentage of treatment failure. This failure has led to second-generation tyrosine kinase inhibitors as second-line treatment such as dasatinib. OBJECTIVES: The objective of the study was to evaluate the efficacy of dasatinib as second-line treatment. MATERIAL AND METHODS: Observational, longitudinal, and retrospective study. Patients with diagnosis of chronic myeloid leukemia that presented failure to first-line treatment were included in the present study; the hematologic response was evaluated at 3, 6, and 12 months, and molecular response at 12 months of follow-up after dasatinib treatment was started. RESULTS: Of a total of 14 patients that were included in the study, a response in the white cell count of 84.6% with a mean response at 4.7 months of follow-up was observed; also 84.6% platelet response with a mean response at 4.7 months of follow-up. Molecular response was also evaluated at a 12-month follow-up, achieving a 50% response with a mean response at 11.08 months of follow-up. A survival rate of 80% at a 12-month follow-up was observed. CONCLUSIONS: The use of dasatinib as a second-line treatment is effective in achieving a sustained hematologic response of 84.6% and a molecular response in 50%, also finding a hematologic response without achieving a total molecular response.

[Nilotinib in patients with chronic myeloid leukemia without response to imatinib]. / Nilotinib en pacientes con leucemia mieloide crónica con falla a imatinib.

BACKGROUND: Resistance and intolerance to imatinib in patients with chronic myeloid leukemia requires alternative therapies. Nilotinib provides a choice as a second-line treatment. The objective of this report was to show the results of a group of patients with chronic myeloid leukemia who received nilotinib as a second-line treatment. METHODS: The medical records of 16 patients of both sexes, of any age, diagnosed with chronic myeloid leukemia, who received nilotinib as a second-line treatment, were reviewed. All of them had received imatinib prior as first-line treatment; the causes to switch to nilotinib were intolerance, resistance and clinical progression of leukemia. RESULTS: The sample was of 16 patients, who achieved at least a hematologic response; 10 were males (62.5%). The age range was 24 to 75 years. Two patients received nilotinib due to intolerance to imatinib; seven due to resistance to imatinib and seven due to lack of response. There was response in the two patients who received nilotinib due to intolerance. One patient died five months after starting nilotinib due to progression of leukemia; four patients achieved major molecular response, two patients had reduced expression of BCR-ABL gene. Six patients continued with high expression of BCR-ABL gene; two of them carrying M244V mutation, and one with a complex karyotype with numerical and structural alterations. CONCLUSIONS: Nilotinib is an option for patients with intolerance or resistance to imatinib.

INTRODUCCIÓN: la resistencia e intolerancia al imatinib en pacientes con leucemia mieloide crónica requiere el uso de otros fármacos, como el nilotinib. El objetivo de este informe es presentar los resultados obtenidos en un grupo de pacientes con leucemia mieloide crónica que recibió tratamiento de segunda línea con nilotinib. MÉTODOS: se incluyeron 16 pacientes con diagnóstico de leucemia mieloide crónica que recibieron tratamiento de segunda línea con nilotinib, después de que no respondieron adecuadamente al imatinib. El cambio de fármaco se debió a intolerancia, resistencia o progresión de la leucemia. RESULTADOS: los 16 pacientes consiguieron al menos respuesta hematológica. Hubo respuesta molecular mayor en dos pacientes en los que el cambio se debió a intolerancia a imatinib. Un paciente falleció a los cinco meses de haber iniciado nilotinib, debido a progresión de la leucemia y hemorragia cerebral. En cinco, el cambio se debió a resistencia a imatinib y progresión de la leucemia; en ellos se logró respuesta molecular mayor. Dos pacientes presentaron reducción de la expresión del gen BCR-ABL. En seis pacientes persistió la elevada expresión del gen BCR-ABL. De estos últimos, dos portaban mutación M244V y uno, cariotipo muy complejo con alteraciones numéricas y estructurales. CONCLUSIONES: nilotinib es una opción viable para tratar a los pacientes con intolerancia o resistencia a imatinib.

[Pregnancy and myeloid leukemia treated with imatinib. Development and monitoring of a patient]. / Embarazo y leucemia mieloide crónica tratada con imatinib. Evolución y monitoreo de una paciente.

BACKGROUND: Imatinib has changed the natural history of chronic myeloid leukemia. There are women with chronic myeloid leukemia in reproductive age with pregnancy desires. The aim of this case was to report the course and outcome of pregnancy in a patient with chronic myeloid leukemia diagnosis treated with imatinib. CLINICAL CASE: A 32 year old female with diagnosis of chronic myeloid leukemia with follow-up of 11 years. She received standard treatment, but she reported poor adherence; therefore, she received imatinib therapy two years after the diagnosis. The patient stopped the treatment herself because she was looking to be pregnant. She presented amenorrhea, which lasted for six weeks; pregnancy was confirmed. During a period of 10 months, she remained untreated and there were no symptoms of leukemia progression. The pregnancy was terminated by cesarean section at 35.5 weeks of gestation. The product was born healthy. In the post-cesarean visit, the lab showed a cell blood count which reported: hemoglobin 8.7 g/dL, hematocrit 25 %, white blood cell 22,000/mL, platelets 170,000/mL. Since October the patient resumed imatinib 600 mg/day. CONCLUSIONS: The prolonged period of treatment with imatinib had no effect on the pregnancy and the product. The molecular monitoring showed the need to reinstall the treatment once the pregnancy finished. The efficacy and safety of treatment allows patients to fulfill life projects that seemed distant in other time.

INTRODUCCIÓN: el tratamiento con imatinib ha modificado la historia natural de la leucemia mieloide crónica, y ha permitido que las mujeres con este padecimiento puedan embarazarse. El objetivo de este reporte es describir el curso y desenlace de un embarazo en una paciente con diagnóstico previo de leucemia mieloide crónica, que recibía tratamiento con imatinib. CASO CLÍNICO: mujer de 32 años con leucemia mieloide crónica de 11 años de evolución. Al diagnóstico se inició tratamiento estándar, pero debido a poca adherencia terapéutica, a los dos años se le prescribió imatinib. Debido al deseo de procrear, la paciente decidió suspender el medicamento. Un mes después acudió a la consulta con amenorrea de seis semanas de evolución; se confirmó embarazo. Durante 10 meses que permaneció sin tratamiento, no tuvo síntomas de progresión de la leucemia. El embarazo se interrumpió por cesárea a las 35.5 semanas de gestación. El neonato aparentemente se encontraba sano. En el transcurso del puerperio quirúrgico, la paciente acudió a consulta; los resultados de la biometría hemática indicaron hemoglobina de 8.7 g/dL, hematócrito de 25 %, leucocitos de 22 000/mL y plaquetas de 170 000/mL. Ese día se reinició tratamiento con 600 mg/día de imatinib. CONCLUSIONES: el tratamiento prolongado con imatinib no tuvo repercusión sobre el embarazo ni el neonato. El monitoreo molecular evidenció la necesidad de re-iniciarlo una vez concluido el embarazo. La eficacia y seguridad de los tratamientos actuales permiten cumplir proyectos de vida que en otro tiempo eran impensables.

Alteraciones cromosómicas secundarias en pacientes con leucemia mieloide crónica, en un hospital de referencia del noreste de México / Secondary Chromosomic Changes in Patients with Myeloid Leukemia in a Reference Hospital in Northeastern Mexico

Introducción: la caracterización del perfil citogenético que presenta una determinada fase de la leucemia mieloide crónica (LMC), está ofreciendo nuevas direcciones para la investigación de la etiología a nivel molecular. En México no existen datos de la descripción cromosómica de esta enfermedad, por lo que el objetivo del presente estudio fue determinar las alteraciones cromosómicas de 56 pacientes con LMC. Diseño: estudio transversal (diagnóstico y estadio). Material y métodos: las muestras de médula ósea de 56 pacientes con LMC en diferentes etapas, fueron sometidas a estudios citogenéticos mediante técnicas de bandeo G e hibridación in situ fluorescente (FISH), con sonda específica para cromosoma Filadelfia (Ph). Resultados: 19% (6/31) de los pacientes en etapa crónica mostró alteraciones cromosómicas secundarias, en contraste con 60% (15/25) observado en aquellos pacientes en etapa acelerada. Las alteraciones cromosómicas secundarias más frecuentes fueron: las trisomías 8 y 19, cromosoma Ph extra e isocromosoma de brazos largos del cromosoma 17. Conclusión: este es el primer trabajo que determina alteraciones cromosómicas secundarias en pacientes mestizos mexicanos con LMC, cuyas frecuencias están de acuerdo con lo reportado para otras poblaciones a nivel mundial.

Introduction: Our aim was to characterize the cytogenetic profile that displays a certain phase of chronic myelogenous leukemia (CML), offering new directions for investigation of the etiology to the molecular level. In Mexico, data does not exist in this regard; thus, the objective of the present study was to determine cytogenetic alterations in 56 Mestizo Mexican patients with LMC. Design: Cross-sectional study (diagnosis and stage) was carried out. Materials and Methods: samples of bone marrow of 56 patients with CML in different phases were analyzed using G banding and fluorescence in situ hybridization (FISH) with DNA probes for Philadelphia chromosome (Ph). Results: 19% of patients in chronic stage showed secondary chromosomal alterations in contrast with an observed 60% in patients in accelerated stage. Most frequent alterations included trisomy 8 and 19, extra Ph chromosome, and isochromosome of thell. Conclusions: We believe this to be the first work that determines secondary chromosomal alterations in Mexican racially mixed patients with LMC. These are in agreement with those reported for other populations at the worldwide level.

[Secondary chromosomic changes in patients with chronic myeloid leukemia in a reference hospital in Northeastern Mexico]. / Alteraciones cromosómicas secundarias en pacientes con leucemia mieloide crónica, en un hospital de referencia del noreste de México.

INTRODUCTION: Our aim was to characterize the cytogenetic profile that displays a certain phase of chronic myelogenous leukemia (CML), offering new directions for investigation of the etiology to the molecular level. In Mexico, data does not exist in this regard; thus, the objective of the present study was to determine cytogenetic alterations in 56 Mestizo Mexican patients with LMC. DESIGN: Cross-sectional study (diagnosis and stage) was carried out. MATERIALS AND METHODS: samples of bone marrow of 56 patients with CML in different phases were analyzed using G banding and fluorescence in situ hybridization (FISH) with DNA probes for Philadelphia chromosome (Ph). RESULTS: 19% of patients in chronic stage showed secondary chromosomal alterations in contrast with an observed 60% in patients in accelerated stage. Most frequent alterations included trisomy 8 and 19, extra Ph chromosome, and isochromosome of the 17. CONCLUSIONS: We believe this to be the first work that determines secondary chromosomal alterations in Mexican racially mixed patients with LMC. These are in agreement with those reported for other populations at the worldwide level.