Bosutinib shows low cross intolerance, in chronic myeloid leukemia patients treated in fourth line. Results of the Spanish compassionate use program.

The role of bosutinib as rescue treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML) patients after failing three previous tyrosine kinase inhibitors (TKIs) is currently unknown. We report here the largest series (to our knowledge) of patients treated with bosutinib in fourth-line, after retrospectively reviewing 30 patients in chronic phase, and pretreated with imatinib, nilotinib, and dasatinib. With a median follow up of 11.1 months, the probability to either maintain or improve their CCyR response was 56.6% (17/30) and 11 patients (36.7%) achieved or maintained their baseline MMR. In patients not having baseline CCyR, the probabilities of obtaining CCyR, MMR, and MR4.5 were 13, 11, and 14%, respectively. The probabilities of obtaining MMR and deep molecular response MR4.5 in patients with baseline CCyR were 40.0% (6/15) and 20.0% (3/15). At 20 months, progression-free survival was 73%. Grade 3-4 hematological toxicities were more frequent in resistant than intolerant patients (45.4 vs. 0.0%). Nonhematological toxicities were also more frequent in resistant patients, being diarrhea the most conspicuous one. Bosutinib seems to be an appropriate treatment option for patients resistant or intolerant to three prior TKI's.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival.

Aportación para el diagnóstico de cansancio en el desempeño del rol de cuidador / Contribution to the diagnosis of caregiver role strain

Objetivos. Determinar la concordancia entre la valoración que el cuidador hace sobre encontrar o no dificultad para desempeñar el papel de cuidador y la valoración de la enfermera. Medir el grado de cansancio de una manera cuantitativa y establecer el punto de corte que magnifique los valores predictivos de esta medida con los medios diagnósticos anteriores. Determinar la asociación entre las características definitorias y los factores relacionados de la North American Nursing Diagnosis Association (NANDA) con la presencia de cansancio. Método. Estudio analítico transversal sobre los cuidadores de personas discapacitadas de una zona básica de salud. Muestra aleatoria simple de 49 sujetos. El grado cuantitativo de cansancio se midió con el cuestionario de Zarit; la concordancia con el índice kappa y la asociación con el test de Spearman. Resultados. La concordancia entre la valoración es de 0,54. El cuestionario de Zarit presenta un punto de interés: 43/44. Encontramos asociación entre el diagnóstico y 4 características definitorias y 5 factores relacionados. Conclusiones. La concordancia entre la valoración de la cuidadora y de la enfermera es moderada. Las cuidadoras con más de 43 puntos en la escala de Zarit estarían cansadas con una alta probabilidad. Para minimizar la incertidumbre diagnóstica es importante la valoración de las características definitorias y los factores relacionados que presentan asociación positiva con el diagnóstico

We analyze difficulties in making a diagnosis of caregiver role strain and aim to suggest improvements in nursing interventions. Aims. To determine the concordance between evaluations made by caregivers and nurses on role strain. To quantitatively measure subjective burden and establish a cut-off point to increase predictive values. To determine the associations among defining characteristics and factors related to caregiver role strain. Method. We performed an analytical, cross-sectional study of the care providers of persons with loss of mobility in a basic health area. Forty-nine subjects were selected by simple random sampling. Quantitative measurement of the degree of strain was measured using the Zarit Burden Interview (ZBI). The concordance between determinations was measured using the kappa statistic and associations were measured using Spearman's test. Results. The concordance between caregivers' and nurses' evaluations was 0.54. The ZBI presented a cut-off point of 43/44. Associations were found among the diagnosis and four defining characteristics and five strain-related factors. Conclusions. Moderate concordance was found between caregivers' and nurses' evaluations. Caregivers with a score of more than 43 points on the ZBI had a high probability of experiencing strain. To minimize diagnostic uncertainty, defining characteristics and strain-related factors should be evaluated