Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs.

PURPOSE: Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy. PATIENTS AND METHODS: The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. RESULTS: MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P<.001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r=0.59; P<.001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P<.001 and absolute r≥0.50 except social functioning r=0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α=.83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method. CONCLUSION: The MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.

Impacto clínico de la cuantificación de la carga mutacional de JAK2V617F en pacientes con neoplasias mieloproliferativas crónicas Ph negativas clásicas / Clinical significance of the quantification of JAK2V617F allele burden in classical Ph-negative myeloproliferative neoplasms

Fundamento y objetivo: La identificación de la mutación V617F del gen JAK2 en pacientes diagnosticados de neoplasias mieloproliferativas crónicas (NMPC) es fundamental en el cribado diagnóstico. Nuestro objetivo fue investigar la asociación entre la cuantificación de la mutación V617F (carga alélica JAK2V617F) y el fenotipo clínico al diagnóstico, y definir el papel de la carga alélica en la predicción de complicaciones. Pacientes y métodos: En el Servicio de Hematología del Hospital Universitario La Paz realizamos un estudio observacional retrospectivo (1987-2011) en 114 pacientes diagnosticados de NMPC y análisis de detección de la mutación V617F: 39 policitemias vera (PV), 71 trombocitemias esenciales y 6 mielofibrosis primarias. El porcentaje de alelos mutados fue evaluado en polimorfonucleares de sangre periférica mediante la técnica quantitative real time polymerase chain reaction (qRT-PCR, «reacción en cadena de la polimerasa cuantitativa en tiempo real»). En función de si la carga tumoral se encuentra entre 1-50% o es>50% los pacientes fueron diagnosticados de JAK2mut heterocigoto u homocigoto, respectivamente. Resultados: Se realizó el análisis cuantitativo por qRT-PCR en los 114 pacientes incluidos en el estudio, detectando la mutación V617F en 69 casos y siendo negativa para los 45 pacientes restantes. Encontramos que la presencia de mutación se asocia con la trombosis, y especialmente con la trombosis arterial. Además, y en la serie completa, la carga alélica homocigótica se asocia con diagnóstico de PV, edad avanzada, leucocitosis, mayor hematopoyesis y esplenomegalia. Conclusiones: La detección de la mutación V617F está asociada a una mayor incidencia de trombosis, leucocitosis y esplenomegalia. Su identificación nos permitiría una mejor estratificación pronóstica de los pacientes diagnosticados de NMPC (AU)

Background and objectives: Our study has investigated the presence of the mutation V617F in the JAK2 gene in patients diagnosed with chronic myeloproliferative neoplasms (MPNs). Furthermore, we determined if JAK2 (V617F) allelic burden associates with a specific clinical phenotype and if its quantification can be used as a marker to predict outcome and complications in patients with MPNs.Patients and methods: A retrospective observational study was conducted from 1987 to 2011 in the Haematology Department of La Paz University Hospital. The allelic burden was measured in 114 patients diagnosed with MPNs: 39 polycythemia vera (PV) patients, 71 essential thrombocythaemia patients and 6 primary myelofibrosis patients. The quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to determinate the percentage of mutated alleles in peripheral blood neutrophils. Patients were divided in 2 groups: heterozygous if the result was≤50% of the tested cells, and homozygous if it was positive in>50% of the cells. Results: Sixty-nine patients were positive for the JAK2 mutation and 45 were negative. Among those positive, the mutation was associated with arterial thrombosis. In addition, we demonstrate in the homozygous group that the V617F mutation is associated to PV, advanced age, leukocytosis, marked haematopoiesis and splenomegaly. Conclusions: The presence of V617F mutation is associated with a higher incidence of thrombosis, leukocytosis and splenomegaly. The identification of mutation on the JAK2 gene could help in a better definition of evolution and prognostic stratification of the myeloproliferative disorders (AU)

[Clinical significance of the quantification of JAK2V617F allele burden in classical Ph-negative myeloproliferative neoplasms]. / Impacto clínico de la cuantificación de la carga mutacional de JAK2V617F en pacientes con neoplasias mieloproliferativas crónicas Ph negativas clásicas.

BACKGROUND AND OBJECTIVES: Our study has investigated the presence of the mutation V617F in the JAK2 gene in patients diagnosed with chronic myeloproliferative neoplasms (MPNs). Furthermore, we determined if JAK2 (V617F) allelic burden associates with a specific clinical phenotype and if its quantification can be used as a marker to predict outcome and complications in patients with MPNs. PATIENTS AND METHODS: A retrospective observational study was conducted from 1987 to 2011 in the Haematology Department of La Paz University Hospital. The allelic burden was measured in 114 patients diagnosed with MPNs: 39 polycythemia vera (PV) patients, 71 essential thrombocythaemia patients and 6 primary myelofibrosis patients. The quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to determinate the percentage of mutated alleles in peripheral blood neutrophils. Patients were divided in 2 groups: heterozygous if the result was≤50% of the tested cells, and homozygous if it was positive in>50% of the cells. RESULTS: Sixty-nine patients were positive for the JAK2 mutation and 45 were negative. Among those positive, the mutation was associated with arterial thrombosis. In addition, we demonstrate in the homozygous group that the V617F mutation is associated to PV, advanced age, leukocytosis, marked haematopoiesis and splenomegaly. CONCLUSIONS: The presence of V617F mutation is associated with a higher incidence of thrombosis, leukocytosis and splenomegaly. The identification of mutation on the JAK2 gene could help in a better definition of evolution and prognostic stratification of the myeloproliferative disorders.