Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Preferencias y limitaciones de los hematólogos para afrontar la complejidad de los síndromes mielodisplásicos / Preferences and limitations of hematologists to address the complexity of myelodysplastic syndromes

La Argentina es un país caracterizado por una distribución heterogénea de su población, de sus recursos económicos y, consiguientemente, del acceso a los servicios de salud, lo cual podría afectar el diagnóstico y tratamiento de los pacientes con síndromes mielodisplásicos. Basados en la complejidad creciente para arribar al diagnóstico, estimar el riesgo e indicar un tratamiento adecuado, hemos conducido una encuesta de veintitrés preguntas para evaluar patrones de práctica clínica. El cuestionario se distribuyó entre los 850 hematólogos argentinos inscriptos al XXII Congreso Argentino de Hematología y 195 (22.9%) fueron contestados. El 40.0% refieren que < 75% de sus pacientes acceden al cariotipo, histología de la médula ósea y citometría de flujo. Este acceso disminuye significativamente por una baja cobertura sanitaria (OR 6.3), en población adulta (OR 3.8), al derivar el estudio citogenético (OR 3.2) y fuera del área metropolitana de Buenos Aires (OR 2.4). Los encuestados evitan terminologías oncológicas (77.0%) al introducir el diagnóstico y utilizan el sistema internacional de predicción o su revisión (74.2%) para estadificar riesgo. Sin embargo, éstos priorizan la edad al seleccionar tratamiento y los pediatras indican preferentemente el trasplante de precursores hematopoyéticos. La mayoría de los hematólogos ha prescripto los tratamientos recomendados, cuyas suspensiones se relacionaron con falta de respuesta (62.7%), con participación reducida en ensayos clínicos (8.9%). Por ende, refieren heterogeneidad en el acceso a las herramientas diagnósticas complementarias con diferencias al momento de indicar un tratamiento, dependiendo de la edad de sus pacientes, sin limitaciones aparentes en su prescripción.

Argentina is a country characterized by a heterogeneous distribution of its population, its economic resources and, consequently, access to health services, which could affect the diagnosis and treatment of patients with myelodysplastic syndromes. Based on the increasing complexity to arrive at the diagnosis, estimate the risk and indicate an adequate treatment, we have conducted a survey of twenty-three questions to evaluate patterns of clinical practice. The questionnaire was distributed among 850 hematologists registered at the XXII Argentine Congress of Hematology, and 195 (22.9%) were answered; 40.0% report that < 75% of their patients access the karyotype, bone marrow histology and flow cytometry. This access decreases significantly due to low health coverage (OR 6.3), in the adult population (OR 3.8), when the cytogenetic study is derived (OR 3.2) and outside the metropolitan area of Buenos Aires (OR 2.4). The respondents avoid oncological terminologies (77.0%) when introducing the diagnosis and use the international prediction system or its review (74.2%) to stage risk. However, they prioritize age when selecting treatment and pediatricians preferentially recommend the transplantation of hematopoietic precursors. Most of the haematologists have prescribed the recommended treatments, whose suspensions were related to lack of response (62.7%), with reduced participation in clinical trials (8.9%). Therefore, they report heterogeneity in the access to complementary diagnostic tools with differences at the time of indicating a treatment, depending on the age of their patients without apparent limitations in their prescription.

Histologia da medula óssea / Bone marrow histology

A biópsia de medula óssea, após a utilização da agulha de Jamshidi, tornou- se um evento de rotina em virtude da simplificação na obtenção do material. A adequação das dimensões da amostra e a diminuição do tempo de descalcificação melhoraram muito a qualidade histológica e possibilitaram ao patologista um aprofundamento da interpretação morfológica das doenças hematológicas e não hematológicas. Para um laudo correto é necessário o conhecimento do tecido hematopoético normal, suas diferentes linhagens celulares, variações dependentes da idade e integração com outros dados clínicos e laboratoriais.

The bone marrow biopsy after the introduction of the Jamshidi needle has come into a routine practice due to the facilitation to obtain good sample. Due to the adequate size of the sample, the decalcification time decreased and consequently the histological quality improved allowing to the pathologist a more deep and precise morphological interpretation and diagnosis of the hematological and non- hematological disorders. For a correct diagnosis, the pathologist should be acquainted with the normal histology of the bone marrow parenchyma, it variations depending on age, as well as with the clinico- laboratorial data to integrate them with the morphological features.