Research advances in role of m6A methylation modification in hematological malignancies / 上海交通大学学报（医学版）

N6-methyladenosine (m6A) has been identified as the most common epigenetic modification of eukaryote mRNA. It can not only mediate multiple processes of RNA metabolism such as RNA splicing, translation and decay under the catalytic regulation of m6A-related enzymes, but also affect the development of bone marrow hematopoiesis by regulating the self-renewal, proliferation and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, many studies have reported that m6A methylation modification plays an important role in the development and progression of hematological malignancies. Targeting inhibition of m6A-related factors contributes to increase the sensitivity of patients with hematological malignancies to therapeutic drugs. This review describes the biological characteristics and hematopoietic regulation mechanisms of m6A methylation modification, and its role in the pathogenesis of hematological malignancies.

Características clínicas y microbiológicas de pacientes con neutropenia febril en un hospital Universitario / Clinical and microbiological characteristics of patients with febrile neutropenia in one Colombian Universitary Hospital

Objetivo: Describir las características clínicas, demográficas, frecuencia, tipo de aislamientos microbiológicos y resistencia a los antimicrobianos de pacientes con neoplasias hematológicas que presentaron como complicación neutropenia febril en el Hospital Universitario de San Ignacio Métodos: Estudio descriptivo observacional, se tomaron datos de historias clínicas de los pacientes adultos hospitalizados en la Unidad de Hematología y Trasplante de Médula Ósea, que cumplieron criterios de neutropenia febril entre enero de 2013 y diciembre de 2014 Resultados: se recolectaron 345 episodios de neutropenia febril, correspondientes a 193 pacientes. Se documentó foco infeccioso en el 68,1% de los episodios, con aislamiento microbiológico en el 62.9% de los episodios, con predominio de bacilos gram negativos, en 63,7% de los casos, seguido por los cocos gram positivos en 27,9% y hongos en 4,9%. En cuanto a los mecanismos de resistencia, en los aislamientos Escherichia coli y Klebsiella peumoniae se encontró producción de Beta Lactamasas de Espectro Extendido (BLEEs) en 17,5 y 13,8%; Carbapenemasas tipo KPC en 1,25 y 2,8% respectivamente. En cuanto a Staphylococcus aureus, se encontró resistencia a meticilina en 6,8% de los aislamientos. Mortalidad asociada a infección en 16,5% de los casos. Conclusión: En pacientes con Neoplasias Hematológicas con neutropenia febril post quimioterapia en el Hospital Universitario de San Ignacio encontramos alta probabilidad de documentación de foco infeccioso, con predominio de microorganismos gram negativos, especialmente enterobacterias; con comportamiento similar en pacientes post trasplante de precursores hematopoyéticos.

Objective: To describe the demographic and clinical characteristics, as well as frequency and type of bacterial isolate and resistance patterns in patients with hematological neoplasms complicated by febrile neutropenia at San Ignacio University Hospital Methods: This is a retrospective observational study. Data were collected from medical records of adult patients admitted in the Hemato-oncology and Bone Marrow Transplant Unit. Inclusion criteria was presence of febrile neutropenia in the setting of a hematological neoplasm from January 2013 to December 2014. Results: 345 episodes of febrile neutropenia from 193 patients were studied. An infectious focus was identified in 68.1% of episodes, and a bacterial isolate was obtained in 62.9% of episodes. The predominant microorganisms were gram-negative rods, gram-positive cocci, and fungi with a frequency of 63.7%, 27.9%, and 4.9% respectively. In term of resistance patterns, Escherichia coli and Klebsiella peumoniae isolates had a frequency of ESBL susceptibility pattern of 17.5% and 13.8% respectively; and a frequency of KPC susceptibility pattern of 1.25% and 2.8% respectively. The frequency of methicillin resistant Staphylococcus aureus was 6.8%. Death associated to infection ocurred in 16.5% of episodes. Conclusions: In patients with hematological neoplasms complicated by febrile neutropenia at San Ignacio University Hospital, we found a high rate of documentation of infectious focus, with a predominance of gram-negative rods, specially Enterobacteriacea; with a similar pattern in receptors of hematopoietic stem cell transplantation.

Treatment of 30 elderly patients with advanced myeloid neoplasm by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm. Methods: From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively. 18 patients received RIC while 12 patients received MAC conditioning regiments consisted of Busulfan, cytarabine, fludarabine or clarithromycin±TBI, respectively. Results: Five patients died early in the conditioning stage, 24 patients successfully engrafted. The median time of neutrophil engraftment was 14(10-18) d, whereas platelet engraftment was 15(10-19) d. Six cases (25%) experienced aGVHD grades Ⅱ, 8 cases (32%) cGVHD, including moderate to severe cGVHD in 2 cases (8%). Seven, 7 and 5 cases developed CMV viremia, pneumonia and herpeszoster, respectively after transplantation, but no patients died of infections. The median follow-up time of the patients was 7(0.5-38) months. Twenty-one patients were still alive. The estimated 2 years OS and LFS were 62.5% (95% CI 39.2%-85.8%) and 59.2% (95% CI 26.9%-91.5%), respectively. Univariate analysis showed that HCT-CI was the only factor influencing OS. Conclusion: Allogeneic hematopoietic stem cell transplantation could improve the survival of elderly patients with myeloid neoplasm.

Treatment of 30 elderly patients with advanced myeloid neoplasm by allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm.@*Methods@#From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively. 18 patients received RIC while 12 patients received MAC conditioning regiments consisted of Busulfan, cytarabine, fludarabine or clarithromycin±TBI, respectively.@*Results@#Five patients died early in the conditioning stage, 24 patients successfully engrafted. The median time of neutrophil engraftment was 14(10-18) d, whereas platelet engraftment was 15(10-19) d. Six cases (25%) experienced aGVHD grades Ⅱ, 8 cases (32%) cGVHD, including moderate to severe cGVHD in 2 cases (8%). Seven, 7 and 5 cases developed CMV viremia, pneumonia and herpeszoster, respectively after transplantation, but no patients died of infections. The median follow-up time of the patients was 7(0.5-38) months. Twenty-one patients were still alive. The estimated 2 years OS and LFS were 62.5% (95% CI 39.2%-85.8%) and 59.2% (95% CI 26.9%-91.5%), respectively. Univariate analysis showed that HCT-CI was the only factor influencing OS.@*Conclusion@#Allogeneic hematopoietic stem cell transplantation could improve the survival of elderly patients with myeloid neoplasm.

A case of multiple myeloma in a poultry worker

BACKGROUND: Livestock breeders including poultry workers are exposed to various agricultural chemicals including pesticides and/or organic solvents. Multiple myeloma is a rare disease in Korea, and few reports have investigated the influence of occupational exposures on multiple myeloma occurrence. CASE PRESENTATION: A 61-year-old male poultry farm worker presented with bone pain and generalized weakness. A bone marrow biopsy was performed, and he was diagnosed with multiple myeloma. The patient had worked in a poultry farm for 16 years and was exposed to various pesticides and organic solvents such as formaldehyde without any proper personal protective equipment. Results of the work reenactment revealed that the concentration of formaldehyde (17.53 ppm) greatly exceeded the time-weighted average (0.5 ppm) and short-term exposure limit (1.0 ppm) suggested in the Korean Industrial Safety and Health Act. CONCLUSIONS: This case report suggests that poultry workers may be exposed to high levels of various hazardous chemicals including pesticides and/or organic solvents. Numerous previous studies have suggested an association between multiple myeloma and exposure to agricultural chemicals; thus, multiple myeloma in this patient might have resulted from the prolonged, high exposure to these chemicals.

Two Cases of Saccharomyces cerevisiae Fungemia in Patients with Hematologic Malignancies / 감염과화학요법

Saccharomyces cerevisiae, also known as "baker's yeast" or "brewer's yeast", and is considered to be a frequent colonizer of human mucosal surfaces. Although it is a very uncommon cause of infections in humans, it can cause wide range of clinical syndromes, including pneumonia, empyema, liver abscess, peritonitis, urinary tract infection, cellulitis, unexplained fever, or septic shock, particularly in immunocompromised hosts. Fungemia is the most severe and well-proven manifestation of S.cerevisiae infections. According to previous studies, the conditions related to immunosupression, such as cancer, HIV infection, use of corticosteroid, neutropenia, stem cell transplantation, solid organ transplantation, burns and heart surgery, appear to be predisposing factors to fungemia. The antifungal agent of choice has not been established. We report two cases of S.cerevisiae fungemia in patients with hematologic malignancies. One was primary fungemia, and the other was presumed to be a catheter related one. Both cases showed a good prognosis with the complete negative conversion of fungemia.

Molecular approach to diagnose BCR/ABL negative chronic myeloproliferative neoplasms

Chronic myeloproliferative neoplasms arise from clonal proliferation of hematopoietic stem cells. According to the World Health Organization myeloproliferative neoplasms are classified as: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, hypereosinophilic syndrome, mast cell disease, and unclassifiable myeloproliferative neoplasms. In the revised 2008 WHO diagnostic criteria for myeloproliferative neoplasms, mutation screening for JAK2V617F is considered a major criterion for polycythemia vera diagnosis and also for essential thrombocythemia and primary myelofibrosis, the presence of this mutation represents a clonal marker. There are currently two hypotheses explaining the role of the JAK2V617F mutation in chronic myeloproliferative neoplasms. According to these theories, the mutation plays either a primary or secondary role in disease development. The discovery of the JAK2V617F mutation has been essential in understanding the genetic basis of chronic myeloproliferative neoplasms, providing some idea on how a single mutation can result in three different chronic myeloproliferative neoplasm phenotypes. But there are still some issues to be clarified. Thus, studies are still needed to determine specific molecular markers for each subtype of chronic myeloproliferative neoplasm.

Linfomas extranodales en el Área Metropolitana de Bucaramanga: 2000-2004 / Extranodal lymphomas in Bucaramanga Metropolitan Area: 2000-2004

Antecedentes: Los linfomas extranodales (LEN) se localizan en cualquier sitio diferente a los ganglios linfáticos, como el tracto gastrointestinal (TGI) y la piel; la mayoría son de tipo linfoma no Hodgkin (LNH). Representan entre el 25-45% de todos los LNH, y el subtipo histopatológico más frecuente corresponde a linfoma difuso de células B grandes (LDCBG). El objetivo de este estudio es identificar algunas características socio-demográficas de los pacientes con linfomas extranodales residentes en el Área Metropolitana de Bucaramanga (AMB), así como otras características propias de los LEN. Metodología: Usando los datos recolectados en el RPC - AMB se calcularon frecuencias de algunas variables (sexo, edad, localización anatómica, tipo histopatológico) de los LEN. Resultados: entre los años 2000-2004 se detectaron 247 casos de linfomas; 72 (29%) correspondieron a LEN. El 58% de los casos ocurrieron en hombres y el 42% en mujeres. Se encontró predominio de la enfermedad en la 6a y 7a década de la vida. Los sitios de mayor presentación fueron TGI (29%), piel (14%), y tejidos blandos (14%). Las clasificaciones más frecuentes para los LEN fueron LNH - NOS (No especificado) (27,7%) y linfoma difuso de células B grandes (19,4%). Conclusiones: Se encontraron semejanzas en las características de los LEN - NH comparado con los datos registrados a nivel mundial. Es necesario promover la implementación de métodos diagnósticos avanzados para este tipo de neoplasias. [Uribe CJ, García CA, Meza EE, Camacho RM, Acevedo DJ. Linfomas extranodales en el Área Metropolitana de Bucaramanga: 2000-2004. MedUNAB 2009; 12:19-21].

Background: Extranodal Lymphomas (ENL) are localized in any site different to the lymph nodes, as the Gastrointestinal Tract and the skin, and in the majority of the cases are Non Hodgkin Lymphoma (NHL). They represent between 25-45% of all the cases of NHL, and the most frequent histopathologycal subtype is the diffuse large-B-cell lymphoma (DLBCL). The purpose of this study is to identify some socio-demographic characteristics and other that are inherent to the ENL in this geographical region between 2000-2004. Methodology: Using data collected by RPC - AMB, were calculated frequencies of some variables (sex, age, anatomic localization, and histopathologycal type). Results: 247 cases of lymphomas were detected between 2000-2004, 72 (29%) were EN-NHL. Men were most frequently affected than women, with 59% and 41% respectively. The disease was most frequent in the 6th and 7th decade of the life. The most involved anatomical sites were the GIT (29%), the skin (14%), and soft tissues (14%). The most frequent histopathologycal types were NHL - NOS (Not Otherwise Specified) (30,4%), DLBCL (15,1%), and Malignant Lymphoma - NOS (13,5%). Conclusions: compared with worldwide data, our study presents similar characteristics of the ENL. It is necessary to promote the improvement in advance diagnosis methods for this kind of neoplasm. [Uribe CJ, García CA, Meza EE, Camacho RM, Acevedo DJ. Extranodal lymphomas in Bucaramanga Metropolitan Area: 2000-2004. MedUNAB 2009; 12:19-21].