D-index as a Risk Factor for Invasive Fungal Infections in Patients With Acute Lymphoblastic Leukemia From a Reference Hematology Center in Bogota.

Introduction Patients with hematologic malignancies are susceptible hosts for the development of invasive fungal infection (IFI), one of the main life-threatening infectious complications faced by these patients. Currently, we have antifungal prophylaxis strategies and antifungal treatment schemes and we recognize that the main risk factor involved is profound and prolonged neutropenia. D-index and cumulative D-index are quantitative parameters, which determine the magnitude of neutropenia, as a function of duration and depth and their value correlates with the occurrence of IFI. Material and methods A case-control study in patients older than 18 years with acute lymphoblastic leukemia (ALL) was admitted between 2009 and 2019 at the National Cancer Institute for induction, consolidation and salvage chemotherapy. Results A total of 167 patients were included, who received 288 cycles of chemotherapy, the latter were considered the unit of analysis. A generalized estimating equations (GEE) model was designed to analyze correlated data; three quantitative and continuous variables of interest were included in this model: age (years), D-index and deep neutropenia (days). For the population D-index, an odds ratio (OR) = 1.000227 (95% CI 1.0002-1.0004); p < 0.001 was obtained. Conclusion D-index is associated with the development of IFI in patients with ALL, with an exponential increase in OR as the absolute value of the D-index increases.

Expert Recommendations for the Diagnosis, Treatment, and Management of Adult B-Cell Acute Lymphoblastic Leukemia in Latin America.

PURPOSE: Despite strong induction chemotherapy response rates, only 30%-40% of patients with adult B-cell acute lymphoblastic leukemia (ALL) attain long-term remission. This study analyzes ALL in Latin America (LA) and recommends diagnosis, treatment, and management protocols. METHODS: The Americas Health Foundation organized a panel of hematologists from Argentina, Brazil, Chile, Colombia, and Mexico to examine ALL diagnosis and therapy and produce recommendations. RESULTS: Lack of regional data, unequal access to diagnosis and therapy, inadequate treatment response, and uneven health care distribution complicate adult ALL management. The panel recommended diagnosis, first-line and refractory treatment, and post-transplantation maintenance. Targeted treatments, including rituximab, blinatumomab, and inotuzumab ozogamicin, are becoming available in LA and must be equitably accessed. CONCLUSION: This review adapts global information on treating ALL to LA. Governments, the medical community, society, academia, industry, and patient advocates must work together to improve policies.

Pregnancy and Delivery Management With Recombinant Factor VIIa in a Glanzmann Thrombasthenia Patient: A Case Report.

The management of pregnancy and delivery in patients with Glanzmann thrombasthenia requires platelet transfusion and recombinant activated factor VII. We report two successful pregnancies in a single patient and propose a protocol for monitoring and treatment. The urgent need for controlled trials and other epidemiological studies is also underscored.

Primary Leptomeningeal B-cell Lymphoma in an Immunocompetent Adult: Case Report.

Primary leptomeningeal lymphoma (PLML) is a rare disease, comprising less than 1% of all lymphomas. Clinical manifestations include headache, encephalopathy, ataxia, cranial nerve palsy, and myelitis. Diagnosis requires a combination of magnetic resonance images (MRI), cytology, flow cytometry of cerebrospinal fluid (CSF), and an extensive workup to rule out systemic lymphoma. We describe the case of a 49-year-old man who developed subacute onset headache, encephalopathy, and blindness. Whole-body examinations, including a bone marrow trephine biopsy, excluded systemic lymphoma. Brain MRI showed leptomeningeal enhancement. Cytology and flow cytometry of CSF found a clonal B-cell population making a diagnosis of PLML. He began treatment with rituximab and high-dose methotrexate (HD-MTX), with progressive clinical improvement. CSF analysis after two cycles and one intrathecal methotrexate dose was normal. Brain and spinal MRI images plus CSF analysis, along with an extensive workup to exclude systemic lymphoma, are necessary to diagnose PLM. Early treatment with HD-MTX alone or in combination with rituximab improves clinical outcomes.

Local Control of Primary Dural Central Nervous System Lymphoma Achieved With Radiotherapy.

Primary central nervous system lymphomas (PCNSL) are extranodal non-Hodgkin's lymphomas (NHL) confined to the brain, leptomeninges, eyes, or spinal cord. Primary leptomeningeal lymphoma (PLML), without parenchymal involvement, synchronous cerebrospinal, or systemic disease is rare. The estimated incidence of PLML is 7% of all PCNSL, which in turn accounts for about 2% of all primary brain tumors and 0.8% of all lymphomas. The incidence of PCNSL in Western countries is approximately five cases per million inhabitants per year, and less than 5% of all primary tumors of the central nervous system (CNS), although it is worth mentioning that the incidence seems to be increasing. The largest series of cases reported in the medical literature collect information from no more than nine patients; in these series, the median age at diagnosis is 57 years; in general, all patients present with cerebrospinal fluid alteration, and the median overall survival rate is close to eight months. With our case series, we aim at sharing the experience of four patients diagnosed and treated at the National Cancer Institute between 2010 and 2020, establishing a correlation of the clinical, imaging, and histopathological presentation, the response to treatment based on radiotherapy and chemotherapy, and the clinical outcomes reported in the medical records.

Validation of the FACT-Lym scale to measure quality of life in Colombian patients with lymphoma / Validación de la escala FACT-Lym para la evaluación de la calidad de vida en pacientes colombianos con linfoma

Abstract Introduction: Instruments for measuring quality of life must be validated before being used in different cultural contexts. There is a specific scale (FACT-Lym) to assess health-related quality of life (HRQOL) in patients with lymphoma, but it has not been validated in Colombia yet. Objective: To determine the clinimetric properties of the FACT-Lym scale in Colombian patients with lymphoma. Materials and methods: A validation study of a scale was conducted based on the classical test theory. The FACT-Lym scale was administered to 301 patients diagnosed with different types of lymphomas and treated at the National Cancer Institute of Colombia, and their sociodemographic and clinical data were recorded. The statistical analysis included exploratory factor analysis, confirmatory factor analysis, construct validity, internal consistency, test-re-test reliability and sensitivity to change. Results: The exploratory factor analysis confirmed a two-factor structure of the scale, while the confirmatory analysis showed adequate adjustment of the model. Internal consistency was measured using the Cronbach's alpha coefficient (>0.8 on the global scale and on each of the factors). Correlation values significantly different from zero were found between the FACT-Lym scale and the FACT-G scale domains. No significant changes were observed in any domain of the FACT-Lym scale after the completion or suspension of treatment. Conclusions: The validation of the FACT-Lym questionnaire in Colombia showed it has a consistent factorial structure and adequate reliability. However, its sensitivity to change should be verified by evaluating its performance in other patient groups.

Resumen Introducción. Los instrumentos para medir la calidad de vida se deben validar antes de ser utilizados en diferentes contextos culturales. En la actualidad existe una escala específica (FACT-Lym) para medir la calidad de vida en pacientes con linfoma, sin embargo esta no ha sido validada en Colombia. Objetivo. Establecer las propiedades clinimétricas de la escala FACT-Lym en pacientes colombianos con linfoma. Materiales y métodos. Se realizó un estudio de validación de escalas según la teoría clásica de test. Se aplicó la escala FACT-Lym a 301 pacientes del Instituto Nacional de Cancerología diagnosticados con diferentes tipos de linfoma y se registraron sus datos sociodemográficos y clínicos. El análisis estadístico incluyó análisis factorial exploratorio, análisis factorial confirmatorio, validez de constructo, consistencia interna, confiabilidad test re-test y sensibilidad al cambio. Resultados. El análisis factorial exploratorio confirmó una estructura de dos factores de la escala, mientras que el análisis confirmatorio mostró un adecuado ajuste del modelo estructural. La consistencia interna se midió con el coeficiente alfa de Cronbach (>0.8 en la escala global y en cada uno de los factores). Se encontraron valores de correlación significativamente diferentes a cero entre la FACT-Lym y los dominios de la escala FACT-G. No se observaron cambios significativos en ninguno de los dominios de la FACT-Lym luego de completar o suspender el tratamiento. Conclusiones. La validación de la escala FACT-Lym en Colombia mostró que esta tiene una estructura factorial consistente y una adecuada confiabilidad. Sin embargo, su sensibilidad al cambio debe verificarse evaluando su desempeño en otras poblaciones.

A Retrospective Analysis of the Treatment Approach to Immune Thrombocytopenia in the Real World.

Introduction Immune thrombocytopenia (ITP) is an acquired cause of thrombocytopenia in both the adult and children populations due to the accelerated destruction of platelets and/or suppressed platelet production. We present a retrospective analysis of a case series of patients in a single teaching institution with the objective of describing the clinical characteristics and different treatment approaches of patients with ITP. Methods A review of electronic health records was performed in the University Hospital Samaritana, Bogota, for inpatients between 2013 and 2016. Data were extracted for the patients with an ITP diagnosis for variables previously chosen and reviewed for descriptive analysis.  Results A total of 55 patients were diagnosed with ITP; of these, 67.3% were female and the median age of this group of patients was 48 years. The majority presented with severe thrombocytopenia with 80% of patients having platelets less than 30000/µL. Of the 55 patients with a final diagnosis of ITP, only 54 received dexamethasone, methylprednisolone, or prednisone as the first-line treatment. The increment in platelet count after seven days of treatment was greater in the group treated with dexamethasone. Conclusion The diagnosis of ITP is of exclusion, there is no gold standard test, however, as it was shown in our results, various unnecessary studies are performed that increase costs during the diagnostic approach. Evidence supports that treatment with high-dose dexamethasone is associated with faster short- and greater long-term efficacy as compared to other steroids, however, it is not always the first choice in real-world patients. It is our belief that the implementation of a guideline will reduce testing and costs, and ensure better treatment options for our patient population.

Myelomastocytic Blast Cell Crisis in Resistant Tyrosine Kinase Inhibitor Chronic Myelogenous Leukemia: Case Report and Review of Literature.

We present the clinical case of a 29-year-old male with a diagnosis of chronic myeloid leukemia (CML) in high-risk chronic phase since February 2010. He started treatment with imatinib at a dose of 400 mg obtaining a hematologic response early but without reaching a cytogenetic response in month 18. Then, dasatinib was prescribed. The BCR-ABL transcription level of 58% was documented. It was decided to start treatment with nilotinib but in March 2017 we diagnosed a progression to blast crisis (BC) of myeloid origin with a bone marrow study that documented 72% of blasts with normal karyotype, also very striking, the concomitant skin infiltration, bone lesions of lytic type and hypercalcemia that required the use of zoledronic acid as an emergency. At the end of chemotherapy induction with 7 + 3 (seven days of cytarabine and three days of idarubicin) chemotherapy associated with bosutinib for 14 days and after several infectious complications, we documented a percentage of blasts by flow cytometry of 29% in the bone marrow and the existence of 46% of cells with basophilic characteristics versus mast cells. A basophilic transformation was suspected versus aggressive systemic mastocytosis with a clonal, nonmastocytic hematological disorder. Levels of serum tryptase and mutation D816V C KIT were requested, which were not possible to perform. Treatment with CLAG-M was proposed, however, the patient died early with hyperleukocytosis and severe thrombocytopenia with central nervous system bleeding.

Acquired Hemophilia Secondary to Soft-tissue Sarcoma: Case Report from a Latin American Hospital and Literature Review.

Acquired hemophilia A is a rare bleeding disorder caused by inhibiting antibodies against factor VIII characterized by the presence of severe bleeding, which in occasions can be lethal. The bleeding manifestations typically have a sudden onset and patients have a negative family and personal histories of bleeding, with a normal prothrombin time (PT) and an extended partial thromboplastin time (PTT). Incidence has been calculated to be between 0.2 and 1.48 cases per million per year. Between 6% and 15% of cases are associated with neoplasms. Here, we present a 52-year-old male with back myxofibrosarcoma who developed acquired hemophilia without response to treatment used and ultimately died. The most common cancers associated with acquired hemophilia are lung and prostate cancer. We found one other case of a patient with Kaposi's sarcoma that was unassociated with HIV infection who presented with severe postoperative bleeding. For bleeding in acquired hemophilia A, the treatments of choice are "bypass" agents, such as recombinant-activated factor VIII (rFVIIa) or activated prothrombin complex concentrate. Any delay in the start of treatment or the usage of insufficient doses is associated with the progression of bleeding symptoms and worsening general condition. In the case of acquired hemophilia secondary to neoplasia, it is recommended that immunosuppressive therapy to eradicate the inhibitors be combined with treatment for the underlying neoplastic disease. In our patient, it was not possible to offer a surgical treatment that enabled the control of the neoplasia, nor he was considered a candidate for chemotherapy or radiotherapy, limiting the treatment to immunosuppressive and "bypass" management.

La leucemia linfoblástica aguda y modelos animales alternativos para su estudio en Colombia / Alternative animal models for acute lymphoblastic leukaemia studies in Colombia

Resumen El pez cebra es un modelo establecido para el estudio del desarrollo en vertebrados y es especialmente útil para la investigación del proceso de hematopoyesis y las enfermedades asociadas a esta. Los linajes principales, los genes y los procesos de desarrollo con los seres humanos son conservados. En los últimos años, el pez cebra se ha utilizado cada vez más como un modelo para estudiar enfermedades hematopoyéticas humanas, incluyendo la leucemia linfoblástica aguda. Esta revisión evidencia la importancia del estudio de esta enfermedad en Colombia debido a las diferencias de la etiología que presenta este tipo de leucemia en comparación con otros países. Además, describe la aplicación del pez cebra como una herramienta alternativa para investigaciones preclínicas de la leucemia linfoblástica aguda. Este modelo es asequible, facilita la experimentación, su manipulación es relativamente simple y tiene gran versatilidad para estudios moleculares y genéticos del cáncer y está disponible en Colombia.

Abstract The zebrafish is an established model for the study of vertebrate development, and it is specially useful for the research into haematopoiesis and diseases associated with this process. Major lineages, genes, and developmental processes are conserved between zebrafish and humans. Thus it has been increasingly used as a model for a number of haematopoietic human diseases, such as acute lymphoblastic leukaemia. This review highlights the importance of the study of this disease in Colombia, because of the differences in its aetiology compared to other countries. It also describes the application of the zebrafish as an alternative tool for pre-clinical research of acute lymphoblastic leukaemia. This model is affordable, facilitates experimentation and handling, and is extremely versatile for molecular and genetic studies into cancer, and it is now available in Colombia.

Prognostic stratification improvement by integrating ID1/ID3/IGJ gene expression signature and immunophenotypic profile in adult patients with B-ALL.

BACKGROUND: Survival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction. METHODS: To improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples. RESULTS: Both techniques were correlated to stratify patients into prognostic groups. An inverse relationship between survival and expression of the three-genes signature was observed and an immunophenotypic profile associated with clinical outcome was identified. Markers CD10 and CD20 were correlated with simultaneous overexpression of ID1, ID3 and IGJ. Patients with simultaneous expression of the poor prognosis gene signature and overexpression of CD10 or CD20, had worse Event Free Survival and Overall Survival than patients who had either the poor prognosis gene expression signature or only CD20 or CD10 overexpressed. CONCLUSION: By utilizing the combined evaluation of these two immunophenotypic markers along with the poor prognosis gene expression signature, the risk stratification can be significantly strengthened. Further studies including a large number of patients are needed to confirm these findings.

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax.

High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia.

BACKGROUND: B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30% lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61% of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. METHODS: We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). RESULTS: We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. CONCLUSIONS: Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.

Resultados del tratamiento del linfoma de células del manto con varios regímenes de inmunoquimioterapia: estudio retrospectivo / Results of mantle cell lymphoma treated with various immunochemotherapy regimens: A retrospective stud

Objetivos: Describir las características clínicas y los resultados del tratamiento inicial de los pacientes con linfoma de células del manto atendidos en el Instituto Nacional de Cancerología (INC) entre los años 2007 y 2011. Métodos: Estudio descriptivo y retrospectivo, tipo serie de casos basado en fuentes secundarias institucionales. Resultados: Se incluyeron 41 pacientes con una edad promedio de 60,5 años (DE ±10,5) y que tenían en su mayoría un estado funcional adecuado. La mayor parte tenía enfermedad avanzada al momento de la presentación (85%). El compromiso de la médula ósea y la afectación extranodal fueron frecuentes, encontrándose en 73% y 39% respectivamente. El diagnóstico histopatológico de la malignidad se realizó en tejido ganglionar en la mayoría de los casos (56%). Los esquemas de quimioterapia de primera línea empleados con más frecuencia fueron R-CHOP y R-HyperCVAD, en 37% y 29% de los casos respectivamente. Tras la quimioterapia de primera línea se logró alcanzar una respuesta completa en 64% de los pacientes, la mediana de duración de la primera remisión fue 9 meses (RIQ0,9 - 15). La neutropenia febril fue una complicación común presentándose en 42% de los casos. Dieciocho individuos recibieron quimioterapia de segunda línea, los esquemas más frecuentemente empleados fueron R-DHAP y R-HyperCVAD. Conclusiones: Las características clínicas de los pacientes son similares a las descritas en series de referencia. Las tasas de respuesta completa y la duración de la primera remisión son inferiores a las publicadas por otros grupos con esquemas similares de tratamiento. © 2014 Instituto Nacional de Cancerología.

Objective: To describe the clinical features and the treatment results achieved with the initial therapy among patients with mantle cell lymphoma treated at the National Cancer Institute (INC) between 2007 and 2011. Methods: Descriptive study, based on secondary institutional sources. Results: A total of 41 patients were included, with a mean age of 60.5 years (Standard deviation SD ± 10.5) and a good functional status. Most of them had advanced disease at initial presentation (85%). Bone marrow involvement and extra-nodal disease were frequent, as they were seen in 73% and 39% of the patients, respectively. Histopathological diagnosis of the malignancy was mainly made on lymph node tissue (56%). First line chemotherapy regimens used with an increased frequency were R CHOP and R- HyperCVAD, in 37% and 29% of the cases, respectively. After first line therapy, a complete response was achieved in 64% of the patients, median duration of the first remission was 9 months (Interquartile range IQR 0.9 - 15). Febrile neutropenia was a frequent complication, seen in 42% of the cases. Eighteen individuals received a second line of chemotherapy, with R DHAP and R HyperCVAD being the regimens most commonly administered. Conclusions: The clinical features of the patients are similar to those described in larger series of patients with the disease described elsewhere. The rate of complete responses, as well as the duration of the first remission after chemotherapy, is inferior when compared with the results of other groups that used similar treatment regimens.

Guía de práctica clínica para el diagnóstico y el tratamiento de las infecciones bacterianas y micóticas en pacientes oncológicos mayores de 15 años con neutropenia febril posquimioterapia de alto riesgo / Recommendations for diagnosis and treatment of bacterial and fungal infections in cancer patients older than 15 years with febrile neutropenia after high-risk chemotherapy: A Clinical Practice Guideline

Objetivos: El tratamiento actual de las neoplasias busca mejorar la sobrevivencia mediante la aplicación de esquemas de quimioterapia intensificada, que produce una neutropenia más profunda y duradera, que favorece el desarrollo de infecciones bacterianas y micóticas invasoras. Este artículo resume las recomendaciones de una guía para el diagnóstico y tratamiento de las infecciones bacterianas y micóticas en pacientes oncológicos mayores de 15 años con neutropenia febril posquimioterapia de alto riesgo. Métodos: Guía de práctica clínica basada en la evidencia. Se realizó la definición de preguntas clínicas, la búsqueda sistemática de literatura, la evaluación crítica de la evidencia y la formulación de recomendaciones. Se desarrolló una evaluación económica sobre la eficiencia de dos esquemas diferentes de tratamiento antimicótico. Resultados: El presente documento incluye recomendaciones para el diagnóstico de infecciones bacterianas y micóticas en paciente con neutropenia, el uso de profilaxis antibiótica y antimicótica, el tratamiento antibiótico empírico, y el tratamiento antimicótico empírico y anticipado en pacientes mayores de 15 años, acorde con la microbiología del contexto colombiano. Conclusiones: La implementación oportuna de las recomendaciones de la guía acorde con el contexto clínico de cada paciente debe contribuir a mejorar la supervivencia y morbilidad infecciosa de los pacientes con neutropenia febril derivada de la quimioterapia.

Objective: Current cancer treatment is intended to improve survival by implementing intensified chemotherapy strategies, which increases the likelihood of neutropenia and favors the development of bacterial and invasive fungal infections. This paper summarizes clinical practice guideline recommendations for the diagnosis and treatment of bacterial and fungal infections in patients older than 15 years with febrile neutropenia after high risk chemotherapy. Methods: Evidence-based clinical practice guideline. A set of clinical questions was defined, a literature search performed, critical appraisal of the evidence, as the development of recommendations. An economic assessment was carried out on two alternative schemes for fungal therapy. Results: This article includes recommendations for the diagnosis of bacterial and fungal infections in neutropenic patients, prophylaxis for bacterial and fungal infections, empiric antimicrobial treatment, empiric and anticipated antifungal therapy in patients over 15 years, according to the microbiology setting in Colombia. Conclusions: Timely implementation of these recommendations according to each clinical context, should contribute to improve survival and reduce infection-derived morbidity in patients with chemotherapy-induced febrile neutropenia.

Platelets promote mitochondrial uncoupling and resistance to apoptosis in leukemia cells: a novel paradigm for the bone marrow microenvironment.

Here we report that leukemia cell lines and primary CD34+ leukemic blasts exposed to platelet rich plasma (PRP) or platelet lysates (PL) display increased resistance to apoptosis induced by mitochondria-targeted agents ABT-737 and CDDO-Me. Intriguingly, leukemia cells exposed to platelet components demonstrate a reduction in mitochondrial membrane potential (ΔΨM) and a transient increase in oxygen consumption, suggestive of mitochondrial uncoupling. Accompanying the ranolazine-sensitive increase in oxygen consumption, a reduction in triglyceride content was also observed in leukemia cells cultured with platelet components indicating that lipolysis and fatty acid oxidation may support the molecular reduction of oxygen in these cells. Mechanistically, platelet components antagonized Bax oligomerization in accordance with previous observations supporting an antiapoptotic role for fatty acid oxidation in leukemia cells. Lastly, substantiating the notion that mitochondrial uncoupling reduces oxidative stress, platelet components induced a marked decrease in basal and rotenone-induced superoxide levels in leukemia cells. Taken together, the decrease in ΔΨM, the transient increase in ranolazine-sensitive oxygen consumption, the reduction in triglyceride levels, and the reduced generation of superoxide, all accompanying the increased resistance to mitochondrial apoptosis, substantiate the hypothesis that platelets may contribute to the chemoprotective sanctuary of the bone marrow microenvironment via promotion of mitochondrial uncoupling.

Tratamiento de rescate de leucemia aguda refractaria o en recaída con el régimen IDA-FLAG: experiencia en la rutina de los servicios / Rescue treatment in refractory or relapsed acute leukemia with the IDA-FLAG scheme: Experience in routine services

Objetivos: Describir tasas de remisión completa de pacientes con leucemia aguda refractaria o en recaída tratados con el esquema IDA-FLAG y establecer la supervivencia global y libre de evento, toxicidad y duración de la remisión completa en servicios rutinarios. Métodos: Estudio retrospectivo de pacientes mayores de 15 años. Se describen variables discretas y continuas mediante frecuencias y medidas de tendencia central. La supervivencia global y libre de evento se determinó por el método de Kaplan-Meir usando la prueba de log-Rank para la comparación entre estratos. Resultados: Fueron incluidos 64 pacientes. No hubo diferencias significativas en las tasas de remisión respecto al sexo, la edad, el tipo de leucemia o la duración de la primera remisión. La toxicidad fue principalmente hematológica y el 100% de los pacientes presentaron neutropenia febril posterior al inicio del tratamiento. La mediana de supervivencia global fue de 5,83 meses y la supervivencia libre de evento fue de 79 días. Se encontraron diferencias significativas en la supervivencia global entre el grupo de pacientes que logró y no logró remisión completa. Conclusiones: El tratamiento de rescate con el régimen IDA FLAG logra inducir remisión completa en un porcentaje significativo de pacientes con leucemia aguda en recaída, con una toxicidad aceptable siendo la principal hematológica. Es necesario realizar estudios prospectivos y con un diseño adecuado para validar la efectividad del mismo y confirmar nuestros hallazgos. © 2013 Instituto Nacional de Cancerología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Objectives: To describe complete remission rates in patients with refractory or relapsed acute leukemia following the IDA-FLAG scheme, and establish the overall and event free survival, toxicity and duration of the complete remission. Methods: Retrospective analysis of patients over 15 years old. Discrete and continuous variables are described by using frequencies and measures of central tendency. Overall and event free survival were determined with the Kaplan-Meier method using the log-Rank test for comparison among categories. Results: A total of 64 patients were included. There were no significant differences in the remission rate as regards sex, type of leukemia, or duration of the first remission. The toxicity was mainly hematological, and 100% of the patients had subsequent febrile neutropenia at the start of the treatment. The median overall survival was 5.83 months, and the event free survival was 79 days. Significant differences were found in the overall survival between the patient group that achieved complete remission and those that did not. Conclusions: Rescue treatment with the IDA-FLAG scheme managed to induce a complete remission in a significant percentage of patients with relapsed acute leukemia, with an acceptable toxicity, which was mainly hematological. Prospective studies are needed with a design suitable for validating its efficacy and to confirm our results. © 2013 Instituto Nacional de Cancerología. Published by Elsevier España, S.L.U. All rights reserved.

Valor diagnóstico del galactomanano y proteína C reactiva (PCR) en pacientes con neoplasia hematolinfoide y neutropenia con factor de riesgo de aspergilosis invasiva / Diagnostic value of galactomannan and C reactive protein (CRP) in patients with neutropenia and hematolymphoid neoplasia risk factor for invasive aspergillosis

Introducción: Es importante tener herramientas serológicas que permitan un diagnóstico precoz de la aspergilosis invasiva. Se evaluó el valor diagnóstico del galactomanano y la PCR en 36 pacientes con neoplasias hematolinfoides y neutropenia, y con factor de riesgo de aspergilosis invasiva. Métodos: Estudio observacional descriptivo de serie de casos, de pacientes neutropénicos, con títulos serológicos de galactomanano y PCR, y seguimiento por 30 días. La detección del antígeno galactomanano fue mediante de Platelia® Aspergillus, donde una DO superior a 0,550 ng/ml fue considerada positiva, y la detección de PCR, de Products VITROSchemistry®, donde resultados >1,0 mg/dl se consideraron elevados. Resultados: De acuerdo con los criterios EOR-TC, 23 pacientes fueron calificados como “sin sospecha”; 11, como “posibles”; y 2, como “probadas”. Respecto a los títulos séricos de galactomanano, 7 de los pacientes presentaron títulos >0,550 ng/ml, por lo cual se los consideró como positivos. Al comparar las funciones de supervivencia se encontró un pronóstico menos favorable en el grupo con resultados positivos. En las funciones de supervivencia, en relación con los resultados de PCR tuvieron un mejor pronóstico los miembros del grupo con PCR negativa. De los 7 pacientes que tuvieron títulos séricos positivos para galactomanano, 85,7% tuvieron títulos mayores de 9 mg/dl de PCR, lo que sugiere una relación entre estas 2 pruebas. Conclusiones: El uso de la detección de galactomanano y la PCR es útil para el diagnóstico de aspergilosis invasiva, ya que existe una correlación entre sus resultados y la evidencia clínica para el diagnóstico de la infección invasiva.