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.

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.

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.

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.