IL-8 in bone marrow and peripheral blood of patients with B-cell acute lymphoblastic leukemia is associated with high regulatory T cell counts, degree of tumor infiltration and expression of CXCR1 in blasts.

INTRODUCTION: Regulatory T cells (Treg cells) in a tumor environment and the expression of forkhead box P3 (FOXP3) in tumor cells have been associated with a poor prognosis. There are few studies evaluating Treg cells and FOXP3 in B-cell acute lymphoblastic leukemia (B-cell ALL). This study aimed to evaluate the frequencies of Treg cells in bone marrow (BM) and peripheral blood (PB) of patients with B-cell ALL and to determine their associations with the circulating cytokine profile and the expression of CXCR1 (IL-8 receptor) in Treg cells, as well as to compare FOXP3 expression in blasts of patients with B-cell ALL and normal lymphoid precursors. METHODS: Samples of BM and PB from patients with B-cell ALL and healthy controls were studied. Treg cells, cytokines, FOXP3 and CXCR1 were evaluated using flow cytometry and analyzed. RESULTS: A total of 20 patients with B-cell ALL and 10 healthy controls were included. In B-cell ALL patients, Treg cell frequencies increased significantly, with higher percentages in the PB. Absolute Treg cell counts were associated with absolute blast counts in the BM and PB and with an IL-8 concentration. The IL-8 and IL-6 levels were associated with the CXCR1 expression in PB Treg cells. In addition, a greater expression of FOXP3 was observed in leukemic blasts than in normal lymphoid precursors. CONCLUSIONS: These results suggest that the presence of Treg cells and cytokines in the tumor environment may correspond to mechanisms to evade the immune response. For that reason, it would be important to monitor these parameters in B-cell ALL to establish their effect on the disease prognosis.

Influence of Dose Intensity in Consolidation with HIDAC and Other Clinical and Biological Parameters in the Survival of AML.

BACKGROUND: The impact of the dose intensity administered in consolidation in Latin America is unknown. This study aimed to evaluate the relative dose intensity (RDI) in consolidation and its impact in overall survival. METHODS: A retrospective study of 86 patients with AML who were diagnosed between 2010 and 2016 with a 2-year follow-up in a fourth-level Colombian hospital was carried out. Clinical characteristics were reported, Kaplan-Meier was used for estimating the overall survival, and Cox regression was used for multivariate analysis. RESULTS: The median overall survival (OS) was 20.83 months, and the median event-free survival (EFS) was 16.83 months. 64.3% of the patients achieved remission after the 7 + 3 chemotherapy induction treatment. Patients under 30 years of age, with white blood cell counts less than 100.000 cells/mm3 who responded to induction treatment had a better OS. Additionally, patients receiving an RDI greater than 0.75 of the planned consolidation dose had better survival. The prognostic variables with impact in the OS were the leukocyte count in peripheral blood at diagnosis, the RDI in consolidation treatment with HIDAC and the response obtained after induction. CONCLUSION: This retrospective study allowed us to know the epidemiology of AML in a reference Colombian Hospital. Additionally, in our knowledge, it is the first study that reports the RDI in consolidation with HIDAC in Latin America as a prognostic factor that directly impacts the OS.

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.

Profilaxis de la candidiasis orofaríngea en pacientes con terapia antineoplásica. Estudio doble ciego comparativo con fluconazol vs placebo

OBJETIVO: demostrar la eficacia y seguridad del fluconazol en la profilaxis de la candidiasis orofaríngea en pacientes con neoplasia hematológica e inmunosuprimidos médicamente. DISEÑO: estudio doble ciego, prospectivo, comparativo con placebo. UBICACION: consulta externa de las instituciones que que participaron. PACIENTES: 53 pacientes ambulatorios con neoplasia hematológica, sin candidiasis orofarígea, comprobada por microbiología, a los cuales se les iniciaba ciclo terapéutico con antineoplásicos. INTERVENCION: doble ciego al azar; administración de 10 ml de jarabe en dosis única diaria conteniendo 50 mg de fluconazol o excipientes, durante todo el período de tratamiento antimicótico tópico o sistémico asociado. PRINCIPAL RESULTADO A EVALUAR: evitar la candidiasis orofarígea. RESULTADOS: 53 pacientes estudiados; 26 recibieron fluconazol y 27 placebo, CLINICA:ninguno de los pacientes que recibieron fluconazol presentó cuadro clínico durante tratamiento; cuatro de los que recibieron placebo sí la presentaron (p<0.02 en favor de fluconazol); adicionalmente, una paciente presentó candiduria y cuadro séptico, obligando a abrir el código. Fue tratada con fluconazol parenteral y curó en corto tiempo. MICROBIOLOGIA: frotis pretratamiento: un paciente colonizado en el grupo placebo (X²=no significativo); postratamiento, cuatro pacientes del grupo placebo tenían presencia de levaduras (P<0.05,en favor de fluconazol). Solo uno de los cultivos pretratamiento se apreció crecimiento, uno de ellos masivo (p<0.05,en favor de fluconazol). SEGURIDAD : cuatro pacientes presentaron eventos adversos. Tres fueron en el grupo que recibió fluconazol, uno de los cuales presentó vómito severo que obligo a la suspensión del tratamiento; otro, disnea moderada asociada a obstrucción de vías aéreas por reacción anafiláctica relacionada con administración concomitante de penicilina, y otro ictericia leve, que cedió espontáneamente al suspender el tratamiento. El otro paciente, que estaba recibiendo placebo, presentó dolores abdominales, tipo cólico, posiblemente relacionados con el empleo concomitante de un antiparasitario. CONCLUSIONES : el fluconazol en dosis única diaria de 50 mg durante el período de terapía inmunosupresora, demostró ser eficaz como profiláctico de la candidiasis orofaríngea, además de fácil cumplimiento por el paciente y muy bien tolerado.