Leucemias Agudas

Sobre: Leucemia linfoblástica aguda; Linfoma linfoblástico; Leucemia mieloide aguda; Leucemia promielocítica aguda y situaciones especiales.Fil: Agriello, Evangelina Edith. No especifíca;Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bullorsky, Laura. No especifíca;Fil: Cazap, Nicolás. No especifíca;Fil: Cranco, Santiago. No especifíca;Fil: Dick, Hernán. No especifíca;Fil: Fernandez, Isolda. No especifíca;Fil: Fischman, Laura. No especifíca;Fil: Funes, María Eugenia. No especifíca;Fil: Gimenez Conca, Alberto. No especifíca;Fil: González, Jacqueline. No especifíca;Fil: Lang, Cecilia. No especifíca;Fil: Mela Osorio, María José. No especifíca;Fil: Navickas, Alicia. No especifíca;Fil: Oliveira, Natalia. No especifíca;Fil: Rey, Irene. No especifíca;Fil: Rivas, Marta. No especifíca;Fil: Suero, Alejandro. No especifíca;Fil: Zanella, Lorena. No especifíca

In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy

IntroductionTreatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase is considered a safe option if suitable molecular monitoring is available. However, the question arises as to which factors can contribute to the maintenance of TFR, and immunologic surveillance of the remaining leukemic cells is believed to be one of them. Argentina Stop Trial is an open-label, single-arm, multicenter trial assessing TFR after tyrosine kinase inhibitors interruption, that after more than 4 years showed a successful TFR rate of 63%.MethodsIn this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.ResultsAt the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (p<0.0001).DiscussionThis NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response

Impact of Ibrutinib in Quality of Life (QoL) in Patients with Chronic Lymphocytic Leukemia (CLL): Preliminary Results of Real-World Experience

Context: Clinical data from controlled trials report an improvement in QoL in patients with CLL in ibrutinib monotherapy. Reallife evidence is necessary to confirm this data. Objective: The disease control when treatment is initiated could lead to decreasedfatigue. It is likely that treatment with ibrutinib could result in animprovement in QoL in our real-world population. Primaryobjective: evaluate impact of ibrutinib treatment in QoL. Wedefined a clinically meaningful improvement 3 points in FACITfatigue score. Secondary Endpoints: Detect a 10% improvement byEQ5D VAS. Correlate baseline and follow-up hemoglobin levels(meaningful improvement 1g/dL). Design: This is a prospective,longitudinal, single arm study enrolling consecutive CLL patientsunder ibrutinib monotherapy either as first or further line oftreatment. Median follow-up was 7 months (range 1-28). Setting:Patients are recruited in an academic referral center in BuenosAires. Interventions: QoL was explored with FACIT-fatigue andEQ5D visual-analogue-scale (VAS) questionnaires (with copyrightpermission). Assessment by results reported by patient questionnaires are completed on months 0-1-3-6 and 12 since the beginningof treatment. Main Outcomes Measures: We are reporting preliminary results after 3 months of treatment compared to baseline.Statistical Analysis: data was analyzed with the Sign Test (BinomialTest). Results: A total of 21 CLL patients who started ibrutinibbetween 2016 and 2018 were included. Median age was 75 years(range 57-84); 12 patients (57%) were males. Ibrutinib was first-linetherapy in 7 patients (33%), second-line in 7 patients (33%) and 7patients (33%) received 3 previous lines. After 3 months oftreatment, the median change in FACIT-fatigue score 3 pointswas reached in 13 patients (62%) as compared to baseline(p=0.024). After 3 months of treatment there was no evidence of amedian change >10% on the EQ5D VAS (p=0.593) nor a significant improvement on hemoglobin level (p=0.105).Conclusions: These results suggest an early improvement of fatiguewithin the first 3 months of treatment with ibrutinib. Longerfollow-up and larger number of patient are necessary to confirm thisdata and determine the further improvements of QoL withcontinuous treatment and correlation with hemoglobin changes.Fil: Mela Osorio, Maria Jose. Fundación Para Combatir la Leucemia; ArgentinaFil: Pavlovsky, Carolina. Fundación Para Combatir la Leucemia; ArgentinaFil: Pavlovsky, Astrid. Fundación Para Combatir la Leucemia; ArgentinaFil: Fernandez, Isolda. Fundación Para Combatir la Leucemia; ArgentinaFil: Massa, Federico Sackmann. Fundación Para Combatir la Leucemia; ArgentinaFil: Ferrari, Luciana. Fundación Para Combatir la Leucemia; ArgentinaFil: Juni, Mariana. Fundación Para Combatir la Leucemia; ArgentinaFil: Riddick, Maximiliano Luis. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Matemáticas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pavlovsky, Miguel A.. Fundación Para Combatir la Leucemia; Argentin

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

PURPOSEDespite 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.METHODSThe Americas Health Foundation organized a panel of hematologists from Argentina, Brazil, Chile, Colombia, and Mexico to examine ALL diagnosis and therapy and produce recommendations.RESULTSLack 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.CONCLUSIONThis 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

Elevated plasma levels of IL-6 and MCP-1 selectively identify CML patients who better sustain molecular remission after TKI withdrawal

Abstract Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is safe under adequate molecular monitoring, but questions remain regarding which factors may be considered predictive for TFR. Argentina Stop Trial (AST) is a multicenter TFR trial showing that 65% of patients sustain molecular remission, and the prior time in deep molecular response (DMR) was associated with successful TFR. Luminex technology was used to characterize cytokines in plasma samples. Using machine learning algorithms, MCP-1 and IL-6 were identified as novel biomarkers and MCP-1low/IL-6low patients showed eightfold higher risk of relapse. These findings support the feasibility of TFR for patients in DMR and MCP-1/IL-6 plasma levels are strong predictive biomarkers

DataSheet_1_In-depth characterization of NK cell markers from CML patients who discontinued tyrosine kinase inhibitor therapy.docx

IntroductionTreatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase is considered a safe option if suitable molecular monitoring is available. However, the question arises as to which factors can contribute to the maintenance of TFR, and immunologic surveillance of the remaining leukemic cells is believed to be one of them. Argentina Stop Trial is an open-label, single-arm, multicenter trial assessing TFR after tyrosine kinase inhibitors interruption, that after more than 4 years showed a successful TFR rate of 63%.MethodsIn this context, we set up an immunological study by flow cytometry in order to analyze specific NK cell subsets from peripheral blood patient samples both at the time of discontinuation as well as during the subsequent months.ResultsAt the time of discontinuation, patients show a mature NK cell phenotype, probably associated to TKI treatment. However, 3 months after discontinuation, significant changes in several NK cell receptors occurred. Patients with a higher proportion of CD56dim NK and PD-1+ NK cells showed better chances of survival. More interestingly, non-relapsing patients also presented a subpopulation of NK cells with features associated with the expansion after cytomegalovirus infection (expression of CD57+NKG2C+), and higher proportion of NKp30 and NKp46 natural cytotoxicity receptors, which resulted in greater degranulation and associated with better survival (pDiscussionThis NK cell subset could have a protective role in patients who do not relapse, thus further characterization could be useful for patients in sustained deep molecular response.</p

PLZF-RAR(alpha), NPM1-RAR(alpha), and other acute promyelocytic leukemia variants: the PETHEMA registry experience and systematic literature review

It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RAR alpha) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RAR(alpha) being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RAR(alpha) and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RAR(alpha) and 2 NPM1-RAR(alpha)), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 x 10(9)/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far