Standardization of molecular monitoring for chronic myeloid leukemia in Latin America using locally produced secondary cellular calibrators

Residual disease in chronic myeloid leukemia (CML) patients undergoing therapy with tyrosine kinase inhibitors (TKIs) is measured by assessing the quantity of transcripts of the BCR-ABL1 fusion gene in peripheral white blood cells. This analysis is based on reverse-transcription quantitative PCR (RT–qPCR) technology; however, the wide array of methods used worldwide has led to large variation in quantitative BCR-ABL1 measurements, which hamper inter-laboratory comparative studiesFil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Medina, M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Tapia, I.. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Mordoh, Jose. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Cross, N. C. P.. Universidad de Southampton Uk; Reino UnidoFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bianchini, Michele. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentin

An unusual translocation, t(1;11)(q21;q23), in a case of chronic myeloid leukemia with a cryptic Philadelphia chromosome

Chronic myeloid leukemia is characterized by the translocation t(9;22)(q34;q11) (Philadelphia chromosome). Although it is not frequent, additional chromosome abnormalities can be detected at diagnosis and some of them have been associated with adverse cytogenetic and molecular outcome. We report a case of Chronic myeloid leukemia presenting the translocation t(1;11)(q21;q23) and a cryptic Philadelphia chromosome. The presence of additional chromosome abnormalities could generate greater genetic instability, promoting the emergence of further alterations. Our findings suggest that t(1;11)(q21;q23) avoided good response to tyrosine kinase inhibitors therapy. The patient evolves with primary resistance and subsequently at the recent control the T315I mutation was detected.Fil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Noriega, Maria Fernanda. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Laudicina, Alejandro. Lexel SRL; ArgentinaFil: Quatrin, Mariana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Bengió, Raquel María. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Are int22h-mediated deletions a common cause of hemophilia?

Hemophilia A (HA) (OMIM 306700) is an X-linked inherited bleeding disorder caused by deleterious mutations in the coagulation factor VIII gene (F8). Even though there is a broad diversity of HA-causative mutations, an uncommon type of rearrangement—a large DNA inversion involving F8 intron 22 (Inv22)—accounts for approximately one half of severely affected patients. Inv22 was formerly described by Lakich et al. [1] and Naylor et al. [2]. A collaborative international effort estimated that Inv22 is the cause of 43% (35%, 7%, and 1% for Inv22 type I, type II, and rare types, respectively) of severe HA cases worldwide with minor geographical or ethnical differences [3], in close agreement with our corresponding Argentinean series (42% of Inv22, and 34% and 7% for type I and type II, respectively) [4]. Naylor et al. [5] indicated that Inv22 originates by homologous recombination between well-defined duplicons (int22h) of 9.5 kb located one copy within F8 intron 22 (int22h-1, h1) and the other, inversely oriented, from a group of two extragenic copies (int22h-3, h3 for Inv22 type I and int22h-2, h2 for type II). It was formerly believed that h2 and h3 were equally oriented (i.e., head to tail). However, Ross et al. [6] determined that h2 and h3 are inversely oriented (i.e., head to head), both embedded in the arms of a large imperfect palindrome (Fig. 1). This finding prompted Bagnall et al. [7] to hypothesize recombination between these arms interchanging the location of the extragenic int22h copies and generating a non-deleterious inversion polymorphism in Xq28, i.e., h123 and h132. In this scenario, Inv22 type I may be generated from intrachromosomal recombination between h1 and h3 on the most frequent variant h123 whereas Inv22 type II may be generated between h1 and h2 on the least frequent h132 (Fig. 1). Moreover, on each of these normal structural variants of the X chromosome, recombination between h1 with either equally oriented copies (h2 or h3) may generate deletions (Del22) or duplications (Dup22) but not inversions [7]. More precisely, Del22 type I would be generated by recombination between h1 and h3 on variant h132 whereas Del22 type II by recombination between h1 and h2 on variant h123 [8] (Fig. 1).Fil: Abelleyro, Miguel Martin. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rossetti, Liliana Carmen. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Radic, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Candela, Miguel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Improved Diagnosis of the Transition to JAK2V617F Homozygosity: The Key Feature for Predicting the Evolution of Myeloproliferative Neoplasms

Most cases of BCR-ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera and primary myelofibrosis are associated with JAK2V617F mutations. The outcomes of these cases are critically influenced by the transition from JAK2V617F heterozygosity to homozygosity. Therefore, a technique providing an unbiased assessment of the critical allele burden, 50% JAK2V617F, is highly desirable. In this study, we present an approach to assess the JAK2V617F burden from genomic DNA (gDNA) and complementary DNA (cDNA) using one-plus-one template references for allele-specific quantitative-real-time-PCR (qPCR). Plasmidic gDNA and cDNA constructs encompassing one PCR template for JAK2V617F spaced from one template for JAK2Wild Type were constructed by multiple fusion PCR amplifications. Repeated assessments of the 50% JAK2V617F burden within the dynamic range of serial dilutions of gDNA and cDNA constructs resulted in 52.5364.2% and 51.4664.21%, respectively. The mutation-positive cutoff was estimated to be 3.65% (mean +2 standard deviation) using 20 samples from a healthy population. This qPCR approach was compared with the qualitative ARMS-PCR technique and with two standard methods based on qPCR, and highly significant correlations were obtained in all cases. qPCR assays were performed on paired gDNA/cDNA samples from 20 MPN patients, and the JAK2V617F expression showed a significant correlation with the allele burden. Our data demonstrate that the qPCR method using one-plus-one template references provides an improved assessment of the clinically relevant transition of JAK2V617F from heterozygosity to homozygosity.Fil: Gonzalez, Mariana Selena. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Medicina Experimental;Fil: de Brasi, Carlos Daniel. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Medicina Experimental;Fil: Bianchini, Michele. DTO. DE GENETICA;Fil: Gargallo, Patricia Martha. INST. DE INVEST. HEMATOLOGICAS;Fil: Stanganelli, Carmen Graciela. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematologicas "mariano R. Castex";Fil: Zalcberg, Ilana. Molecular Biology, Laboratory, Instituto Nacional do Caˆncer, Rio de Janeiro, Brazil;Fil: Larripa, Irene Beatriz. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Medicina Experimental

Cytogenetic Characterization of an Extra Structurally Abnormal Chromosome Associated with Severe Mental Retardation: Inv Dup (15) (q13)

We have studied an extra structually abnormal chromosome (ESAC) in a 13 years old boy with profound mental, psychomotor and speech retardation, behavioral problems, seizures and abnormal electroencephalogram. The examination of the bisatellited ESAC with chromosome banding demonstrated that the karyotype was: 47, XY, +inv dup (15) (pter-->q13::q13-->pter). The cytogenetic characterization of the inv dup (15) is reported with special emphasis on the usefulness of DA/DAPI staining when G-banding is sequentially performed to discard possible heteromorphisms in DA/DAPI positive chromosomes, and the importance of Ag-NOR heteromorphisms to ascertain the maternal origin of the inv dup (15). A U-type exchange between two non-sister chromatids is proposed as its mechanism of formation. The clinical features of the case were consistent with those previously reported in similar cases.Facultad de Ciencias Exacta

Estudios citogenéticos y mecanismos moleculares en los Síndromes Mielodisplásicos

Las alteraciones genéticas debidas a mutaciones, hallazgos cromosómicos balanceados o no, disomía uniparental adquirida, haploinsuficiencia y los fenómenos epigenéticos estarían involucrados al inicio y en la progresión de los SMD. Entre los genes implicados se encuentran el NRAS, FLT3, TP53, RUNX1, p15INK4b, TET2, ASXL1 y RPS14. Un 30-59% de pacientes con SMD de novo presentan cariotipos alterados y este porcentaje se incrementa según el riego de los subtipos FAB o WHO. Las aberraciones citogenéticas más frecuentes son: -5/del(5q) [2%-11%], -7/del (7q) [2%-5%], +8 [3%-12%], del(20q) [2%-4%], –Y [2%-4%] y cariotipos complejos (≥3 alteraciones) [10-20%]. Un 60-90% de los SMD secundarios presentan cariotipos anormales, un aumento de translocaciones y de cariotipos complejos [50%]. Las alteraciones en los cromosomas 5/7 [80%] se asocian con exposición a agentes alquilantes y los rearreglos 11q23 o 21q22 con exposición a inhibidores de topoisomerasa II. El cariotipo ayuda en el diagnóstico, pronóstico, tratamiento y seguimiento de los pacientes. La categorización del riesgo citogenético del IPSS ha sido comprobada aplicando las clasificaciones FAB y WHO, y validada en el WPSS. Aunque el grupo Intermedio es heterogéneo, el Consenso Internacional en Citogenética de los SMD sugiere la continuidad de su utilización hasta que se realice un nuevo estudio multicéntrico.Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; ArgentinaFil: Benasayag, Silvia. Fundagen; ArgentinaFil: Gallino, María Inés. Fundagen; ArgentinaFil: Correa, Walter A. Fundagen; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentin

Estudios citogenéticos y mecanismos moleculares en los Síndromes Mielodisplásicos

Las alteraciones genéticas debidas a mutaciones, hallazgos cromosómicos balanceados o no, disomía uniparental adquirida, haploinsuficiencia y los fenómenos epigenéticos estarían involucrados al inicio y en la progresión de los SMD. Entre los genes implicados se encuentran el NRAS, FLT3, TP53, RUNX1, p15INK4b, TET2, ASXL1 y RPS14. Un 30-59% de pacientes con SMD de novo presentan cariotipos alterados y este porcentaje se incrementa según el riego de los subtipos FAB o WHO. Las aberraciones citogenéticas más frecuentes son: -5/del(5q) [2%-11%], -7/del (7q) [2%-5%], +8 [3%-12%], del(20q) [2%-4%], –Y [2%-4%] y cariotipos complejos (≥3 alteraciones) [10-20%]. Un 60-90% de los SMD secundarios presentan cariotipos anormales, un aumento de translocaciones y de cariotipos complejos [50%]. Las alteraciones en los cromosomas 5/7 [80%] se asocian con exposición a agentes alquilantes y los rearreglos 11q23 o 21q22 con exposición a inhibidores de topoisomerasa II. El cariotipo ayuda en el diagnóstico, pronóstico, tratamiento y seguimiento de los pacientes. La categorización del riesgo citogenético del IPSS ha sido comprobada aplicando las clasificaciones FAB y WHO, y validada en el WPSS. Aunque el grupo Intermedio es heterogéneo, el Consenso Internacional en Citogenética de los SMD sugiere la continuidad de su utilización hasta que se realice un nuevo estudio multicéntrico.Fil: Belli, Carolina Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; ArgentinaFil: Benasayag, Silvia. Fundagen; ArgentinaFil: Gallino, María Inés. Fundagen; ArgentinaFil: Correa, Walter A. Fundagen; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentin

Evaluation of the primitive fraction by functional in vitro assays at the RNA and DNA level represents a novel tool for complementing molecular monitoring in chronic myeloid leukemia

Quantification of BCR-ABL1 mRNA levels in peripheral blood of chronic myeloidleukemia patients is a strong indicator of response to tyrosine-kinase inhibitors (TKI)treatment. However, additional prognostic markers are needed in order to better classify patients. The hypothesis of leukemic stem cells (LSCs) heterogeneity and persistence, suggests that their functional evaluation could be of clinical interest. In this work, we assessed the primitive and progenitor fractions in patients at diagnosis and during TKI treatment using functional in vitro assays, defining a ?functional leukemic burden? (FLB). We observed that the FLB was reduced in vivo in both fractions upon treatment. However, different FLB levels were observed among patients according to their response to treatment, suggesting that quantification of the FLB could complement early molecular monitoring. Given that FLB assessment is limited by BCR-ABL1 mRNA expression levels, we developed a novel detection method of primitive cells at the DNA level, using patient-specific primers and direct nested PCR in colonies obtained from functional in vitro assays. We believe that this methodcould be useful in the context of discontinuation trials, given that it is unknown whether the persistent leukemic clone represents LSCs, able to resume the leukemia upon TKI removal.Fil: Ruiz, María Sol. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Sanchez, María Belén. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Argenomics; ArgentinaFil: Gutierrez, Leandro German. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Instituto Alexander Fleming, Bs. As.; ArgentinaFil: Koile, Daniel Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Yankilevich, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Mosqueira, Celeste. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Cranco, Santiago. Fundaleu; ArgentinaFil: Custidiano, María del Rosario. Hospital Italiano de La Plata; ArgentinaFil: Freitas, Josefina. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; ArgentinaFil: Foncuberta, Cecilia. Instituto Alexander Fleming; ArgentinaFil: Moiraghi, Beatriz. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Pavlovsky, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Pérez, Mariel Ana. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Ventriglia, Verónica. Provincia de Buenos Aires. Hospital Nacional Profesor A. Posadas; Argentina; ArgentinaFil: Sánchez Ávalos, Julio César Américo. Instituto Alexander Fleming; ArgentinaFil: Mordoh, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentin

Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study

In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early.Fil: Bengió, Raquel M.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Riva, Maria E.. Hospital San Mart́n; ArgentinaFil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Lanari, Emilio. Hospital Jose Ramon Vidal ; Gobierno de la Provincia de Corrientes;Fil: Milone, Jorge. Hospital Italiano; ArgentinaFil: Ventriglia, Veronica. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; ArgentinaFil: de Tezanos Pinto, Miguel. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Murro, Hector. No especifíca;Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Contribution of polymorphisms in IFNG and TNF to complications of the allogeneic hematopoietic stem cell transplantation with sibling donors

Las complicaciones del trasplante alogénico de células progenitoras hematopoyéticas (TACPH) relacionado incluyen tiempos variables de engraftment,enfermedad injerto contra huésped (EICH), infeccionesbacterianas y reactivación de citomegalovirus(CMV), entre otras. La existencia de polimorfismosen genes no HLA que codifican citoquinas proinflamatoriastales como el factor de necrosis tumoralalfa (TNF) e interferón gamma (IFNG) condicionaría la aparición de estas complicaciones. Se evaluóel impacto de la variante +1349 CAn del gen INFG y del polimorfismo -308 G/A de TNF en el engraftment y en la EICH en 148 receptores de TACPHrealizados en los centros participantes. Con respecto al engraftment tardío (≥15 días), el análisis multivariado confirmó el poder predictivo desfavorable del genotipo CAno12/no12 (baja producción) de IFNG(OR 3,9; p=0,003), médula ósea (MO) como fuente de células progenitoras (OR 4,6; p=0,013) y bacteriemia (OR 3,0; p=0,033). En relación a EICHa 3-4,las variables independientes fueron el genotipo de baja producción de IFNG (OR 0,1; p=0,008), bacteriemia (OR 3,3; p=0,048) y presencia de CMV(OR3,3; p=0,046). Y con respecto a EICHc, el riesgo fue influenciado por el genotipo -308 GG (producción baja) de TNF (OR 3,3; p=0,038), SP como fuente (OR 5,0; p=0,028), acondicionamiento mieloablativo (OR 3,3; p=0,014) y antecedente de EICHa 2-4 (OR 2,6; p=0,029). Aunque es necesario confirmar estos hallazgos, el genotipo de baja producción de IFNG se asoció con engraftment tardío y menor EICHa, mientras que los genotipos de baja producción de TNF se relacionaron con mayor incidencia de EICHc. Las variantes polimórficas estudiadas contribuirían al desarrollo de complicaciones en pacientes con TACPH relacionado.Complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) include variable engraftment times, acute (aGVHD) and chronic (cGVHD) graft-versus-host diseases, bacterial infections and reactivation of cytomegalovirus (CMV), among others. The existence of polymorphisms in non-HLA genes that encode pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF) and interferon gamma (IFNG) would condition the appearance of these complications. The impact of polymorphic variants +1349 CAn of INFG gene and -308 G/A of TNF was evaluated on the engraftment and GVHD in 148 allo-HSCT recipients with sibling donors. In the multivariate analysis, the genotype CAno12/no12 (low production) of INFG (OR 3.9, p=0.003), bone marrow (BM) as source of progenitor cells (OR 4.6, p=0.013) and bacteremia (OR 3.0, p=0.033) maintained their predictive power with respect to late engraftment (≥15 days). Genotype of low IFNG production (OR 0.1, p=0.008), bacteremia (OR 3.3, p=0.048) and presence of CMV (OR 3.3, p=0.046) showed a significant association with aGVHD 3-4. And with respect to cGVHD, the genotype -308 GG (low production) of TNF (OR 3.3, p=0.038), PB as source (OR 5.0, p=0.028), myeloablative conditioning (OR 3.3, p=0.014) and previous aGVHD 2-4 (OR 2.6, p=0.029). Although it is necessary to confirm these findings, the genotype of lower IFNG production was associated with a later engraftment and less severe aGVHD and genotypes of lower TNF production was related to a higher incidence of cGVHD contributing to the development of complications in allo-HSCT.Fil: Palau Nagore, Maria Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Berro, Mariano. Universidad Austral; ArgentinaFil: Bestach, Yesica Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rivas, M.M.. Universidad Austral; ArgentinaFil: Foncuberta, C.. Instituto Alexander Fleming; ArgentinaFil: Vitriu, A.. Instituto Alexander Fleming; ArgentinaFil: Remaggi, G.. Fundaleu; ArgentinaFil: Martínez Rolón, J.. Fundaleu; ArgentinaFil: Jaimovich, Sebastian Gaston. Fundación Favaloro; ArgentinaFil: Requejo, A.. Fundación Favaloro; ArgentinaFil: Padros, K.. Primer Centro Argentino de Inmunogenética; ArgentinaFil: Rodríguez, M.B.. Primer Centro Argentino de Inmunogenética; ArgentinaFil: Kusminsky, G.. Universidad Austral; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: 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; Argentin