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The cryopreservation and storage of hematopoietic stem cells (HSCs) is usually required in the autologous stem cells transplant setting and, in some cases, for allogenic products. The storage of these products has a validity defined by the storage characteristics, clinical utility and security conditions of the product. Here, we present recommendations elaborated by the Argentinian Group of Bone Marrow Transplantation (GATMO)., El procedimiento de criopreservación y almacenamiento (CyA) de las células progenitoras hematopoyéticas (CPH) es requerido con frecuencia para la realización de un trasplante CPH autólogo y en algunas ocasiones se requiere la CyA de productos celulares alogénicos (CPH o linfocitos). El almacenamiento de estos productos celulares tiene una validez definida por el medio en el que se almacena, la utilidad clínica del producto y las condiciones de seguridad del producto que fue almacenado. Se presentan recomendaciones emitidas por el Grupo Argentino de Trasplante sobre el descarte de productos criopreservados y almacenados.

Complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) include variable engraftment times, acute (aGVHD) and chronic (cGVHD) graft-versus-host diseases, bacterial infec-tions and reactivation of cytomegalovirus (CMV), among others. The existence of polymorphisms in non-HLA genes that encode pro-inflammatory cy-tokines 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 sib-ling donors. In the multivariate analysis, the geno-type CAno12/no12 (low production) of INFG (OR 3.9, p=0.003), bone marrow (BM) as source of pro-genitor 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, Las complicaciones del trasplante alogénico de células progenitoras hematopoyéticas (TACPH) relacionado incluyen tiempos variables de engraftment, enfermedad injerto contra huésped (EICH), infecciones bacterianas y reactivación de citomegalovirus (CMV), entre otras. La existencia de polimorfismos en genes no HLA que codifican citoquinas proinflamatorias tales como el factor de necrosis tumoral alfa (TNF) e interferón gamma (IFNG) condiciona-ría la aparición de estas complicaciones. Se evaluó el impacto de la variante +1349 CAn del gen INFGy del polimorfismo -308 G/A de TNF en el engraftment y en la EICH en 148 receptores de TACPH realizados 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 (pro-ducción 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.

Background. There have been several efforts to predict mortality after autologous stem cell transplantation (ASCT), like the Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI), described by Sorror for allogeneic HSCT. This index has demonstrated its value in ASCT by several groups including us. Nowadays, there is no valid score in the setting of ASCT applicable to the clinical practice combining comorbidities with other patient characteristics.Aims. To describe a comprehensive score including comorbidities with other clinical factors and analyze the impact of this score in non-relapse mortality (NRM), overall survival (OS) and early morbidity end-points (mechanical ventilation, shock or dialysis) after ASCT in a large cohort of patients transplanted in Argentina. Methods. We retrospectively reviewed data of 2068 adult patients who received an ASCT in our centers (01/2000-04/2017) for multiple myeloma or lymphoma. We compared NRM and relapse with Grey test, OS with Kaplan Meyer and long term multivariate analysis (MVA) for NRM with fine-Gray regression. All the factors remaining significant after MVA for NRM were included in the score, and were assigned a value of 1 if the hazard ratio was < 3.5, or 2 if the HR was ≥3.5.Results. Mean age was 51 years; 59% were male, 52% had multiple myeloma (MM), 30% non-Hodgkin lymphoma (NHL) and 18% Hodgkin lymphoma (HL). Fifty-three percent were in CR, 44% in PR and 3% SD/PD; 13% received three or more chemotherapy lines before transplant (heavily pre-treated). Regarding comorbidities, 58% had HCT-CI 0, 29% 1-2 and 13% ≥3. Median follow up was 1.1 years (range 100 days-14 years). Early NRM (day 100) was 3.1%, 1-3 years was 4.7-5.8% and OS (1-5 years) was 89-66%. On MVA risk factors showing an independent significant impact with NRM were: male patients (1 point), age 55-64 (1 point), ≥65 years (2 points), HCT-CI ≥3 (1 point), HL (1 point) and NHL (2 points). The hazard ratio for NRM increased proportionally with the scor, Introducción. Existen en la literatura distintos estudios que han intentado predecir la mortalidad luego del trasplante autólogo de células precursoras hematopoyéticas (TACPH). El más utilizado hasta el presente es el índice de comorbilidades HCT-CI. No hay una herramienta de uso en la práctica diaria que combine diferentes aspectos más allá de las comorbilidades. Objetivo. Desarrollar un nuevo índice que combine las comorbilidades junto con otros factores clínicos y analizar su impacto en la mortalidad libre de enfermedad (MLE) y sobrevida global (SG) en una cohorte de TACPH de Argentina. Como objetivo secundario evaluar la asociación con eventos de morbilidad temprana (ARM, shock y diálisis).Materiales y métodos. Analizamos de manera retrospectiva 2068 historias clínicas de pacientes adultos que recibieron un TACPH en nuestros centros desde enero/2000 y abril/2017 debido a mieloma múltiple o linfomas. Comparamos la MLE y recaída con IC (test de Gray), la SG con logrank (Kaplan-Meier); para los análisis multivariados (AMV) utilizamos Fine-gray para los eventos con riesgo competitivo. Incluimos en el índice todos los factores que resultaron significativos en el análisis multivariado para MLE y asignamos 1 punto para aquellos factores cuyo hazard ratio fue menor de 3.5 y 2 puntos si el HR fue ≥3.5.Resultados. La edad media fue de 51 años (rango 15-75); 59% fueron masculinos, 52% la patología de base era mieloma múltiple, 30% linfoma no Hodgkin y 18% linfoma de Hodgkin. Cincuenta y tres por ciento se encontraba en RC, 44% en RP y 3% con enfermedad estable/progresada; 13% recibió 3 o más líneas de tratamiento quimioterapéutico previo al trasplante (severamente pre-tratados). Con res-pecto a las comorbilidades, 58% tuvo un HCT-CI de riesgo bajo (puntaje 0), 29% intermedio (1-2) y 13% riesgo alto (≥3). La media de seguimiento fue de 1.9 años (rango 100 días-14 años). La MLE temprana (día 100) fue del 3,1%, a largo plazo (1-3 años) de 4,7-5,8% y la SG (1-5 años) 89-66%.Lu

In a multicenter retrospective study, we evaluated the outcome of patients with myelofibrosis (MF) who underwent allogeneic hematopoietic stem cell transplantation (AHCT) in Argentina. A total of 43 patients were included (median age 53; range 23-70; males 56%) who received an AHSCT between 2002 and 2016 in 12 centers; 33 patients had primary MF and 10 patients MF secondary to PV or ET. Donors were related in 30 cases and full match in 38 cases, and the source of stem cells was peripheral blood for all patients. Conditioning regimen was myeloblative (MAC; n=16; Bu ≥9.6 mg/kg) or reduced intensity (RIC; n=27; 13 Bu, 10 Mel and four TBI based). 1-year cumulative incidence of acute grade 2-4 graft versus host disease (GVHD) was 49% and chronic GVHD 11% and the corresponding relapse incidence was 20% (higher in patients with a high DIPSS PLUS; p=0.015). 100-days and 1-year nonrelapse mortality (NRM) was 19% and 37% respectively with the GVHD being the main cause of death. 1-year overall survival (OS) was 55%; in the multivariate analysis pre-transplant factors associated with inferior OS were the HCT-CI (p=0.019), splenomegaly ≥10 cm (p=0.021) and the leukemic transformation (p=0.019). Patients with low HCT-CI (n=17) had be-tter 1-year OS with MAC (MAC vs RIC: 83% vs 41%; p=0.025) whereas those with intermediate-high HCT-CI (n=23) had an inferior 1-year OS with MAC (MAC vs RIC: 22% vs 69%; p=0.040). Our data show that NRM is the main determiner of OS in patients with MF. We should make efforts to control the GVHD and the related infections., A través de un estudio multicéntrico retrospectivo se evaluaron los resultados con trasplante alogénico de células progenitoras hematopoyéticas (TACPH) en pacientes con mielofibrosis (MF) en Argentina. Se incluyeron 43 pacientes (mediana edad 53 años; rango 23-70; varones 56%) que recibieron un TACPH entre 2002 y 2016 en 12 centros. Del total, 33 fueron MF primaria y 10 MF secundaria a PV o TE. Los donantes fueron relacionados en 30 casos y completamente idénticos en 38, y todos recibieron CPH de sangre periférica previo acondicionamiento mieloablativo (MA; n=16; Bu ≥9,6 mg/kg) o de intensidad reducida (IR; n=27; 13 basados en Bu, 10 basados en Mel y cuatro en TBI). Al año, la incidencia de EICHa grado 2-4 fue de 49% y de EICHc de 11%. La incidencia de recaída fue de 20% y fue mayor en pacientes con DIPSS PLUS alto (p=0,015). La mortalidad no relacionada a recaída (MNR) al día 100 fue 19% y al año de 37%, siendo la principal causa de muerte la EICH. La SG al año fue de 55%; en el análisis multivariado los factores pre-trasplante asociados a peor SG fueron el HCT-CI (p=0,019), la presencia de esplenomegalia ≥10 cm (p=0,021) y la transformación leucémica (p=0,019). Los pacientes con HCT-CI bajo (n=17) presentaron mejor SG al año con acondicionamiento MA (MA vs IR: 83% vs 41%; p=0,025) mientras que aquéllos con HCT-CI intermedio-alto (n=23) tuvieron peor SG al año con MA (MA vs IR: 22% vs 69%; p=0,040). Nuestros datos muestran que la SG de estos pacientes está dada sobre todo por la MNR, por lo que se deben realizar esfuerzos para controlar la EICH e infecciones secundarias

Haematopoietic cell transplant activity in the 28 countries comprising Latin America is poorly defined. We conducted a voluntary survey of members of the Latin American Bone Marrow Transplantation Group regarding transplant activity 2009–2012. Collated responses were compared with data of transplant rates from the Worldwide Network for Blood and Marrow Transplantation for other geographic regions. Several socio-economic variables were analysed to determine correlations with transplant rates. In total, 94 teams from 12 countries reported 11519 transplants including 7033 autotransplants and 4486 allotransplants. Annual activity increased from 2517 transplants in 2009 to 3263 in 2012, a 30% increase. Median transplants rate (transplant per million inhabitants) in 2012 was 64 (autotransplants, median 40; allotransplants, median 24). This rate is substantially lower than that in North America and European regions (482 and 378) but higher than that in the Eastern Mediterranean and Asia Pacific regions (30 and 45). However, the Latin America transplant rate is 5–8-fold lower than that in America and Europe, suggesting a need to increase transplant availability. Transplant team density in Latin America (teams per million population; 1.8) is 3–4-fold lower than that in North America (6.2) or Europe (7.6). Within Latin America, there is substantial diversity in transplant rates by country partially explained by diverse socio-economic variables including per capita gross national income, health expenditure and physician density. These data should help inform future health-care policy in Latin America.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P = 0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P = 0.18), and for grades III–IV was 2.6% vs 11.6% (P = 0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P = 0.002) and extensive 5% vs 23.6% (P = 0.01). OS was 74% vs 76% for BM vs PBSCs (P = 0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P = 0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P = 0.005) respectively. In multivariate analysis, aGvHD II–IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1–5.6, P = 0.02) and aGvHD III–IV (HR 8.3 CI 3.4–20.2, Po0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients