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Allogeneic stem cell transplant (alloSCT) is a current treatment option for patients with refractory/relapsed classic Hodgkin lymphoma (CHL), including those who have failed an autologous transplantation. We performed a retrospective multicenter analysis of 113 patients (median age 28 years; range 14-56; 54% males) with refractory/relapsed (R/R) CHL who had undergone alloSCT in Argentina. Kaplan-Meier was used to estimate overall (OS) and progression-free survival (PFS). Relapse rate (RR) and non-relapse mortality (NRM) were estimated with cumulative incidence analysis. Disease status at transplant was complete remission (CR) in 39%, partial remission (PR) in 44%, and stable/progressed disease (S/PD) in 17% of the patients. Donor type was matched related (MRD) in 60%, unrelated (URD) in 19%, and haploidentical (HID) in 21% of the patients. OS and PFS at 2 years were 43% and 27%, respectively, for all the cohort. In the univariate analysis, patients in CR showed better OS (p ≤ 0.001) and PFS (p ≤ 0.001), and lower NRM (p = 0.04). HID had better PFS (p = 0.04) and lower RR (p = 0.02). In the multivariate analysis, CR showed a significant impact on OS and PFS, and HID on PFS. AlloSCT is a feasible procedure in patients with CHL. Those in CR at the time of the transplant had better outcomes. Haploidentical transplantation is associated with better PFS in these patients with poor prognosis.

Individuals with malignancies and COVID-19 have a lower survival compared with the general population. However, the information about the impact of COVID-19 on the whole hematological population is scarce. We aimed to describe the 30th day overall survival (OS) after COVID-19 infection in patients with a hematological disease in Argentina. A completely anonymous survey from the Argentine Society of Hematology was delivered to all the hematologists in Argentina; it started in April 2020. A cut-off to analyze the data was performed in December 2020 and, finally, 419 patients were reported and suitable for the analysis (average age: 58 years, 90% with malignant diseases). After the COVID-19 diagnosis, the 30-day OS for the whole population was 80.2%. From the entire group (419), 101 (24.1%) individuals required intensive care unit admission, where the 30-day OS was 46.6%. Among allogeneic stem cell transplant recipients, the 30-day OS was 70.3%. Factors associated with a low OS were two or more comorbidities, an active hematological disease and history of chemotherapy. In individuals with the three factors, the 30-day OS was 49.6% while the 30-day OS in those without those factors was 100%. Patients with hematological diseases have a higher mortality than the general population. This group represents a challenge and requires careful decision-making of the treatment in order not to compromise the chances of cure.El presente estudio tuvo por objetivo primario conocer la mortalidad de pacientes con enfermedad hematológica que presentaron infección por COVID-19 en Argentina. Para ello se difundió una encuesta desde la Sociedad Argentina de Hematología (SAH) entre los hematológos para informar sobre los pacientes con enfermedades hematológicas y diagnóstico de infección por SARS- CoV-2, entre el 19/4/2020, y el 7/12/2020. Se incluyeron individuos de todas las edades con diagnóstico de enfermedad hematológica benigna o maligna e infección por SARS-CoV-2 confirmada por técnica de RTPCR. Se analizaron 419 pacientes (mediana 58 años; 90% enfermedades malignas). La supervivencia al día 30 fue de 80.2%. La supervivencia fue menor en aquellos que requirieron internación (74.2%), cuidados intensivos (46.6%) y asistencia respiratoria mecánica (36.8%). Entre los trasplantados alogénicos la supervivencia fue 70.3%. Los factores vinculados a la supervivencia global fueron las comorbilidades, el estado de la enfermedad al momento de la infección y el antecedente de quimioterapia. Se pudo establecer un score en el que aquellos que tuvieron un puntaje de 4 alcanzaron una supervivencia del 49.6% al día 30, mientras que la de los pacientes con score 0 fue del 100% a 30 días. En comparación con la población general, los pacientes con enfermedades hematológicas presentan una mayor mortalidad vinculada al COVID-19, motivo por el cual es primordial definir pautas destinadas a disminuir la exposición de los mismos sin comprometer las posibilidades de beneficiarse del tratamiento de la enfermedad de base.

Hematopoietic stem cell transplantation (HSCT) in children is a procedure that is not exempt of severe complications. Admission to the pediatric intensive care unit (PICU) is associated with a high mortality rate. Objectives: To analyze survival and predictors of mortality among children who received a HSCT and were admitted to the PICU, and to develop a mortality prediction model in this population.Retrospective review of children and adolescents who received a HSCT between January 1st, 2005 and December 31st, 2019 and were admitted to the PICU of a tertiary care teaching hospital.Out of 264 children receiving the transplant, 114 were admitted to the PICU. The overall mortality rate was 29% (n = 34). The type of transplant, underlying disease, febrile neutropenia event, cytomegalovirus infection, respiratory failure, graft versus host disease (GVHD), myeloablative chemotherapy, and previous malnutrition were associated with higher mortality rates. In the multivariate analysis, GVHD (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.92-2.98), need for mechanical ventilation (OR: 2.47; 95% CI: 1.39- 5.73), alternative donor transplant (OR: 1.58; 95% CI: 1.14-2.17), and previous malnutrition (OR: 1.78; 95% CI: 1.22-3.89) were associated with a higher mortality rate.In the studied population, 2 out of 3 children who received a HSCT and were admitted to the PICU survived. GVHD, mechanical ventilation, alternative donor transplant, and previous malnutrition were predictors of mortality.Introducción: El trasplante de células progenitoras hematopoyéticas (TPH) en niños es un procedimiento no exento de complicaciones graves. El ingreso de esta población a unidades de cuidados intensivos pediátricos (UCIP) se asocia con elevada mortalidad. Objetivos: Analizar la sobrevida y los factores predictivos de la mortalidad en niños que recibieron TPH e ingresaron a la UCIP y elaborar un modelo predictivo de mortalidad en esta población. Materiales y métodos: Revisión retrospectiva de niños y adolescentes que recibieron un TPH entre el 01/01/2005 y el 31/12/2019 e ingresaron a la UCIP de un hospital universitario de alta complejidad. Resultados: De un total de 264 niños que recibieron el trasplante, 114 ingresaron a la UCIP. La mortalidad general fue del 29% (n = 34). El tipo de trasplante, enfermedad basal, evento de neutropenia febril, infección por citomegalovirus, insuficiencia respiratoria, enfermedad de injerto contra huésped (EICH), quimioterapia mieloablativa y desnutrición previa se asociaron con tasas de mortalidad más elevadas. En el análisis multivariado, la EICH (razón de posibilidades [OR, por su sigla en inglés]: 2,23; intervalo de confianza del 95% [IC 95%]: 1,92-2,98), la necesidad de ventilación mecánica invasiva (OR: 2,47; IC95%: 1,39-5,73), el trasplante de donante alternativo (OR: 1,58; IC 95%: 1,14-2,17) y la desnutrición previa (OR: 1,78; IC 95%: 1,223-3,89) se asociaron con mayor mortalidad. Conclusión: En la población estudiada, dos de cada tres niños que recibieron TPH e ingresaron a la UCIP sobrevivieron. La EICH, ventilación mecánica, trasplante de donante alternativo y desnutrición previa fueron factores predictivos de mortalidad.

There have been several efforts to predict mortality after autologous stem cell transplantation (ASCT), such as the hematopoietic cell transplant-comorbidity index (HCT-CI), described for allogeneic stemcell transplantation and validated for ASCT, but there is no composite score in the setting of ASCT combining comorbidities with other clinical characteristics. Our aim is to describe a comprehensive score combining comorbidities with other clinical factors and to analyze the impact of this score on nonrelapse mortality (NRM), overall survival (OS), and early morbidity endpoints (mechanical ventilation, shock or dialysis) after ASCT. For the training cohort, we retrospectively reviewed data of 2068 adult patients who received an ASCT in Argentina (October 2002 to June 2017) for multiple myeloma or lymphoma. For the validation cohort, we analyzed 2168 ASCTs performed in the Medical College of Wisconsin and Spanish stem cell transplant group (Grupo Espanol de Trasplante Hematopoyetico (GETH)) (January 2012 to December 2018). We first performed a multivariate analysis for NRM in order to select and assign weight to the risk factors included in the score (male patients, aged 55 to 64 and >= 65 years, HCT-CI >= 3, Hodgkin lymphoma and non-Hodgkin lymphoma). The hazard ratio for NRM increased proportionally with the score. Patients were grouped as low risk (LR) with a score of 0 to 1 (686, 33%), intermediate risk (IR) with a score of 2 to 3 (1109, 53%), high risk (HR) with a score of 4 (198, 10%), and very high risk (VHR) with a score of >= 5 (75, 4%). The score was associated with a progressive increase in all the early morbidity endpoints. Moreover, the score was significantly associated with early NRM (day 100: 1.5% versus 2.4% versus 7.6% versus 17.6%) as well as long term (1 to 3 years; 1.8% to 2.3% versus 3.8% to 4.9% versus 11.7% to 14.5% versus 25.0% to 27.4%, respectively; P

We aimed at analyzing the outcome of allogeneic stem cell transplant (ASCT) in adult patients with acute lymphoblastic leukemia (ALL), comparing Haploidentical (Haplo) with HLA-matched (sibling and unrelated) donors. Between 2008 and 2017, we collected data from 236 patients (median age 31 years; range 16–64; 90% HCT-CI 0–1) who underwent unmanipulated ASCT in first complete remission and subsequent remissions in 15 Argentinian centers. Donors were HLA-matched (n = 175; 74%) and Haplo (n = 61; 26%). Two-year overall survival (OS) was 55% (95% CI 47–63) for the HLA-matched group and 49% (95% CI 34–62) for the Haplo group (p = 0.351). For OS, crude HR, adjusted HR for covariates (HR 1.24; 95% CI 0.77–1.99; p = 0.363) and HR including a propensity score in the model (HR 1.22; 95% CI 0.71–2.08; p = 0.414) showed no impact of donor category on the OS. No difference was found in terms of nonrelapse mortality, relapse, leukemia-free survival, and grade 3–4 acute graft-versus-host disease (GVHD); 2-year incidence of chronic GVHD was higher in HLA-matched vs Haplo group (p = 0.028). Patients with ALL who underwent ASCT were young subjects with low HCT-CI. In this setting, a Haplo donor represents an alternative widely available in the absence of an HLA-matched donor. Relapse remains a challenge for all donor categories.

Liver disease in X-linked hyper IgM syndrome (XHIGM) is an important predictor of mortality. In case liver transplantation (LT) is required, a survival benefit is observed when LT is combined with HSCT. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:5 pages:1952-+ ispartof: location:United States status: published

The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score is a useful tool to assess the risk for nonrelapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation. Although the HCT-CI has been investigated in autologous stem cell transplantation (ASCT), its use is limited. To improve on the current use of the HCT-CI score on the morbidity and mortality after ASCT, we assessed the 100-day morbidity defined as orotracheal intubation (OTI), dialysis or shock (vasopressors need), 100-day NRM, early composite morbidity-mortality (combined endpoint that included any previous endpoints), and long-term NRM. We retrospectively reviewed a cohort of 1730 records of adult patients who received an ASCT in Argentinean center's between October 2002 and August 2016. Median follow-up was 1.15 years, and median age was 53 years. Diseases were multiple myeloma (48%), non-Hodgkin lymphoma (27%), and Hodgkin lymphoma (17%); 51% were in complete or partial remission; and 13% received ≥ 3 chemotherapy lines before transplant (heavily pretreated). Early NRM (100-day) was 2.7%, 5.4% required OTI, 4.5% required vasopressors, and 2.1% dialysis, with an early composite morbidity-mortality of 6.8%. Long-term (1 and 3 years) NRM was 4% and 5.2% and overall survival 89% and 77%, respectively. High-risk HCT-CI patients had a significant increase in 100-day NRM compared with intermediate and low risk (6.1% versus 3.4% versus 1.8%, respectively; P = .002), OTI (11% versus 6% versus 4%, P = .001), shock (8.7% versus 5.8% versus 3%, P = .001), early composite morbidity-mortality (13% versus 9 % versus 4.7%, P .001), and long-term NRM (1 year, 7.7% versus 4% versus 3.3%; and 3 years, 10.8% versus 4% versus 4.8%, respectively; P = .002). After multivariate analysis these outcomes remained significant: early composite morbidity-mortality (odds ratio [95% confidence interval] compared with low risk: intermediate risk 2.1 [1.3 to 3.5] and high risk 3.3 [1.9 to 5.9]) and NRM (hazard ratio [95% confidence interval] compared with low risk: intermediate risk .97 [.8 to 2.4] and high risk 3.05 [1.3 to 4.5]). No significant impact was observed in overall survival. Other than comorbidities, significant impact was observed for heavily pretreated patients, age ≥ 55 years, non-Hodgkin lymphoma, and bendamustine-etoposide-citarabine-melphalan conditioning. We confirmed that the HCT-CI had a significant impact on NRM after ASCT, and these findings are mainly due to early toxicity express as 100-day NRM and the 3 main morbidity outcomes as well as the composite endpoint.

Post-transplant lymphoproliferative disorder (PTLD) is a major and potentially life-threatening complication after solid-organ transplantation. The aim of this study was to describe the disease characteristics, clinical practices, and survival related to PTLD in adult orthotopic liver transplant (OLT) recipients in South America. We conducted a survey at four different transplant groups from Argentina, Brazil, and Chile. Among 1621 OLT recipients, 27 developed PTLD (1.7%); the mean age at diagnosis was 53.7 (± 14) yr with a mean time of 39.7 (± 35.2) months from OLT to PTLD diagnosis. Initial therapy included reduction in immunosuppression alone in 23.1% of the patients. Either rituximab or chemotherapy was employed as initial or second-line therapy in 76.9% of the patients. PTLD location was frequently extranodal (80.7%) and mostly involving the transplanted liver (59.3%). The overall survival at one and five yr post-PTLD diagnosis was 53.8% and 46.2%, respectively. Significant univariate risk factors for post-PTLD mortality included lactate dehydrogenase ≥ 250 U/L (HR 9.66, p = 0.02), stage III/IV PTLD (HR 5.34, p = 0.004), and HCV infection (HR 7.68, p = 0.01). In conclusion, PTLD in OLT adult recipients is predominantly extranodal, and although mortality is high, long-term survival is possible.

Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematologicalmalignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identifiedin TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C4T within exon 1. Two hundred and forty five patient/donorpairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors wereassociated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P = 0.02). Regarding survival outcomes,+29CC patients developed higher non relapse mortality (NRM) (1?5 years CC 28?32% vs TC/TT 7?10%; HR 5.1, P = 0.01). Recipientsof +29TT donors experienced a higher relapse rate (1?5 years TT 37?51% vs TC 19?25% vs CC 13%?19%; HR 2.4, P = 0.01) witha decreased overall survival (OS) (1?5 years TT 69?50% vs TC/CC 77?69%; HR 1.9, P = 0.05). Similar to previous myeloablativeunrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors mightbe associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of theseSNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of themost appropriate donor. Fil: Berro, Mariano. Universidad Austral; Argentina 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; Argentina Fil: Rivas, M. M.. Universidad Austral; Argentina Fil: Longo, P.. Universidad Austral; Argentina Fil: Foncuberta, Cecilia. Instituto Alexander Fleming; Argentina Fil: Vitriu, Adriana. Instituto Alexander Fleming; Argentina Fil: Remaggi, Guillermina. Fundaleu; Argentina Fil: Martinez Rolón, Juliana. Fundaleu; Argentina Fil: Jaimovich, Gregorio. Fundación Favaloro; Argentina Fil: Requejo, Alejandro. Fundación Favaloro; Argentina Fil: Feldman, Leonardo. Fundación Favaloro; Argentina Fil: Padros, Karín. Fundación Favaloro; Argentina Fil: Rodriguez, María Beatriz. Fundación Favaloro; Argentina Fil: Shaw, B. E.. Medical College Of Wisconsin; Estados Unidos Fil: 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; Argentina 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; Argentina Fil: Kusminsky, Gustavo. Universidad Austral; Argentina

INTRODUCTION Acute leukemia relapsing after allogeneic stem cell transplantation (AlloSCT) is usually associated with dismal prognosis. Treatment options in this population remain limited. We evaluated the outcomes of second AlloSCT in patients with acute leukemia relapsed after previous AlloSCT in centers from Grupo Argentino de Trasplante de Médula Ósea (GATMO) METHODS AND RESULTS We carried out a retrospective analysis in 21 adult patients who received a second transplant as a salvage treatment for relapsed acute leukemia. Main outcomes were overall survival (OS) and leukemia free survival (LFS). Variables evaluated were re-induction chemotherapy regimen, conditioning regimen, donor type, early immunosuppression tapering, and the use of maintenance treatment. Mean age was 28 years old (range 16-53). Thirteen were under 30 years, 11 were women, 16 were acute myeloid leukemia. Median time from the first transplant to the relapse was 16,3 months (range 2 to 91 moths). Fourteen patients were MRD negative at the time of second AlloSCT (4 of them in aplasia) and 7 were either positive MRD or refractory disease. Almost all patients received a different re-induction chemotherapy regimen as well as a different conditioning compared to the first transplant. Sixteen out of 21 patients were transplanted with a different donor. Patients without graft versus host disease (GVHD) at day 100 started immunosuppression tapering. Considering the 16 patients alive/relapse free at day 100, half of them received maintenance therapy (6 azacitidine, one sorafenib and one dasatinib). With a median follow up of 24 months, 1-year OS and LFS was 62% and 38%. Age was a strong predictor of survival. There were no patients ≥30 years alive or relapse free beyond 6 months of the procedure, while LFS at 2 years was 58% (8/13) in patients younger than 30 years (p=0.0007). One year LFS was 60% for patients receiving any type of maintenance, compared to 33% of patients who did not receive maintenance (p=0.2). There were no differences in changing the donor or the pre-transplant status. CONCLUSION Second AlloSCT for relapsed acute leukemia is a potential curative option. Younger patients showed better outcomes. Patients relapsing after 6 months could have better prognosis. Maintenance treatment after second transplant should be evaluated, however prospective studies are needed in this scenario to draw better conclusions. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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, P

Allogeneic hematopoietic stem cell transplantation (AHSCT) is a curative approach for patients with myelodysplastic syndrome (MDS).In this multicenter retrospective study, we analyzed the outcome of adult patients with MDS who underwent AHSCT in Argentina and evaluated the prognostic factors associated with progression-free survival (PFS), overall survival (OS), cumulative incidence (CI) of relapse, and non-relapse mortality (NRM).We analyzed data from 87 adults (median age: 43 years, range 18-66) who underwent SCT after myeloablative (n = 60) or non-myeloablative conditioning (n = 27), and from related (n = 62) or unrelated (n = 25) donors. For all patients, unadjusted 4-year PFS and OS were 37% and 38%, respectively; no significant differences were found between recipients of related or unrelated donors. One-year CI of relapse and NRM were 21% and 20%, respectively. In the multivariate analysis, intermediate disease risk index (DRI) and acute graft versus host disease AGVHD of all grades (I-IV) were independent variables associated with better PFS and lower relapse CI; only intermediate DRI was associated with better OS.AHSCT is a feasible procedure in Argentina, with more than 30% of the patients achieving long-term survival. Recipients with unrelated donors had at least similar outcome than those with related donors. DRI may be useful to identify patients at higher risk of relapse after transplantation.

Background. Hematopoietic Stem Cell Transplant Comorbidity Index (HCT.CI) score, described by Sorror, is a useful tool to assess the risk for Non Relapse Mortality (NRM) after Allogeneic HSCT. The impact of this score in Autologous HSCT is still to be confirmed. Aims. To determine the impact of HCT.Ci score in the morbidity and mortality after autologous HSCT, assessing the 100 day morbidity defined as orothraqueal intubation (OTI), dialysis or shock (defined as vasopressors need), 100 day mortality, early morbi-mortality (combined end-point by any of the previous end-point) and long term NRM. Materials and Methods. We retrospectively reviewed 1478 medical records of adult patients who received an autologous HSCT in our centre between October 2002 and April 2016. Median age was 49 years (range 16-74 years), 58% were male, prevalent diseases were Multiple Myeloma (48%), Non Hodgkin Lymphoma (27%) and Hodgkin Lymphoma (18%), 49% were in complete remission, 46% received one chemotherapy scheme before transplant, 41% two schemes and 12% three or more (heavily pre-treated). In respect to conditionings, melphalan was used in 48% of the cases, CBV in 25%, BEAM in 8% as well as BendaEAM. Seventy five percent received an infusion of stem cells CD34+≥3x10.6/kg. Regarding comorbidities, 58% had low risk (LR) HCT.CI (score 0), 32% intermediate risk (IR) (1-2) and 11% high risk (HR) (≥3). For univariate analysis we use Chi2 for dichotomic variables, Kaplan-Meier for Overall Survival (OS) and cumulative incidence for NRM; for multivariate analysis we used logistic regression for dichotomic and Cox regression for time dependant variables. Results. Median follow up was 1.9 years. Early mortality (day 100) was 2.8%, 5.6% required OTI, 4.8% required vassopresors and 2.2% dialysis, 1-3 years NRM and OS were 4.3-5.2% and 89-77% respectively. High risk HCT.Ci patients had a significant increase in 100 day mortality compared to IR and LR (7% vs.3% vs. 2% respectively, p=0.002), OTI (12% vs. 7% vs. 4%, p Conclusions. We observed that HCT.CI had a significant impact on Autologous HSCT treatment related mortality basically due to early toxicity express as 100 day mortality and the three main morbidity outcomes as well as the combined end point. This observation should be confirmed in larger series. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Tumor necrosis factor (TNF) has been suggested to act as an autocrine growth factor in chronic B cell malignancies. We have attempted to assess the role of TNFα in relation to the stage of chronic lymphocytic leukemia (CLL) by examining TNFα cytotoxic activity of media conditioned by stimulated and unstimulated peripheral blood mononuclear cells (PBMC) and by separated unstimulated malignant B cells from Rai stage 0 and IV patients. The response of PBMC from stage IV to stimulation with phytohemagglutinin, or bacterial lipopolysaccharide was weak or absent. However, stimulation of stage 0 PBMC induced significantly increased production of TNF. Furthermore, unstimulated stage 0 PBMC and B cells from these cases of stage 0 B CLL spontaneously released TNF in significant excess compared to normal PBMC controls while no TNF activity could be detected in supernatants from unstimulated stage IV PBMC or B cells. These data suggest a possible role for TNF in the progression of CLL.

Allogeneic hematopoietic stem cell transplantation (HSCT) using sibling donors is a life-saving intervention for patients with hematological malignancies. It is recognized that numerous genetic factors in both patient and donor play a role in the outcome of the procedure. TGF beta 1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Several functional polymorphisms have been identified in TGF-B1 gene, such as a single nucleotide polymorphism (SNP) at codon 10 of exon 1. We have previously published significant impact of this SNP on unrelated donor (UD) transplant outcome, predominantly on Non Relapse Mortality (NRM) and acute Graft-vs.-Host-Disease (aGVHD). To date there are no published data in large sibling donor HSCT cohorts looking at survival outcomes. We have hypothesized that TGF-B1 SNP may influence the outcome of sibling donor HSCT similarly to UD. Preliminary data were presented at ASH meeting 2014. Two hundred and seventeen patient/donor pairs who underwent a sibling donor HSCT in our centers were genotyped for the presence of a SNP at codon 10 (rs1982073) by an allele-specific PCR. Transplants took place between January 2000 and January 2015 and the median follow up time was 4.4 years. Median age was 33 years and 58% were male. The prevalent diagnoses were acute myeloid leukemia 64 (29%), acute lymphoid leukemia 49 (23%), lymphoproliferative disorders 28 (13%), myelodysplastic syndrome 26 (12%) and myeloproliferative neoplasm 20 (9%). Early stage of the disease was determined in 42%. Myeloablative conditioning regimens were used in 58% of transplants; the source was PBSC in 90% of the patients. The patients' observed SNP frequencies were TT 23%, TC 55% and CC 22%, and for the donors were 26%, 53% and 21% respectively. No significant impacts were observed in the full cohort analysis. When we analyzed the myeloablative cohort, significant differences were founded. Similarly to what we observed in UD, codon 10 CC patients had a significant increase in 1 year treatment related mortality (32% vs. 9%, p=0.01) and Non Relapse Mortality (NRM) (1-3 years CC 31-31% vs. TC/TT 8-13%, Gray's test p=0.04) (figure 1). A very interesting finding was in donor's genotype. Codon 10 TT donor's receptors experienced a significant increase in aGVHD (72% vs. 49%, p=0.03), with 56% of this grades 2-4. Interestingly this group had no protection in terms of relapse, but the opposite, although not significant (1-3 years TT 36-40% vs. TC 17-34% vs. CC 9-13%, Gray's test p=0.1). Finally TT donors had a significant decrease in Overall Survival (OS) compared to other genotypes (1-3 years TT 69-50% vs. TC/CC 77-69%, log-rank p=0.04) (figure 2). No differences were observed in donor genotype in terms of NRM. Besides confirming that as in UD, patient codon 10 CC had an increase in NRM, we conclude that in sibling donor-myeloablative HSCT codon 10 TT donors might be associated with an increase in aGVHD with no protection in relapse and a significant decrease in OS. These results should be confirmed in larger series. Identification of these SNPs pre-transplant will allow for transplant conditioning and immunosuppression regimens to be tailored to the individual patient, as well as assisting in the most appropriate choice of donor. Disclosures No relevant conflicts of interest to declare.

BACKGROUND The objective of this analysis was to evaluate the role of autologous stem cell transplantation (ASCT) in prolonging disease free survival (DFS) and overall survival (OS) in patients with chronic myeloid leukemia (CML) who received autografts of Philadelphia chromosome (Ph) positive or Ph negative cell harvests. METHODS Over a 4-year period (1994–1999), 53 patients who underwent ASCT for CML were reported to the Argentine Group of Bone Marrow Transplantation (GATMO) Registry. RESULTS Ph negative cell products were harvested in only 18 patients (34%). Comparison of disease status at the time of autograft, duration of neutropenia, thrombocytopenia, days of antibiotics, and transfusional requirements of red blood cells and platelets did not reveal statistical significant differences between the Ph positive group and the Ph negative group. Only days of hospitalization were increased significantly in patients who received Ph positive autografts. Although DFS at 36 months was significantly longer after infusion of Ph negative cell products (54% vs. 14%; P ≤ 0.005), OS differences between the Ph negative group and the Ph positive group (68% vs. 53%; P ≤ 0.134) were not significant. CONCLUSIONS ASCT with Ph negative cell harvests after myeloablative chemotherapy resulted in prolonged periods of hematologic and cytogenetic remission or stable disease after cytogenetic/molecular recurrence in some patients with CML. A superior DFS was observed without any benefit observed for OS. Cancer 2002;95:2339–45. © 2002 American Cancer Society. DOI 10.1002/cncr.10931

Allogeneic hematopoietic stem cell transplantation (HSCT) using sibling donors is a life-saving intervention for patients with hematological malignancies. It is recognized that numerous genetic factors in both patient and donor play a role in outcome. TGF beta 1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes. Several functional polymorphisms have been identified in TGF-B1 gene, such as a single nucleotide polymorphism (SNP) at codon 10 of exon 1. We have previously published significant impact of this SNP on unrelated donor (UD) transplant outcome, predominantly on Non Relapse Mortality (NRM) and acute Graft-vs.-Host-Disease (aGVHD). To date there are no published data in large sibling donor HSCT cohorts that analyze survival outcomes. We have hypothesized TGF-B1 SNP may influence the outcome of sibling donor HSCT similarly to UD. One hundred and sixty six patient/donor pairs who underwent a sibling donor HSCT in our centers were genotyped for the presence of a SNP at codon 10 (rs1982073) by an allele-specific PCR. The transplant took place between January 2000 and March 2014 and the median follow up time was 4.4 years. Median age was 33 years and 59% were male. The prevalent diagnoses were acute myeloid leukemia 54 (32%), acute lymphoid leukemia 33 (20%), lymphoproliferative disorders 24 (14%), myelodysplastic syndrome 21 (13%), myeloproliferative neoplasm 9 (5%), and 42% were in early stage. Myeloablative conditioning regimens were used in 58% of transplants; the source was PBSC in 93.3% of the patients. The patients' observed SNP frequencies were TT 22%, TC 56% and CC 22%, and for the donors were 25%, 57% and 18% respectively. No significant impacts were observed in the full cohort analysis. When we analyzed the myeloablative cohort significant differences were founded. Wild-type donors (TT) experienced a significant increase in relapse incidence compared to other genotypes (1-3 years TT 37-41% vs. TC 15-23% vs. CC 0-0%, Gray's test p=0.01), with a significant decrease in disease free survival (DFS) (1-3 years TT 53-39% vs. TC/CC 73-65%, log-rank p=0.04) and overall survival (OS) (1-3 years TT 64-46% vs. TC/CC 77-67%, log-rank p=0.04) (figures). No differences in terms of NRM were founded. We conclude that in sibling donor-HSCT TGF-B1 wild-type donors might be associated with an increase in relapse and subsequent decrease in DFS and OS. These results should be confirmed in larger series. Identification of these SNPs pre-transplant will allow for transplant conditioning and immunosuppression regimens to be tailored to the individual patient, as well as assisting in the most appropriate choice of donor. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Materials and Methods We retrospectively reviewed 137 medical records of patients older than 50 years receiving an allogeneic hematopoietic stem cell transplant (HSCT) in 9 centers from Argentina. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, source, conditioning and immunosupression. We analyzed the incidence and severity of acute Graft-vs-Host disease (aGVHD) with Chi Square, Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier and Relapse, Non Relapse Mortality y chronic GVHD (cGVHD) with CI. For multivariate analysis (MA) we included variables that in univariate had a p Results Patients characteristics are listed in table 1. Between January 1997 and July 2013, 137 transplants were performed in adults older than 50 years, with a median follow up 1.3 years. Acute GVHD incidence was 41% (19% were grade II and 7.3% III-IV). The only variable associated with aGVH clinically significant (G II-IV) was AML that was protective (14% vs 35%, p Conclusion HSCT is a valid therapeutic option for older patients. In this retrospective analysis of patients older than 50 years, we found that the main risk factors that impact in transplant outcome are patients comorbidities and not age, whereas transplant related toxicities increase with the number of comorbidities and therefore decrease OS and DFS. Beyond the fact that certain disease experienced more aGHVD (AML) or cGVHD and higher NRL (MPN) the other factor significantly related in transplant outcome was the use of tacrolimus vs CSA. Disclosures: No relevant conflicts of interest to declare.

Abstract 2031 Background: The role of High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT) as salvage therapy in relapsed Follicular Lymphoma (FL) has been questioned since the introduction of Rituximab in the treatment of FL. Our objectives were to evaluate the long-term event-free survival (EFS) and overall survival (OS) rates of patients with relapsed or refractory FL who received HDT and ASCT as salvage therapy. Our secondary objective was to compare EFS of patients who received ASCT before and after 2002 (the year Rituximab become fully available for use in our country). Patients and Methods: We conducted a retrospective analysis of 123 consecutive patients with relapsed or refractory FL who had received HDT and ASCT as salvage therapy in five Argentinean transplant centers from 1992 to 2012. Results: One hundred twenty tree patients (median age: 48 years, range: 23–72) were transplanted, 71 (58%) male, 37/106 (35%) had FL Grade 1, 47/106 (44%) FL Grade 2 and 22/106 (21%) FL Grade 3; 75/102 (73%) of patients have a stage III-IV disease at the moment of diagnosis and 27/102 (26%) have a disease stage I-II. Before transplantation 78/121 (64%) patients were in Complete Response (CR), 42/121 (35%) were in Partial Response (PR) and one patient had a Progressive Disease. Fifty four patients (44%) were transplanted before 2002 (before Rituximab era in our country). The conditioning regimens used were CBV 94 (76%), BEAM/BEAC 27 (22%), others regimens two patients; only one patient received TBI containing conditioning regimen and was excluded for conditioning regimen PFS curve calculation. The median time from FL diagnosis to ASCT was 29 (range 1–300) months. The transplant related mortality (until day 90 after ASCT) was 5%. With a median follow-up of 52 (range 0–247)months, the median EFS was reached at 44 months and a plateau on the EFS curve was evident starting at 6 years after ASCT. The 10 years-projected EFS was 36% (Figure 1). The median OS was not reached during follow-up. Median EFS for patients who were transplanted before 2002 (before Rituximab era) and for those who were transplanted after 2002 was 41 months and 47 months respectively [HR 1.01; IC (0.61–1.65); p=0.97]. EFS rates difference was not statically significant between patients who previously transplantation have achieved a CR or a PR, median EFS 47 and 68 months respectively [HR 0,94; IC (0,56–1,58); p= 0,82]. There was no difference in EFS rates between patients who received CBV as conditioning regimen and patients who received BEAM/BEAC, median EFS 57.6 months and 16.3 months respectively [HR 0.67; IC (0,34–1.35); p=0.2]. The median EFS rate for patients with FL Grade 1, FL Grade 2 and FL grade 3 were 58, 44 and 16 months respectively, P for trend = 0.78. Seven cases (5,7%) of secondary malignancies were detected, six cases (6/94; 6,4%) in patients who received CBV as conditioning regimen (urotelial carcinoma, pancreas carcinoma, lynfoprolipherative disorders, non-melanoma skin malignancies and prostate carcinoma) and one case (1/27; 3,7%) in patients who received BEAM (urotelial carcinoma), p=0,85; there were no reports of secondary myelodysplastic syndromes/acute myeloid leukemia. Conclusion: In this study, 50% of the patients analyzed were free from progression after 44 months of ASCT and approximately a 30% of patients achieve long term remission. According to this, patients with relapsed or refractory FL can achieve long-term EFS with HDT followed by ASCT. Disclosures: No relevant conflicts of interest to declare.

Abstract 4554 Introduction: Persistent fever in high risk neutropenic patients (HRNF) after day 5 of empiric treatment is a sign of high susceptibility for IFI with elevated morbidity and mortality. Diagnostic tools in this setting are inaccurate to determine the occurrence of IFI and most patients start with empiric antifungal agents. Drugs are usually associated with increasing costs and toxicity. It is challenging to establish the population of patients in whom in spite of persistent fever and neutropenia, avoidance of antifungal treatment is a reasonable strategy. Methods: We have prospectively allocated 229 HRNF patients in different empiric antimicrobial regimens over a 4.5 year period. In a retrospective revision, there were 33 patients with persistent fever on day 5 of empirical antimicrobial treatment and no evident new infection episode or clinical impairment. In 28 patients, a thorax CT scan was performed as part of the evaluation of persistent fever. The clinical outcome was evaluated regarding the presence or absence of pulmonary infiltrates in the CT scans. Initial empiric antifungal treatment, transfusions, days in hospital, days with neutropenia, antimicrobial treatment, and days with fever were evaluated. Results: Nineteen patients (68%) of 28 presented with pulmonary infiltrates. All of them received antifungal treatment. In 9 patients with normal CT scan antifungal treatment was deferred. The difference of the decision in not giving antifungals according CT scans was highly significant (p Conclusion: In HRNP, normal thorax CT scan changed the clinical decision in not starting antifungal treatment in spite of persistent fever. There was no difference in mortality with patients under antifungal treatment, allowing continuing with this strategy in more patients in the future. Disclosures: No relevant conflicts of interest to declare.

Allogeneic haematopoietic stem cell transplantation (HSCT) using volunteer unrelated donors (UD) is a life-saving intervention for patients with haematological malignancies. It is recognised that numerous genetic factors in both patient and donor play a role in outcome. TGF beta 1 is a member of a highly pleiotrophic family of growth factors involved in the regulation of numerous immunomodulatory processes and may play a role in carcinogenesis. Several functional polymorphisms have been identified, such as a single nucleotide polymorphism (SNP) at codon 10 (c.29T>C, p.L10P) of exon 1. Conflicting data has been published regarding the impact of the SNP on plasma levels and its role in sibling HSCT. To date there are no published data in UD HSCT. We hypothesised that this polymorphism may influence the outcome of UD HSCT by modulating the immune response. We genotyped, for the presence of a SNP at codon 10, a large group of patient/donor pairs (314) who underwent an UD HSCT using a donor provided by the Anthony Nolan Trust, in a UK transplant centre. The transplant took place between 1997 and 2006 and the median follow up time was 5.8 years (0.8–10.18 years). The diagnoses were chronic myeloid leukaemia 69 (21%), acute lymphoid leukaemia 76 (24%), acute myeloid leukaemia 76 (24%), myelodysplasic syndrome 25 (8%), lymphoproliferatives disorders 37 (11.8%) and others 31 (9.9%). Myeloablative conditioning regimens were used in 69.9% of transplants; T-cell depletion was included in 86.9% of conditioning protocols. Sixty eight percent of the transplants were full matched (10/10), and 12.7% were 12/12. The patients’ observed SNP frequencies were TC 55.7%, TT 32% and CC 12.1%, and for the donor were 51%, 34.7% and 14.3% respectively. There were no significant effects of the presence of a SNP in either the patient or donor groups alone. However, when we analysed the impact of the total number of SNPs present in the pair, we found that multiple SNPs (3–4 SNPs vs 2 or less) were associated with a significantly decreased overall survival (OS) (5 years: 30% vs 42%, log-rank p=0.04), disease free survival (DFS) (5 years: 17% vs 25%, log-rank p=0.02) and a higher treatment related mortality (1 and 3 years: 42% and 45% vs 25% and 30%, respectively, log-rank p=0.03). In multivariate analysis there was a trend to improved OS in the pairs with fewer SNPs (HR: 0.7; 95% CI 0.4,1.0; p=0.07). We speculated that the impact of the donor genotype might differ depending on the patient genotype. In patients with a wild type genotype, the donor genotype did not impact significantly on outcome. Conversely, the patients with a SNP at codon 10 (TC or CC), had significantly better DFS when using a donor with a wild type genotype compared to those with a SNP present (5 years: 34% vs 21%; log-rank p= 0.04). In conclusion, we have shown for the first time in a large number of UD HSCT pairs that increased numbers of SNPs in the TGFB1 gene at codon 10 in patients and donors are associated with a worse outcome following UD HSCT. While an exact functional mechanism remains unclear, these data emphasise the importance of pursuing functional analyses of TGF beta in this setting. In addition, identification of these SNPs pre-transplant will allow for transplant conditioning and immunosuppression regimens to be tailored to the individual patient, as well as assisting in the most appropriate choice of donor.

Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

AML is a disease frequently observed in elderly patients (pts) Treating this population with intensive chemotherapy or palliative treatment is a controversial decision. We analysed the available evidence with a decision model tree considering prognosis and comorbidities. Method: A decision tree was designed to model significant events and prognostic variables that have an impact in survival at 5 years. The probabilities of this items were obtained from a literature review and for those items without literature support, assumptions were made by an expert opinion based on investigator’s consensus. Utility of each strategy was defined in an ordinal scale and the preference for each was calculated as the expected utility (utility x probability of the result) Results: Probabilities were: unfavourable prognosis 95%, incidence of comorbidities 48%, death in induction without comorbidities 25%, response to induction in unfavourable prognosis 42%, response to induction in favourable prognosis 63%, adequate performance status after induction without comorbidities 43%, probability of finishing consolidation 64%, survival at 5 years in pts with unfavourable AML 11%, survival at 5 ys in pts with favourable AML 27%. The effect of comorbidities on survival to induction and adequate PS post induction was estimated as 50% higher than in pts without comorbidities. The survival at 5 ys in pts with no response or those who did not complete induction was considered equal to palliative treatment, and S at 5 ys in pts with comorbidities who finished consolidation 30% less than in those with no comorbidities. Utility for “not to treat” was 11, and for “to treat” was 6. The preference for “not to treat” was maintained for any modification of the survival to the induction chemotherapy independently of comorbidities. In sensitivity analysis, the only modification of the observed preference was that “To treat” strategy would be preferable only if the good PS after induction chemotherapy would be observed in 65% of pts or more. In conclusion, the preferred strategy as suggested by the model is “not to treat”, however many relevant questions are still unanswered, reinforcing the need to include these pts in clinical trials for better evidence to base the decisions.

The relapse post ABMT is a terminal stage complication in HD. The allogenic transplant contributes to a different therapeutic approach through the immune anti tumor effect of the Graft versus Host Disease (GVHD) The NST variant of the procedure diminishes the risks of transplant related mortality (TRM) and is associated with induction of mixed hematopoietic chimerism when either HLA-identical sibling or unrelated donor are used, and that powerful GVT effects can be achieved against advanced chemotherapy/resistant hematology disease. The feasibility, risk and effectiveness of the NST, is analyzed in 13 patients with relapsed HD after ABMT. Seven women and six men with a median age of 26 years old. They had received ≥ of 3 therapeutic lines that included the high doses and the ABMT. The period betwen the diagnosis to NST, had a median time of 36 months. The patients were conditioned with Fludarabine based schemes plus: Melphalan 8, Cyclofosfamide 3, TBI 1, Busulfan 1. The sources of stem cells were, with a HLA-identical sibiling donors in 12 patients, and in 1 with non related donor. 4 patients died due to complications associated with the BMT (TRM 28 %): shock 2, sepsis 1, thrombotic microangiophaty 1. Half of the patients developed some form of GVHD, or it was induced by donor lymphocytes infusion. With an average follow up of 15 months (range: 1–56), 7 patients are alive, 5 of them developed GVHD and are in CR, the other 2 have a short follow up (28 and 75 days). Of 4 patients who progressed only 1 present GVHD. The NST is a feasible procedure in HD relapsed post ABMT. The TRM is 28 %. In this group there is a clear relationship between the control of HD and the appearance of GVHD.

In vitro studies were performed in a patient with B-cell chronic lymphocytic leukemia who developed pure red cell aplasia (CLL-PRCA). The patient's irradiated circulating mononuclear blood cells and supernatant markedly inhibited normal marrow erythroid (but not granulocyte-monocyte) progenitor colony proliferation. In contrast, irradiated peripheral blood mononuclear cells and supernatant obtained from a B-CLL patient (Rai stage III) and from a hematologically normal donor, did not affect hematopoietic progenitor colony growth. These findings suggest that the anemia of CLL-PRCA evolves different mechanisms of those causing anemia in CLL, and is mediated through cellular and secretory mechanisms.

Rationale and objectiveHodgkin lymphoma (HL) is largely curable owing to improvements in treatment since the 1960s; nevertheless, high mortality rates have been reported in Central and South America. We describe the current burden of HL in the Central and South American region.MethodsWe obtained regional- and national-level incidence data from 48 population-based cancer registries in 13 countries, and national-level mortality data from the WHO mortality database for 18 countries. We estimated world population age-standardized incidence rates (ASRs) and age-standardized mortality rates (ASMRs) per 100,000 person-years for 2003–2007 and present distributions by histological subtype.ResultsHL incidence rates varied 7-fold in males and 11-fold in females (male-to-female ratio 1:1–2.5:1). The highest ASRs were seen Argentina, Brazil, Costa Rica (males), Cuba (males) and Uruguay (females), whereas the lowest were in Bolivia and El Salvador. ASMRs varied by 4-fold in males and 6-fold in females (male-to-female ratio 1:1–4.3:1), with ASMRs