ALBERT

Description: 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

Description: 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.

Description: Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status〉 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.

Description: 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.

Description: 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

Description: 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.

Description: 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.

Description: 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

Description: Patients with stage I-II A non bulky Hodgkin’s lymphoma (HL) are successfully treated with 2–4 cycles of ABVD plus IF radiotherapy (RT). Although the negative impact in DFS and OS of B symptoms and bulky disease(X) is widely accepted, other risk factors such as number of lymph node regions involved or extensive spleen involvement have also been reported. What is the best treatment for such patients? Is radiotherapy necessary? We report here our experience with protocol HD 98 in 62 patients, with stage I–II HL. Since January 98 we have included 30 individuals without risk factors and 32 with one of the following risk factors: B symptoms (n:11), X (n:9), extensive spleen involvement (n:1) and involvement of more than two lymph node regions (n:11). Other patient characteristics were: age: x 31yrs (15–69), sex: females 31, males :31. Ann Arbor stage IA :11, IB :1, IIA: 36, IIB :14. Histologic subtypes were: LP: 4, NS: 42, MC: 15, lymphocyte rich :1. Patients with favourable features received 4 cycles of ABVD plus IFRT, those with unfavourable factors received 6–8 cycles of ABVD plus RT in areas of bulky or residual disease. Results: 59/61 evaluable patients obtained CR or CRu. Two patients were considered primary resistant. Three patients relapsed at 7, 13 and 30 months after completion of treatment. Autologus bone marrow transplant was performed in four patients. The two primary resistant patients relapsed after the transplant and died with proggressive disease. Those patients transplanted in a chemosensitive relapse are currently in CR. With a median follow up of 46m (13–84) 96.7% of the patients are alive, in CR. Conclusions: In our experience patients with unfavourable stages I–II HL are succesfully treated with 6–8 cycles of ABVD. In such patients RT might only be necessary in areas of bulky or residual disease.

Description: 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.