ALBERT

Description: The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher in pretreated transferred than non-transferred patients (71.8% vs. 44%; p = 0.0009), mainly to NRTI (72.8% vs. 31.1%; p 

Description: INTRODUCTION Anemia is the most frequent cytopenia in lower-risk MDS. Erythropoietic-stimulating agents (ESAs) are commonly used in these patients. The use of ÒclassicalÓ parameters (EPO and ferritin levels) and the revised IPSS (IPSS-R) has been proposed1 (SantiniÕs score) to predict response to ESAs and overall survival (OS) among patients with lower risk MDS by IPSS and a favorable Nordic group score2. OBJECTIVES The main objective of the study was to evaluate overall response rate (ORR) to ESAs and OS according to the proposed SantiniÕs score in an independent and large cohort of anemic lower risk MDS patients receiving treatment with ESAs. METHODS Data from 530 anemic patients with low/int1 risk IPSS de novo MDS (according to FAB and WHO criteria) and sufficient follow-up data available were recorded in Spresas3 (SPanish Registry of Erythropoietic Stimulating Agents Study from GESMD). Two hundred and twenty six patients (42.6% of the patients) were selected according to specific criteria regarding the published SantiniÕs score1: Hb level 350 ng/mL(=1) and IPSS-R very low=0, low=1, intermediate=2 and high=3) yielded a score ranging from 0 to 5. ESAs response rate and overall survival were analysed according to these score. Response to treatment was evaluated according to IWG 2006 response criteria and a multivariate logistic regression analysis was used to identify independent predictors of erythroid response (ER). OS were defined as the time between diagnosis and the corresponding event or last follow up (Feb 2015) and were analyzed using univariable and multivariable Cox proportional hazards regression methods. RESULTS Median age was 77 years (interquartile range [IQR] 25%-75%: 71-83 y), median Hb level at start of treatment was 10 g/dL (IQR25-75: 9-10), median EPO level was 90 (IQR25-75: 27,25-108) and median ferritin level was 338,5 (IQR25-75: 146,5-568,75). Among 139 patients with this data available, 85 patients (61,1%) were RBC transfusion dependent before ESAs treatment. Median time from diagnosis to ESAs treatment was 82 (IQR25-75: 27-353) days. According to the IPSS, 68.6% (N=155) and 31.4% (N=71) were in low and Int-1 risk groups, respectively. Regarding IPSS-R, 23% (N=52), 66.8% (N=151), 9.7% (N=22) and 0.4% (N=1) were in very low, low, intermediate and high risk, respectively. ORR to ESA treatment was 71.2% (N=161), with a median duration of response of 2.06 years. Prognosis factors of ER showed a trend toward to a higher ER among patients in the lower IPSS-R (P〉0.05), low IPSS (p=0.039) and lower EPO levels (p

Description: Abstract 3142 Background: Recent studies indicate that the use of highly effective rituximab (R)-containing primary therapy in Diffuse Large B-cell Lymphoma (DLBCL) makes it more difficult to salvage patients who are refractory or who relapse. To date, peripheral-blood autologous stem-cell transplantation (PBASCT) is the reference treatment for these patients, but the impact of previous exposure to R on the ulterior results of ASCT is still unknown. Patients and methods: We have retrospectively analysed 252 patients (pts) with DLBCL or grade 3B follicular lymphoma with relapsed or refractory disease after at least one rituximab-containing regimen (“R+” group) who received PBASCT in 17 GELTAMO centers, in comparison to a control group of 127 patients who received APBSCT as salvage therapy without previous exposure to rituximab (“R-” group). Patients with refractory disease at transplant were excluded from the analysis. Results: No significant differences between R+ and R- groups were found with respect to age-adjusted IPI at transplant, disease status at salvage therapy and at transplant, nor number or prior chemotherapy regimens. More patients in the R+ group were ≥60 years (30% vs 19%, p=.02). Complete response (CR) (69% v 70%) and overall response (84% v 83%) rates to PBASCT were similar in R+ and R- groups. In multivariate analysis, factors with significant influence on CR rates were: age-adjusted IPI at diagnosis (

Description: Background: Clinical, morphological and genetic characteristics of chronic myelomonocytic leukemia (CMML) are heterogeneous and vary from a myelodysplastic predominant profile to a myeloproliferative one. CMML has a highly variable course, with a median overall survival (OS) of 20 months and 15-30% of progression to acute myeloid leukemia (AML). Cytogenetic abnormalities are present in only 20-40% of cases. CMML-specific cytogenetic risk classification stratifies karyotypes into three groups: low risk (normal karyotype and isolated loss of Y chromosome, -Y), poor risk (trisomy 8, monosomy 7, 7q deletion and complex karyotype) and intermediate risk (all other chromosomal abnormalities). According to this model, 65-85% of patients fall into the low risk cytogenetic category. The aim of this study was to characterize type, frequency and prognostic impact of cytogenetic alterations detected by SNP arrays (SNP-A) in a series of 128 patients with CMML and low risk cytogenetic features or no metaphases. Methods: A retrospective study was performed on 128 patients with CMML. Cases with normal karyotype (n=120), isolated -Y (n=4) and no metaphases (n=4) were selected. Median age at diagnosis was 73 years (range 39-98), there was a 2.4:1 male predominance and 22.4% (28/125) of cases progressed to AML. Median follow up of patients was 26 months (range 1-115). Morphological WHO subtypes were CMML-1 in 104 (81%) cases and CMML-2 in 24 (19%). According to the FAB criteria 82 (64%) cases were included in the myelodysplastic variant (CMML-MD) and 46 (36%) in the myeloproliferative one (CMML-MP). High density SNP-A (Cytoscan HD, Affymetrix) were performed using DNA extracted from bone marrow (n=124) or peripheral blood (n=4) samples at diagnosis. The statistical analysis was performed with SPSS. Kaplan-Meier method was used for OS and progression-free survival (PFS) analysis and log-rank test was used for comparisons between groups. Results: SNP-A revealed novel chromosomal alterations (copy number alterations, CNA, and loss of heterozygosity, LOH) in 66% (85/128) of cases. Among the abnormal cases (CNA plus LOH), 1 alteration was detected in 65% (55/85) of cases, 2 in 20% (17/85) and ≥3 in 15% (13/85). The median size of the affected genome for CNA and LOH was 759 Kb (range 0-142Mb). CNA were detected in 38% (48/128) of cases, most of them being gains and losses smaller than 10Mb. Only 7 CNA were larger than 10Mb, four of them corresponded to patients with isolated -Y and three were novel alterations that had not been detected by conventional G-banding cytogenetics. Most affected regions (detected in 5 cases) were gains in chromosomes 3q, 8p and 21q as well as losses in chromosomes 10q and 12p. LOH were detected in 39% (50/128) of patients. Interstitial LOH larger than 〉25Mb were detected in 30% (39/128) of cases. Recurrent interstitial LOH were detected in: 4q24-4q35 region (12 cases), involving TET2 gene, which is mutated in 40-50% of CMML; and in chromosome 11 (9 cases), 7 of which included 11q13.3-11q25 region, involving CBLgene, mutated in 5-20% of CMML. Although the number of total alterations (1, 2 or ≥3) do not have a survival impact, we found a significant correlation between the size of the affected genome (≥30 Mb, including CNA and LOH) and a poorer OS (OS at 3 years 26% vs. 46%, P=0.039). Regarding type of alterations, cases with interstitial LOH had lower OS than cases without LOH (OS at 3 years 19% vs. 45%, P=0.049). Cases with high risk alterations as defined by CMML-specific cytogenetic risk classification (losses in 7q, gains in 8q and ≥3 CNA) had lower PFS than patients with other aberrations (PFS at 1 year 76% vs. 93%, P=0.036), although statistical significance was not reached for OS (OS at 3 years, 27% vs.49%, P=0.096). Conclusions: SNP-A in CMML patients with low risk cytogenetic features or no metaphases has led to the detection of chromosomal alterations in 66% of cases. Using this technique the prognosis can be better defined, and we can detect a group of patients with worse outcome who could be considered for more intensive treatment. Acknowledgments: Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain (PI 11/02519; PI 11/02010); RTICC, FEDER (RD12/0036/0044; RD12/0036/0014); 2014 SGR225 (GRE) Generalitat de Catalunya; Fundació Internacional Josep Carreras, Obra Social “La Caixa” and Celgene Spain; NHRI-EX103-10003NI, Taiwan. Footnote: Francesc Solé and Lurdes Zamora contributed equally Disclosures Xicoy: Celgene: Honoraria. Sole:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: INTRODUCTION: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard treatment for patients with relapsed or refractory aggressive B-cell lymphoma, and is frequently used as part of first-line therapy in patients with peripheral T-cell lymphoma (PTCL). However, long-term remission rates with this strategy are inferior to 50%, so novel approaches are required. We have designed a prospective multicenter phase II study to evaluate the safety and efficacy of bendamustine as part of conditioning regimen in patients with aggressive lymphomas undergoing ASCT. METHODS: Inclusion criteria were: histologic diagnosis of i) relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or grade 3B follicular lymphoma (FL) in partial response (PR) or complete remission (CR) after salvage therapy, or ii) transformed DLBCL or peripheral T-cell lymphoma (PTCL) in first or subsequent PR or CR. Conditioning regimen consisted of bendamustine (200 mg/m2, days -7 and -6), etoposide (200 mg/m2, days -5 to -2), cytarabine (400 mg/m2, days -5 to -2), and melphalan (140 mg/m2, day -1) (BendaEAM regimen). Primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints were toxicity, response to transplant at 3 months, and overall survival (OS). This trial was registered at EMEA (EUDRACT number 2010-020926-17). RESULTS: Sixty patients (median age 54 years, range 27-70) from 22 Spanish hospitals were included since May 2011 to November 2012. Histologies were: 40 DLBCL, 3 grade 3B FL, 13 transformed DLBCL, and 7 PTCL. 82% of patients have received ³2 lines of treatment prior to ASCT. 37 patients (62%) were in CR at the time of transplant and 23 (38%) in PR. A median number of 4.05 x 106/Kg (range: 1.69-19.80) CD34+ cells were reinfused. All patients (except one who died early) engrafted after a median of 11 (range: 9 to 72) and 14 (range: 4 to 53) days, respectively, to achieve 〉0.5 x109/L neutrophils and 〉20 x109/L platelets. 39 serious adverse events (SAEs) were reported before day +100, including 14 infectious episodes, 2 of them resulting in respiratory failure and death (3.3% of transplant related mortality). Another major SAE was renal toxicity developed by 5 patients (8.3%) after bendamustine administration, reversible in all cases (3 of these patients had developed mild renal failure during previous salvage therapy). Non-relapse mortality after day +100 was 3.3% (1 patient died because of Wernicke's encephalopathy, and 1 patient from infectious complications). Concerning response to transplant, 44 patients (73.3%) achieved CR, 7 (11.7%) PR, and 6 patients (10%) did not respond. Univariate analysis showed that patients who received more than 2 lines of treatment prior to transplant (1 line: 100% of CR post-transplant; 2 lines: 71%; 〉2 lines: 50%; p=0.013), and those who were in PR at transplant (48% vs 89%, p0.1). At the time of analysis, 13 patients (22%) had disease progression and 8 patients (13%) have died (4 from lymphoma, and 4 from other causes). With a median follow-up of 18.9 (9.5 to 32.3) months, the estimated 2-year PFS and OS were 73% and 88%, respectively. CONCLUSIONS: The BendaEAM conditioning regimen is feasible and active in patients with aggressive lymphomas. Toxicity profile is similar to that commonly observed in the ASCT setting, but renal toxicity can occur and should be carefully monitored, especially in patients with prior history of renal failure. Longer follow-up is needed to assess the long-term toxicity and the efficacy of this regimen, although patients who are not in CR before transplant seem to have poorer outcomes. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: We have evaluated the clinical outcome and the prognostic variables in patients with large B-cell non-Hodgkin’s lymphoma (DLBCL) who relapse after autologous stem cell transplantation (ASCT). Methods. One hundred and two patients autografted for DLBCL [58 males (60%) and 44 (40%) females, median age of 49 (18–70) years] reported to the GEL/TAMO Cooperative Group between July 1993 and July 2007 who relapsed at a median time of 9 (range, 2–90) months after ASCT were included in this retrospective multicenter study. Inclusion criteria were to achieve at least a partial response (PR) after transplant and to receive treatment after relapse. After transplant 81 patients (79.4%) had achieved complete remission (CR), 11 (10.8%) uncertain CR, and 10 (9.8%) were partial responders. At relapse or progression, 65 patients (67%) had advanced clinical stage, 28.4% presented with B symptoms, 20 patients (15%) had age older than 60 and 13.8% with a bulky disease. Forty-seven percent of the patients had an age-adjusted IPI 2 or 3 and 52 (53.6%) and 25 (41%) had an elevated LDH or a high beta 2 microglobulin respectively. Regarding treatment at relapse or progression, forty-seven patients (46%) received rituximab, either alone (n=7) or in combination with chemotherapy (n=40), 44 received chemotherapy, 6 involved-field radiotherapy and the remaining 5 patients received a palliative treatment. Finally, 20 patients received a consolidation therapy with a second stem cell transplantation, (9 a second ASCT, and 11 an allogeneic transplant). Results. Overall response (OR) rate was 54% (38.2% CR). Among the 47 patients who received rituximab-based protocols, the OR rate was 70.2% (48.9% CR). With a median follow-up after relapse/progression of 39.3 months (2.6 to 121.8) for surviving patients, the median overall survival (OS) from ASCT failure was 288 days with a median time to progression of 120 days. The actuarial 5-year OS and event-free survival (EFS) for the entire population of relapsed patients were 30.7% and 0%, respectively. Adverse prognostic factors significantly influencing OS and EFS in multivariate analyses were: haemoglobin level