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The molybdenum cofactor deficiency is an autosomal recessive disease, characterized by rapidly progressive and severe neurological damage that mimics a hypoxic-ischemic encephalopathy due to the accumulation of toxic metabolites that cause rapid neurodegeneration after the delivery. It is eventually lethal, in a similar way to the rare isolated sulfite oxidase deficiency. This serious pathology usually causes death in the immediate neonatal period in the more severe variants. We report a case of two consecutive pregnancies with enlarged cisterna magna as the only prenatal pathological finding since 26 weeks of gestation (WG) and the subsequent death of the newborns in the first week after birth. After the second pregnancy, we reached the diagnosis of molybdenum cofactor deficiency due to MOCS1 gene mutation. According to the cases reported in the literature, this is the case with the earliest neuroimage prenatal findings.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph− adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry)

Prognosis for relapsed or refractory (R/R) acute myeloid leukemia (AML) despite salvage therapy is dismal. This phase I dose-escalation trial assessed the safety and preliminary clinical activity of selinexor, an oral exportin-1 (XPO1) inhibitor, in combination with FLAG-Ida in younger R/R AML patients. The aim was to find the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD). Fourteen patients were included, and selinexor dosage was 60 mg (3 patients), 80 mg (3 patients), and 100 mg (7 patients) weekly. No dose-limiting toxicities were reported. Grade ≥3 non-hematologic adverse events (AEs) occurred in 78.6% of patients. Two patients were non MTD evaluable due to early death, and overall, 3 out of 14 patients (21.4%) had fatal AEs. Five out of 12 (42%) response and MTD evaluable patients achieved a complete remission (CR; n=4) or CR with incomplete hematologic recovery (CRi, n=1), and 4 patients (33%) subsequently underwent allogeneic transplantation. The median overall survival (OS) and event-free survival (EFS) were 6.0 (range 0.9-19.3) and 1.1 months (range 0.7-19.3), respectively. Using selinexor 100 mg/weekly, CR/CRi rate of 66.7%, OS 13.6 months (range, 1.6-19.3), and EFS 10.6 months (range, 0.9-19.3). At last follow-up, 3 patients were alive. Selinexor 100 mg/weekly with FLAG-Ida combination in R/R AML showed acceptable tolerability and efficacy, establishing the RP2D of this regimen in future clinical trials. ClinicalTrials.gov Identifier: NCT03661515.

[Background]: The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL)., [Patients and Methods]: Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years., [Results]: Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS., [Conclusion]: Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy., This study was supported in part by the CERCA Program/Generalitat de Catalunya, Spain and the Josep Carreras Leukemia Research Institute, Badalona, Spain.

Background: Genetic information has become critical to understand the development of T-cell acute lymphoblastic leukemia (T-ALL) and to elucidate the origin of disease relapse. Several genetic markers, together with measurable residual disease (MRD), are considered strong predictors of patient outcome. However, the prognostic significance of genetic markers can varie according to treatment. Aim: We used targeted deep sequencing to analyze the genetic profile of 125 T-ALL patients enrolled in three consecutive MRD-oriented trials from the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genomic information was analyzed together with the main clinical and biologic data in a subset of 111 patients with detailed clinical and outcome data to determine the prognostic significance for overall survival (OS) and cumulative incidence of relapse (CIR). Methods: Genetic mutations were detected using a custom gene panel and sequenced on a MiSeq platform. Alignment, variant calling, filtration and annotation of variants were done using standardized pipelines. OS curves were plotted by the Kaplan-Meier method and compared by the log-rank test. CIR was estimated using cumulative incidence functions by competing risks analysis. A Cox proportional hazard regression model was used to identify predictive factors for OS. Statistical significance was set at (two-sided) p-values Results: Recurrently mutated genes found in ≥4/125 patients involved transcription factor tumor suppressor genes (PTEN, BCL11B, RUNX1, GATA3, ETV6), epigenetic regulators (PHF6, DNMT3A, EP300, KMT2C, EZH2, TET2), DNA mismatch repair genes (MSH2), ribosomal (RPL5) and RNA splicing (U2AF1) genes, and genes involved in the RAS/MAPK (NRAS), WNT (FAT1, FAT3), IL7R-JAK-STAT (JAK3, JAK1, IL7R) and NOTCH1 signaling pathways, respectively. Mutations in the latest pathway (NOTCH1 & FBXW7) was found in 88/125 (70%) patients. Clinical-genetic correlations revealed that patients with mutations in JAK3, DNMT3A, N/KRAS, IL7R, MSH2 or in U2AF1 were associated with lower OS (vs unmutated patients). None of the mutated genes had impact on CIR. Upon grouping the mutated genes according to their functional role and potential biological impact on T-ALL, two gene signatures were defined. These included the aging gene signature (DNMT3A and U2AF1) characterized by mutations in genes identified in clonal hematopoiesis of indeterminate potential (CHIP); and the treatment resistance gene signature (JAK3, N/KRAS, IL7R and MSH2), defined by mutations in genes involved in resistance to the ALL therapy. Both clusters identified patients with poorer response to therapy (poorer blast clearance on day 14 of induction treatment and lower CR rates). Therefore, we considered together (worse outcome genetics [WOG] signature) for univariate and multivariate analyses. WOG and MRD level (0.1% cut-off) on day 35 after induction therapy (+35d MRD) showed significant prognostic impact in the univariable and multivariable analyses for OS (3y) with a hazard ratio (95% CI) of 2.4 (1.2; 4.8) and 2.7 (1.4; 5.1), respectively (Table 1). OS according to these two variables allowed risk stratification of T-ALL into low, intermediate- and high-risk (HR) patients with significantly different outcomes (p Conclusion: A genetic signature with independent prognostic significance of MRD has been identified in this cohort of patients included in MRD-oriented trials. This gene signature (WOG) together with MRD could help to improve risk-stratification of adult T-ALL patients and would be of interest in the search for new therapies for HR patients Funding: Support from AECC (GC16173697BIGA); ISCIII (PI19/01828 and PI19/01183), co-funded by ERDF/ESF, "A way to make Europe"/"Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ C González-Gil was supported by AGAUR grant (2020 FI_B2 00210). Figure 1 Figure 1. Disclosures Diaz-Beyá: Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mercadal: Gilead Sciences, Inc.: Honoraria, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tormo: Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Barba: Amgen, Celgene, Gilead, Incyte, Jazz Pharmaceuticals, MSD, Novartis, Pfizer and Roche, Jazz Phar,aceuticals: Honoraria; Cqrlos III heqlth Institute, aSOCIACION espanola contra el cancer, PERIS: Research Funding. Maciejewski: Regeneron: Consultancy; Novartis: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Alexion: Consultancy. Ribera: ARIAD: Consultancy, Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; NOVARTIS: Consultancy, Speakers Bureau; SHIRE: Consultancy, Speakers Bureau.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3–4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome., Supported in part with the grants PI10/01417 from Fondo de Investigaciones Sanitarias and RD12/0036/0029 from RTICC, Instituto de Salud Carlos III, 2014 SGR225(GRE), CERCA Program, Generalitat de Catalunya, Spain, and a funding from ‘La Caixa’ Foundation.

About 25–35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18–60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

Purpose The evaluation of bone marrow infiltration (BMI) is of crucial importance in the staging of lymphoma. Although bone marrow biopsy (BMB) is the reference standard for the evaluation of BMI, it has limitations. PET/CT has become an excellent tool in staging of lymphoma, and bone marrow uptake is correlated with the involvement of lymphoma. The aim of this study was to assess the utility of PET/CT and its concordance with BMB in the detection of BMI in patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). Patients and methods One hundred forty-seven patients with DLBCL (84) and HL (63) were referred for a PET/CT and a BMB (unilateral) at the initial staging. The reference standard was BMB. Results Bone marrow infiltration was detected by PET/CT in 39 (26%) and by BMB in 21 (14%) cases. There was concordance between PET/CT and BMB in 128 patients (87%) (74 DLBCL, 54 HL), 21 with positive PET/CT and BMB results and 107 with negative PET/CT and BMB results. Discordant results were observed in 19 patients (14%); 18 of them with positive PET/CT and negative standard BMB results (not performed in active sites). The sensitivity, specificity, accuracy, as well as positive and negative predictive values of FDG-PET/CT for the detection of BMI were 95%, 86%, 87%, 54%, and 99%, respectively. Conclusions PET/CT detects more bone marrow involvement in DLBCL and HL compared with BMB. Its good concordance with BMB makes it a complementary technique, as it helps select the biopsy site in cases with negative results.

Introduction: Recent studies have shown that young to middle-aged adults who receive a pediatric-inspired chemotherapy regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they achieve good response on MRD testing after induction and/or consolidation therapy. Patients (pts) who are not good MRD responders achieve better outcomes with alloHSCT than their counterparts who do not receive alloHSCT. However, it is not clear if this approach can specifically apply to adult ALL pts with HR features at baseline. The aim of the prospective ALL-HR-11 trial (NCT01540812) from the Spanish PETHEMA Group was to evaluate response of HR Ph-neg adult ALL patients to a different post-induction therapy (chemotherapy or alloHSCT) according to MRD levels (centrally assessed by 8-color flow cytometry [FCM]) at the end of induction (week 5) and consolidation therapy (week 17).. Patients and methods: HR ALL included one or more of the following parameters at baseline: age 30-60y, WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or KMT2A rearrangements or complex karyotype. Induction therapy included vincristine, prednisone, daunorubicin and asparaginase (E coli native or PEG according to center availability) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in pts not achieving CR or in those in CR with MRD≥0.1% at the end of induction. For pts in CR and MRD Results: On April 2019, 307 HR ALL pts were evaluable. Median (range) age was 40 (15-60) y, 192 were males, 211 precursor B-ALL and 96 T-ALL, with a median WBC count of 12.9 (0.2-564) x109/L. Results of Induction-1 (n=304, 3 on induction): therapy-related death: 12(4%), resistance: 39(13%), CR: 253(83%). MRD Conclusions: This trial, in which post-induction therapy was only based on MRD results assessed by FCM, suggests that avoiding alloHSCT does not hamper the outcome of HR Ph-neg adult ALL pts with adequate MRD response after induction and after consolidation. Better post-remission alternative therapies are specially needed for patients with poor MRD clearance. Supported by grants PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain. Disclosures Montesinos: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Research support, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Research support; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Research support, Research Funding, Speakers Bureau. Esteve:Novartis: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Pfizer: Consultancy; Astellas: Consultancy, Speakers Bureau; Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy.

Background and objective. Specific immunochemotherapy is the standard treatment of patients with Burkitt leukemia or lymphoma (BL/L). The BURKIMAB08 trial showed 3-yr overall survival (OS) probability of 72% (Ribera JM et al, Cancer. 2013; 119:1660-8). However, the toxicity was high, and 11% of patients died in complete response (CR). In the BURKIMAB14 trial, dose-intensity of chemotherapy blocks was reduced in patients ≤55 years who achieved CR, with the aim to decrease the death rate without impact on efficacy. We present the results of this trial in 80 patients with BL/L and compare them with those of the BURKIMAB08 trial. Patients and method. All patients received a pre-phase with cyclophosphamide, prednisone and rituximab. Patients in localized stages (I-II non-bulky) received 4 blocks of immunochemotherapy (A1, B1, C1, A2), with 33% reduction of doses of iphosphamide, methotrexate and ARA-C in patients ≤55 years in CR (assessed by PET-CT) after B1 cycle. Patients in stages III-IV and mature B-ALL received 6 immunochemotherapy blocks (A1, B1, C1, A2, B2, C2), with the same dose reduction in cycles C1, A2, B2, C2 in patients ≤55 years in CR after B1 cycle. Patients >55 years received reduced intensity chemotherapy (as in BURKIMAB08) in both induction and post-induction cycles. The CR rate, cumulated incidence of relapse (CIR) and OS were analyzed and compared with those from the BURKIMAB08 trial. Results. From 2014-2019, 80 patients with BL/L were enrolled. Median age (range): 48 (17-80) years, 57 (71%) ≤55 years, 61 males (76%), 15 (19%) patients in stages I-II non-bulky and 65 (81%) in stages III-IV, 25 of whom (38%) had mature B-ALL. 18 patients (23%) were HIV positive, 13 (17%) showed CNS involvement at diagnosis and 23 (31%) bulky mass (>10 cm). 45 patients (60%) had intermediate-high or high IPI. All patients in stages I-II non-bulky showed CR. 4/65 patients in stages III-IV or mature B-ALL are receiving induction therapy, 1/65 withdrew the trial, 7/60 (12%) died in induction, 2/60 (3%) were resistant and 51/60 (85%) achieved CR. Of them, 6 relapsed, 3 withdrew the trial and 3 died in CR (one in the group of localized stage). OS probability at 3 years was 74% (95%CI: 64%-84%) (localized stages 100% [NE], advanced stages 68% [56%-80%], p=0.047, without difference in patients in stages III-IV vs. mature B-ALL, Figure 1). Patients >55 years showed a significantly lower probability of OS (61% [41%-81%] vs. 80% [68%-92%], p=0.022, Figure 2). A lower but non-statistically significant OS probability was observed in HIV-infected vs. non-HIV-positive patients (61% [36%-86%] vs. 78% [67%-89%], p=0.310). The CIR for patients in advanced stage/mature B-ALL was 13% (3%-28%)A trend for lower death rate in CR was observed in BURKIMAB14 vs. BURKIMAB 08 trial (3/62 vs. 16/151, p=0.180), without differences in CIR (9% [3%-21%] vs. 12% [6%-20%]) or in OS (74% [64%-84%] vs. 72% [65%-79%], respectively). Conclusions. The results of the BURKIMAB14 trial are promising, especially for patients in localized stages and for those Supported in part with the grants PI14/01971 FIS, Instituto Carlos III, SGR 288 (GRC) y Fundación "La Caixa". Figure 1. OS according to stage (I-II, vs. III-IV vs. mature B ALL) Figure 2. OS according to age (≤55 y vs >55 y) Figure 1 Disclosures Abrisqueta: Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. Fernandez:Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Terol:Roche: Consultancy; Abbvie: Consultancy; Astra Zeneca: Consultancy; Janssen: Consultancy, Research Funding; Gilead: Research Funding. Gimeno Vázquez:JANSSEN: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Sancho:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Other: Advisory board; Novartis: Honoraria; Kern Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Celltrion: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squib: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Después de una primera PAC donde aprendimos la idea principal de lo que hace que una interfaz sea intuitiva, clara y sencilla; se nos plantea el trabajo de crear diferentes prototipos gráficos de la web Revolutum (a partir del rediseño de wireframes realizados por otros estudiantes en la asignatura Arquitectura de la información).

Background and objective: The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years. Patients and methods: In 2008, three prospective phase II trials in patients older than 55 years were activated: ALLOLD07 for Philadephia (Ph) chromosome-negative ALL, ALLOPHO7 for Ph-positive ALL, and BURKIMABO8 for mature B-ALL. Early death (ED), complete remission (CR), disease-free survival (DFS), overall survival (OS) and toxicity were analyzed. Results: 56, 53 and 21 patients from the ALLOLD07, ALLOPHO7 and BURKIMABO8 trials, respectively, were evaluable. CR was 74%, 87% and 70%, with an ED rate of 13%, 11% and 15%, respectively. The medians of DFS were 8 and 38 months for ALLOLD07 and ALLOPHO7 protocols, not being achieved in the BURKIMABO8 trial (p = 0.001), and the median OS was 12, 37 and 25 months, respectively (p = 0.030). Neutropenia, thrombocytopenia and infections were less frequent in the ALLOPHO7 trial vs. ALLOLD07 and BURKIMAB trials, and renal toxicity and mucositis were more frequent in the BURKIMABO8 trial vs. the ALLOLD07 and ALLOPHO7 trials. ECOG score and WBC count had prognostic significance for OS in ALLOPHO7 and BURKIMABO8 trials, whereas no prognostic factors were identified in ALLOLD07 protocol. Conclusion: Subtype-oriented treatment had an impact in the outcome of older adults with ALL. The poorest outcome was observed in Ph-negative non-Mature B-cell ALL patients, for whom improvements in therapy are clearly needed. (C) 2015 Elsevier Ltd. All rights reserved.

Background. About 25-35% of adult patients with acute lymphoblastic leukemia (ALL) show the Philadelphia (Ph) chromosome. Their outcome has improved with the combination of tyrosine kinase inhibitors (TKI) and chemotherapy, generally followed by allogeneic hematopoietic stem cell transplantation (alloHSCT). However, few series have evaluated the prognostic value of the additional cytogenetic alterations (ACA) to the Ph chromosome, with contradictory results. The aim of this study was to analyse the frequency, type and prognostic significance of ACA to the Ph chromosome in young adults with Ph+ ALL treated with the ALL Ph-08 trial from the PETHEMA group. Patients and methods.Between 2008 and 2016, 95 patients with Ph+ ALL from 30 Spanish hospitals were included in the ALL Ph08 trial. This trial includes concurrent administration of imatinib (600 mg/d) and standard induction and consolidation chemotherapy, followed by alloHSCT (or autologous HSCT if alloHSCT not feasible) and maintenance chemotherapy with imatinib in cases of MRD persistence of reappearance after alloHSCT (Ribera et al, Br J Haematol 2012; 159: 78-81). The cytogenetic reports were centrally reviewed. Major molecular response (MMR) was defined as BCR-ABL/ABL ratio ²0.1% and complete molecular response (CMR) as BCR-ABL/ABL ratio ²0.01% or undetectable. Results. In 74 out of 95 patients the karyotype was evaluable after review (in the remaining 21 cases the diagnosis was carried out by FISH [n=9] or PCR [n=12]). The median age of the 74 patients was 39 years (limits 19-63) and 44 patients (59%) were males. The median WBC count was 17.6x109/L (limits 0.2-390) and 8 out of 66 evaluable patients had CNS involvement at diagnosis. The CR rate was achieved in 72/74 patients (97%) (1 patient did not achieve CR and 1 died during induction therapy). To date, 57 patients underwent to HSCT, of them 46 were in MMR, at least, at the time of HSCT. With a median follow-up of 1.89 years (limits 0.10-7.38) the probabilities of the CR duration, OS and EFS at 4 years were 69% (95%CI: 54%-84%), 39% (23%-55%) and 38% (23%-53%), respectively. Out of 74 patients, 52 (70%) showed at least one ACA and in the remaining 22 (30%) the t(9;22) was the only cytogenetic alteration. No clinical or biologic differences were observed on comparison of the two groups of patients. Twenty (27%) out of 73 evaluable patients showed trisomies and 19 (26%) monosomies. No differences in CR attainment were observed according the presence and type of ACA. The 4-yr. probability of CR duration in patients with t(9;22) and one or more monosomies (monosomal karyotype) vs. those without monosomies was 23% (95%CI: 0%;49%) vs. 88% (77%;99%) (p Conclusions. In young patients with Ph+ ALL treated within the ALL Ph08 trial, the frequency of ACA was high, being trisomies and monosomies shown in similar frequency. The monosomal karyotype was the most important unfavourable prognostic factor in this series of patients. Funded in part by grants PI10/01417 (FIS), RD12-0036-0029 from RTICC, Instituto Carlos III and RD14-SGR225(GRE), Generalitat de Catalunya. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Background and objective. Asparaginase (ASP) is an essential drug for ALL treatment. Two types of E.coli ASP (native and pegylated) are used in clinical trials for treatment of children and adults with ALL, but to our knowledge direct comparison between these two types of ASP in the same protocol has not been performed. This study aimed to compare the efficacy and safety of native vs. PEG-ASP in adult patients with HR, Ph-negative ALL. Patients and methods. HR ALL included one or more of the following parameters at baseline: age 30-60 yr., WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or MLL rearrangements or complex karyotype. Induction therapy consisted of vincristine, prednisone, daunorubicin and ASP (native 10,000 IU/m2, i.v., days 16-20 and 23-27 or PEG 2,000 IU/m2, iv, day 15 depending on center decision) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in patients not achieving CR or in those in CR with MRD≥0.1% at the end of induction, and those patients proceeded to allogeneic HSCT if CR was attained. Patients in CR and MRD Results. Ninety-onepatients received native ASP and 35 PEG-ASP in Induction-1. The two groups of patients were comparable for the main clinical and hematologic ALL parameters. No differences were observed in the CR rate (86% vs. 86%), in the frequency of MRD level Conclusions. In HR, Ph-negative adult ALL patients included in the PETHEMA ALL-HR 11 protocol the type of E.coli ASP (native vs. PEG) did not have impact on response and outcome. Allergic reactions were more frequently seen with native ASP and coagulation abnormalities and hepatic toxicity were most frequent with PEG-ASP. Most of the differences in toxicity can be explained by the schedule of ASP given in consolidation (single dose of native ASP vs. single dose of PEG-ASP in each cycle). Supported in part by grants RD12/0036/0029 (RTICC, FEDER), PI14/01971 FIS, Instituto Carlos III, and SGR225 (GRE), Spain Disclosures No relevant conflicts of interest to declare.

The transfusion of blood components could be needed in certain types of surgical procedures. Blood type components and the requested number of units will depend on the estimated loss of blood, type of surgery, surgical technique to be employed and risk factors for bleeding. Problems can appear when multiple antibodies against common erythrocyte antigens are detected in blood samples and this situation worsens if blood units are requested as quickly as possible. We report a case of a patient with a non frequent erythrocytic phenotype where multiple antibodies acting against high-frequency antigens were detected and who required urgent surgery.

Introduction: Recent studies have shown that young to middle-aged adults who receive a pediatric-inspired chemotherapy regimen for treatment of Ph-neg ALL do not appear to require an alloHSCT if they achieve good response on MRD testing after induction therapy. Patients (pts) who are not good MRD responders achieve better outcomes with alloHSCT than their counterparts who do not receive alloHSCT. However, it is not clear if this approach can be translated to adult ALL pts with HR features at baseline. The aim of the prospective ALL-HR-11 trial from the Spanish PETHEMA Group was to evaluate the response to a differentiated post-induction therapy (chemotherapy or alloHSCT) according to MRD levels (assessed by 8-color, centrally-performed flow cytometry at the end of induction-week 5- and consolidation therapy-week 17-) in HR Ph-neg adult ALL patients. Patients and methods: HR ALL included one or more of the following parameters at baseline: age 30-60 yr, WBC count >30x109/L for B-cell precursor ALL or >100x109/L for thymic T-ALL, pro-B, early or mature T-ALL, 11q23 or MLL rearrangements or complex karyotype. Induction therapy included vincristine, prednisone, daunorubicin and asparaginase (E coli native or PEG according to center availability) for 4 weeks (Induction-1). FLAG-Ida was administered as intensified induction (Induction-2) in pts not achieving CR or those in CR with MRD≥0.1% at the end of induction. For pts in CR and MRD Disclosures No relevant conflicts of interest to declare.

Introduction: Relapses after front-line therapy for Burkitt lymphoma/leukemia (BL) are unfrequent, and there is scarce information about the best rescue strategy for these patients. The objective of this study was to evaluate the incidence of relapse, salvage treatment and prognosis after relapse in patients with BL treated with two consecutive Spanish protocols. Patients and methods: Retrospective study of patients diagnosed with BL in 40 Spanish hospitals betwen January 1997 and October 2014 treated with first line chemotherapy according to protocols PETHEMA LAL-3/97 (specific chemotherapy without rituximab) and BURKIMAB (rituximab plus specific chemotherapy). The demographic, clinical and biological characteristics were collected at the time of diagnosis and at relapse, as well as the salvage treatment and outcomes. Results: 233 patients were diagnosed with Burkitt lymphoma (n=150) or leukemia (n=83) and received first-line therapy according to PETHEMA LAL-3/97 (n=53) and BURKIMAB (n=180) protocols. Baseline characteristics at diagnosis are described in Table 1. A total of 26 patients relapsed, 11 (28%) treated with PETHEMA LAL-3/97 protocol and 15 (10%) with BURKIMAB protocol (p=0.009). The cumulative incidence of relapse at 10 years was 27% (95% CI, 12%-42%) in PETHEMA LAL-3/97 protocol vs.16% (95% CI, 4%-28%) in BURKIMAB protocol (p= 0.013) (Figure 1). Time to relapse was shorter in PETHEMA LAL-3/97 protocol (median of 3.7 months) vs. BURKIMAB protocol (6.3 months), but it was not significant (p=0.506). No differences were observed in relapse incidence between Burkitt leukemia and Burkitt lymphoma in PETHEMA LAL-3/97 protocol (6/31 vs. 5/22, p=1) and BURKIMAB protocol (7/41 vs. 8/107, p=0.124). Out of 15 patients in whom rescue treatment strategy was evaluable, 12 received chemotherapy with high-dose methotrexate and/or cytarabine (4 of the them followed response, CR in 2, followed by SCT in the 2 patients achieving PR [autologous in one and allogeneic SCT in the other]), and the remaining 3 patients received DA-EPOCH-R (n=1, achieving CR), R-ICE (n=1, no response) and paliative care (n=1). At the time of the analysis, only 3 patients are alive. Median overall survival after relapse was 3 months (95% CI, 0.9-5.1) for PETHEMA LAL-3/97 relapsed group and 3.6 months (95% CI, 0.1-7.1) for BURKIMAB relapsed patients group. Conclusions: Patients with Burkitt leukemia/lymphoma treated with specific immunochemotherapy have lower probability of relapse compared with those treated with specific chemotherapy without rituximab. In our series, the most frequent regimens administered for the treatment of relapsed patients were based in high-dose methotrexate and/or cytarabine. The prognosis of relapsed Burkitt leukemia/lymphoma is poor, independently of the type of rescue therapy. Supported by grants RD12/0036/0029 (RTICC, FEDER), Instituto Carlos III, Spain. Disclosures No relevant conflicts of interest to declare.

Introduction Indolent lymphomas represent 40% of all subtypes of non-Hodking's lymphoma, of which follicular lymphoma (FL) is the most frequent. Bendamustine is a dual alkylating agent with demonstrated high efficacy and low toxicity profile in reported clinical trials. We present the preliminary results from the experience of Spanish compassionate use registry of this agent as first-line treatment for indolent lymphoma. Methods Retrospective multicenter analysis of patients with indolent non-Hodgkin lymphomas (iNHL) treated as frontline with Bendamustine plus Rituximab (BR) in compassionate use. Clinical efficacy was evaluated according to Cheson criteria (2007) and toxicity according to CTCAE v3.0 scale. This study has been approved by local ethical committees. Results Patients’ characteristics: There are 96 patients registered (9 centers), with the following diagnoses: FL: 62 (64.5%), marginal zone 24 (25%), Waldenström macroglobulinemia 7 (7.3%) and mantle NHL 3 (3.1%). The main clinical features of the series are: 45% males, median age 64 years (range 36-84), 87.1% ECOG≤ 1, 63% Ann Arbor stage IV, 50.5% high risk FLIPI and 43.7% CIRS ≥ 4. Extranodal involvement was present in 79.1% of the patients, bone marrow involvement in 52% and 11 patients (11.9%) had bulky disease. Treatment consisted in 6 cycles of BR (B-90 mg/m2 D1-2, R-375mg/m2 D1) in 95% patients. Median number of cycles administrated was 6 (range 1-8). G-CSF support was administered in 16.1% of cycles. Response and Safety: Overall response rate was 95%, with 65.5 % CR, 13.1% uCR and 16.4% PR in the 61 evaluable patients. Progression was documented in 4.9% of patients. Three exitus ocurred due to aspergillosis, progression and other not related with LNH. Median follow-up period was 14 months (3-47). In general, treatment was well tolerated; over 461 cycles registered, the most common adverse event was hematological toxicity with grade 3-4 neutropenia in 10.4%, grade 3-4 leucocitopenia in 6.9% and grade 3-4 anemia in 1.9% of the cycles. Other toxicities included all grades infections in 3.2% of patients, gastrointestinal in 3.4%, asthenia in 3.2%, chills in 1.1%, and mucositis 0.4%. Only 9 hospitalizations due to febrile neutropenia were reported. Conclusion Bendamustine plus rituximab was an effective and well tolerated regimen for newly diagnosed patients with indolent NHL. Disclosures: No relevant conflicts of interest to declare.

Introduction Intensive chemotherapy in patients with acute myeloid leukemia (AML) who are 70 years of age or older leads to an overall survival (OS) lower than 30% at one year. This is due to low tolerability of intensive chemotherapy schedules and biological adverse features of this group of patients. Objectives To evaluate the therapeutic results in AML patients who are 70 years of age or older treated with intensive (2+5) or semi-intensive (FLUGA) chemotherapy. Methods Multicenter retrospective study based on data of the epidemiologic AML PETHEMA group Registry to evaluate the OS in patients who are 70 year of age or older that have followed the treatment recommendations of the group (LMA2007/2+5 protocol: idarrubicin 12 mg/m2 for 2 days plus IV cytarabine 200 mg/m2 for 5 days, and two cycles with IV cytarabine 100 mg/m2 for 5 days; LMA2011/FLUGA protocol: 3 induction courses with oral fludarabine 40 mg/m2 for 4 days plus subcutaneous cytarabine 75 mg/m2 for 4 days following maintenance treatment with an outpatient schedule of lower doses of fludarabine plus cytarabine. Patients diagnosed with acute promyelocytic leukemia and/or an ECOG of 4 were excluded. Results Of the 155 patients included from 30 hospitals, 78 were treated according to LMA2007/2+5 scheme and 77 to LMA2011/FLUGA recommendations. Median of age in the FLUGA vs 2+5 was 77 years [70-89] vs 74 years [70-81], p Conclusion In patients who are 70 years of age or older, therapeutic recommendations consisting in semi-intensive chemotherapy (FLUGA) led to an improved OS at 1 year compared with intensive chemotherapy (2+5). In this group of patients achieving CR should be a therapeutic goal because it significantly improves the prognosis. Disclosures: No relevant conflicts of interest to declare.

Background and objective ALL in elderly patients is associated with poor prognosis and many patients are not included in therapeutic trials. Consequently, the results of subtype-oriented protocols in elderly ALL are poorly known. We present the results of three prospective parallel subtype-oriented protocols from the Spanish PETHEMA group in ALL patients older than 55 years. Patients and Methods In 2008 three prospective phase II trials for ALL patients older than 55 yr with the Charlson Comorbidity Index ≤3 were activated: ALLOld07 (Ph-negative patients, NCT01366898, n=54), ALLOPh07 (Ph-positive patients, NCT01376427, n=48) and BURKIMAB08 (mature B-ALL, NCT00388193, n=18). The ALL0ld07 protocol included moderate-dose induction chemotherapy without genotoxic drugs, followed by consolidation and maintenance therapy for 2 years (Gökbuget et al, ASH 2008), the ALL OPh07 included imatinib and dexamethasone for induction followed by maintenance therapy with mercaptopurine and methotrexate and imatinib for 2 years, followed by imatinib for one additional year (Ribera et al, Br J Haematol 2012; 159: 485-488), and the BURKIMAB08 protocol included specific therapy for Burkitt’s lymphoma/leukemia together with rituximab (Ribera et al, Cancer 2013; 119:1660-8). The main outcomes (early death [ED], complete remission [CR], remission duration [RD] and overall survival [OS]) and toxicity (CTCAE v4.0) were compared. Results 40, 45 and 16 patients from ALLOld07, ALLOPh07 and BURKIMAB08, respectively, were evaluable for this study. Patients with mature B-ALL were more frequently male, with poorer general status, higher frequency of bulky disease and higher LDH serum levels, whereas no significant differences were observed on comparison of ALLOld07 and ALLOPh07 patients. The comparison of the main outcomes of the three trials is shown in Table 1. By multivariate analyses for RD the protocol and WBC count were identified as prognostic factors (BURKIMAB08 was considered as reference category), with HR [95%CI] of 6.8 [0.9-52.1], p=0.064, when compared with ALL Old07 and 3.1 [0.4-24.8], p=0.278 when compared with ALL OPh07, global p value=0.042, and HR [95%CI]: 1.004 [1-1.009], p=0.058 for the WBC count, respectively. The ECOG score was the only variable influencing OS (HR [95%CI]: 0.4 [0.2;0.8], p=0.003). Hematological toxicity in induction and consolidation as well as infections were significantly less frequent in ALLOPh07 than in other two trials, whereas renal toxicity was more frequent in BURKIMAB08. Conclusion Risk-adapted therapy in elderly patients with ALL was feasible and produced significantly different results in terms of CR duration, being the best for mature B-ALL and the poorest for Ph-negative ALL. Supported by the grants PI10/01417 from FIS and RD12-0036-0029 from Instituto Carlos III Disclosures: No relevant conflicts of interest to declare.

Plasma exchange (PE) with plasma infusion is the treatment of choice for Thrombotic Thrombocytopenic Purpura (TTP) but doubts remain as to whether all kinds of plasma are equally effective. Since October 2004, a multicentric prospective cohort study is being conducted in Spain to compare Methylene Blue Photoinactivated Plasma (MBPIP) with Fresh Frozen Plasma (FFP) in the treatment of TTP. Sixty-three first episodes of idiopathic TTP were included. MBPIP was used in 38 and FFP in 25. The treatment schedule consisted of daily PE (> 40 mL/kg of body weight) and costicosteroids (1.5 mg/kg/d). Response was defined as the achievement of a platelet count >= 150 x 109/L for at least three consecutive days, normal LDH level and absence of TTP-related symptoms and signs. Recurrence was defined as a fall in platelet count below 50 x 109/L or below 50% of the highest count achieved after response. Response lasting for more than 15 days was considered as remission. The prognostic significance of the kind of plasma used was investigated by logistic regression analysis after adjustment for other variables that had previously been found to influence on response to PE (gender; the Rock score; days from first medical attendance to PE; volume of plasma infused in the first 7 days of treatment). Both groups were comparable with regard to clinical and biological parameters at diagnosis. A severe deficit in ADAMTS13 activity was found in 9 out 12 (75%) patients treated with MBPIP and in 12 out of 16 (75%) patients treated with FFP. When compared to FFP, patients treated with MBPIP required a higher number of PEs (16±13 vs 9±7, p=0.004) and a larger volume of plasma (763±678 ml/kg vs 413±326 ml/kg, p=0.02) to achieve a remission and presented more recurrences while on PE treatment (21 out of 38 vs 6 out of 25, p=0.02). Splenectomy or rituximab was required in eight patients (21%) treated with MBPIP to achieve a remission vs in none out of the 25 patients treated with FFP (p= 0.02). After adjustment for other prognostic variables, patients in the MBPIP group had a lower likelihood of remission by the 8th treatment day (OR: 5.1; 95% CI: 1.6 – 15.9) and a higher risk of recurrence while on PE treatment (OR: 4.2; 95% CI: 1.3 – 13.5). In conclusion, MBPIP is less effective than FFP in the treatment of TTP.