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Background The main causes of failure of allogeneic hematopoietic stem cell transplantation (allo-transplant) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are relapse and transplant-related mortality. Different scores have been designed to predict the prognosis of these patients. The objective of this study was to assess which score or combination has better outcome predictive capacity. Methods Retrospective analysis of patients with AML and MDS who received a first peripheral blood allo-transplant in a single center, between December 2001 and October 2019. Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) and Disease Risk Index (DRI) scores were calculated. For each score and for the HCT-CI/DRI and HCT-CI/EBMT combinations, overall survival (OS), cumulative incidence of relapse (CIR), non-relapse-related mortality (NRM), and graft versus host disease-free relapse-free survival (GRFS) were analyzed. Results 175 patients were evaluated. With a median (range) follow-up of 3.96 (0.32–17.22) years, the 5-year probabilities (95% CI) of OS, CIR, NRM, and GRFS were 36% (28%–44%), 28% (21%–35%), 38% (30%–46%) and 24% (17%–31%), respectively. For OS, only the DRI score selected two groups with statistically significant differences (DRI 0–1: 41% vs. DRI ≥2: 24%; p = 0.011). The combination of DRI 0–1 and HCT-CI 0–2 showed OS probabilities of 45% vs. 26% for those with DRI 0–1 and HCT-CI ≥3; p = 0.041. Conclusions In patients with AML and MDS submitted to allo-transplant, the combination of HCT-CI and DRI scores provided the best stratification for OS.

Resumen Fundamento y objetivo La enfermedad del injerto contra el receptor (EICR) y las infecciones son complicaciones del trasplante alogenico de progenitores hematopoyeticos (alo-TPH). La globulina antitimocitica (ATG) es una estrategia empleada para la profilaxis de la EICR. Este estudio analiza los resultados y la frecuencia de infecciones en funcion del uso de ATG, despues de un alo-TPH de donante no emparentado (DNE) en pacientes con leucemia aguda y sindrome mielodisplasico. Pacientes y metodo Estudio retrospectivo de pacientes que recibieron un alo-TPH de DNE entre diciembre de 2007 y abril de 2019. Se compararon los principales resultados en funcion del uso de ATG. Resultados Se incluyo a 66 pacientes. No se encontraron diferencias significativas en el grupo ATG (n = 50) frente al no ATG (n = 16) en supervivencia global, incidencia acumulada de recaida, mortalidad no debida a recaida o incidencia acumulada de EICR aguda o cronica. Hubo mayor frecuencia de infecciones en el grupo ATG (60 frente a 19%; p = 0,004). Conclusiones En este estudio no se demostro diferencia en los principales resultados del alo-TPH en funcion del uso de ATG, pero hubo mas infecciones en el grupo que recibio ATG.

Background and purpose Graft-versus-host disease (GVHD) and infections are complications after allogeneic stem cell transplantation (alloSCT). Anti-thymocyte globulin (ATG) is a strategy used as prophylaxis for GVHD. The study analyses the outcomes and frequency of infections with or without ATG after an unrelated donor alloSCT in patients with acute leukaemia and myelodysplastic syndrome. Patients and methods Retrospective study of patients receiving an unrelated donor alloSCT between December 2007 and April 2019. The main outcomes were analysed according to use or not of ATG. Results Sixty-six patients were included. No significant differences were found between the ATG group (n = 50) vs. no-ATG group (n = 16) in overall survival, cumulative incidence of relapse, cumulative incidence of non-relapse mortality or cumulative incidence of acute GVHD or chronic GVHD. There was a greater frequency of infections in the ATG group (60% vs. 19%, p = .004). Conclusions In this study, no differences were shown in the main outcomes of alloSCT based on the use of ATG, although more infections were documented in the ATG group.

Introduction The impact of an admission to ICU before stem cell transplantation (SCT) on post-SCT outcome is not well established. Patients and methods We reviewed the medical records of patients who had received a first SCT between 2000 and 2016 in our institution. The outcome of 22 patients who required ICU admission during chemotherapy prior to SCT (ICU group) was compared with 44 matched patients (1:2) who did not need it (NO-ICU group). Results There were no differences in transplant complications, in time to neutrophil and platelet recovery or in the length of hospital stay during SCT between the ICU and NO-ICU groups. However, microbiologically documented infections were more common in the ICU group (16/20) than in the NO-ICU group (18/39) (p = .027). The 5-yr overall survival probability (CI 95%) was 49% (28–70%) in the ICU vs. 45% (29–61%) in the NO-ICU group (p = .353), while the 5-yr incidence of non-relapse mortality was 32% (14–52%) and 24% (12–38%) (p = .333), respectively. Six patients (27%) in the ICU group and 8 (18%) in the NO-ICU group required admission to the ICU during or after the SCT procedure (p = .293). Twelve (54%) patients in the ICU and 22 (50%) in the NO-ICU group died, the causes of death were similar in both groups. Conclusion Our results show that admission to the ICU prior to SCT does not have a negative impact on patient outcomes following SCT and should not be considered as an exclusion criterion for SCT.

Genomics; T-cell acute lymphoblastic leukemia Genòmica; leucèmia limfoblàstica aguda de cèl·lules T Genómica; Leucemia linfoblástica aguda de células T Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients. This project was supported by the 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)/ “La Caixa”. C Gon-zález-Gil was supported by AGAUR grant (ref: 2020 FI_B2 00210).

Altres ajuts: Asociación Española contra el Cáncer (GC16173697BIGA)

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy., Fundació Internacional Josep Carreras; Generalitat de Catalunya, Grant/Award Number: 2017 SGR 288 GRC; Instituto de Salud Carlos III; Ministerio de Salud Carlos III RTICC‐FEDER, Grant/Award Numbers: RD12/0036/0029, RD/0036/044; Obra Social “La Caixa”; Sociedad Española de Hematología y Hemoterapia; Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI14/01971, PI10/01417

Context: B-cell precursor acute lymphoblastic leukemia (BCP ALL) is a genetically heterogeneous neoplasm with >20 biologic subtypes. Each subtype shows specific genetic traits that determine relapse risk and patients' survival. Objectives: To establish the genetic subtype (primary alteration) of adult BCP ALL patients enrolled in the PETHEMA LAL19 trial (NCT 04179929) and to correlate them with measurable residual disease (MRD) level and survival. Patients and Methods: In the LAL19 trial (NCT04179929), Ph-negative patients (18–65 y) with MRD≥0.01% at day+35 or high-risk genetics receive alloHSCT and MRD

Programa para el Tratamiento de Hemopatias Malignas (PETHEMA) Group (Spanish Society of Hematology, SEHH)., The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation)., This work was supported in part by CERCA/Generalitat de Catalunya SGR 2017 288 (GRC), a restricted grant from ‘La Caixa’ and Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms (HARMONY).

Context: There is a debate regarding the impact of t(1;19) (q23;p13) in adult BCP ALL. While the MD Anderson group suggests it may be a low-risk subtype, the German, English, and French study groups have shown no differential outcome, and Italian and SWOG groups have reported poor outcomes. Objective: To analyze the frequency and clinical impact of t(1;19) in a series of adult BCP ALL patients (pts). Design & Patients: A review of 513 adult BCP ALL pts (15 to 60 years) diagnosed between 2003 and 2017 and treated with MRD-oriented protocols of the PETHEMA Group. Interventions: G-banding and FISH were performed on BM samples. Measurable residual disease (MRD) was centrally assessed by multi-parametric flow cytometry. Main Outcomes Measures: Complete response (CR), overall survival (OS) and cumulative incidence of relapse (CIR), assessed by competing risk analysis. Results: Total of 26 pts with t(1;19)/TCF3-PBX1 (representing 5% of all BCP ALL). 9/23 (39%) cases showed isolated t(1;19) while 14/23 (61%) had additional chromosomal aberrations (ACA). Pts with t(1;19) were more likely to be female (73% vs 45%, p=0.006) and pre-B phenotype (63% vs 17%, p Conclusions: Although showing favorable initial treatment response, pts with t(1;19) experience a higher rate of relapse (especially those with ACA to t(1;19)) than the remaining BCP ALL pts, without differences in OS. A deeper genetic analysis may identify markers of poor outcome enabling a more precise risk stratification of t(1;19) pts.

© 2021 The Author(s)., The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients., This project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828) co-funded by ERDF/ESF "A way to make Europe"/ "Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ “La Caixa” P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800).

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)

Background and objective SARS-CoV-2 infection has bimodal distribution in Europe with a first wave in March to June 2020 and a second in September 2020 to February 2021. We compared the frequency, clinical characteristics and outcomes of adults with acute lymphoblastic leukemia (ALL) and infection in the first vs. second pandemic waves in Spain. Patients and Methods In this prospective study the characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome in the two periods were compared. The study ended when vaccination against SARS-CoV-2 was implemented in Spain. Results Twenty eight patients were collected in the first wave and 24 in the second. The median age was 46.5 years (range 20–83). Patients from the first wave had a trend to more severe ALL (higher frequency of patients under induction or submitted to transplantation or under immunosuppressive therapy). No significant differences were observed in need for oxygen support, intensive care unit (ICU) requirement, days in ICU and time to COVID-19 infection recovery. Seventeen patients (33%) died, with death attributed to COVID infection in 15 (29%), without significant differences in the 100 day overall survival (OS) probabilities in the two waves (68% ± 17% vs. 56% ± 30%). The only prognostic factor for OS identified by was the presence of comorbidities at COVID-19 infection (HR: 5.358 [95% CI: 1.875- 15.313]). Conclusion The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time, providing evidence in favor of vaccination priority for these patients., Microabstract The characteristics and outcome of ALL in adults with COVID-19 infection in the first two waves of the pandemic in Spain were compared. The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time. Comorbidities at COVID-19 infection was the only prognostic factor for survival.

Background and objective Patients submitted to haematopoietic stem cell transplantation (HSCT) are at increased risk of late complications, such as second neoplasm (SN). The incidence and risk factors of SN in patients receiving HSCT at a single centre were analyzed. Patients and methods The follow-up of adult patients who received a first HSCT (autologous [auto-HSCT] or allogeneic [allo-HSCT]) between January 2000 and December 2015 was reviewed. We collected their demographic characteristics, the primary disease and type of HSCT, and analyzed the cumulative incidence of SN and their risk factors. Results Of 699 transplanted patients (auto-HSCT, n = 451; allo-HSCT, n = 248), 42 (6%) developed SN (17 haematological and 25 solid), 31 post-auto-HSCT and 11 post-allo-HSCT. Haematologic SN were more frequent after auto-HSCT than after allo-HSCT. The median time between HSCT and SN was 4.09 years [range 0.07–13.15], with no differences between auto-HSCT and allo-HSCT. The cumulative incidence of SN was 5% (95% CI 3–6) at 5 years, 7% (95% CI 5–10) at 10 years and 11% (95% CI 8–15) at 15 years, without differences according to the type of HSCT. Only the age over 40 years correlated with an increased risk of SN. Conclusions In this series, the incidence of post-HSCT SN was similar to that previously described. Patients submitted to an auto-HSCT showed a higher frequency of haematologic SN. A higher incidence of SN was detected in patients older than 40 at the time of HSCT.

Resumen Fundamento y objetivo Los receptores de un trasplante de progenitores hematopoyeticos (TPH) tienen un mayor riesgo de complicaciones tardias, como las segundas neoplasias (SN). Se analizo la incidencia de SN en pacientes receptores de un TPH en un centro. Pacientes y metodos Estudio retrospectivo de pacientes adultos receptores de un primer TPH (autogenico [auto-TPH] o alogenico [alo-TPH]) entre enero de 2000 y diciembre de 2015. Se recogieron sus caracteristicas demograficas, la enfermedad de base y el tipo de TPH, y se analizo la incidencia acumulada de SN y sus factores de riesgo. Resultados De 699 pacientes receptores de un auto-TPH (n = 451) o alo-TPH (n = 248), 42 (6%) desarrollaron una SN (17 hematologicas y 25 solidas), 31 postauto-TPH y 11 postalo-TPH. Se observo un mayor numero de SN hematologicas tras auto-TPH que tras alo-TPH. La mediana de tiempo entre el TPH y la SN fue de 4,09 anos [extremos 0,07-13,15], sin diferencias entre auto-TPH y alo-TPH. La incidencia acumulada de SN post-TPH fue de 5% (IC 95% 3-6) a 5 anos, 7% (IC 95% 5-10) a 10 anos y 11% (IC 95% 8-15) a 15 anos, sin diferencias en funcion del tipo de TPH. Solo la edad superior a los 40 anos se correlaciono con un mayor riesgo de SN. Conclusiones En esta serie, la incidencia de SN post-TPH fue similar a la descrita. Los receptores de un auto-TPH presentaron mayor frecuencia de SN hematologicas. Se detecto una mayor incidencia de SN en pacientes de mas de 40 anos en el momento del TPH.

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.

Background Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of HIV-associated lymphoma. Since the introduction of combined antiretroviral therapy (cART), the prognosis of HIV-related DLBCL has substantially improved, resembling that of the general population. However, non-Hodgkin lymphoma still remains the first cause of AIDS-related deaths. The International Prognostic Index (IPI) is the most widely used score for DLBCL and it has been validated in the rituximab era (R-IPI). However, it has limited accuracy to identify a very high-risk prognostic subset. Although IPI has been demonstrated to be useful for predicting prognosis in HIV-related DLBCL, new scores subsequently developed, such as National Cancer Comprehensive Network IPI (NCCN-IPI), GELTAMO-IPI and a new score, which includes data from peripheral blood count, have not been applied in the HIV setting. The aim of this study was to assess the prognostic significance of the new variables -beta2-microglobulin (β2M), lymphocyte/monocyte (L/M) ratio and red blood cell width (RDW)- and to validate the new scores in a series of homogeneously treated HIV-related DLBCL patients. Methods Retrospective multicentric study of patients with HIV infection diagnosed with DLBCL in 16 hospitals from GELTAMO group in Spain, from 1998 to 2020. All patients were treated with R-CHOP and cART +/- radiotherapy. The main clinical and biological variables were collected. Peripheral absolute neutrophil, lymphocyte and monocyte counts were studied, including L/M ratio and CD4 + lymphocyte count. Moreover, HIV load, serum lactate dehydrogenase (LDH), β2M and RDW were evaluated. Univariable and multivariable analysis were performed using the binary logistic regression model for complete response (CR) rate and Cox proportional-hazards regression model for overall survival (OS) and progression-free survival (PFS). Survival curves were plotted by the Kaplan-Meier method and compared by the log-rank test. The discrimination power of IPI, aaIPI (age-adjusted IPI), R-IPI, NCCN-IPI, GELTAMO-IPI and the new score including L/M ratio (L Bento et al., Br J Haematol. 2020) was assessed by the C-index. Results One hundred and five patients were retrospectively analysed with a median follow up of 7.08 (0.36-25.21) years. The characteristics of the patients are summarized in Table 1. In the univariable analysis, performance status ≥2, extranodal sites ≥2, lymphocytopenia and low L/M ratio were associated with shorter OS and shorter PFS probabilities. Neutropenia was also associated with lower OS and advanced Ann Arbor stage was associated with lower PFS. On the other hand, monocytosis, low CD4 + lymphocyte count, positive HIV load and high values of serum LDH, RDW and β2M had no prognostic impact. By multivariable analysis, only L/M ratio With the aim of validating the prognostic power of each score system, the patients were divided in two groups: patients corresponding with low or intermediate-low risk versus those with intermediate-high or high risk. R-IPI, NCCN-IPI and the new score including L/M ratio showed significant differences in two groups for CR rate, OS and PFS. IPI also significantly discriminated the groups for PFS. NCCN-IPI was the strongest score to discriminate OS with a C-index of 0.638, and the new score including L/M ratio was the best one for CR rate and PFS discrimination, with a C-index of 0.669 and 0.666 respectively. Conclusions Lymphocyte/monocyte ratio is a strong prognostic factor, which can be used in patients with DLBCL and HIV infection. NCCN-IPI and the new score including L/M ratio provided the best discriminative capacity to predict prognosis in patients with HIV-related DLBCL treated with R-CHOP and cART. Supported in part by Gilead Sciences S.L., Spain (GLD19/00121); 2017 SGR288 (GRE) from CERCA Programme/Generalitat de Catalunya, and by funds from Josep Carreras International Foundation and "la Caixa" Foundation. Figure 1 Figure 1. Disclosures Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Salar: Janssen: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Gilead: Research Funding. de la Cruz Vicente: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ferrer Lores: Janssen: Membership on an entity's Board of Directors or advisory committees. Abrisqueta: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria. Sancho: Roche, Janssen, Celgene-BMS, Gilead, Novartis, Takeda: Honoraria, Speakers Bureau; Roche, Janssen, Celgene-BMS, Gilead, Novartis, Incyte, Beigene: Speakers Bureau. Ribera: SHIRE: Consultancy, Speakers Bureau; ARIAD: Consultancy, Research Funding, Speakers Bureau; TAKEDA: Consultancy, Research Funding, Speakers Bureau; NOVARTIS: Consultancy, Speakers Bureau; AMGEN: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau. Navarro: NOVARTIS, Roche: Honoraria; EUSA Pharma: Consultancy; GILEAD, EUSA Pharma: Research Funding.

The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B-cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe-dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B, PAX5, ETV6, ATM, IKZF1, VPREB1, and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B-cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies.

Introduction and objective. Despite a high complete remission (CR) rate obtained with frontline therapy most adults with T-ALL eventually relapse. Although promising therapies are emerging, salvage options for T-ALL are currently limited. Little is known about outcome of patients (pts) with relapsed T-ALL (R T-ALL) treated with contemporary MRD-oriented trials. Our goal was to analyze the outcome of pts with R T-ALL included in two successive MRD-oriented trials (ALL-AR-03 and ALL-HR-11) from the Spanish PETHEMA Group. Methods. Retrospective study of R T-ALL adults diagnosed between 2003 and 2019 and included in the protocols ALL-AR-03 (NCT00853008) and ALL-HR-11 (NCT01540812). The clinical characteristics at baseline and at relapse, salvage therapies and outcomes (CR and OS) were analyzed and a study of prognostic factors for OS was performed. Results Forty-nine patients were identified (ALL-AR-03 [n=27], ALL-HR-11 [n=22]). Median age (range) at diagnosis was 29 (16-58) yrs, 38 males (78%), CNS involvement 6 (12%), mediastinal mass 30 (61%), WBC count 40.8 x109/L (0.6-351.0), early T-cell precursor 11 (23%), pre-T 8 (16%), cortical 16 (33%), mature 9 (18%), T unspecified 5 (10%). Post-induction-1 MRD level ≥0.1%: 14/42 (33%), ≥0.01%: 17/39 (44%). Nine pts (18%) required 2nd induction therapy (resistant disease after induction-1 [n=5], MRD≥0.1% after induction-1 [n=4]). Allogeneic HSCT in CR1: 8 pts. Interval CR1-relapse: 11.2 [0.1-36.7] months. Relapse was located in BM (n=20, 41%), BM+extramedullary (n=16, 33%) and extramedullary (n=13, 26%). CNS at relapse was involved in 18 pts (37%, isolated in 8 cases). Median number of rescue lineages was 2 (range 1-5). The most frequent first salvage schedules were FLAG-Ida (n=24, 49%), HyperCVAD (n=8, 16%) and nelarabine (n=4, 8%) (other schedules in 13 pts). Second CR was attained in 21/48 pts (44%). The patients with poor morphologic and/or poor MRD response after Induction-1 in first line therapy (n=9) did not respond to first salvage therapy (0/9 vs. 21/39, p=0.003). AlloHSCT was performed in 19 pts (15 in CR2) (HLA-identical sibling: 9, URD: 9, haploidentical: 1, myeloablative conditioning: 16). Thirty-nine pts died (progression: 27, toxicity of rescue regimens: 7, TRM: 5) and 9/10 alive patients were submitted to HSCT (the remaining is on rescue therapy). Median OS (95%CI) was 6.1 (4.9-7.2) months, 5yr OS probability 21% (9%-33%) (Figure 1). By multivariable analysis, only the CR after first salvage regimen emerged as favorable prognostic factor for OS (HR 3.110, 95%CI: 1.579-6.124) (Figure 2). Conclusion. This study shows poor outcome of adults with R T-ALL, with CR to first salvage therapy of 44% and a median OS of 6 months. Poor early response to first line therapy correlated with poor response to salvage-1. The only independent predictor for better survival was CR to first salvage regimen. This study highlights the unmet need for novel effective therapies for T-ALL. Supported in part by grant 2017 SGR288 (GRC) Generalitat de Catalunya and "La Caixa" Foundation; ISCIII (PI19/01828), co-funded by ERDF/ESF, "A way to make Europe"/"Investing in your future". Disclosures Ribera: Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau; Pfizer, Amgen: Research Funding. Barba:Amgen, Celgene, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, Shire: Consultancy; Amgen, Celgene, Novartis, Pfizer: Speakers Bureau. Tormo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Giménez Conca:AbbVie: Honoraria, Speakers Bureau.

Background No standardized and widely accepted cytogenetic classification with prognostic impact for adult T-ALL has been proposed to date. Methods Patients with abnormal karyotypes (65/139, 47%) were classified according to the number of chromosomal alterations (Chun K. et al., 2009). Cohort 216 adults T-ALL patients/ NCT00853008 - NCT01540812 /PETHEMA cooperative group. Prognostic impact of karyotype on event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were assessed. Additionally, next-generation sequencing (NGS) experiments were done. Results Greater than three cytogenetic abnormalities were associated with lower rates of both complete remission (CR, 77% vs. 94%; p=0.032) and minimal residual disease (MRD) level Conclusions Compared to BCP-ALL, a lower cut-off to define complex karyotypes based on the presence of ≥3 cytogenetic alterations allows the identification of T-ALL patients with poor prognosis. Interestingly, molecular analyses of patients carrying ≥3 cytogenetic alterations revealed a unique molecular profile that could contribute to understanding the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R-directed) that might improve the response to treatment and outcome of adult T-ALL patients. Funding ISCIII (PI19/01828), co-funded by ERDF/ESF, “A way to make Europe”/”Investing in your future”.

Introduction Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms. Objective The aim of this study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017. Methods In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed. Results Sixty-one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One- and 4-year CIR were 52% and 56%. One- and 4-year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017). Conclusion Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.

Introduction and objective. SARS-CoV-2 pandemic has deeply impacted in Spain. In cancer patients (pts) the lethality has been higher than in normal population, but, little is known on the impact in adults with ALL. Our objective was to analyze the frequency, clinical characteristics and outcome of adult ALL patients infected by SARS-CoV-2. Methods. Between March 1, 2020 and May 31, 2020 (the period of the peak of COVID-19 infection in Spain) two registries from the PETHEMA (Programa Español de Tratamientos en Hematologia) and GETH (Grupo Español de Trasplante Hematopoyético y Terapia Celular) groups were activated to recruit adult patients with ALL and COVID-19 infection confirmed by PCR. The PETHEMA registry was based on ASH proposal (www.ashresearchcollaborative.org/covid-19-registry) and the GETH registry was specifically performed for hematological diseases and COVID-19 infection. Both registries were merged for this study. Eighty-four Spanish centers were contacted and weekly reminds were sent until May 19, 2020. The demographic and clinical characteristics of ALL and COVID-19 infection, the comorbidities, the treatment and outcome were collected. The study was closed for follow in July 10, 2020. Results. Fifty-six of 84 centers answered the survey and 28 patients with ALL and COVID-19 infection were identified in 17 of them, especially on March (n=11) and April (n=15). Median age was 46 (range 20-78) yrs. and 19 were aged over 40 yrs. Fifteen pts were male, 1 was active smoker and 9 showed one or more comorbidities (chronic liver disease [n=2] diabetes [n=1], hypertension [n=5], cardiopathy [n=2], prior malignancy [n=1] and hypogammaglobulinemia [n=1]). ALL was of B-cell precursors in 18 pts (Ph+ in 6) and T in 10. Twenty-six pts were on treatment of LAL (induction [n=10], consolidation [n=3], maintenance [n=1], HSCT [n=5], rescue [n=6], and palliative [n=1]). Eight patients were previously submitted to allogeneic HSCT, CAR T [n=1] or immunotherapy with monoclonal antibodies (inotuzumab, n=4) and 21 were receiving immunosuppressive drugs (corticosteroids in 11, fludarabine in 4, among others). Eleven pts showed neutropenia Conclusion. The frequency of adult patients with ALL and COVID-19 infection can be considered high, given the low incidence of adult ALL. COVID-19 infection was frequent in patients with advanced age and on ALL therapy. The frequency of severe COVID-19 infection and the mortality were high. Supported in part by 2017 SGR288 (GRC) Generalitat de Catalunya and "la Caixa" Foundation. Disclosures Ribera: Pfizer, Amgen, Ariad, Novartis:Consultancy, Speakers Bureau;Pfizer, Amgen:Research Funding.Barba:Amgen, Celgene, Novartis, Pfizer:Speakers Bureau;Amgen, Celgene, Gilead, Jazz Pharmaceuticals, Novartis, Pfizer, Shire:Consultancy.

Introduction Huntingtin-interacting protein 1 (HIP1) binds to inositol and clathrin, which is related to neurodegeneration. Signaling of growth factors receptors through clathrin is one mechanism by which cells regulate intracellular signaling. High levels of HIP1 protein have been observed in breast, colon, kidney, lung, ovarian and prostate cancer and melanoma. Methods Tumor biopsies were obtained from 83 breast cancer patients (p) treated with four cycles of fluorouracil, epirubicin and cyclophosphamide neoadjuvant chemotherapy. Estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6, vimentin and HIP1 were examined by tissue microarray. HER2 was also assessed by chromogenic in situ hybridization and the prognostic and predictive value of HIP1 expression was evaluated. Results HIP1 was evaluated by immunohistochemistry (IHC) in 83 p, considered negative if the result was 0, and positive if it was 1, 2 or 3. The result was 0 in 11 p (13.3%), 1 in 40 p (48.2%), 2 in 25 p (30.1%), and 3 in 7 p (8.4%). Negative HP1 was correlated with poorly differentiated tumors (p=0.021) and triple negative tumors (p=0.038). Negative HIP1 was not correlated with response but HIP1 negative was correlated with shorter time to progression (TTP) (p=0.003) and overall survival (OS) (p=0.009). Conclusions HIP1 could be a prognostic and predictive factor in breast cancer.

Context IKZF1 (Ikaros) deletion has been proposed as a poor prognostic factor in B-cell precursor acute lymphoblastic leukemia (BCP ALL) in children and adults. Objective To analyze the frequency and prognostic impact of IKZF1 deletions in adult BCP ALL patients. To identify the IKZF1 gene expression signature to find patients with different deletion isoforms and therapeutic opportunities. Patients and methods MLPA or SNP array samples of 151 (109 Ph-negative and 42 Ph+) adult BCP ALL patients treated with MRD-oriented protocols from the PETHEMA Group. RNAseq was performed in 48 of them (27 Ph-negative and 21 Ph+). Results Median age was 40 [15–72] years. Ph+ patients showed older age (52 [20;72] vs. 36 [15;68] years, p 1.5 in RNAseq data analysis, we identified a robust IKZF1 deletion gene expression profile. This resulted in 119 significantly upregulated genes after multi-comparison adjustment (i.e. CCND1, LAMA3, SLC2A9, SNAI1, LDHC, CD34, ID3, CDH2, MAF) and 39 downregulated genes (i.e. ROBO1, HES6, KREMEN1, DHCR24, ABHD15). Downregulated genes were involved in Slit/Robo/EMT, Notch, Wnt/beta-catenin, and glucose and fatty acid metabolism pathways, while upregulated genes were involved in focal adhesion, ROS homeostasis, histone modification, anaerobic metabolism, stem cell quiescence, and IL-6/STAT pathways. A significant number of dysregulated gene targets of chemotherapeutic agents (retinoic acid, doxorubicin, cisplatin, gemcitabine) and targeted therapies, such as FAKi, ERKi, BCL2i, mTORi, JAKi, BRKi, EGFRi and CDKi, were identified. Conclusions Adult BCP ALL patients with IKZF1 partial gene deletions showed poor prognosis. Gene expression analysis enables the identification of potentially targetable lesions. Funding Supported in part by a grant from the Instituto de Salud Carlos III, Ministerio de Economia y Competividad, Spain (PI14/01971); 2017 SGR288 (GRC) Generalitat de Catalunya; and support from CERCA Programme/Generalitat de Catalunya, Fundacio Internacional Josep Carreras. The research leading to this invention has received funding from “la Caixa” Foundation.

[Objective and methods]: Pediatric‐inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T‐cell ALL. We analyzed 169 patients with high‐risk T‐cell ALL included in two consecutive trials of the PETHEMA Group (HR‐ALL03 [n = 104] and the more contemporary HR‐ALL11 [n = 65]). [Results]: Patients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease‐free survival (DFS) between both protocols. Patients included in the HR‐ALL11 trial had better 2‐year overall survival (OS) compared with the HR‐ALL03 (65% [95% CI 51%‐79%] vs 44% [95% CI 34%‐54%], P = 0.026). Regarding toxicity, we observed a better safety profile in the HR‐11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in CR1, with 2‐year OS of 67%. [Conclusion]: Patients with T‐cell ALL included in the HR‐11 trial showed better OS than patients in the HR‐03, mostly driven by a reduction of NRM., This work was supported in part by a grant from Generalitat de Catalunya (2017 SGR288 (GRC)); economical support from CERCA Programme/Generalitat de Catalunya and from Fundació Internacional Josep Carreras. The research leading to this invention has received funding from “la Caixa” Foundation. JMR was supported by PI14/01971 from Fondo de Investigaciones Sanitarias. PB was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018‐2020 from Generalitat de Catalunya (BDNS357800) grants.

Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous group of lymphomas that can be divided in two gene expression profiles by means of microarray gene expression profiling (GEP), germi...