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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).

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: 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.

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.

Adults with relapsed/refractory acute lymphoblastic leukemia have an unfavourable prognosis, which is influenced by disease and patient characteristics. To further evaluate these characteristics, a retrospective analysis of 1,706 adult patients with Ph-negative relapsed/refractory B-precursor acute lymphoblastic leukemia diagnosed between 1990-2013 was conducted using data reflecting the standard of care from 11 study groups and large centers in Europe and the United States. Outcomes included complete remission, overall survival, and realization of stem cell transplantation after salvage treatment. The overall complete remission rate after first salvage was 40%, ranging from 35%-41% across disease status categories (primary refractory, relapsed with or without prior transplant), and was lower after second (21%) and third or greater (11%) salvage. The overall complete remission rate was higher for patients diagnosed from 2005 onward (45%, 95% CI: 39%-50%). One- and three-year survival rates after first, second, and third or greater salvage were 26% and 11%, 18% and 6%, and 15% and 4%, respectively, and rates were 2%-5% higher among patients diagnosed from 2005. Prognostic factors included younger age, longer duration of first remission, and lower white blood cell counts at primary diagnosis. This large dataset can provide detailed reference outcomes for patients with relapsed/refractory Ph-negative B-precursor acute lymphoblastic leukemia. clinicaltrials.gov identifier: 02003612.

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...

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.

Among other phenotypic markers, CD11b expression has been considered as an unfavorable prognostic factor, both in terms of overall survival (OS), disease-free survival (DFS), and attainment and duration of complete remissions (CRs) in adult patients with acute myeloid leukemia (AML). Recently, some groups have restricted its prognostic impact to poor prognostic karyotypic risk groups. The aim of this study was to retrospectively analyze the prevalence of CD11b and of CD56 expression in blast cells of 158 AML patients [excluding those with t(15;17)] stratified according to their cytogenetic risk and to correlate these phenotypic characteristics with OS, DFS, and CR. CD11b was more frequently expressed in intermediate and unfavorable cytogenetic prognostic groups (38.9 and 35.5 %, respectively) than in the favorable group (9.5 %). No differences were observed in CD56 expression according to the cytogenetic risk groups. When OS, DFS, and CR were analyzed according to these two markers, no statistical differences were recorded in any cytogenetic risk group. In conclusion, although CD11b was more frequently expressed in blast cells of patients with intermediate and unfavorable cytogenetic risk groups, this feature did not translate into different clinical outcome. Similarly, CD56 positivity did not have any influence on the prognosis of these patients.

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.

Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM) despite the superior efficacy of lenalidomide-based triplet therapy. The aim of this multicenter retrospective study of 227 patients was to characterize those with disease with good response to Ld salvage therapy for RRMM. Obtaining at least a partial response (PR) after the first treatment cycle was the major predictor of a long-lasting response. If Ld is to be considered a treatment choice, at least a PR should be obtained after the first cycle to maintain double-agent therapy safely. Background: Lenalidomide plus dexamethasone (Ld) is still considered an option of care for some selected patients with relapsed or refractory multiple myeloma (RRMM), despite the proven superiority of lenalidomide-based triplet therapy. Up to 20% of patients obtain long-term benefit from Ld alone. The aim of this multicenter retrospective study was to identify and characterize those with good response to Ld salvage therapy, defined as progression-free survival lasting more than 24 months. Patients and Methods: Patients treated with Ld in a consortium of 3 tertiary-care hospitals (Institut Catala d'Oncologia) between 2009 and 2016 were prospectively registered; 227 patients had evaluable data. Results: In multivariate analysis, obtaining partial response after the first therapy cycle was the main independent factor associated with progression-free survival lasting more than 24 months. Together with standard risk cytogenetics, partial response after first cycle was also independently associated with a higher rate of complete response. Previous plasma-cell dyscrasia remained as the only baseline characteristic independently associated with long-lasting responses. High-risk cytogenetics and no history of monoclonal gammopathy of undetermined significance were the only statistically significant negative prognostic factors for overall survival. Patients who had received only one prior therapy showed a trend toward higher overall survival. Conclusion: If Ld is to be considered a treatment choice, at least a partial response should be obtained after the first therapy cycle to maintain double-agent therapy safely.

We have read with interest the article by Rozovski et al. [1], who published a series of 1370 patients with acute myeloid leukemia (AML), 3.3% of whom had central nervous system (CNS) infiltration ...

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.

The karyotype is an important predictor of outcome in acute lymphoblastic leukemia (ALL). Rearrangements of the 11q23 region involving the KMT2A gene confer an unfavorable prognosis. Forty-six adult ALL patients from the PETHEMA Group treated with risk-adapted protocols, with t(v;11q23) were selected for this study. Complete response (CR) was attained in 38 patients; 25 remained in CR after consolidation. Twelve (48%) received allogeneic hematopoietic stem cell transplantation (HSCT) and 13 delayed intensification and maintenance. The 5-year CR duration probability was 37% (95% CI, 19%-55%). A trend for a longer CR duration was observed in patients undergoing HSCT vs. those receiving chemotherapy. The 5-year overall survival (OS) probability was 20% (95% CI, 5%-35%). The OS was better, albeit not significant, in patients with a MRD level< 0.1% after induction (39% [95% CI, 14%-64%] vs. 13% [95% CI, 0%-36%]). Specific treatment approaches are required to improve the outcome of patients with KMT2A-rearrangements.

Objective: Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Methods: Patients with consecutive MM

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.

It is unclear whether higher CD34 + cell doses infused for ASCT have any influence on survival or relapse in patients with lymphoma. We analyzed the correlation of infused CD34 + cell dose with relapse, survival, and hematopoietic recovery in 146 consecutive patients undergoing ASCT for lymphoma. Higher doses (>5 × 106/kg) were significantly correlated with earlier hematopoietic recovery, fewer infectious episodes, lower transfusion needs. No differences were observed in lymphoma outcomes (4-year relapse incidence of 38% [95%CI: 29%–48%] in the lower dose group versus 51% [95%CI: 30%–69%] in the higher dose group, 10-year OS probabilities of 58% [95%CI: 48%–68%] versus 75% [95%CI: 59%–91%], 10-year DFS probabilities of 47% [95%CI: 37%–57%] versus 42% [95%CI: 23%–61%], p = NS for all outcomes). In this series, a higher infused CD34 + cell dose did not correlate with survival or relapse but correlated with earlier hematopoietic recovery and lower resource consumption.

The impact of human immunodeficiency virus (HIV) infection on the outcome of patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma with life-threatening complications requiring intensive care unit (ICU) admission is not well known. The objective of this study was to compare the outcome of patients with lymphoma transferred to the ICU according to HIV infection status. The clinical characteristics, reason for ICU admission, and outcome of 48 consecutive critically ill patients with lymphoma admitted to the ICU from January 2000 to March 2010 was retrospectively analyzed, focusing on their HIV serology status. Thirty-six patients were HIV-negative and 12 patients HIV-positive. Burkitt lymphoma was more frequent in HIV-infected patients, whereas diffuse large B-cell lymphoma was more frequent in HIV-negative patients. The main acute life-threatening diseases precipitating ICU transfer were similar in both groups. Severe neutropenia was more frequent in HIV-positive than in HIV-negative patients. With a median follow-up of 53 months after ICU admission, the overall survival probabilities were 15% (95% confidence interval [CI]: 3-27%) and 17% (95% CI: 0-38%) for HIV-negative and HIV-positive patients, respectively. The 2-year survival probabilities were 34% (95% CI: 10-58%) and 40% (95% CI: 0-43%) for HIV-negative and HIV-positive patients discharged from the ICU, respectively. In this study, HIV infection did not have a negative impact on the outcome of patients with lymphoma admitted to the ICU.

Background: ETP-ALL was included as a provisional identity in the 2016 WHO classification of ALL. This subtype was first identified by Coustan-Smith et al. in 2009. However, this immunophenotype-based classification does not fully enclose all ETP-ALL cases identified by gene expression profile (GEP). Although early studies in small series of ETP-ALL suggested a very poor outcome for ETP ALL more recent and larger series have showed improvement in outcome treating children with a contemporary protocol based on chemotherapy schedules, or after allogeneic stem cell transplantation (allo-SCT) in adults. Aim: To investigate the clinical and biological features of ETP-ALL cases in the Spanish cohort of adult T-cell ALL (T-ALL) patients and to assess the potential impact of high-risk therapy on their outcome. Method: One hundred eighty-five adults with T-ALL treated according to two consecutive MRD-oriented high-risk adult PETHEMA protocols -ALL-HR-2003 (NCT00853008) and ALL-HR-11 (NCT01540812; still ongoing)- were included in this study. The EGIL criteria were used to define the immunologic subtype of T-ALL after central review of immunophenotype reports, and the criteria proposed by Zuurbier et al. (Zuurbier L. et al. Haematologica 2014; 99:94-102) were used to define ETP-ALL. These later criteria consist of a combination of immunophenotypic markers (absence of CD1a-/CD4-/CD8-, cut-off 25%), that resemble those published by Coustan-Smith, with the advantage that include most ETP-ALL cases, as identified by GEP, avoiding the use of partial expression of CD5 marker to immuno-classify these patients. Results: Thirty-four out of 167 evaluable patients (20%) with T-ALL showed an ETP-ALL immunophenotype. Patients with ETP-ALL were older (mean 39 [SD 12] vs. 33 [12] yr; p=0.011), showed more frequently lymph node involvement (79% vs. 56%; p=0.021) and lower WBC counts at diagnosis (mean, 72 [155] vs. 97 [112] x109/L; p=0.004). At genetic level, ETP-ALL patients were associated with the absence of deletions in CDKN2A/B gene cluster (91% vs. 26%; p10% BM blasts on day+14) vs. 37% of non-ETP (p Conclusions: ETP-ALL accounts for 20% of adult T-ALL in the PETHEMA cohort and it is associated with a poorer initial response to treatment (lower CR rate, poorer MRD clearance) than the remaining T-ALL patients. Such poorer outcome is not overcome by allo-SCT in our series. Supported by grants from: Asociación Española Contra el Cáncer, AECC (GC16173697BIGA), Instituto Carlos III (PI14/01971 FI), 2017-SGR288 (GRC), CERCA Program from Generalitat de Catalunya, and "La Caixa" Foundation. Figure 1. Figure 1. Disclosures Montesinos: Daiichi Sankyo: Consultancy, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Patients who are admitted to the intensive care unit (ICU) with hematologic malignancies have a poor prognosis, although outcomes have improved in recent years. This study analyzed ICU mortality, short- and long-term survival, and prognostic factors for 100 consecutive critically ill patients with a hematologic malignancy who were admitted to our polyvalent ICU from January 2000 to May 2006. The median age was 55 years (range, 15-75 years; male-female ratio, 60:40). The main acute life-threatening diseases precipitating ICU transfer were respiratory failure (45 patients, 45%) and septic shock (33 patients, 33%). Forty-two patients (42%) were discharged from the ICU. The ICU mortality rate from 2004 to 2006 was lower than from 2000 to 2003 (49% versus 69%, P.047). The 1- and 2-year probabilities of survival for patients discharged from the ICU were 67% (95% confidence interval [CI], 51%-84%) and 54% (95% CI, 34%-73%), respectively. A multivariate analysis revealed hemodynamic instability (odds ratio, 2.11; 95% CI, 1.17-3.83; P = .014) and mechanical ventilation (odds ratio, 4.27; 95% CI, 1.70-10.74; P = .002) to be the main predictors of a poor survival prognosis. Almost half of patients with hematologic malignancy and life-threatening complications can be discharged from the ICU. Age and underlying disease characteristics do not influence ICU outcome, which is mainly determined by hemodynamic and ventilatory status.

Background and Objectives Although doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is considered the standard chemotherapy regimen for Hodgkin’s lymphoma (HL), information on the results of this therapy in human immunodeficiency (HIV)-related HL is scarce. We analyzed the results of the ABVD regimen and highly active antiretroviral therapy (HAART) in patients with advanced stage, HIV-related HL. Design and Methods From January 1996 to December 2005, 62 HIV-infected patients with newly diagnosed HL were treated in 15 Spanish hospitals. Six to eight cycles of ABVD and HAART were planned. Response to chemotherapy, overall survival (OS) and event-free survival (EFS) were recorded. Results The median age of the patients was 37 years (range, 24–61) and 29 (47%) had a previously known diagnosis of acquired immunodeficiency syndrome. The median CD4 lymphocyte count at diagnosis was 129/μL (range 5–1,209). The histologic subtype of HL was nodular sclerosis in 17 patients (27%), mixed cellularity in 25 (41%), lymphocyte depletion in 10 (16%) and non-specified in the remaining 10 (16%). Twenty-one (34%) patients were in stage III and 41 (66%) in stage IV. The scheduled six to eight ABVD cycles were completed in 82% of cases. Six patients died during induction, 54 (87%) achieved a complete response (CR) and two were resistant. After a median follow-up of 39 and 47 months, 5-year EFS and OS probabilities were 71% (47–95) and 76% (65–87), respectively. An immunological response was observed in 24 out of 43 patients (56%) and a virological response in 27 out of 40 (68%). The immunological response to HAART had a positive impact on OS and EFS ( p =0.002 and p =0.001, respectively). Interpretation and Conclusions In patients with advanced stage, HIV-related HL, treatment with ABVD together with HAART is feasible and effective. This supports the concept that patients with HIV-related HL should be treated in the same way as immunocompetent patients if HAART, adequate supportive therapy and anti-infectious prophylaxis are given concomitantly. An immunological response to HAART has a positive impact on OS and EFS.

Background Oral mucositis (OM) is a common complication of conditioning regimens with high-dose melphalan (HDmel). This retrospective cohort study analyzes the impact of oral cryotherapy (OC) or room temperature saline rinses on the prevention of OM in patients with multiple myeloma (MM) or lymphoid neoplasias submitted to autologous stem cell transplantation (ASCT) in a single center. Patients and methods From August 2006 to July 2011, 134 consecutive patients were enrolled. Two consecutive groups were included: Non-OC (August 2006 to April 2009, 68 patients) and OC (May 2009 to July 2011, 66 cases). MM cases (78, 58%) received HDmel as the conditioning regimen and 56 patients (42%) with lymphoma received BEAM. Results The non-OC and OC groups were comparable for the main clinicobiologic features and type of neoplasia. OM was more frequent and severe in patients receiving BEAM as the conditioning therapy. The group of OC showed less frequent and less severe mucositis and fewer days on antibiotics. No differences were observed in the duration of OM, need for parenteral nutrition and narcotics, and the length of hospital stay on comparison with the OC and non-OC groups. By multivariate analyses, OC was an independent favorable prognostic factor for OM development. Conclusions This study shows that OC is more effective than saline rinses in the prevention of OM in patients with lymphoma and myeloma receiving conditioning regimens with HDmel for ASCT.

Introduction In the last years genome wide profilings have identified recurrent Copy Number Alterations (CNA) in genes potentially involved in the pathogenesis of Acute Lymphoblastic Leukemia (ALL). These studies have identified deletions in B-cell development genes (IKZF1, EBF1, PAX5, TCF3, etc.), cell cycle regulation genes (CDKN2A/B, RB1, TP53, etc.), glucocorticoid resistance genes (BTG1, CREBBP) and growth factor receptors genes (CRLF2, CSF2RA, IL3RA) among others. Some of these CNA (i.e. IKZF1, CDKN2A, CRLF2) have been reported to have prognostic significance in several pediatric series but there are very few data regarding their impact in B-lineage adult ALL. Our aim was to analyze the frequency and prognostic significance of CNA in a series of 125 B-lineage adult ALL patients treated according to risk-adapted protocols from the Spanish PETHEMA Group. Methods Bone marrow or peripheral blood (with significant blast burden) samples from 125 B-lineage adult ALL patients enrolled in risk-adapted protocols from the PETHEMA Group were analyzed at diagnosis. MLPA assays (MRC-Holland) were performed for the following genes: IKZF1, IKZF2, IKZF3, EBF1, CDKN2A/B, PAX5, ETV6, BTG1, RB1, hsa-miR-31, X/Y PAR1 region genes (CRLF2, CSF2RA, IL3RA) and 14q32.33 region genes (IGH D, MTA1, KIAA0284). Fragment analysis was made by Genescan in an ABI-3130 sequencer (Applied Biosystems). Data normalization provided a value indicative of the presence or absence of CNA: 0-0.20 homozygous deletion, 0.21-0.70 heterozygous deletion, 0.71-1.30 normal, 1.31-1.70 heterozygous duplication and 1.71-2.20 homozygous duplication. Results The median age [range] was 40 [15-74] years, 71 (57%) males, median WBC count 12.11 x109/L [0.4-388]. Immunophenotype: pro-B 14 (11%), common 71 (58%), pre-B 26 (21%), mature-B 10 (8%), unavailable 2 (2%). Cytogenetics: normal 16 (13%), hyperdiploid 6 (5%), hypodiploid 2 (2%), t(9:22) 20 (16%), t(1;19) 8 (6%), 11q23/MLL 11 (9%), 8q24/C-MYC 7 (5%), complex 1 (1%), iAMP21 2 (2%), other translocations or deletions 31 (25%), no growth 20 (16%). CNA frequencies of the 125 patients are shown in the table. IKZF1 deletions were significantly associated with EBF1 deletions, high WBC count and Philadelphia (Ph) chromosome. In the IKZF1 deleted cohort whole gene deletions were as frequent as Ik6 isoforms (28% each). A high codeletion rate was detected in genes located in 9p (CDKN2A/B with PAX5, CDKN2A/B with hsa-miR-31 and PAX5 with hsa-miR-31). CDKN2A/B also showed concomitant deletions with ETV6 while PAX5 showed codeletions with BTG1. CDKN2A/B and PAX5 deleted patients had higher WBC counts than non-deleted individuals. Clinical follow-up data was available for 123 patients of the whole series and for the 105 patients of the Ph-negative cohort. Multivariate analysis showed that advanced age, BTG1 deletions and EBF1 deletions were negative prognostic factors for achieving Complete Remission (CR) and WBC count and IKZF1 deletions significantly reduced CR duration in both cohorts. Interestingly, there were significant differences in relapse rates between whole and partial gene IKZF1 deletions. IKZF1 haploinsufficient patients had a probability of CR duration at 3 years of 83% ± 30% vs. 6% ± 12% of partial gene deletion carriers. Advanced age and IKZF1 deletions were predictors for overall survival in the Ph-negative cohort and age>30 years, IKZF1 deletions and hsa-miR-31 deletions were associated with poor prognosis in the whole series. Conclusions In B-lineage adult ALL, deletions of IKZF1, EBF1, BTG1 or hsa-miR-31 are markers with prognostic significance in addition to age and WBC count. Patients with partial IKZF1 gene deletions have a significantly higher probability of relapse than those with whole gene loss. These genetic abnormalities could help to better define prognostic subgroups in adult patients with B-lineage ALL. Supported by the grants PI10/01417 and RD12-0036-0029 from Instituto Carlos III and a grant from the Spanish Society of Hematology and Hemotherapy (2012). Disclosures: No relevant conflicts of interest to declare.

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count200/μL and bone marrow involvement were associated with poor OS (hazard ratio [HR] 3.2 [1.2-8.3] and HR 2.7 [1.1-6.6]) and PFS (HR 3.5 [1.3-9.1] and HR 2.4 [1-5.7]), bone marrow involvement with poor disease-free survival (DFS) (HR 14.4 [1.7-119.7] and Eastern Cooperative Oncology Group (ECOG) score2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

In patients with human immunodeficiency virus (HIV) infection and advanced stage Hodgkin’s lymphoma (HL), treatment with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and highly active antiretroviral therapy (ART) is feasible and effective, and the immunological response to ART has a

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.

Introduction: Allogeneic haematopoietic stem cell transplantation (alloHCT) is a potentially curative approach for patients (pts) with multiple myeloma (MM). The high transplant related mortality (TRM) rate with myeloablative conditioning has resulted in a shift to reduced intensity conditioning regimens (RIC). However, most MM pts who receive an alloRIC ultimately relapse and their treatment remains a challenge. Since alloHCT can modify the biology of the disease, including the immune environment, responses after alloHCT to rescue therapies previously used before alloHCT could be improved. Our main objective was to evaluate the efficacy of regimens including new drugs in MM pts relapsing after alloHCT comparing the efficacy achieved before and after alloHCT. Material and Methods: We report a retrospective multicenter analysis of 126 consecutive pts that underwent alloHCT for MM from 2010 to 2013 at 8 Spanish centers. Results: Baseline pts and transplant characteristics are shown in Table I. The median of prior therapies prior to alloHCT was 3 (1-9), 83% had received previous autologous HCT and 26% had high risk cytogenetic. 71 (56%) and 48 pts (38%) had been treated with regimens containing proteasome inhibitors (PI) and immunomodulatory drugs (IMIDs) before transplantation, respectively. Disease status at transplant was complete remission (CR) in 16 (13%) pts, partial response (PR) or very good PR in 86 (68%) and 24 (18.5%) had relapsed/progressive disease. 35 pts (28%) had active extramedullary disease at transplant. The majority of pts received peripheral blood HCT (90%), RIC (90%) with fludarabine plus melphalan based conditioning regimen (61%) and calcineurin inhibitor plus MTX as GVHD prophylaxis (68%). 19% receiving allo-HCT from an unrelated donor (91% 10/10 HLA matched). All pts engrafted. Grade II-IV acute GVHD occurred in 54% pts (grade IV 8%) and chronic GVHD in 45% (moderate 15%, severe 12%). TRM within the first 100 days after transplant was 6% (overall TRM 28%). 60% pts improved their pre-transplant response, with an overall response rate of 74% (56% CR). After a median follow-up of 92 months for pts alive (22-197), the OS was 51 and 43% at 2 and 5 years respectively. 75 pts (59.5%) relapsed after alloHCT, 57 of them with extramedullary involvement. Median time to relapse was 8 months post-transplant (1-141). The cumulative incidence of relapse was 79% at 3 years. Median OS after relapse was 22 months (8-33). Seventeen out of 75 pts who relapsed received IP both in the pre-transplant and in the post-transplant period. Sixteen pts out of 17 who received IP achieved at least PR pre-transplant while 10 out of these 16 pts responded again to PI post-HCT. Moreover, 1 patient reached a deeper response (CR) post as compared to pre alloHCT (PR) and 1 patient who was refractory pre-alloHCT did respond post-alloHCT. In addition, 6 out of 7 pts who did not respond to IP post-transplant reached stable disease with time to progression (TTP) lasting 4 to 12 months. Twelve out of 75 pts who relapsed received IMIDs both pre and post-alloHCT. Ten pts out of 12 who received IMID pre-alloHCT achieved at least PR, and 8 out of these 10 pts responded again to IMIDs post-alloHCT. Moreover, 1 patient who had been refractory to IMIDs in the pre-transplant period reached CR after alloHCT. In addition, 2 out of 4 pts who were refractory to IMIDs in the post-transplant period reached stable disease with TTP of 8 to 13 months. Remarkably, among pts who respond both in the pre and the post-transplant period to IP or IMIDs, the time to response (TTR) and time to progression (TTP) was similar despite the regimens used in the pre-transplant setting were more aggressive (TTR 3 vs 3.5 and TTP 9 vs 7 months before and after alloHCT for IP, and TTR 4 both before and after alloHCT and TTP 10 vs 9.5 months before and after alloHCT for IMIDs). All but 2 pts received first generation IP pre and post-alloHCT (two pts received carfilzomib) and all but 5 received first generation IMIDs (5 pts were treated with pomalidomide). Conclusions: MM pts relapsing after alloHCT should be considered candidates to receive new drugs, as they can achieve response rates at least in a similar proportion and durability to those observed in the pre-transplant setting. This finding is in contrast to the usual course of the disease outside the alloHCT setting, where response rates and TTP decreases with consecutive lines of treatment. Disclosures Mateos: Janssen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria.

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.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype in non-immunosuppressed and in human immunodeficiency virus (HIV)-positive patients. The prognosis of DLBCL with germinal center (GC) phenotype is better than that of the non-germinal center (non-GC) phenotype by immunohistochemical expression profile (IHC) in some studies but not in others. The frequency and the prognosis of these phenotypic subtypes in DLBCL related to HIV infection is not well known. The objectives of this study were to characterize the IHC by tissue microarray in 98 patients with DLBCL, 34 of whom were HIV-positive, and to evaluate their prognosis. Patients with HIV-related DLBCL with a non-GC pattern had poorer prognosis than patients with non-HIV-related DLBCL with the same pattern, but this difference disappeared when we considered only patients receiving HAART.

Adults with high-risk acute lymphoblastic leukemia (HR-ALL) have a poor outcome with standard chemotherapy and usually undergo unrelated stem cell transplantation (SCT) if a matched sibling donor is not available. We analyzed the outcome of adult patients with unrelated SCT for HR-ALL and studied the possible effect of the hematopoietic stem cell source of the transplant. A total of 149 adult patients (median age, 29 years, range, 15-59 years) with HR-ALL underwent unrelated SCT in 13 Spanish institutions between 2000 and 2007. Patients in first complete remission (CR1) at transplantation had at least one adverse prognostic factor (advanced age, adverse cytogenetics, hyperleukocytosis, or slow response to induction therapy). ALL was in CRI in 81 patients (54%), in second CR (CR2) in 37 patients (25%), in third CR (CR3) in II patients (7%), and with overt disease in 20 patients (13%). The hematopoietic source was unrelated cord blood (UCB) in 62 patients and an unrelated donor (UD) in 87 patients. The patients undergoing UCB-SCT and UD-SCT were comparable in terms of the main clinical and biological features of ALL, except for a higher frequency of patients with more overt disease in the UCB-SCT group. There was no statistically significant difference in overall survival (OS) or disease-free survival (DFS) at 5 years between the 2 groups. Treatment-related mortality (TRM) was significantly lower in the UCB-SCT group (P = .021). The probability of relapse at 1 year was 17% (95% confidence interval [CI], 7%-27%) for the UD-SCT group and 27% (95% CI, 14%-40%) for the UCB-SCT group (P = .088), respectively. Only disease status at transplantation (CR1, 41% [95% CI, 18%-64%] vs CR2, 51% [95% CI, 17%-85%] vs advanced disease, 66% [95% CI, 46%-86%]; P = .001) and the absence of chronic graft-versus-host disease (74% [95% CI, 46%-100%] vs 33% [95% CI, 17%-49%]; P = .034) were significant factors for relapse. All unrelated transplantation modalities were associated with high treatment-related mortality for adult HR-ALL patients without a sibling donor. UCB-SCT and UD-SCT were found to be equivalent options. Disease status at transplantation and chronic GVHD were the main factors influencing relapse in both transplantation modalities. Biol Blood Marrow Transplant 16: 957-966 (2010) (C) 2010 American Society for Blood and Marrow Transplantation