Análisis de factores pronósticos clínicos y biológicos en el linfoma difuso de célula grande B tratado con R-Chop con o sin radioterapia

[spa] El linfoma B difuso de célula grande (LBDCG) constituye un grupo heterogéneo de linfomas desde el punto de vista biológico y clínico. En torno al 20-40% de los pacientes recaen por lo que es importante buscar marcadores pronósticos para tratar de forma diferencial aquellos casos menos susceptibles de ser curados con tratamiento convencional. Con este propósito, hemos estudiado distintos marcadores pronósticos en una serie homogéneamente tratada con R-CHOP con o sin radioterapia para evaluar su capacidad de influir en nuestras decisiones de manejo terapéutico. Desde el punto de vista de los factores relacionados con el tratamiento, la dosis intensidad relativa (DIR) es ampliamente conocida en linfoma Hodgkin pero hay menos evidencias en LBDCG. Mediante este trabajo analizamos la DIR tanto en una cohorte tratada con R-CHOP21 como con R-CHOP14. En nuestra serie no encontramos diferencias en términos de respuesta y supervivencia entre los pacientes tratados con R-CHOP21 o R-CHOP14, lo cual coincide con lo reportado en los ensayos fase III. Se observó una tendencia a una mayor tasa de reducción de DIR en el grupo de RCHOP14. Sin embargo, el impacto de la reducción de la DIR en la respuesta y supervivencia se observó únicamente en el grupo de R-CHOP21. Por tanto, si evitáramos la reducción de la DIR, los regímenes de R-CHOP21 y R-CHOP14 serían equivalentes en términos de respuesta y supervivencia. En pacientes tratados con RCHOP21 se recomiendan, por tanto, medidas de soporte para evitar estas reducciones. Desde el punto de vista de factores clínicos, se han propuesto numerosos índices pronósticos. El más importante y mayormente usado es el índice pronóstico internacional (IPI), posteriormente validado en la era de Rituximab (R-IPI). Sin embargo, el R-IPI a pesar de ser un buen índice, carece de la habilidad de identificar un grupo de muy alto riesgo en la era de Rituximab: el grupo de alto riesgo del R-IPI tiene una supervivencia global (SG) y supervivencia libre de progresión (SLP) a los 4 años mayor del 50%. En los últimos años, se han hecho esfuerzos para intentar mejorar la habilidad discriminativa del IPI, como el NCCN-IPI. En la era pre-Rituximab también se generó el Tumor Score (TS) considerando exclusivamente variables relacionadas con el tumor. En el presente trabajo, se realizó la validación del TS en la era de Rituximab y se confirmó que todas las variables incluidas en el TS original mantenían un papel pronóstico independiente. Asimismo, el TS demostró una mejor identificación de los pacientes de alto riesgo en comparación con el IPI o el NCCN-IPI. Por otra parte, generamos por primera vez un nuevo índice pronóstico con la inclusión de variables del hemograma (ratio linfocitos/monocitos y amplitud de la distribución eritrocitaria) y la beta-2-microglobulina al diagnóstico que es de fácil obtención en la práctica clínica. En comparación con el R-IPI, este nuevo índice demostró una mejor identificación del subgrupo de muy mal pronóstico tanto para SLP como para SG. Asimismo, con este nuevo índice se confirmó un mejor poder discriminativo tanto para SLP como SG. Por último, desde el punto de vista biológico, estudios previos sugieren que los microRNAs (miRNAs) podrían tener un potencial papel pronóstico en pacientes con linfoma. Nosotros identificamos 3 miRNAs (miRNA-1244, miRNA-193-5p y miRNA- 1231) con papel pronóstico tanto para SLP como para SG. Estos pacientes podrían ser susceptibles de ser tratados con mayor o menor intensidad o con la adición de nuevos fármacos.[eng] Diffuse large B cell lymphoma (DLBCL) is a heterogeneous subtype from a biological and clinical point of view. Around 20-40% of the patient´s relapse, so it is important to identify a high-risk population that could benefit from different therapeutic approaches. For this purpose, we have analyzed different prognostic markers in a series homogeneously treated with R-CHOP with or without radiotherapy to evaluate their capacity to influence our therapeutic decisions. Regarding factors related to the treatment, the relative dose intensity (RDI) is a wellknown prognostic factor in Hodgkin lymphoma, but scarce information has been published in DLBCL. Our study analyzed the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14 to evaluate its differential impact when increasing dose density. In our series there were no differences in terms of response or survival between patients treated with R-CHOP21 or R-CHOP14, which coincides with reported phase III clinical trials. A higher rate of RDI reduction was observed in the R-CHOP14 group. However, the impact of RDI reductions on response and survival was only observed in the R-CHOP21. We can conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions. Regarding clinical factors, several scores have been developed. The International Prognostic Index (IPI), lately validated in the rituximab era (R-IPI), has been the most widely used. However, despite being a good prognostic score, it cannot identify a very high-risk subset in the Rituximab era: the high-risk group of R-IPI has a 4-year overall survival (OS) and progression free survival (PFS) higher than 50%. Several attempts have been made to try to improve R-IPI such as the NCCN-IPI. Also, in pre-Rituximab era the Tumor Score (TS) was reported exclusively considering tumor-related variables. In our study, the validation of TS was performed and we confirmed that all variables included in the original TS retain an independent prognostic role. Likewise, TS showed a better identification of patients with high risk prognosis compared to IPI or NCCN-IPI. On the other hand, a new prognosis score including complete blood count variables (lymphocytes/monocytes ratio and red blood cell distribution width) and beta-2- microglobulin at diagnosis is presented for the first time, which is readily available in a real-life practice without additional tests. Compared to R-IPI, this score showed better high-risk assessment for both PFS and OS. Furthermore, better risk discrimination for PFS and OS was confirmed with the new score compared to IPI. Finally, regarding biological factors, previous studies suggest that microRNAs (miRNAs) could have a potential prognostic role in patients with lymphoma. We identified 3 miRNAs (miRNA-1244, miRNA-193-5p and miRNA-1231) with prognostic significance for PFS and OS. These patients could be susceptible to be treated with more or less intensity or with the addition of new drugs.[cat] El limfoma B difús de cèl·lula gran (LBDCG) constitueix un grup heterogeni de limfomes des del punt de vista biològic i clínic. Al voltant del 20-40% dels pacients recauen, per la qual cosa, és important buscar marcadors pronòstics per tractar de forma diferencial aquells casos menys susceptibles de ser curats amb tractament convencional. Amb aquest propòsit, hem estudiat diferents marcadors pronòstics en una sèrie homogèniament tractada amb R-CHOP amb o sense radioteràpia per avaluar la seva capacitat d’influir en les nostres decisions de maneig terapèutic. Des del punt de vista dels factors relacionats amb el tractament, la dosi intensitat relativa (DIR) és àmpliament coneguda en limfoma Hodgkin però hi ha menys evidències en LBDCG. Mitjançant aquest treball analitzem la DIR tant en una cohort tractada amb R-CHOP21 com amb R-CHOP14. En la nostra sèrie no trobem diferències en termes de resposta i supervivència entre els pacients tractats amb RCHOP21 o R-CHOP14, la qual cosa coincideix amb el reportat en els assajos fase III. Es va observar una tendència a una major taxa de reducció de DIR en el grup de RCHOP14. No obstant, l’impacte de la reducció de la DIR en la resposta i supervivència es va observar únicament en el grup de R-CHOP21. Per tant, si evitéssim la reducció de la DIR, els règims de R-CHOP21 i R-CHOP14 serien equivalents en termes de resposta i supervivència. En pacients tractats amb R-CHOP21 es recomana, per tant, mesures de suport per evitar aquestes reduccions. Des del punt de vista de factors clínics, s’han proposat nombrosos índexs pronòstics. El més important i majorment utilitzat és l’índex pronòstic internacional (IPI), posteriorment validat en l’era de Rituximab (R-IPI). No obstant, l’R-IPI tot i ser un bon índex, manca de l’habilitat d’identificar un grup de molt alt risc en l’era de Rituximab: el grup d’alt risc de l’R-IPI té una supervivència global (SG) i supervivència lliure de progressió (SLP) als 4 anys major del 50%. En els últims anys, s’han fet esforços per intentar millorar l’habilitat discriminativa de l’IPI, com l’NCCN-IPI. En l’era pre- Rituximab també es va generar el Tumor Score (TS) considerant exclusivament variables relacionades amb el tumor. Al present treball, es va realitzar la validació del TS en l’era de Rituximab i es va confirmar que totes les variables incloses en el TS original mantenien un paper pronòstic independent. Així mateix, el TS va demostrar una millor identificació dels pacients d’alt risc en comparació amb l’IPI o l’NCCN-IPI. D’altra banda, generem per primera vegada un nou índex pronòstic amb la inclusió de variables de l’hemograma (ràtio limfòcits/monòcits i amplitud de la distribució eritrocitària) i la beta-2-microglobulina al diagnòstic que és de fàcil obtenció en la pràctica clínica. En comparació amb l’R-IPI, aquest nou índex va demostrar una millor identificació del subgrup de molt mal pronòstic tant per SLP com per SG. Així mateix, amb aquest nou índex es va confirmar un millor poder discriminatiu tant per SLP com SG. Finalment, des del punt de vista biològic, estudis previs suggereixen que els microRNAs (miRNAs) podrien tenir un potencial paper pronòstic en pacients amb limfoma. Nosaltres identifiquem 3 miRNAs (miRNA-1244, miRNA-193-5p i miRNA- 1231) amb paper pronòstic tant per SLP com per SG. Aquest pacients podrien ser susceptibles de ser tractats amb major o menor intensitat o amb l’addició de nous fàrmacs

RT-PCR multiplex para la detección simultánea de las mutaciones FLT3-ITD/NPM-1/AML1-ETO asociadas a Leucemia Mieloide Aguda

La Leucemia Mieloide Aguda (LMA) representa un grupo de neoplasias muy heterogéneo. Las aberraciones citogenéticas detectadas en el momento del diagnóstico son el marcador pronóstico más comúnmente utilizado. Sin embargo, el 20% de los casos de LMA presentan un cariotipo normal. Dentro de este grupo de pacientes la presencia de mutaciones del tipo FLT3-ITD se considera de mal pronóstico. Sin embargo, la presencia de la mutación NMP1 o AML1-ETO se asocia a un mejor pronóstico. En este contexto, el objetivo de este trabajo es el desarrollo de una técnica de diagnóstico molecular hematológico, que permita la detección simultánea de mutaciones para estos tres genes. Hemos desarrollado un método basado en la reacción en cadena de la polimerasa (PCR) que permite amplificar y visualizar simultáneamente estos 3 marcadores tanto desde ARN (un paso) como desde ADNc (dos pasos). De las 28 muestras analizadas, 6 (21,42 %) muestras fueron positivas para FLT3-ITD, 7 para NPM-1 (25%) y otras 4 (14,28) para AML1-ETO. Al comparar ambos métodos (ADNc vs ARN) con métodos convencionales los resultados de las 28 muestras estudiadas fue equivalente en el 100% de los casos, demostrando la robustez de los mismos.Acute Myeloid Leukemia (AML) is a heterogeneous group of neoplasms. The cytogenetic aberrations detected at the time of diagnosis are most commonly used as prognostic marker. However, 20% of AML patients exhibit a normal karyotype. Within this group of patients the presence of FLT3 -ITD mutations type is considered of poor prognosis. However, the presence of AML1 –ETO or NMP-1 or mutation is associated with a better prognosis. In this context, the aim of this work is to develop a technique of molecular diagnostic in hematology, allowing the simultaneous detection of mutations for these three genes. We have developed a method based on PCR that simultaneously amplifies and visualizes these three molecular markers both from RNA (one- step) and from cDNA (step two). Of the 28 samples tested, 6 (21.42%) samples were positive for FLT3 -ITD, 7 for NPM- 1 (25% ) and 4 ( 14,28 ) for AML1 -ETO . When comparing the two methods (cDNA vs RNA) by conventional techniques the obtained results from the 28 samples tested was equivalent in 100% of cases, demonstrating the robustness of this development

Screening for Prognostic microRNAs Associated with Treatment Failure in Diffuse Large B Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) treatment with R-CHOP regimen produces 5-year progression-free survival and overall survival of around 60-70%. Our objective was to discover prognostic biomarkers allowing early detection of the remaining 30-40% with poor long-term outcome. For this purpose, we applied a novel strategy: from a cohort of DLBCL patients, treated with standard therapy, a discovery group of 12 patients with poor prognosis (advanced stage III-IV, R-IPI > 2) was formed, consisting of six chemoresistant (refractory/early relapse 3 years) subjects. By using microarray assays, the most differentially expressed miRNAs were defined as an initial set of prognostic miRNA candidates. Their expression was then analyzed in a validation cohort of 68 patients and the three miRNAs with the most significant impact on event-free and overall survival were selected. In the DLBCL cell line U-2932 the transfection with miR-1244 and miR-193b-5p, but not miR-1231, blocked the effect of CHOP on cell viability. A subsequent gene set enrichment analysis in patients revealed the implication of the first two miRNAs in cell cycle control and chemoresistance-related pathways, whereas the last one was involved in immunological processes. In conclusion, this novel strategy identified three promising prognostic markers for DLBCL patients at high risk of failure with standard therapy

Allogeneic Hematopoietic Stem Cell Transplantation in Transformed Follicular Lymphoma (tFL): Results of a Retrospective Multicenter Study from GELTAMO/GETH-TC Spanish Groups

Simple Summary Follicular lymphoma (FL) is the most prevalent subtype of indolent lymphoma, accounting for 70% of all cases. The estimated risk of histological transformation (tFL), such as diffuse large B cell lymphoma (DLBCL), varies from 2-3% per year to 7-8% at 10 years in different series. Treatment after transformation is not clearly established. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be an option for these patients, but it has not been widely explored. We analyze the efficacy and toxicity of alloSCT in 43 patients from 14 Spanish centers. We observed long-term survival in around one third of the patients, especially those who developed chronic graft versus host disease, indicating that alloSCT continues to be a potentially curative option for patients with tFL, mainly due to the graft versus lymphoma effect. Background: Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be a potentially curative option for these patients, but it has not been widely explored. Methods: We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival. Results: A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31-67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2-9.6). Conclusions: Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p <= 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria

Analysis of vaccine responses after anti-CD20 maintenance in B-cell lymphoma in the Balearic Islands. A single reference center experience

IntroductionThe use of maintenance approaches with anti-CD20 monoclonal antibodies has improved the outcomes of B-cell indolent lymphomas but may lead to significant peripheral B-cell depletion. This depletion can potentially hinder the serological response to neoantigens.MethodsOur objective was to analyze the effect of anti-CD20 maintenance therapy in a reliable model of response to neoantigens: SARS-CoV-2 vaccine responses and the incidence/severity ofCOVID-19 in a reference hospital.ResultsIn our series (n=118), the rate of vaccination failures was 31%. Through ROC curve analysis, we determined a cutoff for SARS-CoV-2 vaccine serologic response at 24 months from the last anti-CD20 dose. The risk of severe COVID-19 was notably higher within the first 24months following the last anti-CD20 dose (52%) compared to after this period (just 18%) (p=0.007). In our survival analysis, neither vaccine response nor hypogammaglobulinemia significantly affected OS. While COVID-19 led to a modest mortality rate of 2.5%, this figure was comparable to the OS reported in the general immunocompetent population. However, most patients with hypogammaglobulinemia received intravenous immunoglobulin therapy and all were vaccinated. In conclusion, anti-CD20 maintenance therapy impairs serological responses to SARS-CoV-2 vaccines.DiscussionWe report for the first time that patients during maintenance therapy and up to 24 months after the last anti-CD20 dose are at a higher risk of vaccine failure and more severe cases of COVID-19. Nevertheless, with close monitoring, intravenous immunoglobulin supplementation or proper vaccination, the impact on survival due to the lack of serological response in this high-risk population can be mitigated, allowing for the benefits of anti-CD20 maintenance therapy, even in the presence of hypogammaglobulinemia

Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma; Insights into Its Potential Role in the Era of New Immunotherapeutic and Targeted Therapies: The GETH/GELTAMO Experience

Allo-SCT is a curative option for selected patients with relapsed/refractory (R/R) MCL, but with significant NRM. We present the long-term results of patients receiving allo-SCT in Spain from March 1995 to February 2020. The primary endpoints were EFS, OS, and cumulative incidence (CI) of NRM, relapse, and GVHD. We included 135 patients, most (85%) receiving RIC. After a median follow-up of 68 months, 5-year EFS and OS were 47 and 50%, respectively. Overall and CR rates were 86 and 80%. The CI of relapse at 1 and 3 years were 7 and 12%. NRM at day 100 and 1 year were 17 and 32%. Previous ASCT and Grade 3-4 aGVHD were associated with a higher NRM. Grade 3-4 aGVHD, donor type (mismatch non-related), and the time-period 2006-2020 were independently related to worse EFS. Patients from 1995-2005 were younger, most from HLA-identical sibling donors, and were pretreated less. Our data confirmed that allo-SCT may be a curative option in R/R MCL with low a CI of relapse, although NRM is still high, being mainly secondary to aGVHD. The arrival of new, highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegate allo-SCT to those fit patients who fail these therapies, far away from the optimal timing of treatment

The Genotype of the Donor for the (GT)n Polymorphism in the Promoter/Enhancer of FOXP3 Is Associated with the Development of Severe Acute GVHD but Does Not Affect the GVL Effect after Myeloablative HLA-Identical Allogeneic Stem Cell Transplantation

The FOXP3 gene encodes for a protein (Foxp3) involved in the development and functional activity of regulatory T cells (CD4+/CD25+/Foxp3+), which exert regulatory and suppressive roles over the immune system. After allogeneic stem cell transplantation, regulatory T cells are known to mitigate graft versus host disease while probably maintaining a graft versus leukemia effect. Short alleles (≤(GT)15) for the (GT)n polymorphism in the promoter/enhancer of FOXP3 are associated with a higher expression of FOXP3, and hypothetically with an increase of regulatory T cell activity. This polymorphism has been related to the development of auto- or alloimmune conditions including type 1 diabetes or graft rejection in renal transplant recipients. However, its impact in the allo-transplant setting has not been analyzed. In the present study, which includes 252 myeloablative HLA-identical allo-transplants, multivariate analysis revealed a lower incidence of grade III-IV acute graft versus host disease (GVHD) in patients transplanted from donors harboring short alleles (OR = 0.26, CI 0.08-0.82, p = 0.021); without affecting chronic GVHD or graft versus leukemia effect, since cumulative incidence of relapse, event free survival and overall survival rates are similar in both groups of patients

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor