Search

Abstract: Although broadly used, consolidative autologous hematopoietic stem cell transplantation (auto-HCT) for relapsed/refractory (R/R) T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) has never been specifically investigated. Here, we have analyzed outcomes of auto-HCT for THRLBCL compared with diffuse large cell B-cell lymphoma not otherwise specified (DLBCL). Eligible for this retrospective registry study were adult patients with R/R THRLBCL and DLBCL, respectively, who underwent a first auto-HCT in a salvage-sensitive disease status as assessed by positron emission tomography-computed tomography between 2016 and 2021 and were registered with the European Society for Blood and Marrow Transplantation database. The primary end point was progression-free survival (PFS) 2 years after transplantation. A total of 201 patients with THRLBCL and 5543 with DLBCL were included. There were no significant differences in terms of disease status at HCT, pretreatment lines, and interval from diagnosis to transplant between the cohorts, but patients with THRLBCL were significantly younger, contained a higher proportion of men, and had a better performance status. Compared with DLBCL, THRLBCL was associated with significantly better 2-year PFS (78% vs 59%; P < .001) and overall survival (OS, 81% vs 74%; P = .02) because of a significantly lower 2-year relapse incidence (16% vs 35%; P < .001). On multivariate analysis, favorable relapse risk (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.31-0.7) and PFS (HR, 0.58; 95% CI, 0.41-0.82) of patients with THRLBCL remained significant, whereas OS benefits (HR, 0.78; 95% CI, 0.54-1.12) did not. These results were validated in a propensity score-matched analysis. These data prove auto-HCT as an effective treatment option for salvage-sensitive R/R THRLBCL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990-1994) to 58 years (2015-2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990-1994) to 54 (2015-2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015-2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990-1994) to 70% (2015-2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990-1999) to 46% (2015-2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies., (© 2024. The Author(s).)

Post-transplant cyclophosphamide (PTCY) has been introduced as graft-versus-host disease (GvHD) prophylaxis in mismatched and matched unrelated hematopoietic cell transplant (HCT). However, data comparing outcomes of PTCY or ATG in patients undergoing a 1 antigen mismatched HCT for lymphoproliferative disease are limited. We compared PTCY versus ATG in adult patients with lymphoproliferative disease undergoing a first 9/10 MMUD HCT with a reduced intensity conditioning regimen from 2010 to 2021. Patients receiving PTCY were matched to patients receiving ATG according to: age, disease status at transplant, female to male matching, stem cell source and CMV serology. Grade II-IV acute GvHD at 100 day was 26% and 41% for the ATG and PTCY group, respectively (p = 0.08). Grade III-IV acute GvHD was not significantly different between the two groups. No differences were observed in relapse incidence, non-relapse mortality, progression-free survival, overall survival and GvHD-relapse-free survival at 1 year. The cumulative incidence of 1-year extensive chronic GvHD was 18% in the ATG and 5% in the PTCY group, respectively (p = 0.06). In patients with lymphoproliferative diseases undergoing 9/10 MMUD HCT, PTCY might be a safe option providing similar results to ATG prophylaxis. Due to the limited number of patients, prospective randomized trials are needed., (© 2024. The Author(s).)

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Natural killer/T-cell lymphomas (NKTCL) represent rare and aggressive lymphoid malignancies. Patients (pts) with relapsed/refractory disease after Asparaginase (ASPA)-based chemotherapy have a dismal prognosis. To better define the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), we conducted a retrospective analysis of data shared with the European Society for Blood and Marrow Transplantation (EBMT) and cooperating Asian centers. We identified 135 pts who received allo-HSCT between 2010 and 2020. Median age was 43.4 years at allo-HSCT, 68.1% were male. Ninety-seven pts (71.9 %) were European, 38 pts (28.1%) Asian. High Prognostic Index for NKTCL (PINK) scores were reported for 44.4%; 76.3% had >1 treatment, 20.7% previous auto-HSCT, and 74.1% ASPA-containing regimens prior to allo-HSCT. Most (79.3%) pts were transplanted in CR/PR. With a median follow-up of 4.8 years, 3-year progression-free(PFS) and overall survival were 48.6% (95%-CI:39.5-57%) and 55.6% (95%-CI:46.5-63.8%). Non-relapse mortality at 1 year was 14.8% (95%-CI:9.3-21.5%) and 1-year relapse incidence 29.6% (95%-CI:21.9-37.6%). In multivariate analyses, shorter time interval (0-12 months) between diagnosis and allo-HSCT [HR = 2.12 (95%-CI:1.03-4.34); P = 0.04] and transplantation not in CR/PR [HR = 2.20 (95%-CI:0.98-4.95); P = 0.056] reduced PFS. Programmed cell death protein 1(PD-1/PD-L1) treatment before HSCT neither increased GVHD nor impacted survival. We demonstrate that allo-HSCT can achieve long-term survival in approximately half of pts allografted for NKTCL., (© 2023. The Author(s).)

When using post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis for lymphoma patients, it is currently unknown whether a matched unrelated donor (MUD) or a haploidentical related donor is preferable if both are available. In this study we wanted to test whether using a haploidentical donor has the same results of a MUD. A total of 2140 adults (34% Center for International Blood and Marrow Transplant Research, 66% European Society for Blood and Marrow Transplantation registry) aged ≥18 years who received their first haploidentical hematopoietic cell transplantation (haplo-HCT) or MUD-HCT (8/8 match at HLA-loci A, B, C, and DRB1) for lymphoma using PTCy-based GVHD prophylaxis from 2010 to 2019 were retrospectively analyzed. The majority of both MUD and haploidentical HCTs received reduced intensity/nonmyeloablative conditioning (74% and 77%, respectively) and used a peripheral blood stem cell graft (91% and 60%, respectively) and a 3-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF in 54% and 90%, respectively). Haploidentical HCT has less favorable results versus MUD cohort in terms of overall mortality (hazard ratio [HR= = 1.69; 95% confidence interval [CI], 1.30-2.27; P < .001), progression-free survival (HR=1.39; 95% CI, 1.10-1.79; P = .008), nonrelapse mortality (HR = 1.93; 95% CI, 1.21-3.07; P = .006), platelet engraftment (HR = 0.69; 95% CI, 0.59-0.80; P < .001), acute grade 2-4 GVHD incidence (HR = 1.65; 95% CI, 1.28-2.14; P < .001), and chronic GVHD (HR = 1.79; 95% CI, 1.30-2.48, P < .001). No significant differences were observed in terms of relapse and neutrophil engraftment. Adjusting for propensity score yielded similar results. Whenever MUD is available in a timely manner, it should be preferred over a haploidentical donor when using PTCy-based GVHD prophylaxis for patients with lymphoma., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was first complete remission (CR1) in 78%. Among patients receiving allogeneic HCT (alloHCT), myeloablative conditioning (MAC), reduced intensity conditioning (RIC) and in-vivo T-cell depletion (TCD) were used in 54%, 46%, and 59% respectively. Total body irradiation (TBI) was the conditioning backbone in 61% of MAC and 26% of RIC transplants. One-year overall survival (OS) and progression-free survival (PFS) rates were comparable after alloHCT and autologous HCT (autoHCT). Among alloHCT recipients, MAC with TBI significantly improved OS and PFS, independently of CR1, age, Karnofsky index and TCD. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Hodgkin lymphoma (HL) patients who relapse after autologous-stem-cell- transplantation (auto-SCT) have traditionally had a poor prognosis. We analyzed 1781 adult HL patients who relapsed between 2006 and 2017 after a first auto-SCT. The 4-year overall survival (OS) after relapse continuously increased from 32% for patients relapsing in 2006-2008, to 63% for patients relapsing in 2015-2017 (p = 0.001). The improvement over time was predominantly noted in patients who had an early relapse (within 12 months) after auto-SCT (p = 0.01). On multivariate analysis, patients who relapsed in more recent years and those with a longer interval from transplant to relapse had a better OS, whereas increasing age, poor performance status, bulky disease, extranodal disease and presence of B symptoms at relapse were associated with a worse OS. Brentuximab vedotin (BV), checkpoint inhibitors (CPI) and second transplant (SCT2; 86% allogeneic) were used in 233, 91 and 330 patients respectively. The 4-year OS from BV, CPI, and SCT2 use was 55%, 48% and 55% respectively. In conclusion, the outcome after post-transplant relapse has improved significantly in recent years, particularly in the case of early relapse. These large-scale real-world data can serve as benchmark for future studies in this setting., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamide-based haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD-). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD-). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared with PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Published data describing the efficacy and safety of autologous stem-cell transplantation (autoSCT) in post-transplant lymphoproliferative disorders (PTLD) is limited to case reports. This is a retrospective analysis of 21 patients reported to the EBMT registry who received an autoSCT for PTLD post solid organ transplant (SOT). Median age at autoSCT was 47 (range: 22-71) years. The commonest SOTs were kidney (48%) and liver (24%). Commonest histologies included DLBCL-type PTLD (14/21) and plasmacytoma-like PTLD (3/21). Patients received a median of two lines of therapy (range: 1-4) pre-autoSCT. ECOG performance status pre-autoSCT was 0 in 14% and 1 in 86%. Remission status pre-autoSCT was CR 47% and PR 38%. BEAM conditioning was used in 57% and high-dose melphalan in 10%. The median follow-up post-autoSCT was 64 months for alive patients. 3-year PFS was 62% [95% confidence interval (CI) 44-87%] and 3-year OS was 61% [95% CI:43-86]. There were 12 deaths, including four related to autoSCT. 100-day non-relapse-mortality (NRM) was 14% and 1-year NRM was 24%. This study suggests that autoSCT, although feasible and with potential therapeutic activity, is associated with a high NRM, primarily driven by infectious toxicity. A multi-disciplinary approach, expert microbiological input and stringent patient selection are required to optimise outcomes., (© 2021. Crown.)

Background Aims: Around 50 000 autologous stem cell transplantations are done each year worldwide using cryopreserved peripheral blood stem cells (PBSCs). Cryopreservation is time-consuming and expensive. Since 2007, several retrospective studies have shown that PBSCs can be stored at 4°C for 2-3 days, allowing autologous stem cell transplantation in patients with multiple myeloma receiving high-dose melphalan. Data with non-cryopreserved PBSCs in patients autografted for lymphoma following longer pre-conditioning regimens are limited. In addition, no controlled comparison has been able to detect unforeseen differences., Methods: The authors compared outcomes of 94 consecutive adult patients with lymphoma (66 with Hodgkin lymphoma) autografted in our department in Oran (Algeria) using PBSCs stored at 4°C, from 2009 to 2018, with patients receiving cryopreserved stem cells reported to the European Society for Blood and Marrow Transplantation registry. Patients autografted in Oran were matched with patients receiving cryopreserved PBSCs in the registry (four controls per patient in Oran)., Results: Neutrophil engraftment was significantly faster with cryopreserved PBSCs (P = 0.003). By day 10, only 17% of patients receiving non-cryopreserved PBSCs engrafted versus 48% for cryopreserved PBSCs. Likewise, platelet recovery to 20 000/mm 3 was significantly faster in patients receiving cryopreserved PBSCs (P = 0.01). However, all patients in both groups had recovered by day 20. There were no significant differences in non-relapse mortality (9% versus 7%, P = 0.4), relapse incidence (22% versus 32%, P = 0.13), progression-free survival (70% versus 61%, P = 0.4) or overall survival (85% versus 75%, P = 0.3)., Conclusions: This analysis suggests that, in patients with lymphoma receiving pre-transplant regimens such as carmustine, etoposide, cytarabine and melphalan, PBSCs stored at 4°C for up to 6 days can be used safely in centers with no cryopreservation facility. However, the kinetics of hematopoietic recovery showed a significant, albeit small, delay in engraftment for both neutrophils and platelets, which favors the use of cryopreservation if available., (Copyright © 2021 International Society for Cell & Gene Therapy. All rights reserved.)

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD)., Methods and Patients: Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported., Results: 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS., Conclusions: This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.

Autologous hematopoietic stem cell transplantation (ASCT) is curative for a proportion of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL). However, there is a small group of patients with high-risk of relapse after ASCT that might benefit from other approaches. We conducted a retrospective analysis on 126 patients treated with tandem ASCT-reduced intensity conditioning (RIC)-allogeneic-SCT and reported to the EBMT registry to analyze the efficacy and safety of this approach. Patients were included if they had received an ASCT followed by a planned RIC-SCT in <6 months without relapse between the procedures. The median time between diagnosis and ASCT was 16 months (2-174). The median number of lines prior to ASCT was two (33% of the patients received >3 lines). Forty-one percent were transplanted with active disease. The median follow-up was 44 months (6-130). Three-year-progression-free survival (PFS), overall survival (OS), incidence of relapse (IR), and non-relapse mortality (NRM) after the tandem were 53% (45-64), 73% (65-81), 34% (24-42), and 13% (8-21), respectively. This is the largest series analyzing the efficacy and safety of a tandem approach in R/R HL. The low NRM and IR with promising PFS and OS suggest that this might be an effective procedure for a high-risk population.

The purpose of this study was to analyze the results of second autologous hematopoietic stem cell transplantation (ASCT2) for patients with relapsed/refractory Hodgkin lymphoma (HL) after a first transplantation (ASCT1). Outcomes for 56 patients receiving an ASCT2 registered in the EBMT database were analyzed. The 4-year cumulative incidences of non-relapse mortality and disease relapse/progression were 5% and 67%, respectively. The 4-year overall survival (OS) and progression-free survival (PFS) were 62% and 28%. In univariate analysis, relapse of HL within 12 months of ASCT1 was associated with a worse OS (35% versus 76%, p  = 0.01) and PFS (19% versus 29%, p  = 0.059). Chemosensitivity at ASCT2 predicted better outcomes (4-year OS 72% versus 29%, p  = 0.002; PFS 31% versus 12%, p  = 0.015). This series shows that ASCT2 is a safe procedure and a relatively effective option for patients with late relapses after ASCT1 and with chemosensitive disease who are not eligible for an allogeneic transplant.

Indications for autologous (auto-HCT) and allogeneic transplantation (allo-HCT) in relapsed/refractory Hodgkin lymphoma (rrHL) have been long established. The expectation is that long-term outcomes have significantly improved over time with increased experience in these procedures. The objective of this study was to assess whether this is the case and to identify further areas of improvement. A total of 13,639 adult patients receiving an auto-HCT or allo-HCT for rrHL were reported to the European Society for Blood and Marrow Transplantation (EBMT) over a 25-year period. Regarding auto-HCT, recipients are younger, interval between diagnosis and transplant shorter, peripheral blood has become the universal stem cell source and the use of total body irradiation is almost non-existent in recent years. Allo-HCT is currently mostly used as a second transplant; recipients are younger, fitter and less frequently, chemorefractory. Reduced intensity conditioning protocols have vastly replaced myeloablative protocols. Increasing numbers of haplo-HCT have been reported. Both in auto-HCT and allo-HCT, NRM, PFS and OS have significantly improved but relapse remains the main cause of treatment failure. A better selection of patients and improvements in the supportive care has resulted in a reduction in the NRM. Relapse after HCT remains unchanged and further research is needed.

Purpose: To compare the outcomes of patients with Hodgkin or non-Hodgkin lymphoma undergoing nonmyeloablative haploidentical or unrelated cord blood (UCB) hematopoietic cell transplantation., Patients and Methods: We retrospectively studied 740 patients with Hodgkin lymphoma (n = 283, 38%) and non-Hodgkin lymphoma (n = 457, 62%) age 18-75 years who received transplantations from 2009 to 2016. Data were reported to the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation, Eurocord, or Center for International Blood and Marrow Transplant Research. Of the 526 patients who received haploidentical transplantation, 68% received bone marrow and 32% received peripheral blood. All patients received a uniform transplantation conditioning regimen (2 Gy of total-body irradiation, cyclophosphamide, and fludarabine) and graft-versus-host disease prophylaxis (calcineurin inhibitor and mycophenolate). In addition, patients who received a haploidentical transplantation received posttransplantation cyclophosphamide., Results: Compared with haploidentical bone marrow and peripheral-blood transplantations and adjusted for age, lymphoma subtype, and disease status, survival was lower after UCB transplantation (hazard ratio [HR], 1.55; P = .001; and HR, 1.59; P = .005, respectively). Similarly, progression-free survival was lower after UCB transplantations compared with haploidentical bone marrow and peripheral-blood transplantations (HR, 1.44; P = .002; and HR, 1.86; P < .0001), respectively. The 4-year overall and progression-free survival rates after UCB transplantation were 49% and 36%, respectively, compared with 58% and 46% after haploidentical bone marrow transplantation and 59% and 52% after peripheral-blood transplantation, respectively. Lower survival was attributed to higher transplantation-related mortality after UCB transplantation compared with haploidentical bone marrow and peripheral-blood transplantation (HR, 1.91; P = .0001; and HR, 2.27; P = .0002, respectively)., Conclusion: When considering HLA-mismatched transplantation for Hodgkin or non-Hodgkin lymphoma, the data support haploidentical related donor transplantation over UCB transplantation.

Systemic anaplastic large cell lymphoma (sALCL) is a rare histological entity expressing the CD30 antigen that comprises around 11% of peripheral T-cell lymphoma. We analysed the outcome of patients with relapsed/refractory sALCL treated with autologous stem cell transplantation (auto-HCT). We included 65 adult patients (42 males; median age, 44 years); 24 patients had an ALK-ve sALCL. Fifty-one patients had chemosensitive disease at the time of transplant. Ten patients (15%) were treated with brentuximab vedotin (BV) before auto-HCT (median number of doses: 5). The median follow-up for surviving patients was 35 months (3-71). Three-year cumulative incidence of nonrelapse mortality and of relapse were 1.7% and 34%, respectively. Three-year progression-free survival and overall survival were 64% and 73%, respectively. No prognostic factors for any of the outcomes analysed were found in univariate analysis. There were no significant differences in any of the outcomes between patients who had received BV and the remainder. This is the largest analysis presented so far analysing the role of auto-HCT in patients with relapsed/refractory sALCL, showing a promising PFS and OS in this high-risk population. The potential impact of the administration of BV as salvage strategy before the procedure needs to be further elucidated.

Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.

Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T-cell (PTCL; 88), diffuse large B-cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post-transplant cyclophosphamide. Median follow-up of alive patients was 32 months. On multivariate analysis, acute graft-versus-host disease (GVHD) grade 2-4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression-free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23-63 months). Overall survival (OS) at 3 years was 27% (95% CI 22-33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31-53) compared with 20% (95% CI 14-24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25-51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.

This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor., (© 2019 by The American Society of Hematology.)

More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group., (Copyright © 2018. Published by Elsevier Inc.)

Background: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo-SCT) remains challenging., Methods: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo-SCT at European Society for Blood and Marrow Transplantation-participating centers between 2010 and 2014., Results: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo-SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow-up for surviving patients in the BV group (33 months vs 23 months; P<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%)., Conclusions: BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV., (© 2018 American Cancer Society.)

A recent shortage of melphalan has prompted the use of alternatives to BEAM (BCNU, Etoposide, Cytarabine, Melphalan) conditioning for autologous stem cell transplantion (ASCT). The BEAC (BCNU, Etoposide, Cytarabine, Cyclophosphamide) regimen has been employed as a conditioning regimen in lymphoma patients. However, there have been recent concerns about the toxicity of BEAC. We conducted a retrospective analysis of the EBMT database comparing the outcome of patients conditioned using BEAC with a matched cohort of patients conditioned with BEAM. In the BEAC cohort (n = 383), 25 patients died from non-relapse mortality (NRM) events (32% owing to MOF or cardiac toxicity). In the BEAM cohort (n = 766) there were 34 NRM events (23% owing to MOF or cardiac toxicity). The 1-year cumulative incidence of NRM was 4% in the BEAC cohort and 3% in the BEAM group (p = ns). The 2-year relapse/progression rate was 32% with BEAC and 33% with BEAM (p = ns). At 2 years the progression-free survival (PFS) and overall survival (OS) were 63% and 78% for BEAC and 63% and 77% for BEAM-conditioned patients (p = ns for PFS and OS). The toxicity observed with BEAC conditioning as measured by NRM was similar to that seen with BEAM. The outcomes following BEAC were similar to those seen with BEAM, suggesting that BEAC is a safe conditioning regimen.

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy., (© 2018 British Society for Haematology and John Wiley & Sons Ltd.)

The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.

Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.

Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative treatment option for relapsed follicular lymphoma (FL), yet questions remain about the optimal timing. This study analyzed long-term outcomes and associated factors among recipients of allo-HCT with FL., Methods: Patients with relapsed FL who underwent allo-HCT from 2001 to 2011 with a human leukocyte antigen (HLA)-matched donor were included. Outcome analyses for overall survival (OS), progression-free survival (PFS), transplant-related mortality (TRM), and disease relapse/progression were calculated. A multivariate analysis was performed to determine factors associated with outcomes, and a prognostic score for treatment failure was developed in a subset analysis of patients., Results: In all, 1567 patients with relapsed FL were included; the median follow-up was 55 months. The 5-year probabilities of OS and PFS were 61% and 52%, respectively. The 5-year cumulative incidences of disease progression/relapse and TRM were 29% and 19%, respectively. Chemoresistant disease, older age, heavy pretreatment, poor performance status (PS), and myeloablative protocols were predictors for worse survival. The prognostic score, using age, lines of prior therapy, disease status, and PS, stratified patients into 3 groups-low, intermediate, and high risk-with 5-year PFS rates of 68%, 53%, and 46%, respectively, and 5-year OS rates of 80%, 62%, and 50%, respectively., Conclusions: Allo-HCT should be considered for patients with relapsed FL and available HLA-matched donors. Outcomes are better in earlier phases of the disease, and reduced-intensity conditioning should be preferred. The prognostic score presented here can assist in counseling patients and determining the time to proceed to transplantation. Cancer 2018;124:1733-42. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre-transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow-up for survivors was 41 months. Patients in the BV group were more heavily pre-treated (median pre-allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre-allograft BV had no impact on acute graft-versus-host disease (GVHD), non-relapse mortality, cumulative incidence of relapse, progression-free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45-0·92; P < 0·02). Older age, poor performance status, use of pre-transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success., (© 2018 John Wiley & Sons Ltd.)

Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy-two percent of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, P = .049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant., (© 2017 Wiley Periodicals, Inc.)

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G-CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (<2 × 10 6 CD 34+ cells/kg body weight) at the first mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum-containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers., (© 2016 Wiley Periodicals, Inc.)

Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively. BEAM, Z-BEAM and R-BEAM groups were well balanced for age, time from diagnosis to ASCT and disease status at ASCT. The cumulative incidences of relapse (IR) at 2 years were 34, 34 and 32% for Z-BEAM, R-BEAM and BEAM, respectively. By multivariate analysis, there were no significant differences with Z-BEAM or R-BEAM compared with BEAM for IR, non-relapse mortality, event-free survival or overall survival. With the caveat that the limitations of registry analyses have to be taken into account, this study does not support adding radioimmunotherapy or R to BEAM in ASCT for relapsed FL. However, we cannot rule out the existence a particular subset of patients who could benefit from Z-BEAM conditioning that cannot be identified in our series, and this should be tested in a randomized trial.

Background: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years., Patients and Methods: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study., Results: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT., Conclusions: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies, including a reduced intensity allogeneic transplant (RICalloSCT). We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting., Patients and Methods: A total of 183 patients, median age 45 years (range 21-69), had undergone an autoSCT at a median of 30 months before the RICalloSCT. Before the RICalloSCT, they had received a median of four lines (range 3-10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%)., Results: With a median follow-up of 59 months, the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post-autoSCT and RICalloSCT was 14 and 43 months, respectively. The 5-year relapse/progression rate, progression-free survival and overall survival were 16%, 48% and 51%, respectively, and were associated with age and disease status at RICalloSCT., Conclusion: These data suggest that an RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no difference in the RI.

Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.

The aim of this registry-based retrospective study was to analyze the outcome of second allogeneic hematopoietic SCT (alloHSCT&#95;2) performed in patients with lymphoma who had relapsed after a first allogeneic transplant (alloHSCT&#95;1). Patients ⩾18 years who had received an alloHSCT&#95;2 for lymphoma relapse between 2000 and 2011 were eligible. One hundred and forty patients were identified. The diagnosis was Hodgkin lymphoma (HL) in 31%, diffuse large B-cell lymphoma in 14%, T-cell lymphoma in 12%, indolent lymphoma in 19%, mantle cell lymphoma in 16% and other lymphomas in 8% of the patients. The median interval from alloHSCT&#95;1 to alloHSCT&#95;2 was 19 (range 4-116) months. Disease status at alloHSCT&#95;2 was chemosensitive in 46%, refractory in 43% and unknown in 11% of the patients. Three-year PFS, OS, relapse incidence and nonrelapse mortality were 19%, 29%, 58% and 23%, respectively. PFS and OS were significantly affected by refractory disease at alloHSCT&#95;2 and a short interval between alloHSCT&#95;1 and alloHSCT&#95;2. Long-term PFS was observed across all lymphoma subsets except for aggressive B-cell lymphoma. In conclusion, alloHSCT&#95;2 is feasible and can result in long-term disease control in patients with lymphoma recurrence after alloHSCT&#95;1, in particular if relapse occurs late and is chemosensitive.

The objective of this registry study was to analyse the outcome of patients who underwent allogeneic or autologous haematopoietic stem cell transplantation (HSCT) for hepatosplenic T-cell lymphoma (HSTL), a rare and extremely aggressive peripheral T-cell lymphoma subtype. Patients were eligible if they had histologically verified HSTL and underwent HSCT between 2003 and 2011. Seventy-six patients were identified in the European Society for Bone and Marrow Transplantation database. Additional baseline and follow-up information could be obtained from the referring centres for 36 patients. Eleven of these were excluded following histopathology review, leaving 25 patients in the final study cohort (alloHSCT 18, autoHSCT 7). With a median follow-up of 36 months, 2 patients relapsed after alloHSCT, resulting in a 3-year progression-free survival of 48%. After autoHSCT, 5 patients relapsed and subsequently died. This study indicates that graft-versus-lymphoma activity conferred by alloHSCT can result in long-term survival for a substantial proportion of patients with HSTL.

Extra-nodal NK/T lymphoma (ENKTL) is rare and more frequently encountered in East Asia. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) for ENKTL is unclear. Twenty-eight evaluable patients who had undergone HDT-ASCT in Europe from 2000-2009 were studied. The median age was 47 years and patients had received a median of two lines of prior therapy. Some 57% of patients were not in complete remission or beyond first complete remission at HDT-ASCT. The 1-year non-relapse mortality (NRM) was 11%; 2-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 52%, respectively. Notably, the 2-year PFS and OS for those with stage III/IV disease were 33% and 40%, respectively, with no relapses beyond 1-year post-HDT-ASCT. This is the largest analysis of HDT-ASCT for patients with ENKTL reported from the Western hemisphere. Survival is comparable to East Asian cohorts and outcomes are encouraging for patients with advanced disease.

Background: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period., Patients: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission., Results: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission., Conclusions: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis. Experience with allo-SCT for ATL appears encouraging but is limited to Japanese series. This retrospective analysis of the EBMT registry revealed 21 HTLV-I seropositive ATL including 7 acute and 12 lymphoma subtypes. Four patients received auto-SCT and rapidly died from ATL. Out of 17 allo-SCT (4 myeloablative, 13 reduced intensity), 6 are still alive (4 were in CR1 at SCT). Eleven patients died within 2 years, eight from relapse/progression and three from transplant toxicity. Six of seven informative patients who lived >12 months had chronic GVHD. Overall these results indicate that allo-SCT but not auto-SCT may salvage a subset of ATL patients, supporting the existence of graft vs ATL effect also in non-Japanese patients.

Background: Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting., Patients and Methods: Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients., Results: Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation., Conclusions: MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.