A randomized phase II study comparing consolidation with a single dose of 90Y ibritumomab tiuxetan vs. maintenance with rituximab for two years in patients with newly diagnosed follicular lymphoma responding to R-CHOP. Long-term follow-up results.

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

Correction to: An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Correction to: J Cancer Res Clin Oncol (2017) 143:2059-2066 DOI 10.1007/s00432-017-2445-z.

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

PURPOSE: This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. METHODS: This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). RESULTS: The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. CONCLUSIONS: The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m2 i.v. (days -3 and -2) plus melphalan 70 mg/m2 i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT.

Stratifying diffuse large B-cell lymphoma patients treated with chemoimmunotherapy: GCB/non-GCB by immunohistochemistry is still a robust and feasible marker.

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous group of aggressive lymphomas that can be classified into three molecular subtypes by gene expression profiling (GEP): GCB, ABC and unclassified. Immunohistochemistry-based cell of origin (COO) classification, as a surrogate for GEP, using three available immunohistochemical algorithms was evaluated in TMA-arranged tissue samples from 297 patients with de novo DLBCL treated by chemoimmunotherapy (R-CHOP and R-CHOP-like regimens). Additionally, the prognostic impacts of MYC, BCL2, IRF4 and BCL6 abnormalities detected by FISH, the relationship between the immunohistochemical COO classification and the immunohistochemical expression of MYC, BCL2 and pSTAT3 proteins and clinical data were evaluated. In our series, non-GCB DLBCL patients had significantly worse progression-free survival (PFS) and overall survival (OS), as calculated using the Choi, Visco-Young and Hans algorithms, indicating that any of these algorithms would be appropriate for identifying patients who require alternative therapies to R-CHOP. Whilst MYC abnormalities had no impact on clinical outcome in the non-GCB subtype, those patients with isolated MYC rearrangements and a GCB-DLBCL phenotype had worse PFS and therefore might benefit from novel treatment approaches.

Epstein-Barr virus-associated diffuse large B-cell lymphoma: diagnosis, difficulties and therapeutic options.

Epstein Barr Virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) most frequently affects elderly patients, without previous immunosuppression, with frequent extra-nodal involvement and whose disease runs an aggressive clinical course with high International Prognostic Index (IPI) scores. Various EBV-related transforming mechanisms, much favored by immunosenescence, have been described, including activation of the NFKB transcriptional program. Elderly patients show poor survival after treatment with conventional CHOP regimens, even after addition of Rituximab. Younger patients, however, have a better outcome with a similar prognosis to EBV-negative DLBCL cases. New therapeutic strategies, including treatments targeting EBV, new drugs directed against specific pathways constitutively activated in these lymphomas, and new specific conjugate antibodies against molecules usually expressed in the tumor cells, such as CD30, are described.

CD 30-positive transformed follicular lymphoma: two case reports and literature review.

AIMS: Here we report two cases of follicular lymphoma that transformed to CD30 positive diffuse large B cell lymphoma and review the literature on this topic. RESULTS: The first case represents an example of early transformation of conventional low-grade follicular lymphoma to CD30-positive large B cell lymphoma. Immunoglobulin (Ig)H and cytogenetic identity was demonstrated between both components. High-dose and auto-stem cell transplant (SCT) was applied and complete response was achieved. The second case represents an example of d'emblee transformation of intrafollicular neoplasia to CD30-positive large B cell lymphoma. Immunoglobulin K deleting element (IgKde) and cytogenetic identity between both phases was demonstrated. The patient was in partial response after four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). CONCLUSIONS: CD30 expression was found to be associated in these cases to the transformation event and could be considered a therapeutic target to add to conventional immunochemotherapeutic regimens, even in combination with auto-SCT. We suggest looking for CD30 expression in transformed follicular lymphoma cases.

Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial.

We conducted a multicentre, phase II study of interim positron emission tomography (PET) as a guide to risk-adapted therapy in high-risk patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients achieving negative fluorodeoxyglucose (FDG)-PET after three courses of R-MegaCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) received three additional courses, whereas PET-positive patients received two courses of R-IFE (rituximab, ifosfamide, etoposide) followed by BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem-cell transplantation. The primary endpoint was progression-free survival (PFS). 71 patients (median age 55 years, range 25-69) were enrolled. With a median follow-up of 42·8 months (range 7·2-58·4), the estimated 4-year PFS and overall survival (OS) were 67% and 78%, respectively, for the global series. Patients in complete remission after interim PET (N = 36) had significantly better 3-year PFS than those with partial response (N = 30) [81% vs. 57%, Hazard ratio (HR) = 2·6, 95% confidence interval (CI) = 1·02-6·65] but not a statistically significant longer OS. A retrospective PET central review was done for 51 patients. According to semiquantitative analysis, 3-year PFS (81% vs. 33%; HR = 6·9, 95% CI = 2·35-20·6) and OS (95% vs. 33%, HR = 19·4, 95% CI = 3·89-97·0) were significantly better for negative than for positive interim PET patients. Early PET assessment is valuable for risk stratification in DLBCL; for this purpose semiquantitative evaluation is a better predictor than visual criteria.

Mannose-binding lectin gene variants and infections in patients receiving autologous stem cell transplantation.

BACKGROUND: Serious infections are common in patients undergoing autologous stem cell transplantation (ASCT) mainly because of the effects of immunosuppression. The innate immune system plays an important role in the defense against different infections. Mannose binding lectin (MBL) is a central molecule of the innate immune system. There are several promoter polymorphisms and structural variants of the MBL2 gene that encodes for this protein. These variants produce low levels of MBL and have been associated with an increased risk for infections. METHODS: Prospective cohort study. The incidence, severity of infections and mortality in 72 consecutive patients with hematologic diseases who underwent ASCT between February 2006 and June 2008 in a tertiary referral center were analyzed according to their MBL2 genotype. INNO-LiPA MBL2 was used for MBL2 gene amplification and genotyping. Relative risks (RR) (IC95%) as measure of association were calculated. Multivariate analysis was performed using logistic regression. RESULTS: A statistically significant higher number of fungal infections was found in patients with MBL2 variants causing low MBL levels (21.1%versus1.9%, p=0.016). In this MBL2 variant group infection was more frequently the cause of mortality than in the MBL2 wild-type group (p=0.05). Although not statistically significant, there was a higher incidence of major infections in the MBL2 variant group as well as a higher number of infections caused by gram-positive bacteria. CONCLUSIONS: Low-producer MBL2 genotypes were associated with an increased number of fungal infections in ASCT patients, which would suggest that MBL has a protective role against such infections. ASCT patients with MBL2 variant genotypes are more likely to die as a result of an infection.

Contribution of cerebrospinal fluid sCD19 levels to the detection of CNS lymphoma and its impact on disease outcome.

Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell-associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.

Impact of prior rituximab on outcomes of autologous stem-cell transplantation in patients with relapsed or refractory aggressive B-cell lymphoma: a multicentre retrospective Spanish group of lymphoma/autologous bone marrow transplant study.

The use of highly effective rituximab-containing therapy for treating diffuse large B-cell lymphoma (DLBCL) makes it more difficult to salvage relapsed or refractory patients. Autologous stem-cell transplantation (ASCT) is the reference treatment for these patients, but the impact of previous exposure to rituximab on the subsequent results of ASCT remains unknown. We analysed 248 patients with relapsed or refractory DLBCL or grade 3B follicular lymphoma pre-treated with rituximab as part of first-line therapy (R+ group) who received ASCT, in comparison with a control group of 127 patients without previous exposure to rituximab (R- group). The complete remission (CR) rates were similar in both groups. Multivariate analysis identified age-adjusted International Prognostic Index at diagnosis, extranodal involvement and disease status at transplant, and the number of previous chemotherapy lines as independent factors with a negative influence on CR rate. Compared with R- patients, those in the R+ group had a significantly better progression-free survival (63% vs. 48% at 5 years) and overall survival (72% vs. 61% at 5 years). This observation was independent of other prognostic factors that affected these outcomes. In conclusion, ASCT is no less effective in patients with relapsed or refractory aggressive B-cell lymphoma pre-treated with first-line rituximab-containing therapy than in rituximab-naive patients.

First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial.

BACKGROUND: No standard first-line systemic treatment for mucosa-associated lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to assess the safety and activity of a response-adapted combination of bendamustine plus rituximab as upfront treatment for this type of lymphoma. METHODS: In a multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with MALT lymphoma at any site and stage and treated them with bendamustine (90 mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks. Inclusion criteria were measurable or evaluable disease, age 18-85 years, and unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising in the stomach after failure of Helicobacter pylori eradication and primary cutaneous cases after failure of local therapies. Exclusion criteria included evidence of histological transformation, CNS involvement, and active hepatitis B or C virus or HIV infection. After three cycles, patients achieving complete response received one additional cycle (total four cycles) and those achieving partial response received three additional cycles (total six cycles). The primary endpoint was 2-year event-free survival. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01015248. FINDINGS: 60 patients from 19 centres in Spain were enrolled between May 27, 2009, and May 23, 2011, and received treatment; 57 patients were evaluable for the primary endpoint. Only 14 (25%) patients needed more than four cycles of treatment. After a median follow-up of 43 months (IQR 37-51), median event-free survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97) and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4 adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile neutropenia or infections were reported in three (5%) and four (7%) patients, respectively. INTERPRETATION: This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma. FUNDING: Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.

First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group.

UNLABELLED: The prognosis for fit patients with mantle cell lymphoma has improved with intensive strategies. Currently, the role of maintenance/consolidation approaches is being tested as relapses continue to appear. In this trial we evaluated the feasibility, safety and efficacy of rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine followed by consolidation with (90)Y-ibritumomab tiuxetan. Patients received six cycles followed by a single dose of (90)Y-ibritumomab tiuxetan. Thirty patients were enrolled; their median age was 59 years. Twenty-four patients finished the induction treatment, 23 achieved complete remission (77%, 95% confidence interval 60-93) and one patient had progressive disease (3%). Eighteen patients (60%), all in complete remission, received consolidation therapy. In the intent-to-treat population, failure-free, progression-free and overall survival rates at 4 years were 40% (95% confidence interval 20.4-59.6), 52% (95% confidence interval 32.4-71.6) and 81% (95% confidence interval 67.28-94.72), respectively. For patients who received consolidation, failure-free and overall survival rates were 55% (95% confidence interval 31.48-78.52) and 87% (95% confidence interval 70-100), respectively. Hematologic toxicity was significant during induction and responsible for one death (3.3%). After consolidation, grade 3-4 neutropenia and thrombocytopenia were observed in 72% and 83% of patients, with a median duration of 5 and 12 weeks, respectively. Six (20%) patients died, three due to secondary malignancies (myelodysplastic syndrome and bladder and rectum carcinomas). In conclusion, in our experience, rituximab-hyperCVAD alternated with rituximab-methotrexate-cytarabine and followed by consolidation with (90)Y-ibritumomab tiuxetan was efficacious although less feasible than expected. The unacceptable toxicity observed, especially secondary malignancies, advise against the use of this strategy. TRIAL REGISTRATION: clinical.gov identifier: NCT2005-004400-37.

Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas.

Outcome of Antifungal Combination Therapy for Invasive Mold Infections in Hematological Patients is Independent of the Chosen Combination.

Invasive mold infection (IMI) remains a major cause of mortality in high-risk hematological patients. The aim of this multicenter retrospective, observational study was to evaluate antifungal combination therapy (ACT) for proven and probable IMI in hematological patients. We analyzed 61 consecutive cases of proven (n=25) and probable (n=36) IMI treated with ACT collected from eight Spanish hospitals from January 2005 to December 2009. Causal pathogens were: Aspergillus spp (n=49), Zygomycetes (n=6), Fusarium spp (n=3), and Scedosporium spp (n=3). Patients were classified in three groups according to the antifungal combination employed: Group A, liposomal amphotericin B (L-AmB) plus caspofungin (n=20); Group B, LAmB plus a triazole (n=20), and Group C, voriconazole plus a candin (n=21). ACT was well tolerated with minimal adverse effects. Thirty-eight patients (62%) achieved a favorable response (35 complete). End of treatment and 12-week survival rates were 62% and 57% respectively, without statistical differences among groups. Granulocyte recovery was significantly related to favorable response and survival (p<0.001) in multivariate analysis. Our results suggest that comparable outcomes can be achieved with ACT in high risk hematological patients with proven or probable IMI, whatever the combination of antifungal agents used.

[Comparison of two initial mobilizing strategies of peripheral blood stem cells for autologous transplantation in patients with lymphoma and human immunodeficiency virus infection]. / Comparación de dos estrategias iniciales de movilización de progenitores hematopoyéticos de sangre periférica para trasplante autogénico en pacientes con linfomas e infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Several studies have demonstrated the feasibility of autologous stem cell transplantation (ASCT) in patients with lymphoma and human immunodeficiency virus (HIV) infection. HIV infection has been described as a risk factor for poor mobilization. The aim of this study was to compare the results of two mobilization strategies of peripheral blood stem cells (PBSC) in patients with lymphoma and HIV infection in seven Spanish hospitals. PATIENTS AND METHODS: The following variables were collected: demographic, clinical and biological features, previous chemotherapies and outcomes, as well as mobilization's strategies (classified in two groups: 1) G-CSF, and 2) G-CSF + chemotherapy). RESULTS: Between January 2000 and May 2010, 42 patients with lymphoma and HIV infection were referred for ASCT. The rate of successful mobilization (collection >1.60 × 10(6) CD34 cells/kg) with the first regimen was 67%, with no differences between those patients mobilized with G-CSF or with G-CSF + chemotherapy (16 [72%] and 12 [60%], respectively; p=0.382). The status of the lymphoma at the time of mobilization was the only factor for successful mobilization (20/22 patients [91%] in complete remission [CR] mobilized adequately versus 5/12 [58%] in partial remission [PR]; p=0.038). CONCLUSIONS: In patients with lymphoma and HIV infection, mobilization with G-CSF was as effective as mobilization with chemotherapy followed by G-CSF. The stage of disease prior to the mobilization was the main risk factor for the success of mobilization, with better results in patients mobilized in remission of the lymphoma.

FLAGIDA-lite is an effective regimen for patients between 70 and 80 years with acute myeloid leukemia or refractory anemia with excess blasts-2 and is feasible as outpatient treatment.

We investigated a FLAGIDA-lite protocol (fludarabine 40 mg/m(2)/d orally days 1-5, cytarabine 20 mg/m(2)/d subcutaneously days 1-5, G-CSF 300 µg/d subcutaneously days 1-5, and idarrubicin 15 mg/m(2)/d orally days 1-3) in 38 consecutive patients older than 70 years of age with acute myeloid leukemia (32 patients) or refractory anemia with excess blasts-2 (six patients) and no prior therapy. Seventy-nine percent had intermediate/unfavorable karyotype and 79% had a high comorbidity. Overall response was 55% [complete response (CR) 47%] and 37% were refractory. CR rate was 52% in patients between 71 and 79 years of age and 38% in patients 80 years or older. The 4-week induction mortality was 16% (8% in patients between 70 and 79 years of age and 32% in patients 80 years or older). Overall survival (OS) at 3 years was 22% (31.3% in patients between 70 and 79 years and 15.4% in patients 80 years or older). Relapse-free survival (RFS) at 3 years was 15%. A total of 65 cycles (47 as induction and 18 as consolidation) were administered, 46 of them (70%) in an outpatient setting. In summary, this FLAGIDA-lite protocol is an effective and well-tolerated option for patients between the ages of 70 and 79 years with acute myeloid leukemia or refractory anemia with excess blasts-2 and is usually feasible as outpatient treatment, but is not beneficial for most patients 80 years or older.

High-dose therapy and autologous stem cell transplantation in first relapse for diffuse large B cell lymphoma in the rituximab era: an analysis based on data from the European Blood and Marrow Transplantation Registry.

Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the benefit of ASCT in patients achieving a second complete remission after salvage chemotherapy by retrospectively comparing the disease-free survival (DFS) after ASCT for each patient with the duration of the first complete remission (CR1). Between 1990 and 2005, a total of 470 patients who had undergone ASCT and reported to the European Blood and Bone Transplantation Registry with Medical Essential Data Form B information were evaluated. Of these 470 patients, 351 (74%) had not received rituximab before ASCT, and 119 (25%) had received rituximab before ASCT. The median duration of CR1 was 11 months. The median time from diagnosis to ASCT was 24 months. The BEAM protocol was the most frequently used conditioning regimen (67%). After ASCT, the 5-year overall survival was 63% (95% confidence interval, 58%-67%) and 5-year DFS was 48% (95% confidence interval, 43%-53%) for the entire patient population. Statistical analysis showed a significant increase in DFS after ASCT compared with duration of CR1 (median, 51 months versus 11 months; P < .001). This difference was also highly significant for patients with previous exposure to rituximab (median, 10 months versus not reached; P < .001) and for patients who had experienced relapse before 1 year (median, 6 months versus 47 months; P < .001). Our data indicate that ASCT can significantly increase DFS compared with the duration of CR1 in relapsed diffuse large B cell lymphoma and can alter the disease course even in patients with high-risk disease previously treated with rituximab.