Cardiovascular diseases after high-dose chemotherapy and autologous stem cell transplant for lymphoma: A Danish population-based study.

Cardiovascular diseases, especially congestive heart failure (CHF), are known complications of anthracyclines, but the risk for patients undergoing high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) is not well established. With T-cell therapies emerging as alternatives, studies of long-term complications after HDT-ASCT are warranted. Danish patients treated with HDT-ASCT for aggressive lymphoma between 2001 and 2017 were matched 1:5 on sex, birth year and Charlson comorbidity score to the general population. Events were captured using nationwide registers. A total of 787 patients treated with HDT-ASCT were identified. Median follow-up was 7.6 years. The risk of CHF was significantly increased in the HDT-ASCT population compared to matched comparators with an adjusted hazard ratio (HR) of 5.5 (3.8-8.1). The 10-year cumulative incidence of CHF was 8.0% versus 2.0% (p < 0.001). Male sex, ≥2 lines of therapy, hypertension and cumulative anthracycline dose (≥300 mg/m2 ) were risk factors for CHF. In a separate cohort of 4089 lymphoma patients, HDT-ASCT was also significantly associated with increased risk of CHF (adjusted HR of 2.6 [1.8-3.8]) when analysed as a time-dependent exposure. HDT-ASCT also increased the risk of other cardiac diseases. These findings are applicable for the benefit/risk assessment of HDT-ASCT versus novel therapies.

Canadian cancer trials group LY.17: A randomized phase II study evaluating novel salvage therapy pre-autologous stem cell transplant in relapsed/refractory diffuse large B-cell lymphoma-outcome of rituximab-dose-intensive cyclophosphamide, etoposide, cisplatin (R-DICEP) versus R-GDP.

The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.17 trial evaluated a dose-intensive chemotherapy approach using a single cycle of inpatient R-DICEP (rituximab, dose-intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol-specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R-DICEP or to 3 cycles of R-GDP. The overall response rate (ORR) was 65.6% for R-DICEP and 48.6% for R-GDP. The ASCT rate was 71.9% versus 54.3%, and 1-year progression-free survival rate was 42% versus 32%, respectively, for R-DICEP versus R-GDP. Although the improvement in ORR for R-DICEP versus R-GDP exceeded the pre-specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3-5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents.

Busulfan, melphalan and carfilzomib high-dose chemotherapy and autologous haematopoietic stem cell transplantation in multiple myeloma.

The standard of care for fit, newly diagnosed multiple myeloma patients includes induction therapy followed by consolidative high-dose chemotherapy with melphalan and autologous stem cell transplant (AHSCT). Intensified preparative regimens, such as busulfan and melphalan (BuMel), have shown promise to lengthen progression-free survival (PFS). We previously reported that the addition of bortezomib to BuMel improved PFS compared to melphalan alone in CIBMTR-matched controls. We now integrate the second-generation protease inhibitor, carfilzomib, before and after BuMel (BuMelCar) in a phase I/II trial with carfilzomib. Patients with NDMM, relapsed/refractory MM (RRMM) and those failing prior AHSCT were eligible. Primary end-points were safety and tolerability. Secondary end-points included minimal residual disease negativity rates, PFS and OS. The study enrolled 19 patients. 73% were high risk either due to R-ISS III status, adverse genetics or relapsed after prior AHSCT. The maximum tolerated dose (MTD) of carfilzomib was determined to be 36 mg/m2. Noted grade 3 toxicities were febrile neutropenia (79%), mucositis (21%) and diarrhoea (16%). The 2-year PFS for the whole cohort and MTD was 89% and 100% respectively. 80% of all patients and 82% of patients in the MTD cohort achieved MRD negativity. Further studies regarding this regimen are planned.

Historical Perspective of High-Dose Therapy Followed by Autologous Stem Cell Transplantation in Multiple Myeloma.

BACKGROUND: High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) has become part of standard of care (SOC) in newly diagnosed multiple myeloma. In this review, we provide a historical perspective on ASCT since its introduction in the 1990s. SUMMARY: Overall survival (OS) benefit for HDT followed by ASCT was demonstrated in studies comparing HDT with ASCT to standard-dose therapy (SDT) before the era of novel agents. Conditioning is done with melphalan 200 mg/m2. Lower doses (MEL140, MEL150) for older patients with comorbidities are safe and have comparable results. The addition of busulfan to melphalan improves progression-free survival (PFS) but not OS. HDT with ASCT after induction with novel agents prolongs PFS but not OS compared to SDT alone. The benefit is more evident in patients with high-risk cytogenetics. Mobilization can be achieved with granulocyte colony-stimulating factor alone, but is improved with the addition of chemotherapy. Plerixafor reduces mobilization failure and enables sufficient stem cell collection after induction with novel agents. ASCT is safe with a low rate of mortality (1%), and selected patients can be managed as outpatients. KEY MESSAGES: HDT followed by ASCT remains part of SOC due to its PFS benefit and relatively low toxicity.

Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial.

Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies longitudinally in ultra-high-risk patients with MM receiving risk-adapted, intensive anti-CD38 combined therapy in the Myeloma UK (MUK) nine trial. Despite continuous intensive therapy, seroconversion was achieved in all patients, but required a greater number of vaccinations compared to healthy individuals, highlighting the importance of booster vaccinations in this population. Reassuringly, high antibody cross-reactivity was found with current variants of concern, prior to Omicron subvariant adapted boostering. Multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM.

Peri-treatment adverse events of primary mediastinal non-seminomatous germ cell tumors.

Primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) are rare but life-threatening thoracic cancers. We report our experience from eight patients with peri-treatment adverse events. By analyzing changes in tumor extent, serum tumor markers, and pathologies between diagnosis and transfer, those events could be attributed to postbiopsy respiratory insufficiency, growing teratoma syndrome, secondary histiocytic malignancy, and PMNSGCT progression. Subjecting patients to respiratory therapy, conventional or high-dose chemotherapy, and surgery controlled the disease, with five of the eight patients surviving disease free. These outcomes indicate that integrated appropriate and timely approaches are important in tackling peri-treatment adverse events.

Current Management of Refractory Germ Cell Tumors.

PURPOSE OF REVIEW: Germ cell tumors (GCTs) are the most common solid tumors affecting men between ages of 20 and 34 years. Most of the cases, even in advanced disease, will have good prognosis. However, around 20-30% of advanced disease will be refractory or develop relapse after treatment. Herein, we review the current management of refractory/relapsed GCTs. RECENT FINDINGS: Salvage treatment of GCTs has been a controversial topic for the last few decades. Conventional dose chemotherapy (CDCT), high-dose chemotherapy (HDCT) with stem cell infusion, and surgical salvage were proven to be effective and curative options in some cases. The international randomized trial (TIGER) will ultimately answer which chemotherapy approach may be optimal. Furthermore, the usage of immunotherapy is still under investigation with limited data so far in the setting of relapsed/refractory GCTs. Curative paradigms including with CDCT and HDCT are possible, although novel approaches beyond HDCT are still needed to eliminate mortality from this disease.

Outcomes of older patients with primary central nervous system lymphoma treated in routine clinical practice in the UK: methotrexate dose intensity correlates with response and survival.

Data on older patients with primary central nervous system lymphoma (PCNSL) are scarce. Comorbidities and performance status frequently compromise outcomes in this group. Medical records for consecutive patients ≥65 years (n = 244) with PCNSL diagnosed 2012-2017 from 14 UK centres were retrospectively reviewed. Of these 192 patients received methotrexate (MTX)-based treatment. Patients were categorised based on clinician's treatment choice into 'palliative' (n = 52), 'less intensive: MTX ± rituximab ± alkylators' (n = 74) and 'intensive: MTX/cytarabine combinations' (n = 118) groups. Complete remission (CR) rate, two-year progression-free survival (PFS) and overall survival (OS) rates were 49%, 11% and 24% for the less intensive and 69%, 40% and 50% for the intensive groups. Treatment-related mortality (TRM) was 6·8% for MTX-treated patients. Median MTX cumulative dose was 8·8 g/m2 (range 1·5-21) over a median of three cycles. Higher relative dose intensity of MTX (MTX-RDI) was associated with improved PFS and OS in both groups adjusting for age, Eastern cooperative oncology group (ECOG) score and baseline parameters. Two-year PFS and OS for patients receiving four or more induction cycles followed by consolidation (n = 36) were 65% and 70% respectively. Older patients completing MTX-based induction and consolidation had clinical outcomes similar to those in younger cohorts. These retrospective data suggest that maximising MTX-RDI and delivering consolidation in a subgroup of older patients may improve clinical outcomes.

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.

Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Gray Zone Lymphoma: A US Multicenter Collaborative Study.

High-dose therapy (HDT) and autologous hematopoietic cell transplantation (auto-HCT) has been anecdotally prescribed in gray zone lymphoma (GZL), showing encouraging efficacy. We conducted a multicenter retrospective study aimed at assessing outcomes after auto-HCT in 32 patients with GZL treated at 9 transplantation centers in the United States. The median age of patients at transplantation was 38 years (range, 18 to 70 years), and the majority were male (n = 21; 66%). The median number of lines of therapy before transplantation was 2 (range, 1 to 4). BEAM was the most commonly prescribed regimen (n = 23; 72%). The median duration of follow-up for surviving patients was 34 months (range, 1 to 106 months). Median overall survival (OS) was not reached. The 3-year progression-free survival (PFS) and OS for all patients were 69% and 78%, respectively. Three-year PFS and OS were 100% for patients who received only 1 line of therapy before auto-HCT versus 65% (PFS, P = .25) and 75% (OS, P = .39) for those receiving >1 line. The cumulative incidence of relapse/progression was 4% at 1 year post-transplantation and 31% at 3 years post-transplantation. The 3-year nonrelapse mortality was 0%. These findings suggest that HDT and auto-HCT is an effective treatment in patients with GZL. Our findings ideally require confirmation in a larger cohort of patients, preferably in the setting of large prospective multicenter randomized controlled trials. However, we acknowledge that such studies could be difficult to conduct in patients with GZL owing to the disease's rarity. Alternatively, a multicenter prospective study that includes tissue banking and a data registry is warranted to help better understand the biology and natural history of the disease.

Distinctive Infectious Complications in Patients with Central Nervous System Lymphoma Undergoing Thiotepa, Busulfan, and Cyclophosphamide-conditioned Autologous Stem Cell Transplantation.

We investigated the incidence of viral, fungal, bacterial, and parasitic infections observed in 57 patients with central nervous system lymphoma after thiotepa, busulfan, and cyclophosphamide-conditioned autologous stem cell transplantation (TBC-ASCT) and 79 patients with systemic non-Hodgkin lymphoma after traditional carmustine, etoposide, cytarabine, and melphalan-conditioned ASCT (BEAM-ASCT). Twenty of 57 (35%) TBC-ASCT patients had detectable viremia with human herpesvirus 6, cytomegalovirus, adenovirus, or BK virus, versus 9 of 79 (11%) BEAM-ASCT patients. Eight TBC-ASCT patients had clinically relevant viral infections (4 human herpesvirus 6, 2 cytomegalovirus, 1 adenovirus, 2 BK virus), versus 0 in the BEAM-ASCT group. Four TBC-ASCT patients suffered infections from either a fungal or parasitic pathogen versus 1 BEAM-ASCT patient. TBC was associated with greater risk of viral reactivation compared with BEAM, independent of other factors (hazard ratio, 4.42; 95% confidence interval, 1.9 to 11.3; P < .001). Prolonged lymphopenia and steroid use in the peri- and post-ASCT period did not explain these observed differences. The pathogenesis of these unusual infections in TBC-ASCT patients remains incompletely understood, and may involve more potent immune suppression with TBC conditioning. Clinicians should be aware of these differences in infection risk in TBC-ASCT patients, which more closely parallel those seen in allogenic hematopoietic cell transplantation recipients. New prophylactic approaches to help minimize these infections should be considered in this population.

A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.

High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden.

Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T Cell Lymphomas as Front-Line Consolidation or in the Relapsed/Refractory Setting: A Systematic Review/Meta-Analysis.

To date, no prospective randomized trials exist comparing high-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) against conventional therapy for management of peripheral T cell lymphomas either as upfront consolidation or in the relapsed/refractory setting. Available data supporting this approach are limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature. Our search identified 1586 publications, but only 27 (n = 1368) met our inclusion criteria. In the front-line setting, pooled analysis of only prospective studies showed rates of progression-free survival (PFS) of 33% (95% confidence interval [CI], 14% to 56%), overall survival (OS) of 54% (95% CI, 32% to 75%), relapse/progression of 26% (95% CI, 20% to 33%), and transplantation-related mortality (TRM) of 2% (95% CI, 0% to 5%); for retrospective studies, rates of PFS, OS, relapse/progression, TRM, and secondary malignancies were 55% (95% CI, 40% to 69%), 68% (95% CI, 56% to 78%), 36% (95% CI, 24% to 48%), 6% (95% CI, 2% to 11%), and 7% (95% CI, 2% to 14%), respectively. On the other hand, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the relapsed/refractory setting showed pooled rates of PFS, OS, relapse/progression, and TRM of 36% (95% CI, 32% to 40%), 47% (95% CI, 43% to 51%), 51% (95% CI, 39% to 62%), and 10% (95% CI, 5% to 17%), respectively. Among the various histologic subtypes, PFS and OS rates appear to be higher in anaplastic large cell lymphoma, regardless of disease stage. In the absence of a multicenter, randomized controlled trial comparing HDT/auto-HCT to a nontransplantation strategy, the findings of this systematic review/meta-analysis may represent the best evidence supporting the role of HDT/auto-HCT for treatment of peripheral T cell lymphomas as front-line consolidation or in the relapsed/refractory setting.

15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau.

In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12 years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.

Beware the "red herring".

A young patient with relapsed diffuse large B-cell lymphoma presented with new onset respiratory symptoms and hypereosinophilia in the early stage post high-dose therapy/autologous stem cell rescue. Here, we present a step-wise practical approach to this unexpected laboratory finding for a not uncommon infective complication in the immunosuppressed patient.

Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study.

Salvage therapy followed by high-dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R-DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18-65 years, Eastern Cooperative Oncology Group performance score 0-2, with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) were eligible. R-Dexa-BEAM was given for two cycles followed by stem cell mobilization and HDT. Primary endpoint of the trial was progression-free-survival (PFS). One hundred and three patients were included: aggressive NHL (aNHL): diffuse large B-cell lymphoma 55, mantle cell lymphoma 7, follicular lymphoma (FL) grade 3: 5, indolent Lymphoma (iNHL): FL grade 1-2: 29, marginal zone lymphoma 6, Immunocytoma 1. The overall response rate after salvage therapy was 62% for aNHL and 78% for iNHL patients. 66% of patients with aNHL and 86% with iNHL underwent HDT. Treatment-related mortality for HDT was 1·3%. For aNHL patients, the median PFS was 0·83 years with 44% alive at the median follow-up of 7·3 years. Corresponding figures for iNHL were: median PFS 3·7 years and 72% alive after 8 years. The combination of rituximab with DexaBEAM followed by HDT resulted in high response rates and sustained remissions in responders. R-DexaBEAM followed by HDT can be considered a valid salvage option for NHL.

Autologous hematopoietic stem cell transplantation in chemotherapy-sensitive lymphoblastic lymphoma: treatment outcome and prognostic factor analysis.

OBJECTIVE: The study evaluated the effectiveness of autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of lymphoblastic lymphoma (LL). METHODS: We retrospectively analyzed the data from 41 patients with chemotherapy-sensitive LL who underwent hematopoietic stem cell transplantation (HSCT) from December 1989 to December 2009 in a single institution. RESULTS: HSCT was conducted as first-line consolidation therapy and salvage therapy in 36 and 5 patients, respectively. The median follow-up was 97.1 months (range, 24.6-173.1 months). The 5-year overall survival (OS) and event-free survival (EFS) rate were 64% and 47% for the initially treated patients, respectively, and were both 20% for the relapsed ones. Bone marrow (BM) involvement and chemotherapy cycles prior to transplantation were identified as significant prognostic factors for EFS in multivariate analysis. CONCLUSIONS: These results confirm that AHSCT is a reasonable option for chemotherapy-sensitive LL patients in first complete remission (CR1).

Early failure of frontline rituximab-containing chemo-immunotherapy in diffuse large B cell lymphoma does not predict futility of autologous hematopoietic cell transplantation.

The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P <.001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.