scholarly journals The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis

2021 ◽  
Vol 100 (11) ◽  
pp. 2733-2744
Author(s):  
Ramona Wullenkord ◽  
Philipp Berning ◽  
Anna-Lena Niemann ◽  
Klaus Wethmar ◽  
Sarah Bergmann ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
B Cell Lymphomas ◽  
First Line ◽  
First Line Therapy ◽  
Remission Status ◽  
Line Therapy ◽  
Relapsed Disease

Abstract Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0–163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.

High Dose Chemotherapy with Autograft in First Relapse May Overcome the Poor Prognosis of Diffuse Large B-Cell Lymphoma Patients with MYC/BCL2 Co-Expression

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1976-1976
Author(s):  
Francesco Maura ◽  
Anna Dodero ◽  
Alessio Pellegrinelli ◽  
Martina Pennisi ◽  
Liliana Franca Devizzi ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Refractory Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Extranodal Disease ◽  
First Relapse

Abstract The immunohistochemical (ICH) co-expression of MYC and BCL2 (double expressors, DE) has been emerging as a strong and reproducible risk factor in diffuse large B cell lymphoma (DLBCL) patients (pts) treated with R-CHOP. Our aim was to analyze the prognostic value of the co-expression in DLBCL pts treated with high-dose chemotherapy followed by autologous stem cell transplantation at first relapse. In this retrospective study, we analyzed a cohort of 64 young [median age 53, (range18-70)] and/or fit DLBCL pts treated between 2003 and 2015 at the Istituto Nazionale dei Tumori Milano. All pts relapsed at median time of 4.9 months after a Rituximab-based chemotherapy (48 R-CHOP-like and 16 other intensive regimens). All pts were considered fit and eligible for high-dose chemotherapy salvage treatment. Tumor samples were analyzed by ICH for MYC and BCL2 (40%/70% threshold). Germinal B-Cell (GBC) and Activated B-Cell (ABC) DLBCL classification was done with ICH as established by the Hans algorithm. Pts characteristics at relapse were: refractory: 37/64 (58%), Ann Arbor stage≥3: 42/64 (65%), IPI score≥2: 26/60 (43%); Extranodal disease: 37/64 (58%); Bulky (defined as max diameter ≥5 cm): 29/64 (45%); CNS involvement: 8/64 (12.5%). Twenty-nine of 64 (45%) pts responded to salvage high-dose therapy (CR,PR) and 25 of them underwent autologous stem cell transplantation (ASCT). Among 39 (61%) refractory pts to first salvage intensive chemotherapy approaches, 11 (28%) responded after third or fourth chemo-immunotherapy salvage lines and underwent ASCT as well. Overall the reasons for not receiving ASCT were: refractory disease (n=20), poor mobilization (n=3), the occurrence of significant infection or toxic complications during the salvage therapy (n=4) or patient decision (n=1). ICH MYC and BCL2 positive expression was observed in 31 (48%) and 39 (61%) pts respectively. Among them, 17 (26%) were characterized by BCL2 and MYC co-expression. According with Hans algorithm, 23 (56%) and 18 (44%) DLBCL pts were classified as GBC and ABC-DLBCL. DE pts did not show any significant differences compared to others in terms of age, IPI score, presence of extranodal disease, BM infiltration, CNS involvement at relapse, refractory disease or relapse occurrence less than 1 year after first line therapy, and proportion of ABC-DLBCL subtype. Considering the whole pts cohort 5-years progression free survival (PFS) and overall survival (OS) were 27.3% (95% CI, 21.1%-33,4%) and 40.6% (95% CI, 33.2%-48%) respectively. In univariate analysis, pts with disease relapsed less than 1 year after first line therapy were characterized by a significant worse outcome in terms of 5-years PFS [11.5% (95% IC 6.1%-16.9%) vs 72.2% (95% IC 60%-84.4%] and OS [24.5% (95% IC 16.9%-32.1%) vs 84.4% (95% IC 74%-94.8%)] (p=0.0001 and p=0.0009 respectively). Similar results were observed comparing pts with refractory disease to first line therapy with others [5-years PFS 11.7% (95% IC, 5.9%-17.5%) vs 48.2% (95% IC, 37.1%-59.3%)] and 5-years OS [19.9% (95% IC, 11.8%-28%) vs 67.9% (95% IC, 57.6%-78.2%)] (p=0.0003 and p=0.001 respectively). Other variables at first relapse associated with worse outcome in terms of PFS and OS were IPI score ≥2 and presence of bulky disease. In contrast, DE patients did not shown any significant differences compared to other patents in term of 5-years PFS [39.7 (95% IC, 27.5-51.9) vs 25.1 (95% IC, 18.4-31.8), p=0.5] and 5-years OS [40.8 (95% IC, 32.3-49.3) vs 22.2 (95% IC, 5-39.4), p=0.8]. Furthermore singularly ICH MYC or BCL2 expression did not influence neither PFS nor OS. These data suggest that salvage programs with high dose chemotherapy with autograft in first relapse may overcome the previously reported poor prognosis associated with ICH MYC/BCL2 co-expression. The most significant and robust prognostic factor among DLBCL pts in first relapse is still represented by refractoriness and the time of relapse. Disclosures No relevant conflicts of interest to declare.

Lenalidomide, Bendamustine, and Rituximab As First-Line Therapy For Patients >65 Years With Mantle Cell Lymphoma: Preliminary Results From The Nordic Lymphoma Group MCL4 (LENA-BERIT) Phase I-II Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4377-4377 ◽  
Author(s):  
Mats Jerkeman ◽  
Alexandra Albertsson-Lindblad ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Riikka Räty ◽  
...  
Keyword(s):  
Phase I ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mantle Cell

Abstract Background Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. For elderly patients, however, no standard therapy has been defined. In the current trial, we investigate if the addition of lenalidomide (LEN) to rituximab (R)+bendamustine (B) (B 90 mg/m2 D1-2 and R 375 mg/m2 D1) followed by maintenance with LEN for 7 months may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods Eligibility criteria were age > 65 years, or ≤ 65 years, unable to tolerate high dose chemotherapy, with untreated mantle cell lymphoma, stage II-IV. BR was given for 6 cycles q4w. In the phase I part, the MTD of LEN was established as 10 mg days 1-14 during the induction phase, cycles 2-6. Prednisolone 20 mg days 1-14 was given during cycle 2. When LEN was initially given from cycle 1, we encountered unexpected grade III-IV toxicity in the form of cutaneous and allergic reactions. In the maintenance phase, LEN single therapy was given as follows: cycles 7-8 - 10 mg days 1-21, cycles 9-13 - 15 mg days 1-21. Results The trial was concluded June 1, 2013, after inclusion of 51 patients, of whom 24 were in the phase I part. The median age is 72 years. According to MIPI, 55% were high risk. Presently, 29 patients are evaluable for response after 6 cycles LBR. ORR is 28/29 (97%), CR+CRu 23 (79%). 17 out of 28 evaluable patients (61%) were MRD-negative after 6 cycles. After a median follow-up of 18 months, the median PFS has not been reached, and the estimated PFS at 2 years is 74%. Eight patients have died, 3 due disease progression, 3 due to treatment related toxicity, 1 of lung cancer in a heavy smoker, 1 of CMML. Overall survival at 2 years is 87%. Conclusions When omitted in cycle 1, lenalidomide in combination with R-bendamustine is feasible as first-line therapy in older patients with MCL, and is associated with a high response rate, also as assessed by MRD. The long term efficacy of this regimen remains to be established by longer follow-up. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Salvage Regimens With Autologous Transplantation for Relapsed Large B-Cell Lymphoma in the Rituximab Era

2010 ◽  
Vol 28 (27) ◽  
pp. 4184-4190 ◽  
Author(s):  
Christian Gisselbrecht ◽  
Bertram Glass ◽  
Nicolas Mounier ◽  
Devinder Singh Gill ◽  
David C. Linch ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Large B Cell

Purpose Salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT) is the standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL). Salvage regimens have never been compared; their efficacy in the rituximab era is unknown. Patients and Methods Patients with CD20+ DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP). Responding patients received high-dose chemotherapy and ASCT. Results The median age of the 396 patients enrolled (R-ICE, n = 202; R-DHAP, n = 194) was 55 years. Similar response rates were observed after three cycles of R-ICE (63.5%; 95% CI, 56% to 70%) and R-DHAP (62.8%; 95 CI, 55% to 69%). Factors affecting response rates (P < .001) were refractory disease/relapse less than versus more than 12 months after diagnosis (46% v 88%, respectively), International Prognostic Index (IPI) of more than 1 versus 0 to 1 (52% v 71%, respectively), and prior rituximab treatment versus no prior rituximab (51% v 83%, respectively). There was no significant difference between R-ICE and R-DHAP for 3-year event-free survival (EFS) or overall survival. Three-year EFS was affected by prior rituximab treatment versus no rituximab (21% v 47%, respectively), relapse less than versus more than 12 months after diagnosis (20% v 45%, respectively), and IPI of 2 to 3 versus 0 to 1 (18% v 40%, respectively). In the Cox model, these parameters were significant (P < .001). Conclusion In patients who experience relapse more than 12 months after diagnosis, prior rituximab treatment does not affect EFS. Patients with early relapses after rituximab-containing first-line therapy have a poor prognosis, with no difference between the effects of R-ICE and R-DHAP.

scholarly journals A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Blood ◽  
2020 ◽  
Author(s):  
Norbert Schmitz ◽  
Lorenz H Truemper ◽  
Krimo Bouabdallah ◽  
Marita Ziepert ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
First Line Therapy ◽  
Line Therapy

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

scholarly journals Curability of relapsed childhood B-cell non-Hodgkin's lymphoma after intensive first line therapy: a report from the Societe Francaise d'Oncologie Pediatrique

Blood ◽  
1993 ◽  
Vol 81 (8) ◽  
pp. 2003-2006 ◽  
Author(s):  
T Philip ◽  
O Hartmann ◽  
R Pinkerton ◽  
JM Zucker ◽  
JC Gentet ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Marrow Transplant ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
First Line Therapy ◽  
Line Therapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract The very high cure rate in advanced B-cell non-Hodgkin's lymphoma in children using intensive multiagent therapy has been previously reported by the French Societe Francaise d'Oncologie Pediatrique lymphoma Malin B type (LMB) group. To address the issue of salvageability in an unselected group of patients who had all received the same front-line therapy, the outcome of relapses following the LMB 84 (216 patients) protocol have been reviewed. Fourteen percent of patients achieving complete remission (CR) relapsed, ie, 27 of 195. Relapse sites comprised the central nervous system (CNS) alone (6 cases), lung or mediastinum (2 cases), abdomen (8 cases), head and neck (2 cases), or multifocal (9 cases). There were three early deaths due to disease. Twenty-four patients received rescue chemotherapy regimens and 15 were treated with high-dose chemotherapy and bone marrow rescue (1 allogeneic). Of these, 9 were in second CR, 4 in second partial remission, and 2 treated during progressive disease. One died in CR from treatment-related toxicity. Ten relapsed postbone marrow transplant and 4 are alive disease free and probably cured. Two of the long-term survivors had some delay during initial chemotherapy due to toxicity and two were isolated CNS relapses. Twelve of 27 patients did not proceed to megatherapy (12 of 12 died).

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