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Sökning: WFRF:(Wahlin Bjorn E.)

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1.
  • Harrysson, S., et al. (författare)
  • Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden
  • 2021
  • Ingår i: Blood Cancer Journal. - : SPRINGERNATURE. - 2044-5385. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007-2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n=3550, median age 69 years), whereas 14% did not (n=594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7-66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7-24.6, n=847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5-3.6, n=118) overall, and 8.0% (95% CI: 6.0-10.6, n=48) among patients with high CNS-IPI (4-6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.
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  • Zucca, Emanuele, et al. (författare)
  • Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy
  • 2019
  • Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 134:4, s. 353-362
  • Tidskriftsartikel (refereegranskat)abstract
    • The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m(2) IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (>= 90%). Toxicity grade >= 3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored.
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  • Wahlin, Bjorn E., et al. (författare)
  • Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times
  • 2012
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 156:2, s. 225-233
  • Tidskriftsartikel (refereegranskat)abstract
    • The prognostic value of grading follicular lymphoma has been debated since the 1980s. There is consensus that World Health Organization (WHO) grades 1 and 2 are indolent, but not whether grades 3A or 3B are aggressive. We retrospectively reviewed the follicular lymphoma diagnoses according to the 2008 WHO classification in all diagnostic specimens from a population-based cohort of 505 patients with a median follow-up time of 10.0 years (range, 4.616.0). After excluding 43 patients with concomitant diffuse large B-cell lymphoma, 345 remained with grade 12, 94 with grade 3A, and 23 with grade 3B follicular lymphoma. Grades 12 and 3A seemed equally indolent, with indistinguishable clinical courses, even in patients receiving anthracyclines. Compared with grades 13A and independently of clinical factors, grade 3B correlated with higher mortality (P = 0.008), but outcome was improved after upfront anthracycline-containing therapy (P = 0.015). In contrast to grade 13A patients, grade 3B patients experienced no relapses or deaths beyond 5 years of follow-up. Furthermore, patients with grade 3B were predominantly male and seldom presented with bone-marrow involvement. We conclude that follicular lymphoma grade 13A is indolent and incurable with conventional therapy. Grade 3B appears to be an aggressive but curable disease.
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6.
  • Wahlin, Bjorn Engelbrekt, et al. (författare)
  • Higher World Health Organization grades of follicular lymphoma correlate with better outcome in two Nordic Lymphoma Group trials of rituximab without chemotherapy
  • 2014
  • Ingår i: Leukemia and Lymphoma. - 1042-8194 .- 1029-2403. ; 55:2, s. 288-295
  • Tidskriftsartikel (refereegranskat)abstract
    • A common treatment for follicular lymphoma is rituximab monotherapy. To identify patients for whom this regimen is adequate as first-line therapy, we applied the World Health Organization (WHO) classification for grading follicular lymphoma in a prospective central pathology review of the biopsies of previously untreated patients in two randomized trials of rituximab without chemotherapy. In the first trial (n(1) = 53), higher WHO grades correlated with longer time to next treatment, independently of clinical prognostic factors (p = 0.030); the finding was replicated in the second trial (n(2) = 221; p = 0.019). Higher grades were associated with better treatment responses (p = 0.018). Furthermore, also grades externally confirmed by independent local pathologists correlated with time to next treatment (p = 0.048). Flow cytometry in a separate patient series showed that the intensity of CD20 increased with the malignant cell size (p < 0.00005). In conclusion, WHO grade 1 follicular lymphoma correlates with inferior outcome after rituximab monotherapy. WHO grading might provide a clinically useful tool for personalized therapy.
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7.
  • Wahlin, Björn Engelbrekt, et al. (författare)
  • T cells in tumors and blood predict outcome in follicular lymphoma treated with rituximab
  • 2011
  • Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:12, s. 4136-4144
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose:T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.Experimental Design:Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations.Results:In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046).Conclusions:We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells.
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8.
  • Lockmer, Sandra, et al. (författare)
  • Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity : Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
  • 2018
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:33, s. 3315-3323
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.Methods: Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m(2), and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations.Results: At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%.Conclusion: Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.
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9.
  • Tesfa, Daniel, et al. (författare)
  • The role of BAFF and G-CSF for rituximab-induced late-onset neutropenia (LON) in lymphomas
  • 2021
  • Ingår i: Medical Oncology. - : HUMANA PRESS INC. - 1357-0560 .- 1559-131X. ; 38:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Mechanisms for late-onset neutropenia (LON) after rituximab treatment are poorly defined both for non-Hodgkin lymphoma (NHL) and for autoimmune disorders. We performed a case-control analysis of a prospective cohort of 169 evaluable consecutive rituximab-treated NHL patients to assess cytokines involved in neutro- and lymphopoiesis (G-CSF, SDF1, BAFF, APRIL) and inflammation (CRP) as possible LON mechanisms. Fifteen patients (9%) developed LON (peripheral blood /PB/ absolute neutrophil counts /ANC/<0.5 G/L, all with marked depletion of CD20(+) B-lymphocytes in bone marrows); they were compared with 20 matched NHL controls without LON. At start of LON, significantly higher PB G-CSF and BAFF levels (P=0.0004 and 0.006, respectively), as well as CRP rises were noted compared to controls; these G-CSF and BAFF and most CRP values returned to levels of the controls in post-LON samples. G-CSF (but not BAFF) changes correlated to CRP rises (but not to ANC levels). BAFF levels correlated significantly to absolute monocyte counts and PB large granular lymphocyte counts (but not to ANC, C-CSF or CRP values). No changes of SDF1 or APRIL levels were noted. Neither LON cases nor controls displayed anti-neutrophil autoantibodies. Collectively, LON in NHL patients was timewise related to transient bursts of blood G-CSF and BAFF concentrations, suggesting that these neutro- and lymphopoiesis growth factors play a role in emergence of rituximab-induced LON, and that inflammation may be a trigger for G-CSF production during LON.
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