25 results on '"Stevens WBC"'
Search Results
2. Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma: Final results of the HOVON 105/ALLG NHL 24 study.
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Bromberg JEC, Issa S, van der Holt B, van der Meulen M, Dirven L, Minnema MC, Seute T, Durian M, Cull G, van der Poel MWM, Stevens WBC, Zijlstra JM, Brandsma D, Nijland M, Mason KD, Beeker A, Abrahamse-Testroote MCJ, van den Bent MJ, de Jong D, and Doorduijn JK
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carmustine therapeutic use, Cytarabine therapeutic use, Methotrexate therapeutic use, Prednisolone therapeutic use, Quality of Life, Rituximab therapeutic use, Teniposide therapeutic use, Middle Aged, Adolescent, Young Adult, Adult, Aged, Central Nervous System Neoplasms pathology, Lymphoma therapy
- Abstract
Background: Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months., Methods: One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18-70 years with WHO performance status 0-3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively., Results: For event-free survival, the hazard ratio was 0.85, 95% CI 0.61-1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39-59) and 53% (43-63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term., Conclusions: Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
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- 2024
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3. R-CODOX-M/R-IVAC versus DA-EPOCH-R in patients with newly diagnosed Burkitt lymphoma (HOVON/SAKK): final results of a multicentre, phase 3, open-label, randomised trial.
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Chamuleau MED, Stenner F, Chitu DA, Novak U, Minnema MC, Geerts P, Stevens WBC, Zenz T, van Imhoff GW, Wu KL, Demandt AMP, Kersten MJ, Terpstra WE, Tick LW, Deeren D, Van Den Neste E, Gregor M, Veelken H, Böhmer LH, Caspar CB, Mutsaers P, Refos JM, Sewsaran R, Fu L, Seefat RL, Uyl-de Groot CA, Dirnhofer S, Van Den Brand M, de Jong D, Nijland M, and Lugtenburg P
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- Humans, Male, Female, Etoposide, Vincristine, Rituximab therapeutic use, Methotrexate, Cytarabine, Cyclophosphamide adverse effects, Doxorubicin, Antineoplastic Combined Chemotherapy Protocols adverse effects, Prednisolone therapeutic use, Burkitt Lymphoma diagnosis, Burkitt Lymphoma drug therapy
- Abstract
Background: Patients with newly diagnosed high-risk Burkitt lymphoma are treated with high-intensity immune-chemotherapy regimens such as R-CODOX-M/R-IVAC or with lower-intensity regimens such as DA-EPOCH-R. The aim of this study was to make a formal comparison between these regimens., Methods: This multicentre, phase 3, open-label, randomised study was done in 26 clinical centres in the Netherlands, Belgium, and Switzerland. Eligible patients were aged 18-75 years with newly diagnosed high-risk Burkitt lymphoma without CNS involvement. Patients were randomly assigned to two cycles of R-CODOX-M/R-IVAC (R-CODOX-M: rituximab 375 mg/m
2 on day 1 and 9, cyclophosphamide 800 mg/m2 on day 1, cyclophosphamide 200 mg/m2 on days 2-5, vincristine 1·5 mg/m2 on days 1 and 8, doxorubicin 40 mg/m2 on day 1, and methotrexate 3000 mg/m2 on day 10; R-IVAC: rituximab 375 mg/m2 on days 3 and 7, iphosphamide 1500 mg/m2 on days 1-5, etoposide 60 mg/m2 on days 1-5, and cytarabin 2000 mg/m2 on day 1 and 2) or six cycles of DA-EPOCH-R (dose-adjusted etoposide 50-124 mg/m2 on days 1-4, prednisolone 120 mg/m2 on days 1-5, vincristine 0·4 mg/m2 on days 1-4, dose-adjusted cyclophosphamide 480-1866 mg/m2 on day 5, dose-adjusted doxorubicin 10-24·8 mg/m2 on days 1-4, rituximab 375 mg/m2 on days 1 and 5). Patients older than 65 years received a dose modified R-CODOX-M/R-IVAC. All drugs were intravenous except for prednisolone, which was oral. Patients also received four intrathecal CNS administrations with cytarabin (70 mg) and four with methotrexate (15 mg). Patients were stratified by centre, leukemic disease, and HIV-positivity. The primary endpoint was progression-fee survival. All analyses were done by modified intention-to-treat, excluding randomly assigned patients who were subsequently found to have CNS involvement or diagnosis other than Burkitt lymphoma at study entry. This study is registered with the European Clinical Trial Register, EudraCT2013-004394-27., Findings: Due to a slow accrual, the study was closed prematurely on Nov 15, 2021. Between Aug 4, 2014, and Sept 17, 2021, 89 patients were enrolled and randomly assigned to receive R-CODOX-M/R-IVAC (n=46) or DA-EPOCH-R (n=43). Five patients were excluded after random assignment (three in the R-CODOX-M/R-IVAC group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and two CNS involvement] and two in the DA-EPOCH-R group [one diagnosis other than Burkitt lymphoma at study entry according to local pathology and one CNS involvement]. 84 remaining patients were included in the modified intention-to-treat analysis. 73 (87%) of 84 patients were male, 76 (90%) presented with stage III or IV disease, and nine (11%) had HIV-positive Burkitt lymphoma. Median patient age was 52 years (IQR 37-64). With a median follow-up of 28·5 months (IQR 13·2-43·7), 2-year progression-free survival was 76% (95% CI 60-86%) in the R-CODOX-M/R-IVAC group and 70% (54-82%) in the DA-EPOCH-R group (hazard ratio 1·42, 95% CI 0·63-3·18; p=0·40). There were two deaths in the R-CODOX-M/R-IVAC group (one infection [treatment related] and one due to disease progression [not treatment related]) and one death in the DA-EPOCH-R group (COVID-19 infection [treatment related]). In the R-CODOX-M/R-IVAC group, four patients went off-protocol because of toxic effects, versus none in the DA-EPOCH-R group. Patients treated with R-CODOX-M/R-IVAC had more infectious adverse events (24 [56%] of 43 patients had at least one grade 3-5 infection vs 14 [34%] of 41 patients in the DA-EPOCH-R group)., Interpretation: The trial stopped early, but the available data suggest that while DA-EPOCH-R did not result in superior progression-free survival compared with R-CODOX-M/R-IVAC, it was associated with fewer toxic effects and need for supportive care. DA-EPOCH-R appears to be an additional valid therapeutic option for patients with high-risk Burkitt lymphoma without CNS involvement., Funding: The Dutch Cancer Society and the Schumacher-Kramer Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2023
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4. Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma.
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Berendsen MR, van Bladel DAG, Hesius E, Berganza Irusquieta C, Rijntjes J, van Spriel AB, van der Spek E, Pruijt JFM, Kroeze LI, Hebeda KM, Croockewit S, Stevens WBC, van Krieken JHJM, Groenen PJTA, van den Brand M, and Scheijen B
- Abstract
Patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) occasionally develop diffuse large B-cell lymphoma (DLBCL). This mostly results from LPL/WM transformation, although clonally unrelated DLBCL can also arise. LPL/WM is characterized by activating MYD88
L265P (>95%) and CXCR4 mutations (~30%), but the genetic drivers of transformation remain to be identified. Here, in thirteen LPL/WM patients who developed DLBCL, the clonal relationship of LPL and DLBCL together with mutations contributing to transformation were investigated. In 2 LPL/WM patients (15%), high-throughput sequencing of immunoglobulin gene rearrangements showed evidence of >1 clonal B-cell population in LPL tissue biopsies. In the majority of LPL/WM patients, DLBCL presentations were clonally related to the dominant clone in LPL, providing evidence of transformation. However, in 3 patients (23%), DLBCL was clonally unrelated to the major malignant B-cell clone in LPL, of which 2 patients developed de novo DLBCL. In this study cohort, LPL displayed MYD88L265P mutation in 8 out of eleven patients analyzed (73%), while CXCR4 mutations were observed in 6 cases (55%). MYD88WT LPL biopsies present in 3 patients (27%) were characterized by CD79B and TNFAIP3 mutations. Upon transformation, DLBCL acquired novel mutations targeting BTG1, BTG2, CD79B, CARD11, TP53, and PIM1 . Together, we demonstrate variable clonal B-cell dynamics in LPL/WM patients developing DLBCL, and the occurrence of clonally unrelated DLBCL in about one-quarter of LPL/WM patients. Moreover, we identified commonly mutated genes upon DLBCL transformation, which together with preserved mutations already present in LPL characterize the mutational landscape of DLBCL occurrences in LPL/WM patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)- Published
- 2023
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5. A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma.
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van Bladel DAG, Stevens WBC, Kroeze LI, de Groen RAL, de Groot FA, van der Last-Kempkes JLM, Berendsen MR, Rijntjes J, Luijks JACW, Bonzheim I, van der Spek E, Plattel WJ, Pruijt JFM, de Jonge-Peeters SDPWM, Velders GA, Lensen C, van Bladel ER, Federmann B, Hoevenaars BM, Pastorczak A, van der Werff Ten Bosch J, Vermaat JSP, Nooijen PTGA, Hebeda KM, Fend F, Diepstra A, van Krieken JHJM, Groenen PJTA, van den Brand M, and Scheijen B
- Subjects
- Humans, Retrospective Studies, Neoplasm Recurrence, Local, Immunoglobulins, Hodgkin Disease diagnosis, Hodgkin Disease genetics, Hodgkin Disease pathology, Lymphoma, Lymphoma, T-Cell
- Abstract
Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is underinvestigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements was performed in paired cHL diagnoses and recurrences among 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal Ig rearrangements were detected by next-generation sequencing (NGS) in 69 of 120 (58%) diagnoses and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24 of 34 patients (71%). Clonally unrelated cHL was observed in 10 of 34 patients (29%) as determined by IG-NGS clonality assessment and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of >2 years, ∼60% of patients with cHL for whom the clonal relationship could be established showed a second primary cHL. Clonal TCR gene rearrangements were identified in 14 of 125 samples (11%), and TCL-associated gene mutations were detected in 7 of 14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged >50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based Ig/TCR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation., (© 2023 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.)
- Published
- 2023
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6. Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA.
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Veltmaat N, Zhong Y, de Jesus FM, Tan GW, Bult JAA, Terpstra MM, Mutsaers PGNJ, Stevens WBC, Mous R, Vermaat JSP, Chamuleau MED, Noordzij W, Verschuuren EAM, Kok K, Kluiver JL, Diepstra A, Plattel WJ, van den Berg A, and Nijland M
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- Humans, DNA Copy Number Variations, Epigenesis, Genetic, Herpesvirus 4, Human genetics, Genomics, Epstein-Barr Virus Infections genetics, Lymphoproliferative Disorders genetics, Cell-Free Nucleic Acids genetics
- Abstract
Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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7. Reclassification of diffuse large B cell lymphoma to large B cell lymphoma with IRF4 rearrangement in an adult population.
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Hesius EAM, van Laar L, Oosterveld M, van Spriel AB, Scheijen B, Leeuwis JW, Marres HAM, Groenen PJTA, Stevens WBC, van der Spek E, van den Brule AJC, Hoevenaars BM, Hebeda KM, and van den Brand M
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- Humans, Gene Rearrangement, In Situ Hybridization, Fluorescence, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Follicular pathology
- Abstract
Aims: Large B cell lymphoma with IRF4 rearrangement (LBCL-IRF4) is a new entity in the 2017 revised World Health Organisation (WHO) classification that was initially mainly reported in children. After identification of a 79-year-old patient, we assessed how often IRF4 rearrangements can be detected in adult diffuse large B cell lymphomas (DLBCLs) which have to be reclassified to LBCL-IRF4 based on fluorescence in-situ hybridisation (FISH) for IRF4., Methods and Results: With FISH, we studied the presence of IRF4 rearrangements in 238 lymphomas that were diagnosed as DLBCL according to the previous WHO classification of 2008., Conclusions: In addition to the index patient, an IRF4 rearrangement was detected in another five of 237 patients (2%). The immunohistochemical profile of these five IRF4 rearranged lymphomas was consistent with previous reports of LBCL-IRF4. One case was recognised to represent transformation of follicular lymphoma rather than de-novo LBCL-IRF4. BCL6 rearrangements were found in two cases of LBCL-IRF4; BCL2 and MYC rearrangements were excluded. Patients presented with limited stage disease with involvement of the head and neck in three patients, and involvement of the lung and thyroid in two others. This study shows that, although rare, LBCL-IRF4 should also be considered in older patients and at localisations other than the head and neck region., (© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.)
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- 2023
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8. Detection of Second Primary Lymphoma in Late Diffuse Large B-cell Lymphoma Recurrences.
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Berendsen MR, Bladel DAGV, Hesius E, de Groot FA, Kroeze LI, Rijntjes J, Luijks JACW, Hoevenaars B, Halilovic A, Nooijen P, Bladel EV, Jonge-Peeters S, Lensen C, Pruijt H, van der Spek E, Vermaat JSP, Hess C, Hebeda KM, Stevens WBC, van Krieken JHJM, van den Brand M, Groenen PJTA, and Scheijen B
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- Humans, Neoplasm Recurrence, Local pathology, Herpesvirus 4, Human, Transplantation, Autologous, Epstein-Barr Virus Infections pathology, Hematopoietic Stem Cell Transplantation, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse drug therapy
- Abstract
Approximately one-third of patients with diffuse large B-cell lymphoma (DLBCL) relapse and often require salvage chemotherapy followed by autologous stem cell transplantation. In most cases, the clonal relationship between the first diagnosis and subsequent relapse is not assessed, thereby potentially missing the identification of second primary lymphoma. In this study, the clonal relationship of 59 paired DLBCL diagnoses and recurrences was established by next-generation sequencing-based detection of immunoglobulin gene rearrangements. Among 50 patients with interpretable results, 43 patients (86%) developed clonally related relapsed disease. This was observed in 100% of early recurrences (<2 years), 80% of the recurrences with an interval between 2 and 5 years, and 73% of late recurrences (≥5 years). On the other hand, 7 (14%) out of 50 patients displayed different dominant clonotypes in primary DLBCL and clinical recurrences, confirming the occurrence of second primary DLBCL; 37% of DLBCL recurrences that occurred ≥4 years after diagnosis were shown to be second primary lymphomas. The clonally unrelated cases were Epstein-Barr virus positive in 43% of the cases, whereas this was only 5% in the relapsed DLBCL cases. In conclusion, next-generation sequencing-based clonality testing in late recurrences should be considered in routine diagnostics to distinguish relapse from second primary lymphoma, as this latter group of patients with DLBCL may benefit from less-intensive treatment strategies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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9. Genetic and Microenvironment Features Do Not Distinguish Follicular Lymphoma Patients Requiring Immediate or Deferred Treatment.
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Stevens WBC, Los-de Vries GT, Langois-Jacques C, Clear AJ, Stathi P, Sander B, Rosenwald A, Calaminici M, Hoster E, Hiddemann W, Gaulard P, Salles G, Klapper W, Xerri L, Burton C, Tooze RM, Smith AG, Buske C, Scott DW, Natkunam Y, Advani R, Sehn LH, Raemaekers J, Gribben J, Lockmer S, Kimby E, Kersten MJ, Maucort-Boulch D, Ylstra B, van Dijk E, and de Jong D
- Abstract
Competing Interests: The authors have no conflicts of interest to disclose.
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- 2023
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10. Genomic and microenvironmental landscape of stage I follicular lymphoma, compared with stage III/IV.
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Los-de Vries GT, Stevens WBC, van Dijk E, Langois-Jacques C, Clear AJ, Stathi P, Roemer MGM, Mendeville M, Hijmering NJ, Sander B, Rosenwald A, Calaminici M, Hoster E, Hiddemann W, Gaulard P, Salles G, Horn H, Klapper W, Xerri L, Burton C, Tooze RM, Smith AG, Buske C, Scott DW, Natkunam Y, Advani R, Sehn LH, Raemaekers J, Gribben J, Kimby E, Kersten MJ, Maucort-Boulch D, Ylstra B, and de Jong D
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- Genomics, Histones genetics, Humans, Programmed Cell Death 1 Receptor metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Translocation, Genetic, Lymphoma, Follicular genetics
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Although the genomic and immune microenvironmental landscape of follicular lymphoma (FL) has been extensively investigated, little is known about the potential biological differences between stage I and stage III/IV disease. Using next-generation sequencing and immunohistochemistry, 82 FL nodal stage I cases were analyzed and compared with 139 FL stage III/IV nodal cases. Many similarities in mutations, chromosomal copy number aberrations, and microenvironmental cell populations were detected. However, there were also significant differences in microenvironmental and genomic features. CD8+ T cells (P = .02) and STAT6 mutations (false discovery rate [FDR] <0.001) were more frequent in stage I FL. In contrast, programmed cell death protein 1-positive T cells, CD68+/CD163+ macrophages (P < .001), BCL2 translocation (BCL2trl+) (P < .0001), and KMT2D (FDR = 0.003) and CREBBP (FDR = 0.04) mutations were found more frequently in stage III/IV FL. Using clustering, we identified 3 clusters within stage I, and 2 clusters within stage III/IV. The BLC2trl+ stage I cluster was comparable to the BCL2trl+ cluster in stage III/IV. The two BCL2trl- stage I clusters were unique for stage I. One was enriched for CREBBP (95%) and STAT6 (64%) mutations, without BLC6 translocation (BCL6trl), whereas the BCL2trl- stage III/IV cluster contained BCL6trl (64%) with fewer CREBBP (45%) and STAT6 (9%) mutations. The other BCL2trl- stage I cluster was relatively heterogeneous with more copy number aberrations and linker histone mutations. This exploratory study shows that stage I FL is genetically heterogeneous with different underlying oncogenic pathways. Stage I FL BCL2trl- is likely STAT6 driven, whereas BCL2trl- stage III/IV appears to be more BCL6trl driven., (© 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.)
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- 2022
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11. Novel Approaches in Molecular Characterization of Classical Hodgkin Lymphoma.
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van Bladel DAG, Stevens WBC, van den Brand M, Kroeze LI, Groenen PJTA, van Krieken JHJM, Hebeda KM, and Scheijen B
- Abstract
Classical Hodgkin lymphoma (cHL) represents a B-cell lymphoproliferative disease characterized by clonal immunoglobulin gene rearrangements and recurrent genomic aberrations in the Hodgkin Reed-Sternberg cells in a reactive inflammatory background. Several methods are available for the molecular analysis of cHL on both tissue and cell-free DNA isolated from blood, which can provide detailed information regarding the clonal composition and genetic alterations that drive lymphoma pathogenesis. Clonality testing involving the detection of immunoglobulin and T cell receptor gene rearrangements, together with mutation analysis, represent valuable tools for cHL diagnostics, especially for patients with an atypical histological or clinical presentation reminiscent of a reactive lesion or another lymphoma subtype. In addition, clonality assessment may establish the clonal relationship of composite or subsequent lymphoma presentations within one patient. During the last few decades, more insight has been obtained on the molecular mechanisms that drive cHL development, including recurrently affected signaling pathways (e.g., NF-κB and JAK/STAT) and immune evasion. We provide an overview of the different approaches to characterize the molecular composition of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.
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- 2022
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12. Persistent symptoms of fatigue, neuropathy and role-functioning impairment among indolent non-Hodgkin lymphoma survivors: A longitudinal PROFILES registry study.
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Ekels A, van de Poll-Franse LV, Posthuma EFM, Kieffer J, Issa DE, Koster A, Nijziel MR, Pruijt JHFM, Stevens WBC, Tick LW, and Oerlemans S
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- Fatigue epidemiology, Fatigue etiology, Humans, Longitudinal Studies, Quality of Life psychology, Registries, Surveys and Questionnaires, Survivors psychology, Lymphoma, Non-Hodgkin complications, Lymphoma, Non-Hodgkin epidemiology, Lymphoma, Non-Hodgkin therapy, Peripheral Nervous System Diseases epidemiology, Peripheral Nervous System Diseases etiology
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Little is known about the long-term health-related quality of life (HRQoL) and persistence of symptoms among patients with indolent non-Hodgkin lymphoma (iNHL). This large population-based longitudinal study therefore investigated the long-term HRQoL and persistence of symptoms and identified associated sociodemographic, clinical and psychological factors. Patients diagnosed between 1999 and 2014 and four or more months after diagnosis were invited to participate in a longitudinal survey. Sociodemographic and clinical data were obtained from the Netherlands Cancer Registry. The EORTC QLQ-C30 and CLL-16 were completed by 669 patients (74% response rate). Patients completed on average four questionnaires. Primary treatment was active surveillance (52%), systemic therapy (31%) or radiotherapy (13%). Respectively, 36% reported persistent fatigue, 33% persistent neuropathy and 25% persistent role-functioning impairment. This was 2-3 times higher than in the age- and sex-matched normative population. Up to 10 years after diagnosis, scores remained relatively stable without clinically relevant changes. Comorbidities, psychological distress, shorter time since diagnosis, systemic therapy, younger age, education level and having no partner were associated with worse outcomes (all ps < 0.05). Up to a third of patients with iNHL experience long-term persistent symptoms which do not improve over time. Early recognition of symptoms will help in providing tailored supportive care for those in need., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2022
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13. Biological and Clinical Implications of Gene-Expression Profiling in Diffuse Large B-Cell Lymphoma: A Proposal for a Targeted BLYM-777 Consortium Panel as Part of a Multilayered Analytical Approach.
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de Groot FA, de Groen RAL, van den Berg A, Jansen PM, Lam KH, Mutsaers PGNJ, van Noesel CJM, Chamuleau MED, Stevens WBC, Plaça JR, Mous R, Kersten MJ, van der Poel MMW, Tousseyn T, Woei-A-Jin FJSH, Diepstra A, Nijland M, and Vermaat JSP
- Abstract
Gene-expression profiling (GEP) is used to study the molecular biology of lymphomas. Here, advancing insights from GEP studies in diffuse large B-cell lymphoma (DLBCL) lymphomagenesis are discussed. GEP studies elucidated subtypes based on cell-of-origin principles and profoundly changed the biological understanding of DLBCL with clinical relevance. Studies integrating GEP and next-generation DNA sequencing defined different molecular subtypes of DLBCL entities originating at specific anatomical localizations. With the emergence of high-throughput technologies, the tumor microenvironment (TME) has been recognized as a critical component in DLBCL pathogenesis. TME studies have characterized so-called "lymphoma microenvironments" and "ecotypes". Despite gained insights, unexplained chemo-refractoriness in DLBCL remains. To further elucidate the complex biology of DLBCL, we propose a novel targeted GEP consortium panel, called BLYM-777. This knowledge-based biology-driven panel includes probes for 777 genes, covering many aspects regarding B-cell lymphomagenesis (f.e., MYC signature, TME, immune surveillance and resistance to CAR T-cell therapy). Regarding lymphomagenesis, upcoming DLBCL studies need to incorporate genomic and transcriptomic approaches with proteomic methods and correlate these multi-omics data with patient characteristics of well-defined and homogeneous cohorts. This multilayered methodology potentially enhances diagnostic classification of DLBCL subtypes, prognostication, and the development of novel targeted therapeutic strategies.
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- 2022
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14. Web-Based Return of Individual Patient-Reported Outcome Results Among Patients With Lymphoma: Randomized Controlled Trial.
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Oerlemans S, Arts LPJ, Kieffer JM, Prins J, Hoogendoorn M, van der Poel M, Koster A, Lensen C, Stevens WBC, Issa D, Pruijt JFM, Oosterveld M, van der Griend R, Nijziel M, Tick L, Posthuma EFM, and van de Poll-Franse LV
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- Humans, Internet, Netherlands, Patient Reported Outcome Measures, Lymphoma therapy, Research Design
- Abstract
Background: There has been a cultural shift toward patient engagement in health, with a growing demand from patients to access their results., Objective: The Lymphoma Intervention (LIVE) trial is conducted to examine the impact of return of individual patient-reported outcome (PRO) results and a web-based self-management intervention on psychological distress, self-management, satisfaction with information, and health care use in a population-based setting., Methods: Return of PRO results included comparison with age- and sex-matched peers and was built into the Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship registry. The self-management intervention is an adaptation of a fully automated evidence-based intervention for breast cancer survivors. Patients with lymphoma who completed the web-based questionnaire were equally randomized to care as usual, return of PRO results, and return of PRO results plus self-management intervention. Patients completed questionnaires 9 to 18 months after diagnosis (T0; n=227), 4 months (T1; n=190), 12 months (T2; n=170), and 24 months (T3; n=98)., Results: Of all invited patients, 51.1% (456/892) responded and web-based participants (n=227) were randomly assigned to care as usual (n=76), return of PRO results (n=74), or return of PRO results and access to Living with lymphoma (n=77). Return of PRO results was viewed by 76.7% (115/150) of those with access. No statistically significant differences were observed for psychological distress, self-management, satisfaction with information provision, and health care use between patients who received PRO results and those who did not (P>.05). Use of the self-management intervention was low (2/76, 3%), and an effect could therefore not be determined., Conclusions: Return of individual PRO results seems to meet patients' wishes but had no beneficial effects on patient outcome. No negative effects were found when individual PRO results were disclosed, and the return of individual PRO results can therefore be safely implemented in daily clinical practice., Trial Registration: Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/5790., International Registered Report Identifier (irrid): RR2-10.1186/s13063-017-1943-2., (©Simone Oerlemans, Lindy Paulina Johanna Arts, Jacobien M Kieffer, Judith Prins, Mels Hoogendoorn, Marjolein van der Poel, Ad Koster, Chantal Lensen, Wendy Bernadina Catharina Stevens, Djamila Issa, Johannes F M Pruijt, Margriet Oosterveld, René van der Griend, Marten Nijziel, Lidwine Tick, Eduardus F M Posthuma, Lonneke V van de Poll-Franse. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.12.2021.)
- Published
- 2021
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15. Axillary lymph nodes on PET in Hodgkin lymphoma after COVID-19 vaccination.
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Arens AIJ, Hebeda KM, Hutchings M, Plattel WJ, and Stevens WBC
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- 2021
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16. Extent of radiological response does not reflect survival in primary central nervous system lymphoma.
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van der Meulen M, Postma AA, Smits M, Bakunina K, Minnema MC, Seute T, Cull G, Enting RH, van der Poel M, Stevens WBC, Brandsma D, Beeker A, Doorduijn JK, Issa S, van den Bent MJ, and Bromberg JEC
- Abstract
Background: In primary central nervous system lymphoma (PCNSL), small enhancing lesions can persist after treatment. It is unknown whether a difference in response category (complete response [CR], complete response unconfirmed [CRu], or partial response [PR]) reflects survival. We aimed to determine the value of a central radiology review on response assessment and whether the extent of response influenced progression-free and/or overall survival., Methods: All patients in the HOVON 105/ALLG NHL 24 study with at least a baseline MRI and one MRI made for response evaluation available for central review were included. Tumor measurements were done by 2 independent central reviewers, disagreements were adjudicated by a third reviewer. Crude agreement and interobserver agreement (Cohen's kappa) were calculated. Differences in progression-free and overall survival between different categories of response at the end-of-protocol-treatment were assessed by the log-rank test in a landmark survival-analysis., Results: Agreement between the central reviewers was 61.7% and between local and central response assessment was 63.0%. Cohen's kappa's, which corrects for expected agreement, were 0.44 and 0.46 (moderate), respectively. Progression agreement or not was 93.3% (kappa 0.87) between local and central response assessment. There were no significant differences in progression-free and overall survival between patients with CR, CRu, or PR at the end-of-protocol-treatment, according to both local and central response assessment., Conclusions: Reliability of response assessment (CR/CRu/PR) is moderate even by central radiology review and these response categories do not reliably predict survival. Therefore, primary outcome in PCNSL studies should be survival rather than CR or CR/CRu-rate., (© The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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- 2021
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17. Molecular Genetics of Relapsed Diffuse Large B-Cell Lymphoma: Insight into Mechanisms of Therapy Resistance.
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Berendsen MR, Stevens WBC, van den Brand M, van Krieken JH, and Scheijen B
- Abstract
The majority of patients with diffuse large B-cell lymphoma (DLBCL) can be treated successfully with a combination of chemotherapy and the monoclonal anti-CD20 antibody rituximab. Nonetheless, approximately one-third of the patients with DLBCL still experience relapse or refractory (R/R) disease after first-line immunochemotherapy. Whole-exome sequencing on large cohorts of primary DLBCL has revealed the mutational landscape of DLBCL, which has provided a framework to define novel prognostic subtypes in DLBCL. Several studies have investigated the genetic alterations specifically associated with R/R DLBCL, thereby uncovering molecular pathways linked to therapy resistance. Here, we summarize the current state of knowledge regarding the genetic alterations that are enriched in R/R DLBCL, and the corresponding pathways affected by these gene mutations. Furthermore, we elaborate on their potential role in mediating therapy resistance, also in connection with findings in other B-cell malignancies, and discuss alternative treatment options. Hence, this review provides a comprehensive overview on the gene lesions and molecular mechanisms underlying R/R DLBCL, which are considered valuable parameters to guide treatment.
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- 2020
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18. Health-related quality of life after chemotherapy with or without rituximab in primary central nervous system lymphoma patients: results from a randomised phase III study.
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van der Meulen M, Bakunina K, Nijland M, Minnema MC, Cull G, Stevens WBC, Baars JW, Mason KD, Beeker A, Beijert M, Taphoorn MJB, van den Bent MJ, Issa S, Doorduijn JK, Bromberg JEC, and Dirven L
- Subjects
- Central Nervous System, Health Status, Humans, Rituximab, Surveys and Questionnaires, Central Nervous System Neoplasms drug therapy, Quality of Life
- Abstract
Background: The impact of rituximab on health-related quality of life (HRQoL) in primary central nervous system lymphoma patients is not well known. We determined the impact of rituximab added to standard high-dose methotrexate-based treatment on HRQoL in patients in a large randomised trial., Patients and Methods: Patients from a large phase III trial (HOVON 105/ALLG NHL 24), randomly assigned to receive standard chemotherapy with or without rituximab and followed by 30 Gy whole brain radiotherapy (WBRT) in patients ≤60 years, completed the EORTC QLQ-C30 and QLQ-BN20 questionnaires before and during treatment, and up to 24 months of follow-up or progression. Differences between treatment arms over time in global health status, role functioning, social functioning, fatigue, and motor dysfunction were assessed. Differences ≥10 points were deemed clinically relevant. The effect of WBRT on HRQoL was analysed in irradiated patients., Results: A total of 160/175 patients eligible for the HRQoL study completed at least one questionnaire and were included. Over time, scores improved statistically significantly and were clinically relevant in both arms. Between arms, there were no differences on any scale (range: -3.8 to +4.0). Scores on all scales were improved to a clinically relevant extent at 12 and 24 months compared with baseline in both arms, except for fatigue and motor dysfunction at 12 months (-7.4 and -8.8, respectively). In irradiated patients (n = 59), scores in all preselected scales, except motor dysfunction, remained stable up to 24 months compared with shortly after WBRT, overall mean difference ranging between 0.02 and 4.570., Conclusion: Compared with baseline, treatment resulted in improved HRQoL scores. The addition of rituximab to standard chemotherapy did not impact HRQoL over time. WBRT did not result in deterioration of HRQoL in the first 2 years., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2020 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)
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- 2020
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19. HOVON110/ReBeL Study: Results of the Phase I Part of a Randomized Phase I/II Study of Lenalidomide, Rituximab With or Without Bendamustine in Patients With Relapsed/Refractory Follicular Lymphoma.
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Stevens WBC, Bakunina K, Cuijpers M, Chamuleau M, Beeker A, Fijnheer R, Hebart H, Visser HPJ, Doorduijn JK, Linton K, Dreyling M, de Jong D, and Kersten MJ
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- 2020
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20. Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium.
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Rosenwald A, Bens S, Advani R, Barrans S, Copie-Bergman C, Elsensohn MH, Natkunam Y, Calaminici M, Sander B, Baia M, Smith A, Painter D, Pham L, Zhao S, Ziepert M, Jordanova ES, Molina TJ, Kersten MJ, Kimby E, Klapper W, Raemaekers J, Schmitz N, Jardin F, Stevens WBC, Hoster E, Hagenbeek A, Gribben JG, Siebert R, Gascoyne RD, Scott DW, Gaulard P, Salles G, Burton C, de Jong D, Sehn LH, and Maucort-Boulch D
- Subjects
- Aged, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Immunoglobulin G genetics, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Prednisone administration & dosage, Prognosis, Prospective Studies, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Rituximab administration & dosage, Survival Rate, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Gene Rearrangement, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse mortality, Proto-Oncogene Proteins c-myc genetics, Translocation, Genetic
- Abstract
Purpose: MYC rearrangement ( MYC -R) occurs in approximately 10% of diffuse large B-cell lymphomas (DLBCLs) and has been associated with poor prognosis in many studies. The impact of MYC- R on prognosis may be influenced by the MYC partner gene (immunoglobulin [IG] or a non-IG gene). We evaluated a large cohort of patients through the Lunenburg Lymphoma Biomarker Consortium to validate the prognostic significance of MYC-R (single-, double-, and triple-hit status) in DLBCL within the context of the MYC partner gene., Methods: The study cohort included patients with histologically confirmed DLBCL morphology derived from large prospective trials and patient registries in Europe and North America who were uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy or the like. Fluorescence in situ hybridization for the MYC , BCL2 , BCL6 , and IG heavy and light chain loci was used, and results were correlated with clinical outcomes., Results: A total of 5,117 patients were identified of whom 2,383 (47%) had biopsy material available to assess for MYC -R. MYC -R was present in 264 (11%) of 2,383 patients and was associated with a significantly shorter progression-free and overall survival, with a strong time-dependent effect within the first 24 months after diagnosis. The adverse prognostic impact of MYC- R was only evident in patients with a concurrent rearrangement of BCL2 and/or BCL6 and an IG partner (hazard ratio, 2.4; 95% CI, 1.6 to 3.6; P < .001)., Conclusion: The negative prognostic impact of MYC -R in DLBCL is largely observed in patients with MYC double hit/triple-hit disease in which MYC is translocated to an IG partner, and this effect is restricted to the first 2 years after diagnosis. Our results suggest that diagnostic strategies should be adopted to identify this high-risk cohort, and risk-adjusted therapeutic approaches should be refined further.
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- 2019
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21. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study.
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Bromberg JEC, Issa S, Bakunina K, Minnema MC, Seute T, Durian M, Cull G, Schouten HC, Stevens WBC, Zijlstra JM, Baars JW, Nijland M, Mason KD, Beeker A, van den Bent MJ, Beijert M, Gonzales M, de Jong D, and Doorduijn JK
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Antimetabolites, Antineoplastic administration & dosage, Antineoplastic Agents, Immunological administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Central Nervous System Neoplasms drug therapy, Lymphoma drug therapy, Methotrexate administration & dosage, Rituximab administration & dosage
- Abstract
Background: The prognosis for primary CNS lymphoma has improved with the use of high-dose methotrexate-based chemotherapy, but patient outcomes remain poor. Rituximab, a chimeric monoclonal antibody that targets the CD20 cell surface protein, has substantial activity in systemic CD20-positive diffuse large B-cell lymphoma, but its efficacy in primary CNS lymphoma is unknown and low penetration of the large rituximab molecule through the blood-brain barrier could limit its effect. We aimed to investigate the addition of rituximab to a high-dose methotrexate-based chemotherapy regimen in patients with newly diagnosed primary CNS lymphoma., Methods: This intergroup, multicentre, open-label, randomised phase 3 study was done at 23 hospitals in the Netherlands, Australia, and New Zealand. Non-immunocompromised patients aged 18-70 years with newly diagnosed primary CNS lymphoma were randomly assigned (1:1) to receive methotrexate-based chemotherapy with or without intravenous rituximab. We used a web-based randomisation system with stratification by centre, age, and Eastern Cooperative Oncology Group-WHO performance status, and a minimisation procedure. All group assignment was open label and neither investigators nor patients were masked to allocation. All patients were treated with two 28-day cycles of induction chemotherapy, consisting of intravenous methotrexate 3 g per m
2 on days 1 and 15, intravenous carmustine 100 mg per m2 on day 4, intravenous teniposide 100 mg per m2 on days 2 and 3, and oral prednisone 60 mg per m2 on days 1-5, with (R-MBVP) or without (MBVP) intravenous rituximab 375 mg per m2 on days 0, 7, 14, and 21 in cycle one and days 0 and 14 in cycle two. Patients with response at the end of induction subsequently received high-dose cytarabine and, in patients aged 60 years or younger, low-dose whole-brain radiotherapy. The primary endpoint was event-free survival, with events defined as not reaching complete response or complete response unconfirmed at the end of treatment, or progression or death after response; analysis was adjusted for age and performance score. Patients were analysed on a modified intention-to-treat basis. This trial is registered with the Nederlands Trial Register, number NTR2427, and the Australian New Zealand Clinical Trials Registry, number ACTRN12610000908033. The trial was closed on May 27, 2016, after achieving complete accrual, and follow-up is ongoing., Findings: Between Aug 3, 2010, and May 27, 2016, we recruited 200 patients (109 men and 91 women; median age was 61 years [IQR 55-67]). We randomly assigned 100 patients to MBVP and 99 patients to R-MBVP. One patient was randomly assigned to the R-MBVP group but found to be ineligible because of an incorrect diagnosis and was excluded from all analyses. After a median follow-up of 32·9 months (IQR 23·9-51·5), 98 patients had had an event (51 in the MBVP group and 47 in the R-MBVP group), of whom 79 had died (41 in the MBVP group and 38 in the R-MBVP group). Event-free survival at 1 year was 49% (95% CI 39-58) in the MBVP group (no rituximab) and 52% (42-61) in the R-MBVP group (with rituximab; hazard ratio 1·00, 95% CI 0·70-1·43, p=0·99). Grade 3 or 4 adverse events occurred in 58 (58%) patients in the MBVP group and 63 (64%) patients in the R-MBVP group, with infections (24 [24%] patients receiving MBVP vs 21 [21%] patients receiving R-MBVP), haematological toxicity (15 [15%] vs 12 [12%]), and nervous system disorders (ten [10%] vs 15 [15%]) being the most common. Life-threatening or fatal serious adverse events occurred in 12 (12%) patients in the MBVP group and ten (10%) patients in the R-MBVP group, and five (5%) patients in the MBVP group and three (3%) in the R-MBVP group died from treatment-related causes., Interpretation: We found no clear benefit of addition of rituximab to methotrexate, carmustine, teniposide, and prednisone chemotherapy in primary CNS lymphoma. Therefore, the results of this study do not support the use of rituximab as a component of standard treatment in primary CNS lymphoma., Funding: Roche, the Dutch Cancer Society, and Stichting STOPhersentumoren., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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22. High prevalence of MYD88 and CD79B mutations in intravascular large B-cell lymphoma.
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Schrader AMR, Jansen PM, Willemze R, Vermeer MH, Cleton-Jansen AM, Somers SF, Veelken H, van Eijk R, Kraan W, Kersten MJ, van den Brand M, Stevens WBC, de Jong D, Abdul Hamid M, Tanis BC, Posthuma EFM, Nijland M, Diepstra A, Pals ST, Cleven AHG, and Vermaat JSP
- Subjects
- Biomarkers, Tumor, Biopsy, Humans, Immunohistochemistry, Lymphoma, Large B-Cell, Diffuse mortality, CD79 Antigens genetics, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse genetics, Mutation, Myeloid Differentiation Factor 88 genetics
- Published
- 2018
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23. Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.
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Oosten LEM, Chamuleau MED, Thielen FW, de Wreede LC, Siemes C, Doorduijn JK, Smeekes OS, Kersten MJ, Hardi L, Baars JW, Demandt AMP, Stevens WBC, Nijland M, van Imhoff GW, Brouwer R, Uyl-de Groot CA, Kluin PM, de Jong D, and Veelken H
- Subjects
- Adolescent, Adult, Aged, Burkitt Lymphoma complications, Burkitt Lymphoma economics, Burkitt Lymphoma mortality, Carmustine economics, Carmustine therapeutic use, Cyclophosphamide economics, Cyclophosphamide therapeutic use, Cytarabine economics, Cytarabine therapeutic use, Etoposide economics, Etoposide therapeutic use, Female, HIV Infections complications, HIV Infections economics, HIV Infections mortality, Humans, Ifosfamide economics, Ifosfamide therapeutic use, Male, Melphalan economics, Melphalan therapeutic use, Methotrexate economics, Methotrexate therapeutic use, Middle Aged, Neoplasm Staging, Retrospective Studies, Rituximab economics, Rituximab therapeutic use, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Burkitt Lymphoma drug therapy, Cost-Benefit Analysis, HIV Infections drug therapy
- Abstract
Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.
- Published
- 2018
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24. Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium.
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Stevens WBC, Mendeville M, Redd R, Clear AJ, Bladergroen R, Calaminici M, Rosenwald A, Hoster E, Hiddemann W, Gaulard P, Xerri L, Salles G, Klapper W, Pfreundschuh M, Jack A, Gascoyne RD, Natkunam Y, Advani R, Kimby E, Sander B, Sehn LH, Hagenbeek A, Raemaekers J, Gribben J, Kersten MJ, Ylstra B, Weller E, and de Jong D
- Subjects
- Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Biomarkers analysis, Cyclophosphamide, Doxorubicin, Humans, Lymphoma, Follicular drug therapy, Prednisone, Prognosis, Rituximab, Trisomy, Vincristine, Antigens, CD analysis, Antigens, Differentiation, Myelomonocytic analysis, CD8 Antigens analysis, Chromosomes, Human, Pair 18 genetics, Enhancer of Zeste Homolog 2 Protein analysis, Lymphoma, Follicular diagnosis, Receptors, Cell Surface analysis
- Abstract
In follicular lymphoma, studies addressing the prognostic value of microenvironment-related immunohistochemical markers and tumor cell-related genetic markers have yielded conflicting results, precluding implementation in practice. Therefore, the Lunenburg Lymphoma Biomarker Consortium performed a validation study evaluating published markers. To maximize sensitivity, an end of spectrum design was applied for 122 uniformly immunochemotherapy-treated follicular lymphoma patients retrieved from international trials and registries. The criteria were: early failure, progression or lymphoma-related death <2 years versus long remission, response duration of >5 years. Immunohistochemical staining for T cells and macrophages was performed on tissue microarrays from initial biopsies and scored with a validated computer-assisted protocol. Shallow whole-genome and deep targeted sequencing was performed on the same samples. The 96/122 cases with complete molecular and immunohistochemical data were included in the analysis. EZH2 wild-type ( P =0.006), gain of chromosome 18 ( P =0.002), low percentages of CD8+ cells ( P =0.011) and CD163+ areas ( P =0.038) were associated with early failure. No significant differences in other markers were observed, thereby refuting previous claims of their prognostic significance. Using an optimized study design, this Lunenburg Lymphoma Biomarker Consortium study substantiates wild-type EZH2 status, gain of chromosome 18, low percentages of CD8+ cells and CD163+ area as predictors of early failure to immunochemotherapy in follicular lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP [-like]), while refuting the prognostic impact of various other markers., (Copyright© 2017 Ferrata Storti Foundation.)
- Published
- 2017
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25. Centralised multidisciplinary re-evaluation of diagnostic procedures in patients with newly diagnosed Hodgkin lymphoma.
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Stevens WBC, van Krieken JH, Mus RDM, Arens AIJ, Mattijssen V, Oosterveld M, de Kruijf EJFM, de Vries F, Koster A, van der Maazen R, and Raemaekers J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Combined Modality Therapy, Female, Hodgkin Disease therapy, Humans, Male, Middle Aged, Radiotherapy, Young Adult, Hodgkin Disease diagnosis, Patient Care Team
- Abstract
Background: Hodgkin Lymphoma (HL) is highly curable when treated accurately. The challenge is to cure patients with the minimal risk of long-term complications. For that, optimal initial diagnostics are required to determine the optimal treatment plan. We offer non-academic hospitals in our Regional Comprehensive Cancer Centre network a centralised review of all diagnostic procedures from patients with newly diagnosed HL. We report our experience on concordances and discrepancies between local findings and central review results., Patients and Methods: A haematologist and radiation oncologist at the Hodgkin Radboud University Nijmegen Medical Centre outpatient clinic examined all patients with newly diagnosed HL between February 2006 and May 2010. In a multidisciplinary lymphoma conference, diagnostic information is reviewed and treatment advice formulated. Discordant findings in pathology, staging and therapy were recorded as 'minor', no therapeutic consequences or 'major', adapted therapy advice., Results: Altogether, 125 patients were included. Pathology review showed 86% concordance, with 4% major discordance, mainly nodular lymphocyte predominant sub-type. Revision of initial staging was concordant in 77%; however 15% major discordance of which most were upstaged. This resulted in 19% treatment adaption., Conclusion: Our findings highlight the discrepancies in interpretation of diagnostic tests. We advocate centralised review process for all newly diagnosed patients with HL.
- Published
- 2012
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