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Erschienen in: Annals of Hematology 11/2019

12.09.2019 | Original Article

Evaluation of cerebrospinal clonal gene rearrangement in newly diagnosed non-Hodgkin’s lymphoma patients

verfasst von: Boaz Nachmias, Veronica Sandler, Elena Slyusarevsky, Galina Pogrebijski, Svetlana Kritchevsky, Dina Ben-Yehuda, Neta Goldschmidt, Moshe E. Gatt

Erschienen in: Annals of Hematology | Ausgabe 11/2019

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Abstract

Overt central nervous system (CNS) involvement in aggressive non-Hodgkin’s lymphoma (NHL) is rare at diagnosis. Much effort is put to identify risk factors for occult CNS involvement, and the risk assessment of CNS relapse. Prophylactic treatment carries risk of adverse events and its efficacy is not clear. Detection of cerebrospinal fluid molecular gene rearrangement (GRR) as a method to detect occult disease has been studied in acute leukemia and primary CNS lymphoma. To date, the capacity of a positive GRR in newly diagnosed NHL patients to predict CNS relapse has not been addressed. We retrospectively studied the prognostic value of GRR in cerebrospinal fluid samples of 148 newly diagnosed patients with high grade NHL. We demonstrate that positive GRR at diagnosis does not affect PFS or OS and did not predict CNS relapse. However, although numbers were small, repeated positive samples (≥ 2) correlated with a higher risk for CNS relapse (p = 0.048), possibly stressing the need for an aggressive preventive approach.
Literatur
6.
Zurück zum Zitat Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ (2016) CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 34:3150–3156. https://doi.org/10.1200/JCO.2015.65.6520 CrossRefPubMed Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ (2016) CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 34:3150–3156. https://​doi.​org/​10.​1200/​JCO.​2015.​65.​6520 CrossRefPubMed
8.
Zurück zum Zitat Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3067. https://doi.org/10.1200/JCO.2013.54.8800 CrossRefPubMedPubMedCentral Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA, Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin's Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32:3059–3067. https://​doi.​org/​10.​1200/​JCO.​2013.​54.​8800 CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Pongers-Willemse MJ, Seriu T, Stolz F, d'Aniello E, Gameiro P, Pisa P, Gonzalez M, Bartram CR, Panzer-Grümayer ER, Biondi A, San Miguel JF, van Dongen J (1999) Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia. Leukemia 13:110–118CrossRef Pongers-Willemse MJ, Seriu T, Stolz F, d'Aniello E, Gameiro P, Pisa P, Gonzalez M, Bartram CR, Panzer-Grümayer ER, Biondi A, San Miguel JF, van Dongen J (1999) Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets: report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia. Leukemia 13:110–118CrossRef
12.
Zurück zum Zitat Benevolo G, Stacchini A, Spina M, Ferreri AJM, Arras M, Bellio L, Botto B, Bulian P, Cantonetti M, Depaoli L, di Renzo N, di Rocco A, Evangelista A, Franceschetti S, Godio L, Mannelli F, Pavone V, Pioltelli P, Vitolo U, Pogliani EM, on behalf of the Fondazione Italiana Linfomi (2012) Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination. Blood 120:3222–3228. https://doi.org/10.1182/blood-2012-04-423095 CrossRefPubMed Benevolo G, Stacchini A, Spina M, Ferreri AJM, Arras M, Bellio L, Botto B, Bulian P, Cantonetti M, Depaoli L, di Renzo N, di Rocco A, Evangelista A, Franceschetti S, Godio L, Mannelli F, Pavone V, Pioltelli P, Vitolo U, Pogliani EM, on behalf of the Fondazione Italiana Linfomi (2012) Final results of a multicenter trial addressing role of CSF flow cytometric analysis in NHL patients at high risk for CNS dissemination. Blood 120:3222–3228. https://​doi.​org/​10.​1182/​blood-2012-04-423095 CrossRefPubMed
14.
Zurück zum Zitat Abramson JS, Hellmann M, Barnes JA, Hammerman P, Toomey C, Takvorian T, Muzikansky A, Hochberg EP (2010) Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer 116:4283–4290. https://doi.org/10.1002/cncr.25278 CrossRefPubMed Abramson JS, Hellmann M, Barnes JA, Hammerman P, Toomey C, Takvorian T, Muzikansky A, Hochberg EP (2010) Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer 116:4283–4290. https://​doi.​org/​10.​1002/​cncr.​25278 CrossRefPubMed
15.
Zurück zum Zitat Ferreri AJM, Bruno-Ventre M, Donadoni G, Ponzoni M, Citterio G, Foppoli M, Vignati A, Scarfò L, Sassone M, Govi S, Caligaris-Cappio F (2015) Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with diffuse large B-cell lymphoma treated in the rituximab era. Br J Haematol 168:654–662. https://doi.org/10.1111/bjh.13194 CrossRefPubMed Ferreri AJM, Bruno-Ventre M, Donadoni G, Ponzoni M, Citterio G, Foppoli M, Vignati A, Scarfò L, Sassone M, Govi S, Caligaris-Cappio F (2015) Risk-tailored CNS prophylaxis in a mono-institutional series of 200 patients with diffuse large B-cell lymphoma treated in the rituximab era. Br J Haematol 168:654–662. https://​doi.​org/​10.​1111/​bjh.​13194 CrossRefPubMed
16.
Zurück zum Zitat Guirguis HR, Cheung MC, Mahrous M, Piliotis E, Berinstein N, Imrie KR, Zhang L, Buckstein R (2012) Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol 159:39–49. https://doi.org/10.1111/j.1365-2141.2012.09247.x CrossRefPubMed Guirguis HR, Cheung MC, Mahrous M, Piliotis E, Berinstein N, Imrie KR, Zhang L, Buckstein R (2012) Impact of central nervous system (CNS) prophylaxis on the incidence and risk factors for CNS relapse in patients with diffuse large B-cell lymphoma treated in the rituximab era: a single centre experience and review of the literature. Br J Haematol 159:39–49. https://​doi.​org/​10.​1111/​j.​1365-2141.​2012.​09247.​x CrossRefPubMed
19.
Zurück zum Zitat Goldschmidt N, Horowitz NA, Hefetz V et al (2019) Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse. Leuk Lymphoma 60:1–9. https://doi.org/10.1080/10428194.2018.1564823 CrossRef Goldschmidt N, Horowitz NA, Hefetz V et al (2019) Addition of high-dose methotrexate to standard treatment for patients with high-risk diffuse large B-cell lymphoma contributes to improved freedom from progression and survival but does not prevent central nervous system relapse. Leuk Lymphoma 60:1–9. https://​doi.​org/​10.​1080/​10428194.​2018.​1564823 CrossRef
Metadaten
Titel
Evaluation of cerebrospinal clonal gene rearrangement in newly diagnosed non-Hodgkin’s lymphoma patients
verfasst von
Boaz Nachmias
Veronica Sandler
Elena Slyusarevsky
Galina Pogrebijski
Svetlana Kritchevsky
Dina Ben-Yehuda
Neta Goldschmidt
Moshe E. Gatt
Publikationsdatum
12.09.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 11/2019
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-019-03798-5

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