Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience

Rudresha H. A.; Tamojit Chaudhuri; Kuntegowdanahalli C Lakshmaiah; Govind Babu; K. N. Lokesh; L. K. Rajeev

doi:10.4103/2278-330X.221341

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Original Article : Leukemia & Lymphoma

06 (

); 165-168

doi:

10.4103/2278-330X.221341

Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience

Rudresha H. A.¹, Tamojit Chaudhuri^1,, Kuntegowdanahalli C Lakshmaiah¹, Govind Babu¹, K. N. Lokesh¹, L. K. Rajeev¹

1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

*Corresponding author: Dr. Tamojit Chaudhuri. tamojit.cnmc@gmail.com

Published: 2020-12-22

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Background: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin's lymphoma which occurs in both immunocompromised and immunocompetent patients. It has an overall poor prognosis in spite of a multimodality treatment approach including chemotherapy and radiotherapy. This study attempts to further delineate the clinicopathological, immunohistochemical, and radiological profile of PCNSL at Kidwai Memorial Institute of Oncology, Karnataka, India. Materials and Methods: All the pathologically confirmed PCNSL cases between January 2010 and June 2016, at our center, were analyzed retrospectively. The influence of potential prognostic parameters on overall survival (OS) was investigated by log-rank test and Cox regression analysis. Results: Of the 26 PCNSL patients, 17 (65.3%) were males. Median age at diagnosis was 42.5 years. None of the patients had HIV or Epstein-Barr virus positivity and only four patients (15.4%) had B-symptoms. The most common location in the brain was cerebral hemispheres in 15 patients (57%) and 10 patients (38.5%) had multiple intracranial lesions. Histologically, all were diffuse large B-cell lymphomas, except one case of anaplastic large cell lymphoma. Immunohistochemically, 18 patients (69%) had MUM 1 positivity and 20 cases (77%) belonged to nongerminal center subtype. DeAngelis protocol was followed in 24 patients (92%), and among this cohort, Memorial Sloan Kettering Cancer Center Class 1 (n = 17) and Class 2 (n = 7) patients had a median OS of 25 months and 11 months, respectively. Conclusion: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify more effective primary chemotherapy regimens to further improve the treatment outcome.

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References

Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.
Ferreri AJ, Blay JY, Reni M, Pasini F, Gubkin A, Tirelli U, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas. Ann Oncol 2002;13:531-8.
Zhang X, Chen QH, Farmer P, Nasim M, Demopoulos A, Devoe C, et al. Central nervous system lymphoma in immunocompetent patients: The North Shore-Long Island Jewish Health System experience. J Clin Neurosci 2013;20:75-9.
Raoux D, Duband S, Forest F, Trombert B, Chambonnière ML, Dumollard JM, et al. Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance. Neuropathology 2010;30:232-40.
Miller DC, Hochberg FH, Harris NL, Gruber ML, Louis DN, Cohen H. Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989. Cancer 1994;74:1383-97.
Cheung MC, Pantanowitz L, Dezube BJ. AIDS-related malignancies: Emerging challenges in the era of highly active antiretroviral therapy. Oncologist 2005;10:412-26.
Pasricha S, Gupta A, Gawande J, Trivedi P, Patel D. Primary central nervous system lymphoma: A study of clinicopathological features and trend in Western India. Indian J Cancer 2011;48:199-203.
Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 2006;24:4570-4.
Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, et al. Primary central nervous system lymphoma: The Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 2006;24:5711-5.
DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002;20:4643-8.
Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 2013;31:3061-8.
Sierra del Rio M, Rousseau A, Soussain C, Ricard D, Hoang-Xuan K. Primary CNS lymphoma in immunocompetent patients. Oncologist 2009;14:526-39.
Gualco G, Weiss LM, Barber GN, Bacchi CE. Diffuse large B-cell lymphoma involving the central nervous system. Int J Surg Pathol 2011;19:44-50.
Makhdoomi R, Nayil K, Rayees A, Kirmani A, Ramzan A, Khalil MB, et al. Primary CNS lymphoma in immunocompetent: A review of literature and our experience from Kashmir. Turk Neurosurg 2011;21:39-47.
Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: The International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003;21:266-72.
Bessell EM, Graus F, Lopez-Guillermo A, Lewis SA, Villa S, Verger E, et al. Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: Long-term survival and prognostic factors. Int J Radiat Oncol Biol Phys 2004;59:501-8.
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103:275-82.
Hattab EM, Martin SE, Al-Khatib SM, Kupsky WJ, Vance GH, Stohler RA, et al. Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: A retrospective analysis of 31 cases. Mod Pathol 2010;23:235-43.
Camilleri-Broët S, Crinière E, Broët P, Delwail V, Mokhtari K, Moreau A, et al. A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: Analysis of 83 cases. Blood 2006;107:190-6.
Song MK, Chung JS, Joo YD, Lee SM, Oh SY, Shin DH, et al. Clinical importance of Bcl-6-positive non-deep-site involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma. J Neurooncol 2011;104:825-31.
Jahnke K, Korfel A, O'Neill BP, Blay JY, Abrey LE, Martus P, et al. International study on low-grade primary central nervous system lymphoma. Ann Neurol 2006;59:755-62.
Tomlinson FH, Kurtin PJ, Suman VJ, Scheithauer BW, O'Fallon JR, Kelly PJ, et al. Primary intracerebral malignant lymphoma: A clinicopathological study of 89 patients. J Neurosurg 1995;82:558-66.
Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, et al. Non-Hodgkin's lymphoma of the brain: Can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 1992;23:9-17.
Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP, et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: Cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 2000;89:1359-70.
Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: A report of NABTT 96-07. J Clin Oncol 2003;21:1044-9.

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[1] Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: Evolving concepts and practical applications. Blood 2011;117:5019-32.

[2] Ferreri AJ, Blay JY, Reni M, Pasini F, Gubkin A, Tirelli U, et al. Relevance of intraocular involvement in the management of primary central nervous system lymphomas. Ann Oncol 2002;13:531-8.

[3] Zhang X, Chen QH, Farmer P, Nasim M, Demopoulos A, Devoe C, et al. Central nervous system lymphoma in immunocompetent patients: The North Shore-Long Island Jewish Health System experience. J Clin Neurosci 2013;20:75-9.

[4] Raoux D, Duband S, Forest F, Trombert B, Chambonnière ML, Dumollard JM, et al. Primary central nervous system lymphoma: Immunohistochemical profile and prognostic significance. Neuropathology 2010;30:232-40.

[5] Miller DC, Hochberg FH, Harris NL, Gruber ML, Louis DN, Cohen H. Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts General Hospital experience 1958-1989. Cancer 1994;74:1383-97.

[6] Cheung MC, Pantanowitz L, Dezube BJ. AIDS-related malignancies: Emerging challenges in the era of highly active antiretroviral therapy. Oncologist 2005;10:412-26.

[7] Pasricha S, Gupta A, Gawande J, Trivedi P, Patel D. Primary central nervous system lymphoma: A study of clinicopathological features and trend in Western India. Indian J Cancer 2011;48:199-203.

[8] Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 2006;24:4570-4.

[9] Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, et al. Primary central nervous system lymphoma: The Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 2006;24:5711-5.

[10] DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002;20:4643-8.

[11] Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 2013;31:3061-8.

[12] Sierra del Rio M, Rousseau A, Soussain C, Ricard D, Hoang-Xuan K. Primary CNS lymphoma in immunocompetent patients. Oncologist 2009;14:526-39.

[13] Gualco G, Weiss LM, Barber GN, Bacchi CE. Diffuse large B-cell lymphoma involving the central nervous system. Int J Surg Pathol 2011;19:44-50.

[14] Makhdoomi R, Nayil K, Rayees A, Kirmani A, Ramzan A, Khalil MB, et al. Primary CNS lymphoma in immunocompetent: A review of literature and our experience from Kashmir. Turk Neurosurg 2011;21:39-47.

[15] Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A, et al. Prognostic scoring system for primary CNS lymphomas: The International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003;21:266-72.

[16] Bessell EM, Graus F, Lopez-Guillermo A, Lewis SA, Villa S, Verger E, et al. Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: Long-term survival and prognostic factors. Int J Radiat Oncol Biol Phys 2004;59:501-8.

[17] Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103:275-82.

[18] Hattab EM, Martin SE, Al-Khatib SM, Kupsky WJ, Vance GH, Stohler RA, et al. Most primary central nervous system diffuse large B-cell lymphomas occurring in immunocompetent individuals belong to the nongerminal center subtype: A retrospective analysis of 31 cases. Mod Pathol 2010;23:235-43.

[19] Camilleri-Broët S, Crinière E, Broët P, Delwail V, Mokhtari K, Moreau A, et al. A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: Analysis of 83 cases. Blood 2006;107:190-6.

[20] Song MK, Chung JS, Joo YD, Lee SM, Oh SY, Shin DH, et al. Clinical importance of Bcl-6-positive non-deep-site involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma. J Neurooncol 2011;104:825-31.

[21] Jahnke K, Korfel A, O'Neill BP, Blay JY, Abrey LE, Martus P, et al. International study on low-grade primary central nervous system lymphoma. Ann Neurol 2006;59:755-62.

[22] Tomlinson FH, Kurtin PJ, Suman VJ, Scheithauer BW, O'Fallon JR, Kelly PJ, et al. Primary intracerebral malignant lymphoma: A clinicopathological study of 89 patients. J Neurosurg 1995;82:558-66.

[23] Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, et al. Non-Hodgkin's lymphoma of the brain: Can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 1992;23:9-17.

[24] Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP, et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: Cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 2000;89:1359-70.

[25] Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: A report of NABTT 96-07. J Clin Oncol 2003;21:1044-9.

Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience

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