J Korean Med Sci.  2012 Nov;27(11):1378-1384. 10.3346/jkms.2012.27.11.1378.

Successful Treatment of Primary Central Nervous System Lymphoma without Irradiation in Children: Single Center Experience

• Yoon JH
• Kang HJ
• Kim H
• Lee JW
• Park JD
• Park KD
• Shin HY
• Ahn HS

• KMID: 2157950
• DOI: http://doi.org/10.3346/jkms.2012.27.11.1378

Abstract

Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.

Keyword

Primary CNS Lymphoma; Children; Irradiation

MeSH Terms

Adolescent
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Central Nervous System Neoplasms/diagnosis/*drug therapy
Child
Child, Preschool
Cyclophosphamide/therapeutic use
Cytarabine/therapeutic use
Disease-Free Survival
Doxorubicin/therapeutic use
Etoposide/therapeutic use
Female
Humans
Hydrocortisone/therapeutic use
Infant
Leucovorin/therapeutic use
Lymphoma, Non-Hodgkin/diagnosis/*drug therapy
Male
Methotrexate/therapeutic use
Prednisone/therapeutic use
Recurrence
Retrospective Studies
Tomography, X-Ray Computed
Treatment Outcome
Vincristine/therapeutic use
Cytarabine
Doxorubicin
Etoposide
Cyclophosphamide
Hydrocortisone
Prednisone
Vincristine
Leucovorin
Methotrexate

Figure

• 

  Fig. 1 Event-free survival (EFS) of 6 patients with PCNS. Estimated 5-yr EFS rate is 83.3%.

• 

  Fig. 2 Patient 2 and patient 6 had their primary tumor in multiples site including cerebellum and third ventricle, and left parietal area, respectively. After systemic and intrathecal chemotherapy, their tumors were completely resolved.

Reference

1. Abla O, Sandlund JT, Sung L, Brock P, Corbett R, Kirov I, Griffin TC, Blaser S, Weitzman S. A case series of pediatric primary central nervous system lymphoma: favorable outcome without cranial irradiation. Pediatr Blood Cancer. 2006. 47:880–885.

2. Porto L, Kieslich M, Schwabe D, Yan B, Zanella FE, Lanfermann H. Central nervous system lymphoma in children. Pediatr Hematol Oncol. 2005. 22:235–246.

3. Abla O, Weitzman S. Primary central nervous system lymphoma in children. Neurosurg Focus. 2006. 21:e8.

4. Choi SY, Kim NK, Kwon SY, Han JW, Won SC, Lyu CJ. Experience of childhood non-Hodgkin lymphoma with central nervous system involvement at diagnosis. Clin Pediatr Hematol Oncol. 2007. 14:183–191.

5. Abla O, Weitzman S, Blay JY, O'Neill BP, Abrey LE, Neuwelt E, Doolittle ND, Baehring J, Pradhan K, Martin SE, et al. Primary CNS lymphoma in children and adolescents: a descriptive analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG). Clin Cancer Res. 2011. 17:346–352.

6. Blay JY, Ongolo-Zogo P, Sebban C, Carrie C, Thiesse P, Biron P. Primary cerebral lymphomas: unsolved issues regarding first line treatment, follow up, late neurological toxicity and treatment of relapses. Ann Oncol. 2000. 11:Suppl 1. 39–44.

7. Said JA, Waters BG, Cousens P, Stevens MM. Neuropsychological sequelae of central nervous system prophylaxis in survivors of childhood acute lymphoblastic leukemia. J Consult Clin Psychol. 1989. 57:251–256.

8. McAllister LD, Doolittle ND, Guastadisegni PE, Kraemer DF, Lacy CA, Crossen JR, Neuwelt EA. Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma. Neurosurgery. 2000. 46:51–60.

9. Gaynon PS, Steinherz PG, Bleyer WA, Ablin AR, Albo VC, Finklestein JZ, Grossman NJ, Novak LJ, Pyesmany AF, Reaman GH, et al. Improved therapy for children with acute lymphoblastic leukemia and unfavorable presenting features: a follow-up report of the Children's Cancer Group Study CCG-106. J Clin Oncol. 1993. 11:2234–2242.

10. Park ES, Kim H, Lee JW, Lim JY, Kang HJ, Park KD, Shin HY, Ahn HS. Treatment outcomes in children with Burkitt lymphoma and L3 acute lymphoblastic leukemia treated using the lymphoma malignancy B protocol at a single institution. Korean J Hematol. 2011. 46:96–102.

11. Yoon JH, Park JA, Kim EK, Kang HJ, Shin HY, Ahn HS. Improvement of induction remission rate by modifying the dose of idarubicin for relapsed childhood acute lymphoblastic leukemia. J Korean Med Sci. 2009. 24:281–288.

12. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006. 56:106–130.

13. Salzburg J, Burkhardt B, Zimmermann M, Wachowski O, Woessmann W, Oschlies I, Klapper W, Wacker HH, Ludwig WD, Niggli F, et al. Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Muenster group report. J Clin Oncol. 2007. 25:3915–3922.

14. Hochberg FH, Baehring JM, Hochberg EP. Primary CNS lymphoma. Nat Clin Pract Neurol. 2007. 3:24–35.

15. Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol. 1999. 43:199–201.

16. DeAngelis LM, Iwamoto FM. An update on therapy of primary central nervous system lymphoma. Hematology Am Soc Hematol Educ Program. 2006. 311–316.

17. Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, Thomson JW, Murray KJ. 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.

18. Cairo MS, Gerrard M, Sposto R, Auperin A, Pinkerton CR, Michon J, Weston C, Perkins SL, Raphael M, McCarthy K, et al. Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood. 2007. 109:2736–2743.

19. Abrey LE, Yahalom J, DeAngelis LM. Treatment for primary CNS lymphoma: the next step. J Clin Oncol. 2000. 18:3144–3150.

20. Watanabe T, Katayama Y, Yoshino A, Komine C, Yokoyama T, Fukushima T. Long-term remission of primary central nervous system lymphoma by intensified methotrexate chemotherapy. J Neurooncol. 2003. 63:87–95.

21. Ferreri AJ, Abrey LE, Blay JY, Borisch B, Hochman J, Neuwelt EA, Yahalom J, Zucca E, Cavalli F, Armitage J, et al. Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol. 2003. 21:2407–2414.

22. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomized phase 2 trial. Lancet. 2009. 374:1512–1520.

23. Ferreri AJ, Reni M, Pasini F, Calderoni A, Tirelli U, Pivnik A, Aondio GM, Ferrarese F, Gomez H, Ponzoni M, et al. A multicenter study of treatment of primary CNS lymphoma. Neurology. 2002. 58:1513–1520.

24. Pels H, Schmidt-Wolf IG, Glasmacher A, Schulz H, Engert A, Diehl V, Zellner A, Schackert G, Reichmann H, Kroschinsky F, et al. Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol. 2003. 21:4489–4495.

25. Khan RB, Shi W, Thaler HT, DeAngelis LM, Abrey LE. Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol. 2002. 58:175–178.

26. Sung KH, Lee EH, Kim YZ. Factors influencing the response to high dose methotrexate-based vincristine and procarbazine combination chemotherapy for primary central nervous system lymphoma. J Korean Med Sci. 2011. 26:551–560.

27. Hottinger AF, Iwamoto FM, Karimi S, Riedel E, Dantis J, Park J, Panageas KS, Lassman AB, Abrey LE, Fleisher M, et al. YKL-40 and MMP-9 as serum markers for patients with primary central nervous system lymphoma. Ann Neurol. 2011. 70:163–169.

28. Ferreri AJ, Reni M. Prognostic factors in primary central nervous system lymphomas. Hematol Oncol Clin North Am. 2005. 19:629–649.

29. Song MK, Chung JS, Joo YD, Lee SM, Oh SY, Shin DH, Yun EY, Kim SG, Seol YM, Shin HJ, et al. Clinical importance of Bcl-6-positive non-deepsite involvement in non-HIV-related primary central nervous system diffuse large B-cell lymphoma. J Neurooncol. 2011. 104:825–831.