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Leukemias and lymphomas: Treatment and prophylaxis of the central nervous system

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Central nervous system (CNS)-directed therapy is required for many acute leukemia patients and for nearly all aggressive or high-grade non-Hodgkin’s lymphoma patients as part of an overall chemotherapy plan for disease eradication. The CNS therapy decisions differ for overt disease treatment versus prophylactic treatment and take into consideration the type of leukemia or lymphoma, the age of the patient, and other prognostic factors. A variety of CNS-directed therapies are used for prevention or treatment of CNS disease in acute leukemias or aggressive lymphomas: intrathecal medications (cytosine arabinoside, methotrexate, or both in combination with hydrocortisone) with or without cranial or craniospinal irradiation, intrathecal medication only with intensive systemic chemotherapy, or high-dose chemotherapy specifically chosen for CNS penetrance. Any type of CNS-directed therapy, whether intrathecal chemotherapy, high-dose systemic chemotherapy, or irradiation, may cause acute or delayed (late) toxicity. Ongoing clinical trial research aims to reduce the risk of toxicity from CNS-directed therapy while preserving or improving treatment efficacy.

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References and Recommended Reading

  1. Bleyer WA, Poplack DA: Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries. Semin Oncol 1985, 12:131–148.

    PubMed  CAS  Google Scholar 

  2. Gokbuger N, Hoeltzer D: Meningeosis leukaemica in adult acute lymphoblastic leukemia. J Neurol Oncol 1998, 38:167–180.

    Article  Google Scholar 

  3. Keldsen N, Michalski W, Bentzen SM, et al.: Risk factors for central nervous system involvement in non-Hodgkin’s lymphoma. Acta Oncol 1996, 35:703–708.

    PubMed  CAS  Google Scholar 

  4. Horak ID, Kremer AB, Magrath IT: Management of histologically aggressive lymphomas with a high risk of CNS disease. Baillieres Clin Haematol 1996, 9:707–727.

    Article  PubMed  CAS  Google Scholar 

  5. Van Dongen-MelmanJE, De Groot A, Van DongenJJ, et al.: Cranial irradiation is the major cause of learning problems in children treated for leukemia and lymphoma: a comparative study. Leukemia 1997, 11:1197–2000. This is an older comparative study that well illustrates the long-term impact of cranial irradiation on survivors of leukemia and lymphoma.

    Article  PubMed  Google Scholar 

  6. Haddy TB, Adde MA, McCalla J, et al.: Late effects in long-term survivors of high-grade non-Hodgkin’s lymphomas. J Clin Oncol 1998, 16:2070–2079.

    PubMed  CAS  Google Scholar 

  7. Claviez A, Neubauer B, Link J, Scheppenheim R: Intracerebral hemorrhage as a late complication after CNS treatment of childhood lymphoma. Klin Padiatr 1998, 210:406–408.

    Article  PubMed  CAS  Google Scholar 

  8. Loning L, Zimmerman M, Reiter A, et al.: Secondary neoplasms subsequent to Berlin-Frankfurt-Munster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Blood 2000, 95:2770–2775.

    PubMed  CAS  Google Scholar 

  9. Margolin JF, Poplack DG: Acute lymphoblastic leukemia. In Principles and Practice of Pediatric Oncology, edn 5. Philadelphia: Lippincott Williams and Wilkins; 2005.

    Google Scholar 

  10. Sham RL, Phatak PD, Kouides PA, et al.: Hematologic neoplasia and the central nervous system. Am J Hematol 1999, 62:234–238.

    Article  PubMed  CAS  Google Scholar 

  11. Sheehan T, Cuthbert RJG, Parker AC: Central nervous system involvement in haematological malignancies. Clin Lab Haematol 1989, 11:331–338.

    PubMed  CAS  Google Scholar 

  12. Bruyn GAW, Zwetsloot CP, van NieuwkoopJA, et al.: Cranial nerve palsy as a presenting feature of secondary plasma cell leukemia. Cancer 1987, 60:906–909.

    Article  PubMed  CAS  Google Scholar 

  13. Pinkel D, Woo S: Prevention and treatment of meningeal leukemia in children. Blood 1994, 84:355–366.

    PubMed  CAS  Google Scholar 

  14. Nesbit ME, Sather H, Robinson LL, et al.: Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Cancer Res 1982, 42:674–680.

    PubMed  CAS  Google Scholar 

  15. Schrappe M, Reiter A, Riehm H: Prophylaxis and treatment of neoplastic meningeosis in childhood acute lymphoblastic leukemia. J Neurooncol 1998, 38:159–165.

    Article  PubMed  CAS  Google Scholar 

  16. Gibson BES, Wheatley K, Hann IM, et al.: Treatment strategy and long term results in paediatric patients treated in consecutive UK AML trials. Leukemia 2000, 19:2130–2138.

    Article  CAS  Google Scholar 

  17. Pui CH, Evans WE: Acute lymphoblastic leukemia. N Engl J Med 1998, 339:605–615.

    Article  PubMed  CAS  Google Scholar 

  18. Duval M, Suciu S, Ferster A, et al.: Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organization for Research and Treatment of Cancer-Children’s Leukemia group phase 3 trial. Blood 2002, 99:2734–2739.

    Article  PubMed  CAS  Google Scholar 

  19. Bostrom BC, Sensel MR, Sather H, et al.: Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard risk acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood 2003, 101:3809–3817. This large randomized trial demonstrates the impact that systemic drug therapy has on EFS as it relates to CNS relapse rates.

    Article  PubMed  CAS  Google Scholar 

  20. Mitchell CD, Richards SM, Kinsey SE, et al.: Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukemia: results of the UK Medical Research Council ALL97 randomized trial. Brit J Haematol 2005, 129:734–745.

    Article  CAS  Google Scholar 

  21. Nesbit ME, Robison LL, Littman PS, et al.: Presymptomatic central nervous system therapy in previously untreated childhood acute lymphoblastic leukemia: comparison of 1800 rad and 2400 rad. A report from the Children’s Cancer Study Group. Lancet 1981, 8218:461–466.

    Article  Google Scholar 

  22. Bleyer WA, Sather HN, Nickerson HJ, et al.: Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low risk childhood acute lymphoblastic leukemia: a report of the CCG 106 study by the Children’s Cancer Group. J Clin Oncol 1991, 9:1012–1021.

    PubMed  CAS  Google Scholar 

  23. Tubergen DG, Gilchrist GS, O’Brien RT, et al.: Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features. J Clin Oncol 1993, 11:527–537.

    PubMed  CAS  Google Scholar 

  24. Nachman JB, Sather HN, Sensel MG, et al.: Augmented post-induction therapy for children with high risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 1998, 338:1663–1671.

    Article  PubMed  CAS  Google Scholar 

  25. Cortes J, O’Brien SM, Pierce S, et al.: The value of high dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood 1995, 86:2091–2097.

    PubMed  CAS  Google Scholar 

  26. Kantarjian HM, O’Brien S, Smith TL, et al.: Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphoblastic leukemia. J Clin Oncol 2000, 18:547–561.

    PubMed  CAS  Google Scholar 

  27. Pui CH, Dahl GV, Kalwinsky DK, et al.: Central nervous system leukemia in children with acute nonlymphoblastic leukemia. Blood 1985, 66:1062–1067.

    PubMed  CAS  Google Scholar 

  28. Stevens RF, Hann IM, Wheatley K, et al.: Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukemia: results of the United Kingdom Medical Research Council’s 10th AML trial. Br J Haematol 1998, 101:130–140.

    Article  PubMed  CAS  Google Scholar 

  29. Woods WG, Neudorf S, Gold S, et al.: A comparison of allogeneic bone marrow transplant, autologous bone marrow transplant, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 2001, 97:56–62.

    Article  PubMed  CAS  Google Scholar 

  30. Creutzig U, Ritter J, Zimmermann M, et al.: Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Munster 93. J Clin Oncol 2001, 19:2705–2713.

    PubMed  CAS  Google Scholar 

  31. Abbott BL, Rubnitz JE, Tong X, et al.: Clinical significance of central nervous system involvement at diagnosis of pediatric acute myeloid leukemia: a single institution’s experience. Leukemia 2003, 17:2090–2096.

    Article  PubMed  CAS  Google Scholar 

  32. Bisschop MM, Revesz T, Bierings M, et al.: Extramedullary infiltrates at diagnosis have no prognostic significance in children with acute myeloid leukemia. Leukemia 2001, 15:46–49.

    Article  PubMed  CAS  Google Scholar 

  33. Cassileth PA, Sylvester LS, Bennett JM, et al.: High peripheral blast count in adult acute myelogenous leukemia is a primary risk factor for CNS leukemia. J Clin Oncol 1988, 6:495–500.

    PubMed  CAS  Google Scholar 

  34. Bishop JF, Matthews JP, Young GA, et al.: A randomized study of high dose cytarabine in induction in acute myeloid leukemia. Blood 1996, 87:1710–1717.

    PubMed  CAS  Google Scholar 

  35. Herzig RH: High dose ara-C in older adults with acute leukemia. Leukemia 1996, 10(Suppl 1):S10-S11.

    PubMed  Google Scholar 

  36. Castagnola C, Nozza A, Corso A, et al.: The value of combination therapy in adult acute myeloid leukemia with central nervous system involvement. Haematologica 1997, 82:577–580.

    PubMed  CAS  Google Scholar 

  37. Cairo MS, Sposto R, Perkins SL, et al.: Burkitt’s and Burkitt-like lymphoma in children and adolescents: a review of the Children’s Cancer Group experience. Brit J Haematol 2003, 120:660–670.

    Article  Google Scholar 

  38. Gururangan S, Sposto R, Cairo MS, et al.: Outcome of CNS disease at diagnosis in disseminated small noncleaved-cell lymphoma and B-cell leukemia: a Children’s Cancer Group Study. J Clin Oncol 2000, 18:2017–2025.

    PubMed  CAS  Google Scholar 

  39. Patte C, Michon J, Behrendt H, et al.: Results of the LMB 89 protocol for childhood B-cell lymphoma and leukemia (ALL). Study of the SFOP. Med Pediatr Oncol 1997, 27:358.

    Google Scholar 

  40. Reiter A, Schrappe M, Tiemann M, et al.: Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy; a report of the Berlin-Frankfurt-Munster Group trial NHL BFM 90. Blood 1999, 94:3294–3306.

    PubMed  CAS  Google Scholar 

  41. Sandlund JT, Murphy SB, Santana VM, et al.: CNS involvement in children with newly diagnosed non-Hodgkin’s lymphoma. J Clin Oncol 2000, 18:3018–3024.

    PubMed  CAS  Google Scholar 

  42. Burkhardt B, Woessmann W, Zimmerman M, et al.: Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol 2006, 24:491–499.

    Article  PubMed  Google Scholar 

  43. Cairo MS, Sposto R, Hoover-Regan M, et al.: Childhood and adolescent large cell lymphoma: a review of the Children’s Cancer Group experience. Am J Hematol 2003, 72:53–63.

    Article  PubMed  Google Scholar 

  44. Laver JH, Kraveka JM, Hutchinson RE, et al.: Advanced stage large cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate dose methotrexate and high dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol 2005, 23:541–547.

    Article  PubMed  CAS  Google Scholar 

  45. Blaney S, Poplack D: New cytotoxic drugs for intrathecal administration. J Neurooncol 1998, 38:219–223.

    Article  PubMed  CAS  Google Scholar 

  46. Gaynon PS, Angiolillo AL, Franklin JL, Reaman GH: Childhood Acute Lymphoblastic Leukemia in Cancer Medicine, edn 7. Hamilton, Ontario: Holland-Frei; 2006.

    Google Scholar 

  47. Blaney S, Balis F, Murphy R, et al.: A phase 1 study of intrathecal mafosfamide in patients with refractory meningeal malignancies. Proc Am Soc Clin Oncol 1992, 11:113.

    Google Scholar 

  48. Slavc I, Schuller E, Czech T, et al.: Intrathecal mafosfamide therapy for pediatric brain tumors with meningeal dissemination. J Neurooncol 1998, 38:213–218.

    Article  PubMed  CAS  Google Scholar 

  49. Slavc I, Schuller E, Falger J, et al.: Feasibility of longterm intraventricular therapy with mafosfamide and etoposide: experience in 26 children with disseminated malignant brain tumors. J Neurooncol 2003, 64:239–247.

    Article  PubMed  Google Scholar 

  50. Blaney S, Heideman R, Berg S, et al.: Phase 1 clinical trial of intrathecal topotecan in patients with neoplastic meningitis. J Clin Oncol 2003, 21:143–147.

    Article  PubMed  CAS  Google Scholar 

  51. Berg S, Balis F, Zimm S, et al.: Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies. J Clin Oncol 1992, 10:143–148.

    PubMed  CAS  Google Scholar 

  52. Sandor V, Stark-Vancs V, Peterson D, et al.: Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma. J Clin Oncol 1999, 16:3000–3006.

    Google Scholar 

  53. Soussain C, Suzan F, Hoang-Xuan K, et al.: Results of intensive chemotherapy followed by hematopoietic stem cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 2001, 19:742–749.

    PubMed  CAS  Google Scholar 

  54. Cheng T, Forsyth P, Chaudhry A, et al.: High-dose thiotepa, busulfan, cyclophosphamide and ASCT without whole-brain radiotherapy for poor prognosis primary CNS lymphoma. Bone Marrow Transplant 2003, 31:679–685.

    Article  PubMed  CAS  Google Scholar 

  55. Pels H, Schulz H, Manke O, et al.: Intraventricular and intravenous treatment of a patient with refractory primary CNS lymphoma using rituximab. J Neurooncol 2002, 59:213–216.

    Article  PubMed  CAS  Google Scholar 

  56. Pels H, Schultz H, Schlegel U, et al.: Treatment of CNS lymphoma with the anti-CD 20 antibody rituximab: experience with two cases and review of the literature. Onkologie 2003, 26:351–354.

    Article  PubMed  CAS  Google Scholar 

  57. Rubenstein JL, Combs D, Rosenberg J, et al.: Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood 2003, 101:466–468.

    Article  PubMed  CAS  Google Scholar 

  58. Bomgaars L, Geyer JR, Franklin J, et al.: Phase 1 trial of intrathecal liposomal cytarabine in children with neoplastic meningitis. J Clin Oncol 2004, 22:3916–3921.

    Article  PubMed  CAS  Google Scholar 

  59. Glantz MJ, LaFollette S, Jaeckle KA, et al.: Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999, 17:3110–3116. This is a well-conducted, small randomized trial that evaluates a novel CNS drug therapy against a standard CNS drug therapy, with positive results.

    PubMed  CAS  Google Scholar 

  60. Mosher AM, Adamson PC, Gillespie AJ, et al.: Intraventricular concentration times time (C x T) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma. Cancer 1999, 85:511–516.

    Article  Google Scholar 

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  1. Children’s Hospital Los Angeles, 4650 Sunset Boulevard, 90027, Los Angeles, CA, USA

    Janet L. Franklin MD, MPH

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  1. Janet L. Franklin MD, MPH
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  2. Jonathan Finlay MB, ChB
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Franklin, J.L., Finlay, J. Leukemias and lymphomas: Treatment and prophylaxis of the central nervous system. Curr Treat Options Neurol 8, 335–345 (2006). https://doi.org/10.1007/s11940-006-0023-9

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