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Therapy

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma

Leukemia volume 19, pages 945–952 (2005)Cite this article

Abstract

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15–64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50–116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

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References

  1. Jaffe ES, Harris NL, Stein H, Vardiman JW . World Health Organisation Classification of Tumours. Pathology and Genetics of Tumours of the Haematopoietic and Lymphoid Tissues. IARC WHO Classification of Tumours, (ed). Lyon: IARC Press, 2001.

    Google Scholar 

  2. Magrath IT, Janus C, Edwards BK, Spiegel R, Jaffe ES, Berard CW et al. An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults. Blood 1984; 63: 1102–1111.

    CAS  PubMed  Google Scholar 

  3. Bowman WP, Shuster JJ, Cook B, Griffin T, Behm F, Pullen J et al. Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study. J Clin Oncol 1996; 14: 1252–1261.

    Article  CAS  PubMed  Google Scholar 

  4. Patte C, Auperin A, Michon J, Behrendt H, Leverger G, Frappaz D et al. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001; 97: 3370–3379.

    Article  CAS  PubMed  Google Scholar 

  5. Murphy SB, Bowman WP, Abromowitch M, Mirro J, Ochs J, Rivera G et al. Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine. J Clin Oncol 1986; 4: 1732–1739.

    Article  CAS  PubMed  Google Scholar 

  6. Reiter A, Schrappe M, Parwaresch R, Henze G, Muller-Weihrich S, Sauter S et al. Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage – a report of the Berlin–Frankfurt–Munster Group. J Clin Oncol 1995; 13: 359–372.

    Article  CAS  PubMed  Google Scholar 

  7. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med 1993; 329: 987–994.

  8. Soussain C, Patte C, Ostronoff M, Delmer A, Rigal-Huguet F, Cambier N et al. Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols. Blood 1995; 85: 664–674.

    CAS  PubMed  Google Scholar 

  9. Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J et al. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol 1996; 14: 925–934.

    Article  CAS  PubMed  Google Scholar 

  10. Hoelzer D, Ludwig WD, Thiel E, Gassmann W, Loffler H, Fonatsch C et al. Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 1996; 87: 495–508.

    CAS  PubMed  Google Scholar 

  11. Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M et al. Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol 1999; 17: 2461–2470.

    Article  CAS  PubMed  Google Scholar 

  12. Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M et al. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 2001; 19: 4014–4022.

    Article  CAS  PubMed  Google Scholar 

  13. Levine AM, Forman SJ, Meyer PR, Koehler SC, Liebman H, Paganini-Hill A et al. Successful therapy of convoluted T-lymphoblastic lymphoma in the adult. Blood 1983; 61: 92–98.

    CAS  PubMed  Google Scholar 

  14. Coleman CN, Picozzi Jr VJ, Cox RS, McWhirter K, Weiss LM, Cohen JR et al. Treatment of lymphoblastic lymphoma in adults. J Clin Oncol 1986; 4: 1628–1637.

    Article  CAS  PubMed  Google Scholar 

  15. Slater DE, Mertelsmann R, Koziner B, Higgins C, McKenzie S, Schauer P et al. Lymphoblastic lymphoma in adults. J Clin Oncol 1986; 4: 57–67.

    Article  CAS  PubMed  Google Scholar 

  16. Hoelzer D, Gokbuget N, Digel W, Faak T, Kneba M, Reutzel R et al. Outcome of adult patients with T-lymphoblastic lymphoma treated according to protocols for acute lymphoblastic leukemia. Blood 2002; 99: 4379–4385.

    Article  CAS  PubMed  Google Scholar 

  17. Nademanee A, Schmidt GM, O'Donnell MR, Snyder DS, Parker PA, Stein A et al. High-dose chemoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy during first complete remission in adult patients with poor-risk aggressive lymphoma: a pilot study [see comments]. Blood 1992; 80: 1130–1134.

    CAS  PubMed  Google Scholar 

  18. Freedman AS, Takvorian T, Neuberg D, Mauch P, Rabinowe SN, Anderson KC et al. Autologous bone marrow trans-plantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study. J Clin Oncol 1993; 11: 931–936.

    Article  CAS  PubMed  Google Scholar 

  19. Verdonck LF, Dekker AW, de Gast GC, Lokhorst HM, Nieuwenhuis HK . Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission. J Clin Oncol 1992; 10: 644–646.

    Article  CAS  PubMed  Google Scholar 

  20. Santini G, Coser P, Chisesi T, Porcellini A, Sertoli R, Contu A et al. Autologous bone marrow transplantation for advanced stage adult lymphoblastic lymphoma in first complete remission. Report of the Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG). Ann Oncol 1991; 2 (Suppl 2): 181–185.

    Article  PubMed  Google Scholar 

  21. Milpied N, Ifrah N, Kuentz M, Maraninchi D, Colombat P, Blaise D et al. Bone marrow transplantation for adult poor prognosis lymphoblastic lymphoma in first complete remission. Br J Haematol 1989; 73: 82–87.

    Article  CAS  PubMed  Google Scholar 

  22. Sweetenham JW, Liberti G, Pearce R, Taghipour G, Santini G, Goldstone AH . High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European Group for Bone Marrow Transplantation. J Clin Oncol 1994; 12: 1358–1365.

    Article  CAS  PubMed  Google Scholar 

  23. Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Norbert P et al. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol 2002; 13: 1264–1274.

    Article  CAS  PubMed  Google Scholar 

  24. Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D et al. Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma 2004; 45: 761–767.

    Article  CAS  PubMed  Google Scholar 

  25. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML et al. A revised European-American classification of lymphoid neoplasms: A proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361–1392.

    CAS  PubMed  Google Scholar 

  26. Haralambieva E, Schuuring E, Rosati S, van Noesel C, Jansen P, Appel I et al. Interphase fluorescence in situ hybridization for detection of MYC/8q24 breakpoints on routine histologic sections: validation in Burkitt lymphomas from three geographic regions. Genes Chromosomes Cancer 2004; 40: 10–18.

    Article  CAS  PubMed  Google Scholar 

  27. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17: 1244–1253.

    Article  CAS  PubMed  Google Scholar 

  28. The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 1997; 89: 3909–3918.

  29. Braziel RM, Arber DA, Slovak ML, Gulley ML, Spier C, Kjeldsberg C et al. The Burkitt-like lymphomas: a Southwest Oncology Group study delineating phenotypic, genotypic, and clinical features. Blood 2001; 97: 3713–3720.

    Article  CAS  PubMed  Google Scholar 

  30. Au WY, Horsman DE, Gascoyne RD, Viswanatha DS, Klasa RJ, Connors JM . The spectrum of lymphoma with 8q24 aberrations: a clinical, pathological and cytogenetic study of 87 consecutive cases. Leuk Lymphoma 2004; 45: 519–528.

    Article  CAS  PubMed  Google Scholar 

  31. Murphy SB . Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol 1980; 7: 332–339.

    CAS  PubMed  Google Scholar 

  32. Bernstein JI, Coleman CN, Strickler JG, Dorfman RF, Rosenberg SA . Combined modality therapy for adults with small noncleaved cell lymphoma (Burkitt's and non-Burkitt's types). J Clin Oncol 1986; 4: 847–858.

    Article  CAS  PubMed  Google Scholar 

  33. Lopez TM, Hagemeister FB, McLaughlin P, Velasquez WS, Swan F, Redman JR et al. Small noncleaved cell lymphoma in adults: superior results for stages I-III disease. J Clin Oncol 1990; 8: 615–622.

    Article  CAS  PubMed  Google Scholar 

  34. McMaster ML, Greer JP, Greco FA, Johnson DH, Wolff SN, Hainsworth JD . Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. J Clin Oncol 1991; 9: 941–946.

    Article  CAS  PubMed  Google Scholar 

  35. Longo DL, Duffey PL, Jaffe ES, Raffeld M, Hubbard SM, Fisher RI et al. Diffuse small noncleaved-cell, non-Burkitt's lymphoma in adults: a high-grade lymphoma responsive to ProMACE-based combination chemotherapy. J Clin Oncol 1994; 12: 2153–2159.

    Article  CAS  PubMed  Google Scholar 

  36. Divine M, Lepage E, Briere J, Pautier P, Dupriez B, Lederlin P et al. Is the small non-cleaved-cell lymphoma histologic subtype a poor prognostic factor in adult patients? A case-controlled analysis. The Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 1996; 14: 240–248.

    Article  CAS  PubMed  Google Scholar 

  37. Nicola MD, Carlo-Stella C, Mariotti J, Devizzi L, Massimino M, Cabras A et al. High response rate and manageable toxicity with an intensive, short-term chemotherapy programme for Burkitt's lymphoma in adults. Br J Haematol 2004; 126: 815–820.

    Article  PubMed  Google Scholar 

  38. Reiter A, Schrappe M, Ludwig WD, Tiemann M, Parwaresch R, Zimmermann M et al. Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 2000; 95: 416–421.

    CAS  PubMed  Google Scholar 

  39. Le Gouill S, Lepretre S, Briere J, Morel P, Bouabdallah R, Raffoux E et al. Adult lymphoblastic lymphoma: a retrospective analysis of 92 patients under 61 years included in the LNH87/93 trials. Leukemia 2003; 17: 2220–2224.

    Article  CAS  PubMed  Google Scholar 

  40. Daenen S, van Imhoff GW, van den Berg E, de Kam PJ, Haaxma-Reiche H, Vellenga E et al. Improved outcome of adult acute lymphoblastic leukaemia by moderately intensified chemotherapy which includes a ‘pre-induction’ course for rapid tumour reduction: preliminary results on 66 patients. Br J Haematol 1998; 100: 273–282.

    Article  CAS  PubMed  Google Scholar 

  41. Sweetenham JW, Santini G, Qian W, Guelfi M, Schmitz N, Simnett S et al. High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group. J Clin Oncol 2001; 19: 2927–2936.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands

    G W van Imhoff & H C Kluin-Nelemans

  2. Hovon Data Center, Erasmus MC, Rotterdam, The Netherlands

    B van der Holt & L A M H Meulendijks

  3. Department of Hematology, University Medical Center Nijmegen St Radboud, Nijmegen, The Netherlands

    M A MacKenzie & J M M Raemaekers

  4. Department of Hematology, VU Medical Center, Amsterdam, The Netherlands

    G J Ossenkoppele

  5. Department of Internal Medicine, Leyenburg Hospital, The Hague, The Netherlands

    P W Wijermans

  6. Department of Internal Medicine, Meander MC, Amersfoort, The Netherlands

    M H H Kramer

  7. Department of Hematology, Erasmus MC, Rotterdam, The Netherlands

    M B van 't Veer & P Sonneveld

  8. Department of Hematology, Maastricht University Hospital, Maastricht, The Netherlands

    H C Schouten

  9. Department of Internal Medicine, Isala Clinics, Zwolle, The Netherlands

    M van Marwijk Kooy

  10. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands

    M H J van Oers

  11. Department of Pathology, Groningen University Hospital, Groningen, The Netherlands

    P M Kluin

  12. Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    L F Verdonck

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Correspondence to G W van Imhoff.

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From the Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands. For The Dutch–Belgian Hemato-Oncology Cooperative Group (HOVON). Supported by the Dutch Cancer Foundation, Koningin Wilhelmina Fonds.

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van Imhoff, G., van der Holt, B., MacKenzie, M. et al. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma. Leukemia 19, 945–952 (2005). https://doi.org/10.1038/sj.leu.2403733

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