Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL
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The feasibility and efficacy of cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL (intermediate DLBCL/BL) have never been reported. The effects of adding rituximab to CODOX-M/IVAC have not been published either. Fifteen consecutive patients with a median age of 39 years were treated with modified CODOX-M/IVAC regimen (particularly, reducing the dose of methotrexate to 3 g/m2) with or without rituximab at our institution. Although all patients developed grade 4 neutropenia and grade 3/4 thrombocytopenia/anemia, 93% had febrile neutropenia, 60% showed transaminase elevation, and 40% had mucositis/stomatitis (all grade 3), there were no treatment-related deaths. Two of nine patients treated with rituximab developed biphasic late-onset neutropenia. Thirteen patients (87%) showed complete responses. The remaining two patients had refractory disease; one had presented with peritoneal dissemination and complex chromosomal abnormalities, while the other had double IGH–MYC and IGH–BCL2 translocations. The estimated 5-year overall and progression-free survival were 87% each, with a median follow-up of 74 months. In conclusion, our modified CODOX-M/IVAC regimen is well tolerated and highly effective in Japanese adult patients with BL and intermediate DLBCL/BL, warranting a larger study for confirmation.
KeywordsCODOX-M/IVAC Burkitt lymphoma Burkitt-like lymphoma Rituximab
This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (to T.W. and K.T.).
Conflict of interest
- 1.Diebold J, Jaffe ES, Raphael M, Warnke RA. Burkitt lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumours. Pathology and genetics: tumours of hematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer; 2001. p. 181–4.Google Scholar
- 2.Leoncini L, Raphel M, Stein H, Harris NL, Jaffe ES, Kluin PM. Burkitt lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of tumours, WHO classification of tumours of hematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer; 2008. p. 262–4.Google Scholar
- 4.The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997; 89:3909–18.Google Scholar
- 6.Kluin PM, Harris NL, Stein H, Leoncini L, Raphael M, Campo E, et al. B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. World Health Organization classification of tumours, WHO classification of tumours of hematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer; 2008. p. 265–6.Google Scholar
- 9.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 leukaemia with high-dose fractionated cyclophosphamide and co-ordinated high-dose methotrexate and cytarabine. J Clin Oncol. 1986;4:1732–9.PubMedGoogle Scholar
- 10.Patte C, Philip T, Rodary C, Zucker JM, Behrendt H, Gentet JC, et al. High survival rate in advanced-stage B-cell lymphomas and leukaemia’s without CNS involvement with a short intensive polychemotherapy: results from the French Pediatric Oncology Society of a randomized trial of 216 children. J Clin Oncol. 1991;9:123–32.PubMedGoogle Scholar
- 19.Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, et al. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY 10 trial). Blood. 2008;112:2248–60.PubMedCrossRefGoogle Scholar
- 21.Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large B-cell lymphoma; a randomized controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–91.PubMedCrossRefGoogle Scholar
- 22.Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for the patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone; results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106:3725–32.PubMedCrossRefGoogle Scholar
- 26.Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports (RADAR) project. Blood. 2009;113:4834–40.PubMedCrossRefGoogle Scholar
- 29.Abramson JS, Barnes JA, Toomey CE, Jacobsen ED, Armand P, Takvorian T, et al. Rituximab added to CODOX-M/IVAC is highly effective in HIV-negative and HIV-positive Burkitt lymphoma. Blood. 2008; 112:abstract 3595.Google Scholar
- 30.Mohamedbhai SG, Lowry L, Goldstone AH, Linch DC, Ardeshna KM. Rituximab in combination with CODOX-M/IVAC: toxicity and efficacy in 17 adults with non-HIV related B-cell non-Hodgkin lymphomas with >95% proliferation index. Br J Haematol. 2009;145(1):36.Google Scholar
- 31.Barnes JA, LaCasce AS, Feng Y, Toomey C, Neuberg D, Hochberg EP, et al. Rituximab added to CODOX-M/IVAC has no clear benefit compared to CODOX-M/IVAC alone in adult patients with Burkitt lymphoma. Blood. 2009; 114:abstract 1667.Google Scholar
- 37.NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0. (Cited 9 Aug 2006) Available from http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.
- 38.The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 1993; 329:987–94.Google Scholar