Komplette Remission eines langjährig therapierefraktären
sekundär hochmalignen Non-Hodgkin-Lymphoms nach Therapie
mit Bendamustin und CD 20-Ak (Rituximab)

Zusammenfassung.

Hintergrund: Die CD 20-Antikörper (Ak)-Therapie gewinnt innerhalb der Behandlungskonzepte niedrigmaligner Non-Hodgkin-Lymphome zunehmend an Bedeutung. Für die Behandlung hochmaligner Non-Hodgkin-Lymphome mit dem CD 20-Ak liegen vergleichsweise wenige Daten vor. Wir beschreiben den Fall eines sechs Jahre bekannten, sekundär hochmalignen, ausgesprochen therapierefraktären, zentroblastischen B-Zell-Lymphoms im Stadium IV A, das nach CD 20-Ak Therapie in Kombination mit Bendamustin eine komplette Remission mit einem rezidivfreien Intervall von 22 Monaten aufweist. Kasuistik: Im Dezember 1994 wurde bei einem damals 47-jährigen Mann ein niedrigmalignes, zentrozytisch-zentroblastisches B-Zell-Lymphom diagnostiziert. Das erste Rezidiv im August 1995 zeigte eine Transformation in ein hochmalignes, zentroblastisches B-Zell-Lymphom. Die etablierten Rezidivtherapien führten lediglich zu einem einmaligen progressfreien Intervall von 6 Monaten unter Interferon α, bei einem ausgeprägten therapieinduzierten Nebenwirkungsspektrum im Sinne einer dosislimitierenden Panmyelopathie (WHO III), einer sensiblen peripheren Neuropathie (WHO II) sowie einer Thrombose der V. axillaris und V. brachialis (WHO III). Nach Applikation der anti-CD 20-Medikation in Standarddosierung in Kombination mit Bendamustin im Februar 1999 kann bei komplikationsloser Verträglichkeit 22 Monate nach Therapieende noch immer Rezidivfreiheit beobachtet werden. Schlussfolgerung: Der CD 20-Ak-Therapie scheint in der Behandlung therapierefraktärer hochmaligner Non-Hodgkin-Lymphome hinsichtlich des Erreichens einer länger währenden Remission eine Bedeutung zuzukommen.

Complete Remission of a Long Lasting Chemotherapy Refractory Secondarily High-grade B-cell Lymphoma after Therapy with Bendamustine and CD 20-antibody (Rituximab).

Background: During the last few years therapies using CD 20-antibodies have gained increasing importance for the treatment of low-grade non-Hodgkin's lymphomas. However, only limited data are available on CD 20-antibodies for treatment of high-grade non-Hodgkin's lymphomas. Here, we describe the case of a secondarily high-grade, therapy-refractory centroblastic B-cell-lymphoma, followed up for 6 years. After the therapy with CD 20-antibody in combination with bendamustin the patient has still a complete remission in the 22 months follow-up control. Case history: In december 1994 a 47-year old male patient has been diagnosed with a low-grade, centrocytic-centroblastic B-cell-lymphoma. The patient suffered the first relapse in August 1995 and the histology showed a transformation into a high-grade, centroblastic B-cell-lymphoma. Further relapses occured despite all established therapies. The longest disease-free survival of almost six months was achieved by interferon α. However, a variety of pronounced therapy-induced side effects has been observed, such as dose-limiting panmyelopathia (WHO III), peripheric neuropathia and a thrombosis of the V. axillaris and V. brachialis (WHO III). In february 1999 the standard scheme of anti-CD 20-medication in combination with bendamustin was applied without complications, achieving a complete remission which still persists 22 months after the end of therapy. Conclusion: The CD 20-antibody therapy may play a role for the treatment of refractory high-grade non-Hodgkin's lymphomas in order to achieve a longer lasting remission.

Schlüsselwörter:

Sekundär hochmalignes zentroblastisches Non-Hodgkin-Lymphom - B-Zell-Lymphom - CD 20-Antikörper - Komplette Remission

Key words:

Secondarily high-grade non-Hodgkin's lymphoma - B-cell lymphoma - CD 20-antibody - Complete remission

Literatur

• 1 Coiffer B, Haioun C, Ketterer N. et al . Rituximab (anti-CD 20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma. A multicenter phase II study.  Blood. 1998;  92 (6) 1927-1932
• 2 Colombat P, Salles G, Brousse N. et al . Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation.  Blood. 2001;  97 (1) 101-106
• 3 Czuczman M S. CHOP plus rituximab chemoimmuntherapy of indolent B-cell lymphoma.  Semin Oncol. 1999;  26 (5 Suppl 14) 88-96
• 4 Czuczman M S, Grillo-Lopez A J, Jonas C. et al . Chemotherapy of low-grade lymphoma with the anti-CD20 antibody IDEC-C2B8 in combination with CHOP chemotherapy.  Cancer Invest. 1996;  14 (Suppl 1) 59-61
• 5 Czuczman M S, Grillo-Lopez A J, White C A. et al . Treatment of patients with low-grade B-cell lymphoma with combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy.  J Clin Oncol. 1999;  17 (1) 268-276
• 6 Engert A, Trümper L. Phase-II Studie mit dem monoklonalen CD20-Antikörper (IDEC-C2B8) bei Patienten mit rezidivierten aggressiven B-Zell-Non-Hodgkin-Lymphomen. Köln; 1999
• 7 Feuring-Buske M, Kneba M, Unterhalt M. et al . IDEC-C2B8 (Rituximab) anti-CD20 antibody treatmant in relapsed advanced-stage follicular lymphomas: results of a phase-II study of the german low-grade lymphoma study group.  Ann Hematol Sep. 2000;  79 (9) 493-500
• 8 Foran J M, Cunningham D, Coiffier B. et al . Treatment of mantle-cell-lymphoma with Rituximab (chimeric monoclonal anti-CD 20 antibody): analysis of factors associated with response.  Ann Oncol. 2000;  1 (Suppl 1) 117-121
• 9 Foran J M, Rohatiner A Z, Cunningham D. et al . European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma.  J Clin Oncol. 2000;  18 (2) 317-324
• 10 Ghielmini M. et al . The effect of Rituximab on patients with follicular and mantle-cell lymphoma. Swiss Group for Clinical Cancer Research.  Ann Oncol. 2000;  1 (1 Suppl 1) 123-126
• 11 Hainsworth J D. Rituximab as first-line systemic therapy for patients with low-grade lymphoma.  Semin Oncol. 2000;  27 (6 Suppl 12) 25-29
• 12 Maloney D G, Grillo-Lopez A J, Bodkin D J. et al . IDEC-C2B8: results of phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.  J Clin Oncol Oct. 1997;  15 (10) 3266-3274
• 13 McLaughlin P. et al . Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.  J Clin Oncol. 1998;  16 (8) 2825-2833
• 14 Piro L D, White C A, Grillo-Lopez A J. et al . Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma.  Ann Oncol Jun. 1999;  10 (6) 655-661
• 15 Shan D, Ledbetter J A, Press O W. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies.  Blood. 1998;  91 1644-1652
• 16 Tedder T F, Engel P. CD20: a regulator of cell-cycle progression of B-lymphocytes.  Immunol Today. 1994;  15 450-454
• 17 Vose J M, Link B K, Grossbard M L. et al . Phase II Study of Rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's Lymphoma.  J Clin Oncol. 2001;  15;19 (2) 389-397
• 18 Weidmann E, Kim Z C, Geduldig K. et al . Palliative treatment of high-grade non-Hodgkin's lymphoma with Bendamustine: a phase II study.  Onkologie. 2000;  23 (7) Abstract 0582
• 19 Wilson W H. Chemotherapy sensitization by Rituximab: experimental and clinical evidence.  Semin Oncol Dec. 2000;  27 (6 Suppl 12) 30-36