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DOI: 10.1055/s-2001-12093
Neuropathie durch Hochdosis-Chemotherapie mit Cyclophosphamid bei Morbus Werlhof
Neuropathy after cyclophosphamide high dose chemotherapy in a Morbus Werlhof patientPublication History
Publication Date:
31 December 2001 (online)
Anamnese und klinischer Befund: Eine 24-jährige Patientin litt seit 20 Jahren an einer autoimmunen idiopathischen thrombozytopenischen Purpura (M.Werlhof) und war erfolglos mit Glukokortikoiden, Splenektomie, Immunglobulinen, Immunsuppressiva und Vincristin behandelt worden. Nach einem zweiten Cyclophosphamid-Behandlungszyklus und autologer peripherer Stammzelltransplantation entwickelten sich akut Symptome einer distal betonten, peripheren sensorischen und motorischen Polyneuropathie.
Untersuchungen: Bei Aufnahme zeigten sich bei guten Allgemeinzustand ausgeprägte medikamentös induzierte cushingoide Veränderungen und generalisierte petechiale Blutungen bei 1000 Thrombozyten /µl.
Therapie und Verlauf: Nach Gabe von 2,5 g/m 2 Cyclophosphamid und Stammzelltransplantation entwickelte sich innerhalb einer Woche eine distale Polyneuropathie mit Blasenentleerungsstörung. Durch Computer- und Kernspintomographie konnten Blutungen oder Hirnschädigungen ausgeschlossen werden. Die Beschwerden besserten sich auch unter Therapie mit Steroiden, Carbamazepin und Amitriptylin nur langsam. Bei unveränderter Thrombozytopenie starb die Patientin 4 Monate später an einer akuten Hirnblutung.
Folgerung: Als wahrscheinliche Genese der Polyneuropathie wird eine direkte Neurotoxizität von Cyclophosphamid angesehen; die Kasuistik demonstriert einen möglichen kausalen Zusammenhang.
Neuropathy after cyclophosphamide high dose chemotherapy in a Morbus Werlhof patient
Personal history: A 24 year old patient with longstanding autoimmune idiopathic thrombocytopenic purpura (M. Werlhof) was treated with glucocorticoids, immunoglobulins, splenectomy, immunosuppression and vincristin without lasting success. After a second treatment cycle with cyclosphosphamide and autologous peripheral stem cell transplantation she acutely develpod symptoms of a peripheral sensoric and motoric polyneuro-pathy.
Medical examination: At admission she was in good general health, but had steroid-induced Cushing‘s symptoms, generalized petechial bleeding and thrombocytopenia (1000/µl).
Therapy and course: After 2.5 g/m2 cyclophosphamide and stem cell transplantation distally pronounced polyneuropathy developed within a week with bladder insufficiency. Major bleeding or brain damage were excluded, and symptoms only partially reversed when treated with steroids, carbamazepine and amitriptyline. Thrombocytopenia persisted, and the patient died 4 month later from acute brain hemorrhage.
Conclusions: Direct neurotoxicity has to be assumed as the likely causative agent in this case, illustrating the possibility of peripheral neuropathic lesions by high dose cyclophosphamide treatment.
Literatur
- 1 Atra A, Gerrard M, Hobson R. et al . Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non Hodgkin‘s lymphoma (B-NHL) - results of the UKCCSG 9003 protocol. Br J Cancer. 1998; 77 2281-2285
- 2 Ayash L J, Elias A, Ibrahim H. et al . High dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma. J Clin Oncol. 1998; 16 1000-1007
- 3 Bird J M, Cummins D, Machin S J. Cyclophosphamide for chronic relapsing thrombotic thrombocytopenic purpura. Lancet. 1990; 336 565-566
- 4 Brodsky R A. Biology and management of acquired severe aplastic anemia. Curr Opin Oncol. 1998; 10 95-99
- 5 Cagnoni P J, Nieto Y, Shpall E J. et al . High-dose chemotherapy with autologous hematopoietic progenitor-cell support as part of combined modality therapy in patients with inflammatory breast cancer. J Clin Oncol. 1998; 16 1661-1668
- 6 Grimbacher B, Huber M, Kalden P. et al . Successful treatment of gastronintestinal vasculitis due to systemic lupus erythematosus with intravenous pulse cyclophosphamide: A clinical case report and review of the literature. Br J Rheumatol. 1998; 37 1023-1028
- 7 Guglielmotti A, Aquilini L, D‘Onofrio E. et al . Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice. Clin Exp Rheumatol. 1998; 16 149-154
- 8 Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am. 1998; 27 927-943
- 9 Kalaycio M, Mendez Z, Pohlman B. et al. . Continuous-infusion granisetron compared to ondansetron for the prevention of nausea and vomiting after high-dose chemotherapy. J Cancer Res Clin Oncol. 1998; 124 265-9
- 10 Kushner B H, Heller G, Cheung N K. et al . High risk of leukemia after short-term dose-intensive chemotherapy in young patients with solid tumors. J Clin Oncol. 1998; 16 3016-3020
- 11 Margolin B K, Doroshow J H, Ahn C. et al . Treatment of germ cell cancer with two cycles of high-dose ifosfamide, carboplatin, and etoposide with autologous stem-cell support. J Clin Oncol. 1996; 14 2631-2637
- 12 Marit G, Thiessard F, Faberes C. et al . Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study. Leukemia. 1998; 12 1447-1456
- 13 McCowage G B, Friedman H S, Mohgrabi A. et al . Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. Med Pediatr Oncol. 1998; 30 75-80
- 14 Ponticelli C, Edefonti A, Ghio L. et al . Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. Nephrol Dial Transplant. 1993; 8 1326-1332
- 15 Schagen S B, van Dam F SAM, Muller M J. et al . Cognitive deficits after postoperative adjuvant chemotherapy for breast cancer. Cancer. 1999; 85 640-650
- 16 Sommerkamp H. Hemorrhagic cystitis after high dose chemotherapy. An interdisciplinary problem. Urologe. 1998; 37 516-521
- 17 Weaver C H, West W, Schwartzberg L. et al . The rationale for performing autologous peripheral bloood stem cell transplants in community cancer centers. Oncologist. 1998; 3 346-353
Korrespondenz
PD Dr. med. Dipl. Chem. Johannes Schulze
Institut für Medizinische Biometrie und Statistik der
Medizinischen Universität Lübeck
Ratzeburger Allee 160
23538 Lübeck
Phone: 0451/500-2784
Fax: 0451/500-2999
Email: Johannes.Schulze@medinf.mu-luebeck.de