Serious cutaneous toxicity following ifosfamide, gemcitabine and vinorelbine therapy in a patient with relapsed Hodgkin lymphoma and ichthyosis

Authors: H. Mociková 1;  E. Konířová 1;  J. Stříteský 2
Authors‘ workplace: Univerzita Karlova v Praze, 1. lékařská fakulta, I. interní klinika – klinika hematologie VFN 1;  Univerzita Karlova v Praze, Ústav patologie 1. LF 2
Published in: Čas. Lék. čes. 2009; 148: 434-437
Category: Case Report


Nodular sclerosis classical Hodgkin lymphoma, clinical stage IIB with cervical and axillar lymph node involvement was histologically proven in a 47-year-old male patient with a long-lasting history of ichthyosis. Skin histology revealed only nonspecific lichenoid inflammatory changes. Patient was treated with six cycles of combined chemotherapy: doxorubicin, bleomycin, vinblastine and dacarbazine. 15 months after initial treatment the first relapse of Hodgkin lymphoma was histologically confirmed and involvement of lymph nodes was identical with initial staging. Patient was successfully treated with six cycles of chemotherapy: ifosfamide, carboplatinum and etoposide followed by radiotherapy. The above mentioned chemotherapies did not cause serious cutaneous toxicity. 4 years after previous therapy the second relapse of Hodgkin lymphoma occurred with axillar and inguinal lymph node involvement. Skin histology confirmed nonspecific lichenoid inflammatory changes. Patient was treated with three cycles of combined chemotherapy: ifosfamide, gemcitabine, vinorelbine and prednisone. This chemotherapy caused neutropenia WHO grade 4 after each cycle and a serious diffuse toxoallergic cutaneous reaction with bullous erythema developed. Several skin lesions fulfilled criteria for cutaneous WHO grade 3 and 4 toxicity. We assumed that combined toxic effect of gemcitabine and vinorelbine resulted in serious cutaneous toxicity under pre-existing condition of diffuse ichthyosis. The cutaneous toxicity subsequently resolved and residual lymph nodes were irradiated.

Key words:
Hodgkin lymphoma, ichthyosis, gemcitabine, vinorelbine.


1. Oki Y, Younes A. Current role of gemcitabine in the treatment of Hodgkin lymphoma. Leuk Lymphoma 2008; 49: 883–889.

2. Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin‘s lymphoma. Haematologica 2007; 92: 35–41.

3. Rizos E, Milionis HJ, Pavlidis N, Elisaf MS. Acquired icthyosis: a paraneoplastic skin manifestation of Hodgkin‘s disease. Lancet Oncol 2002; 3: 727.

4. Ennibi K, Rabhi M, Al Bouzidi A, et al. Acquired ichthyosis revealing a Hodgkin‘s disease. Rev Med Interne 2008; 29: 418–420.

5. Introcaso CE, Kantor J, Porter DL, Junkins-Hopkins JM. Cutaneous Hodgkin‘s disease J Am Acad Dermatol 2008; 58: 295–298.

6. Rubenstein M, Duvic M. Cutaneous manifestations of Hodgkin‘s disease. Int J Dermatol 2006; 45: 251–256.

7. Jain S, Nigam S, Kumar N, Reddy BS. Cutaneous relapse in Hodgkin‘s disease: a case report. Acta Cytol 2005; 49: 191–194.

8. Guitart J, Fretzin D. Skin as the primary site of Hodgkin‘s disease: a case report of primary cutaneous Hodgkin‘s disease and review of its relationship with non-Hodgkin‘s lymphoma Am J Dermatopathol 1998; 20: 218–222.

9. Pagliaro JA, White SI. Specific skin lesions occurring in a patient with Hodgkin‘s lymphoma. Australas J Dermatol 1999; 40: 41–43.

10. Estines O, Grosieux-Dauger C, Derancourt C, et al. Paraneoplastic acquired ichthyosis revealing non-Hodgkin’s lymphoma. Ann Dermatol Venereol 2001; 128: 31–34.

11. Rabhi M, Ennibi K, Harket A, et al. Acquired ichthyosis disclosing non-Hodgkin’s malignant lymphoma. Internal Medicine 2007; 46: 397–399.

12. Ghislain PD, Roussel S, Marot L, et al. Acquired ichthyosis disclosing Hodgkin‘s disease. Simultaneous recurrence. Presse Med 2002; 31: 1126–1128.

13. Milionis HJ, Elisaf MS. Psoriasiform lesions as paraneoplastic manifestation in Hodgkin’s disease. Ann Oncol 1998; 9: 449–452.

14. Batista MD, Takano D, Lopes RD, et al. Paraneoplastic pemfigus associated with non-Hodgkin lymphoma. Dermatol Online J 2008; 14: 11.

15. Lucker GP, Steijlen PM. Acrokeratosis paraneoplastica (Bazex syndrome) occurring with acquired ichthyosis in Hodgkin‘s disease. Br J Dermatol 1995; 133: 322–325.

16. Simon Z, Tarr T, Tóth L, et al. Cutaneous vasculitis as an initiating paraneoplastic symptom in Hodgkin lymphoma. Rheumatol Int 2008; 28: 719–723.

17. Todd T, Raj S, Camilleri D. Intermediate dose gemcitabine-cisplatin combination chemotherapy without treatment delay for cytopenia followed by autografting – a new standard of care in relapsed or refractory Hodgkin lymphoma? Ann Hematol 2009 May 6. doi10.1007/s00277-009-0734-6.

18. Oki Y, Pro B, Fayad LE, et al. Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma. Cancer 2008; 112: 831–836.

19. Validire P, Fermé C, Brice P, et al. A multicenter study of gemcitabine-containing regimen in relapsed or refractory Hodgkin‘s lymphoma patients. Anticancer Drugs 2008; 19: 309–315.

20. Mendler JH, Kelly J, Voci S, et al. Bortezomib and gemcitabine in relapsed or refractory Hodgkin‘s lymphoma. Ann Oncol 2008; 19: 1759–1764.

21. Cashen AF, Bartlett NL. Salvage regimens for Hodgkin lymphoma. Clin Adv Hematol Oncol 2008; 6: 517–524.

22. Bartlett NL, Niedzwiecki D, Johnson JL, et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol 2007; 18: 1071–1079.

23. Müller-Beissenhirtz H, Kasper C, Nückel H, Dührsen U. Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma, results of a phase II single center study. Ann Hematol 2005; 84: 796–801.

24. Chau I, Watkins D, Cunningham D. Gemcitabine and its combinations in the treatment of malignant lymphoma. Clin Lymphoma 2002; 3: 97–104.

25. Cole PD, Schwartz CL, Drachtman RA, et al. Phase II study of weekly gemcitabine and vinorelbine for children with recurrent or refractory Hodgkinęs disease: A Children’s Oncology Group report. J Clin Oncol 2009; 27: 1456–1461.

26. Brandes A, Reichmann U, Plasswilm L, Bamberg M. Time- and dose-limiting erysipeloid rash confined to ares of lymphedema following treatment with gemcitabine a report of three cases. Anticancer drugs 2000; 11: 15–17.

27. Imen A, Amal K, Ines Z. Bullous dermatosis associated with gemcitabine therapy for non-small-cell lung carcinoma. Respir Med 2006; 100: 1463–1465.

28. Bishton M, Lush RJ, Byrne JL. Ifosfamide, etoposide and epirubicin is an effective combined salvage and peripheral blood stem cell mobilisation regimen for transplant-eligible patients with non-Hodgkin lymphoma and Hodgkin disease. Br J Hematol 2007; 136: 752–761.

29. Bonfante V, Viviani S, Devizzi L, et al. High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin’s disease. Eur J Haematol Suppl 2001; 64: 51–55.

30. Maubec E, Oberlin O, Belhadi K, Roujeau JC. Subcutaneous inflammatory edema induced by MINE chemotherapy. Ann Dermatol Venereol 2001; 128: 534–537.

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