Keio Bone Marrow Transplant Program, Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

Correspondence to: Dr T Mori, Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-6562, Japan

We describe a healthy peripheral blood stem cell (PBSC) donor who developed a cutaneous reaction, erythema exsudativum multiforme, during the administration of granulocyte colony-stimulating factor (G-CSF) for mobilization. The cutaneous lesions were located on his hips, apart from the site of G-CSF injection. Treatment with topical corticosteroid was commenced, and the lesions resolved completely within a week. Adverse cutaneous reactions induced by G-CSF have been reported infrequently in healthy donors. Further documentation of cases and their full evaluation will be of great importance for both physicians and PBSC donor. Bone Marrow Transplantation (2000) 26, 239-240.

granulocyte colony-stimulating factor; peripheral blood stem cell donor; erythema exsudativum multiforme; side-effect

Granulocyte colony-stimulating factor (G-CSF) has been widely used to ameliorate chemotherapy-induced neutropenia by promoting myeloid reconstitution. In addition, G-CSF-mobilized peripheral blood stem cells (PBSC) are becoming an acceptable alternative to marrow for both allogeneic and autologous hematopoietic stem cell transplantation. Although general anesthesia and multiple bone marrow aspiration are not required in PBSC donors, PBSC donation requires exposure to G-CSF and one or more leukapheresis sessions, which are not always without side-effects. Early side-effects related to the administration of G-CSF are usually minimal, and may include bone pain, headache, fatigue, insomnia and nausea.^1,2,3 In healthy individuals, adverse cutaneous reactions induced by G-CSF have been reported infrequently and their characteristics have not been well documented.^3,4,5 We describe our observation of a PBSC donor developing a G-CSF-associated cutaneous reaction which was not located at the site of injection of G-CSF.

Case report

A 40 year-old Japanese man underwent bone marrow harvest for his HLA-matched sister who suffered from chronic phase chronic myelogenous leukemia (CML). Four months later, the patient developed late graft rejection. We decided to treat her with a second transplant using G-CSF-mobilized allogeneic PBSC from the same donor. The donor's past medical history was unremarkable in terms of any illnesses, including autoimmune diseases. After informed consent was obtained, the donor received G-CSF (lenograstim) subcutaneously at a dose of 5 g/kg every 12 h for 5 days. G-CSF was injected into both shoulders alternately. On the 3rd day after starting G-CSF, the donor started complaining of fever and itchy skin eruptions on his hips (Figure 1). The eruption was clinically diagnosed as erythema exsudativum multiforme by dermatologists. G-CSF was continued. On the 5th day, WBC count rose to 43.8 ´ 10⁹/l, and the donor underwent leukapheresis on the 5th and 6th days of G-CSF therapy. Bacterial and fungal cultures were performed and were negative. Topical corticosteroid treatment with difluprednate was initiated, and the eruptions completely resolved within a week. Histological evaluation of the skin eruptions was not performed.

Discussion

Several adverse cutaneous reactions have been reported in response to G-CSF. They have included pyoderma gangrenosum, folliculitis and vasculitis, in addition to local reactions at the site of injection.^6,7,8 However, the association between G-CSF and cutaneous reactions is usually difficult to assess in patients because those who receive G-CSF are likely to have complex illnesses and to take other medications.^8,9,10 However, if such reactions are observed in a healthy individual receiving G-CSF, such as a PBSC donor, they are most likely due to G-CSF and could be evaluated as its adverse effects. In such healthy individuals, in addition to local cutaneous reactions at the site of injection, some cutaneous manifestations have also been reported.^3,4,5 However, the clinical characteristics of the skin lesions have not been described in detail. In the present case, the donor developed erythema exsudativum multiforme while receiving no other medications except G-CSF, and the lesion resolved after discontinuation of G-CSF. Thus, the development of erythema exsudativum multiforme in this donor was considered a skin reaction due to G-CSF. The pathogenetic mechanism of erythema exsudativum multiforme in this donor remains unclear. It could have been due to an allergic reaction to G-CSF. The modulation of the expression of adhesion molecules in endothelial cells, as suggested by a previous report,¹⁰ is another possibility. In conclusion, we think that physicians should be aware of possible cutaneous reactions associated with G-CSF, and further documentation of cases and their full evaluation will be of great importance for both physicians and PBSC donors.

1 Murata M, Harada M, Kato S et al. Peripheral blood stem cell mobilization and apheresis: analysis of adverse events in 94 normal donors. Bone Marrow Transplant 1999; 24: 1065-1071, MEDLINE

2 Anderlini P, Donato M, Chan K-W et al. Allogeneic blood progenitor cell collection in normal donors after mobilization with filgrastim: the MD Anderson Cancer Center experience. Transfusion 1999; 39: 555-560, Article MEDLINE

3 Anderlini P, Przepiorka D, Champlin R, Korbling M. Biologic and clinical effects of granulocyte colony-stimulating factor in normal individuals. Blood 1996; 88: 2819-2825, MEDLINE

4 Paul C, Giachetti S, Pinquier L et al. Cutaneous effects of granulocyte colony-stimulating factor in healthy volunteers. Arch Dermatol 1998; 134: 111-112, MEDLINE

5 Sato N, Sawada K, Takahashi T et al. A time course study for optimal harvest of peripheral blood progenitor cells by granulocyte colony-stimulating factor in healthy volunteers. Exp Hematol 1994; 22: 973-978, MEDLINE

6 Samlaska CP, Noyes DK. Localized cutaneous reactions to granulocyte colony-stimulating factor. Arch Dermatol 1993; 129: 645-646, MEDLINE

7 Asnis LA, Gaspari AA. Cutaneous reactions to recombinant cytokine therapy. J Am Acad Dermatol 1995; 33: 393-410, MEDLINE

8 Takagi S, Ohsaka A, Taguchi H et al. Pyoderma gangrenosum following cytosine arabinoside, aclarubicin and granulocyte colony-stimulating factor combination therapy in myelodysplastic syndrome. Int Med 1998; 37: 316-319,

9 Sasaki O, Yokoyama A, Uemura S et al. Drug eruption caused by recombinant human G-CSF. Int Med 1994; 33: 641-643,

10 Glass LF, Fotopoulos T, Messina JL. A generalized cutaneous reaction induced by granulocyte colony-stimulating factor. J Am Acad Dermatol 1996; 34: 455-459, MEDLINE

Figure 1 Erythema exsudativum multiforme on the hips of the donor observed on the 4th day of G-CSF therapy.