Irreversible alopecia due to busulphan in a 7-year-old girl

ARTICLE

Auteur(s) : Maria Perez-Crespo¹, Isabel Betlloch¹, Irene Ballester¹, Ana Lucas¹, Javier Mataix¹, Maria Niveiro²

¹Department of Dermatology, Hospital General Universitario de Alicante, Avenida Pintor Baeza s/n, E-03010 Alicante, Spain
²Department of Pathology, Hospital General Universitario de Alicante, Spain

A 7-year-old girl presented with a 3-year diffuse alopecia. She had a history of Blackfan-Diamond syndrome and had undergone an allogeneic bone marrow transplant (BMT) from her brother in 2004. Immunosuppressant treatment consisted of busulphan (4 mg/kg/day, total dose 288 mg) and cyclophosphamide (60 mg/kg/day, total dose 2 g). During the treatment the patient suffered grade 2-3 acute graft versus host disease, which resolved with systemic corticoids. The patient had also received granulocytic colony growth factors, cyclosporine and mycophenolate mophetil. At the time of consultation she was not undergoing any treatment. The family had noticed her hair loss a few days after the transplant and it progressively worsened.

On examination of the scalp there was diffuse non-scarring alopecia which was most pronounced in the parietal and temporal regions (figure 1A). There were no signs of inflammation or desquamation of the scalp. The body hair was not affected. Blood analysis and chest X-ray showed no alterations. Differential diagnoses of alopecia secondary to chronic graft versus host disease (GVHD) and irreversible alopecia following chemotherapy were considered. A biopsy was taken that showed a decrease in the density of terminal hair follicles. There was no perifollicular inflammatory infiltrate or alterations in the existing hair follicles (figure 1B).

Since there were no clinical or analytical data suggestive of GVHD and in view of the compatible anatomopathological results, the patient was diagnosed as having irreversible alopecia due to busulphan. An autologous hair transplant was suggested.

Discussion

In all the published cases the patients received a pre-BMT conditioning regimen with chemotherapy. Busulphan is the agent most frequently used. Permanent alopecia occurs in approximately half of adult patients who take busulphan and undergo a BMT [1]. Moreover, a direct relationship was found between permanent alopecia and the blood concentration of this chemotherapy drug [1].

Cases of irreversible alopecia have been reported with pre-BMT chemotherapy drugs other than busulphan, such as cyclophosphamide plus etoposide, etoposide plus total body irradiation or carboplatin and thiotepa [2]. Some patients had non-haematological neoplasms [2]. Receiving an allogeneic transplant or being female seems to increase the risk [1]. In children, there is a 24.3%-42% [3] risk of permanent alopecia after a bone marrow transplant. Risk factors may be an older age and previous cranial irradiation [4]. The relationship with GVHD is controversial, since an association has only been shown in certain studies [1-4].

The mechanism is unknown. It may involve destruction of germinal cells or acute damage of the matrix keratinocytes, which die in the hypodermis instead of entering the catagen phase [5]. According to our knowledge, there are no published cases of irreversible alopecia in patients treated with busulphan or other chemotherapy drugs who did not undergo a BMT after chemotherapy, which may indicate that this procedure plays an important pathogenic role. Alopecia may be due in part to the inflammatory cells of the graft attacking the follicles, which would explain the greater risk in allogeneic BMT patients.

Treatment is difficult due to its scarring nature. The only effective treatment is hair transplant, although autologous transplants do not usually obtain good aesthetic results. However, there is one case published of successful allogeneic hair transplant in which the bone marrow donor was also the hair donor [6].

This type of alopecia is a permanent adverse effect that causes great psychological distress, especially in children. It may occur very frequently since busulphan is a drug that is widely used in pre-BMT conditioning regimens. Consequently the patient and his family should be suitably informed.

Acknowledgments

References

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3 Izaki S, Goto H, Okuda K, Matsuda M, Watanabe Y, Fujioka K, et al. Long-term follow-up of busulfan, etoposide, and nimustine hydrochloride (ACNU) or melphalan as conditioning regimens for childhood acute leukemia and lymphoma. Int J Hematol 2007; 86: 253-60.

4 Vowels M, Chan LL, Giri N, Russell S, Lam-Po-Tang R. Factors affecting hair regrowth after bone marrow transplantation. Bone Marrow Transplant 1993; 12: 347-50.

5 Tosti A, Piraccini BM, Vincenzi C, Misciali C. Permanent alopecia after busulfan chemotherapy. Br J Dermatol 2005; 152: 1056-8.

6 Rosati P, Bergamo A. Allogenic hair transplant in a bone marrow transplant recipient. Dermatol Surg 1999; 25: 664-5.