Alemtuzumab therapy for refractory idiopathic hypereosinophilic syndrome


We would like to report the novel use of alemtuzumab (MabCampath; Schering) as maintenance therapy for a patient with refractory idiopathic hypereosinophilic syndrome (IHES).

The patient, a 39-year-old female, presented in January 1992 to dermatologists with palmar keratoderma, widespread pruritic rash, fevers and malaise. Biopsy showed a vesicular reaction with plentiful eosinophils throughout the dermis and epidermis. Poor response to topical steroids prompted referral for tertiary review. A provisional diagnosis of IHES was made on the basis of persistent peripheral blood eosinophilia of 2–6 × 109/l, exclusion of other causes of eosinophilia and marrow findings of increased mature eosinophils with normal cytogenetics (Chusid et al, 1975). The patient received many treatments reported as useful in IHES including steroids, interferon, cyclosporine, hydoxyurea, CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone), etoposide, methotrexate, PUVA (psoralens, ultraviolet A) and cladribine, all with variable and unsustained responses. During this period, her condition deteriorated with several skin flares and computerized tomography evidence of pulmonary infiltrates.

By February 2000, she had developed progressive sero-negative erosive arthropathy, deterioration in ECHO appearance, marked weight loss because of hypercatabolism and recurrent fevers. She was referred to our unit for consideration of a non-myeloablative peripheral blood stem cell (PBSC) transplant from a single DR-mismatched sister. Previous reports of transplantation in IHES have shown resolution of peripheral blood eosinophilia and improved cardiac function (Fukushima et al, 1995: Sigmund & Flessa, 1995).

The patient was admitted in September 2000 for conditioning with fludarabine, melphalan and alemtuzumab. It was noted that during this time her eosinophilia resolved and her well-being improved. Unfortunately she failed to engraft and, despite infusion of additional PBSC, she developed autologous reconstitution with persisting eosinophilia. She remained unwell with recurrent skin flares, progressive arthropathy and cutaneous ulcers complicated by methicillin-resistant Staphylococcus aureus infection.

Despite recent reports (Cools et al, 2003), a trial of imatinib mesylate 400–600 mg (Glivec; Novartis) for 4 weeks proved unsuccessful in this patient, with no reduction in peripheral blood eosinophil count. In view of the marked eosinopenia noted following the use of alemtuzumab during transplant conditioning, we initiated weekly doses of 20 mg. Prior to this we had confirmed strong CD52 expression on her eosinophils. It has previously been shown that CD52 is a glycosylphosphatidylinositol-anchored molecule expressed on human eosinophils but not on neutrophils, and that its blocking has an inhibitory effect on the respiratory burst and generation of oxygen radicals that mediate tissue damage by eosinophils (Elsner et al, 1996).

The patient is now 2·5 years post-transplant and maintained on alemtuzumab (30 mg) every 3 weeks. The regimen was selected because of difficult venous access, the moderately severe side-effects experienced during infusions (hypotension and chest pain), which occur especially if the eosinophil count is high, and patient compliance. She continues on prophylactic penicillin, aciclovir and cotrimoxazole. Her haemoglobin, platelets and neutrophils remain in the normal range although she is lymphopenic (< 0·15 × 109/l). She has excellent control of her cutaneous symptoms, improvement in her joints and ECHO appearance and a marked subjective improvement in the quality of her life. Eosinophil counts taken pre- and post-alemtuzumab infusions continue to show a good but transient response (Table I), with marked improvement especially in cutaneous symptoms reported by the patient post infusions.

Table I.  Blood counts taken pre- and post-alemtuzumab infusions showing the selective reductions in eosinophils.
Date of infusionDate of full blood countEosinophils (×109/l)Hb (g/dl)Platelets (×109/l)White cell count (×109/l)Neutrophils (×109/l)

We plan to maintain the patient indefinitely on this protocol, having already explored alternatives such as bone marrow transplantation and Glivec without success.

In summary, we report a patient with IHES whose symptoms and signs are well controlled on alemtuzumab therapy, which has resulted in a selective depletion of eosinophils. Despite the well-recognized immunosuppressive effects of alemtuzumab, the treatment has not resulted in any infectious complications.