Progression of Undiagnosed Cutaneous T-Cell Lymphoma During Efalizumab Therapy

A 32-year-old man presented with a 2-year history of a pruritic, erythematous dermatitis. A skin biopsy was performed, and he was diagnosed with psoriasis. Treatment was administered with topical corticosteroids, acitretin, UV-B twice per week, and efalizumab, 80 mg, subcutaneous injections each week for 4 months without success. Within 3 months of stopping efalizumab therapy, he developed tumors on his face and ears and presented to the university clinic for evaluation. Other physical findings included alopecic scalp plaques, erythroderma sparing skin folds, palmar and plantar desquamation, erythematous plaques on his back, and no palpable lymphadenopathy.

Abnormal peripheral blood laboratory results included white blood cell count, 15 400/μL (normal, 4000-11 000/μL); absolute lymphocyte count, 9360/μL (normal, 1000-4000/μL); absolute CD3 count, 2215/μL (normal, 1240-1840/μL); absolute CD8 count, 945/μL (normal, 262-787/μL); and lactate dehydrogenase level, 470 U/L (normal, 85-285 U/L). His absolute CD4 count of 1252/μL was normal (normal, 693-1319/μL), and no Sézary cells or dominant T-cell clones were detected. (To convert white blood cells and lymphocytes to ×10⁹/L, multiply by 0.001; to convert lactate dehydrogenase to microkatals per liter, multiply by 0.167.)

Skin biopsy specimens revealed atypical lymphocytes forming Pautrier microabscesses in the epidermis. Medium to large lobulated lymphocytes with highly irregular nuclei were present in dense dermal lymphoid infiltrates. Immunohistochemical stains showed a predominance of helper T-cells (CD3⁺, CD4⁺, and CD5⁺) that did not express CD7 and CD30. Tumor-stage erythrodermic mycosis fungoides was diagnosed. Retrospective review of preefalizumab skin biopsy specimens from the face revealed dermal perifollicular lymphocytic infiltrates with atypical cells and follicular epidermotropism consistent with pilar mycosis fungoides.

Over the next 2 months, further tumor development occurred on the face, ears, chest, and back despite bexarotene therapy (Figure). He underwent 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy, 1 cycle of bexarotene and denileukin treatment, 4 cycles of etoposide, cisplatin, high-dose aracytine, and methylprednisolone (ESHAP) salvage chemotherapy, and vorinostat therapy, but the tumors persisted.

An allogenic peripheral blood stem cell transplant from an HLA-matched sibling was performed owing to the severe refractory cutaneous T-cell lymphoma. He had almost complete tumor resolution but subsequently developed 2 cutaneous tumors requiring irradiation and tapering of immunosuppressive therapy. One year after transplantation, he remained in remission and has graft-vs-host disease.

Efalizumab-associated lymphoproliferative diseases include 3 cases among the 2980 patients treated during the clinical trials vs none in the placebo group.^{1 - 2} Other efalizumab-associated lymphoproliferative disease cases in the literature include a 54-year-old man with a 37-year history of psoriasis who developed atypical CD8⁺ cutaneous T-cell lymphoma after 1 year of efalizumab treatment (1 mg/kg/wk).³ A 55-year-old man who died from B-cell lymphoma–associated complications after treatment with efalizumab has also been reported. Neither dose nor total duration of efalizumab treatment in this patient was specified.⁴

We acknowledge that the natural course of our patient's cutaneous T-cell lymphoma, had he not been exposed to efalizumab, is unclear. The timing of the tumor-stage progression and initiation of efalizumab treatment in our patient, although not direct evidence of causation, raises suspicion. Efalizumab avoidance, or at least extreme caution with its use, is warranted for patients with a history of lymphoma.

Correspondence: Dr Hernandez, Department of Dermatology (MC 624), University of Illinois at Chicago, 808 S Wood St, Room 376 CME, Chicago, IL 60612 (claudiah@uic.edu).

Financial Disclosure: Dr Hernandez is or has been a speaker, investigator, and consultant for Genentech, Amgen, Centocor, Biogen, Idec, and Abbott Laboratories. Dr Worobec has been an investigator or consultant for Ligand Pharmaceuticals, Seattle Genetics, and Merck.