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Originally published as JCO Early Release 10.1200/JCO.2008.18.6270 on October 14 2008 © 2008 American Society of Clinical Oncology.
Chronic Lymphocytic Leukemia With Eyelid Involvement Responding to Alemtuzumab
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy
Istituto di Oculistica, Università Cattolica del Sacro Cuore, Roma, Italy
Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Roma, Italy
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy
International Centre for Genetic Engineering and Biotechnology, Outstation Monterotondo, Roma, Italy
Istituto di Ematologia, Università Cattolica del Sacro Cuore, Roma, Italy
A 61-year-old man was diagnosed in another hematological department as having chronic lymphocytic leukemia (CLL) in 1998. One year later, because of progressive stage II CLL characterized by doubling lymphocytes count after 6 months, increase of splenomegaly, and the appearance of B symptoms, the patient was treated with fludarabine, obtaining partial remission of disease. Starting from 2000, due to progression of disease, the patient underwent a cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen plus interferon-
Cutaneous involvement is far less common in B-cell compared with T-cell leukemias or lymphomas.1 Because of impaired immune competence of patients with CLL and the use of alkylating agent and purine analogs, the insurgence of other malignant disease such as basal or squamous cell carcinoma is eightfold higher as compared with the healthy population.2 Sometimes the lesion can be caused by cutaneous seeding by leukemic cells, (leukemia cutis, [LC]), or the by the development of large B-cell lymphoma in patients with CLL (Richter's syndrome).3 Histopatologically, three main architectural patterns of specific skin infiltrations in CLL has been reported as patchy perivascular and periadnexal, nodular diffuse, and band-like types.3 The mean duration of CLL before skin manifestation was 39 months, and rarely did skin lesions represent the first sign of the disease.3 Specific leukemic infiltrates developed at the site of herpes simplex zoster eruption, as a generalized lesion or confined to limited areas as head and neck, trunk, or extremities.3 While cutaneous Richter's syndrome had bad prognosis, LC does not significantly affect patient survival.4 Treatment of LC in CLL patients until now has been the use of alkylating agent, nucleoside analogs such as fludarabine and cladribine, or interferon-  or local radiotherapy.3-6 Recently, regression of LC in the CLL patients has been observed after the treatment with the toll-like receptor 7/8 antagonist imiquimod.7 The use of alemtuzumab in this setting of disease is never reported. We now report, to our knowledge, the first case of palpebral LC in CLL successfully treated with low-dose alemtzumab. To our knowledge, this is the first case reported in literature who described eyelid localizations successfully treated with low-dose alemtuzumab. This article has shown that alemtuzumab is an effective option for treatment of LC in patient affected by CLL. In our case, LC developed 8 years after the CLL diagnosis without influencing patient survival.3 The use of low-dose alemtuzumab (10 mg three times a week as target dose) as previously reported8-11 reduces the risk of toxicities and infection, especially if the T-helper lymphocyte count was constantly more than 200/mm3, and stringent antimicrobial prophylaxis and periodical viral tests were performed during alemtuzumab treatment. This patient probably acquired 17p deletion during the course of the disease because of the long history of disease, and this chromosomal abnormality is reported to be unresponsive to standard chemotherapy, while responsive to alemtuzumab therapy.12 Using alemtuzumab as the choice of low-dose therapy was due to the fact that, as our patient was 71 years old with a progressive 17p- CLL/LC and three previous line of polichemotherapies, the only therapeutical option was a palliative therapy. Low-dose alemtuzumab (10 mg as target dose; 240 mg as total induction therapy) could allow our patient to obtain a clinical response, reducing the adverse effect of the drug itself because of the expression of CD52 in the surface of T cells and neoplastic B cells. Our patient achieved a minimum of 400/mm3 T-helper lymphocytes during alemtuzumab therapy, and never experienced unknown fever, infection disease, CMV reactivation, nor pancytopenia, and he never needed hospitalization. Considering the tolerability of low-dose alemtuzumab induction therapy, the high risk of relapse due to biologic data, and the absence of other therapeutical options, we decided to start with a maintenance therapy. After 6 months, the patient is showing persistent resolution of palpebral LC and continuous partial response for CLL, so the manteinance therapy will be continued during the next months. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
NOTES published online ahead of print at www.jco.org on October 13, 2008 REFERENCES 1. Agnew KL, Ruchlemer R, Catovsky D, et al: Cutaneous findings in chronic lymphocytic leukaemia. Br J Dermatol 150:1129-1135, 2004[CrossRef][Medline] 2. Manusow D, Weinerman BH: Subsequent neoplasia in chronic lymphocytic leukemia. JAMA 232:267-269, 1975 3. Cerroni L, Zenahlik P, Höfler G, et al: Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia: A clinicopathologic and prognostic study of 42 patients. Am J Surg Pathol 20:1000-1010, 1996[CrossRef][Medline] 4. Colburn DE, Welch MA, Giles FJ: Skin infiltration with chronic lymphocytic leukemia is consistent with a good prognosis. Hematology 7:187-188, 2002[CrossRef][Medline] 5. Robak E, Robak T, Biernat W, et al: Successful treatment of leukaemia cutis with cladribine in a patient with B-cell chronic lymphocytic leukaemia. Br J Dermatol 147:775-780, 2002[CrossRef][Medline] 6. Várkonyi J, Zalatnai A, Timár J, et al: Secondary cutaneous infiltration in B cell chronic lymphocytic leukemia. Acta Haematol 103:116-121, 2000[CrossRef][Medline] 7. Spaner DE, Miller RL, Mena J, et al: Regression of lymphomatous skin deposits in a chronic lymphocytic leukemia patient treated with the toll-like receptor-7/8 agonist, imiquimod. Leuk Lymphoma 46:935-939, 2005[CrossRef][Medline] 8. Laurenti L, Piccioni P, Tarnani M, et al: Low-dose intravenous alemtuzumab therapy in pretreated patients affected by chronic lymphocytic leukemia: A single center experience. Haematologica 90:1143-1145, 2005 9. Laurenti L, Piccioni P, Tarnani M, et al: Immune recovery after low-dose Campath therapy in a group of pretreated patients affected by B-cell chronic lymphocytic leukemia. Leukemia 19:153-154, 2005[Medline] 10. Karlsson C, Norin S, Kimby E, et al: Alemtuzumab as first-line therapy for B-cell chronic lymphocytic leukemia: Long-term follow-up of clinical effects, infectious complications and risk of Richter transformation. Leukemia 20:2204-2207, 2006[CrossRef][Medline] 11. Laurenti L, Piccioni P, Cattani P, et al: Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: Incidence and treatment with oral ganciclovir. Haematologica 89:1248-1252, 2004 12. Bolli N, Di Ianni M, Simonetti S, et al: Treating two concurrent B-cell and T-cell lymphoid neoplasms with alemtuzumab monotherapy. Lancet Oncol 5:64-65, 2004[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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; at the same time the positivity of CD38 (73%) and ZAP-70 (41%) was detected. Fluorescent in situ hybridization analysis showed trisomy of chromosome 12, as expected by morphological analysis and 17p deletion. The mutational status of variable region of heavy chain immunoglobin discovered a mutated status (variable heavy chain 3-49). Because of stable stage II disease with bad biologic parameter in theheavily pretreated patient, a stringent follow-up was adopted. In October 2006, at routine check-up, the patient showed a bilateral painless nodular infiltration of the eyelids, similar to multiple chalazions. Two nodules were localized in each upper lid and one in each lower lid. In the next follow-up, 5 months later, because of the enlargement of the lids lesions, we decided to biopsy of eyelid's infiltrations (
