CD52 expression in hairy cell leukemia

Quigley, Michael; Bethel, Kelly; Sharpe, Robert W.; Saven, Alan

doi:10.1002/ajh.10428

Cited by 40 publications

(12 citation statements)

References 23 publications

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“…Although several reports showed CD52 expression in HCL cells and suggested the clinical use of alemtuzumab in HCL [11, 12], there exists only one report which actually showed the effectiveness of alemtuzumab against refractory HCL [13]. Therefore, before introducing alemtuzumab, we confirmed CD52 expression in the patient’s cells and the effectiveness of alemtuzumab against tumor cells in vitro by flow-cytometric analysis.…”

Section: Discussionsupporting

confidence: 57%

“…Once bound to CD52, alemtuzumab fixes complement, which leads to cell lysis of the target cells, and induces antibody-dependent cellular cytotoxicity [9, 10]. More than 90% of HCL cases have been shown to express CD52 antigen [11, 12], and alemtuzumab has recently been used successfully in the treatment of refractory HCL [13]. Here, we present a 72-year-old Japanese man with HCLv refractory to various chemotherapies including rituximab.…”

Section: Introductionmentioning

confidence: 99%

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Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab

Sasaki

Sugimoto²,

Mori³

et al. 2008

Acta Haematol

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A 72-year-old Japanese man presented with 43.1 × 10⁹/l hairy cells and apparent splenomegaly. The leukemia cells had unevenly distributed microvilli and round nuclei with dense chromatin and one or two clear nucleoli, lacked CD25 expression and were negative for tartrate-resistant acid phosphatase. The case was diagnosed as hairy cell leukemia variant (HCLv) and proved refractory to various chemotherapies, including cladribine, pentostatin, interferon-α, CHOP and rituximab. Because of the CD52 expression, we treated the patient with alemtuzumab. Pretreatment with 22.5 Gy to the spleen reduced the spleen size from 12 to 4 cm below the left costal margin, and the number of circulating leukemic cells decreased from 229.0 to 63.6 × 10⁹/l. Subsequent administration of 24.0 mg of alemtuzumab eliminated leukemic cells in the peripheral blood on day 12, and the spleen was not palpable after the administration of 54.0 mg of alemtuzumab. In vitro treatment with alemtuzumab confirmed the cytotoxic effect against the patient’s leukemic cells in the presence of complement. This is the first report showing clinical effectiveness of splenic irradiation and alemtuzumab against refractory HCLv.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab

Sasaki

Sugimoto²,

Mori³

et al. 2008

Acta Haematol

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“…In contrast, whereas alemtuzumab could theoretically be useful in this setting because of the common expression of CD52 on hairy cells, use of this agent comes at the cost of additional prolonged immunosuppression. 68 A prospective randomized trial has recently been designed by Robert J. Kreitman at the National Institutes of Health to address the question of optimal scheduling of rituximab and cladribine (http://clinicaltrials. gov/ct2/show/NCT00781235?recr ϭ Open&cond ϭ Hairyϩ CellϩLeukemia&rank ϭ 3).…”

Section: What Should Be Done With Mrdmentioning

confidence: 99%

How I treat hairy cell leukemia

Grever

2010

Blood

139

124

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The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of ␣-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed this disease into a highly treatable form of leukemia, and patients with the classic form of this rare leukemia now have a near-normal life expectancy. However, other clinical entities mimicking this disease do not respond; thus, accurate diagnosis is important. Immunophenotypic features in classic hairy cell leukemia show that the leukemic cells express CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high percentage of durable complete remissions with modern therapy, the long-term disease-free survival curves have not reached a plateau. Many patients who achieve a complete remission by morphologic criteria have minimal residual disease demonstrable by either flow cytometry or immunohistochemical staining, and this population may be at higher risk for earlier relapse. Continued clinical research is essential to optimize therapy for this disease. (Blood. 2010;115:21-28) IntroductionIn 1958, Bouroncle et al described a series of patients with leukemic reticuloendotheliosis. 1 Although this collection of cases established that the previously described isolated reports actually represented a distinct hematologic malignancy, the classic manuscript contained a very thorough presentation of the many clinical facets of this disease now known as hairy cell leukemia (HCL). Furthermore, it established that therapeutic intervention was limited either to careful titration of alkylating agents or to splenectomy. The ability to alter the clinical course of the patients with this rare form of leukemia did not substantially change until the introduction of ␣-interferon in 1984. 2 Shortly thereafter, observations that a purine nucleoside analog (pentostatin) could induce a high degree of complete remissions (eg, 75%-89%) in this previously "untreatable" chronic leukemia changed the natural history of HCL in record time. [3][4][5][6][7][8] Another purine nucleoside analog (cladribine) produced remarkably high remission rates (eg, 91%) with a single course of therapy. 9,10 The outstanding results with this agent delivered as a single course of therapy led to cladribine being the initial therapy selected by most hematologists. Many of the initial studies with this agent excluded patients with active infection from enrollment, but studies from multiple institutions confirmed the high complete remission rate with this drug. [11][12][13][14] Thus, patients who are treated with either purine nucleoside analog as front-line therapy will achieve a high rate of complete remission (75%-90%). 7,10 The long-term studies reported at 5 to 10...

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“…of alemtuzumab in a number of lymphoid and non-lymphoid neoplasms such as hairy cell leukemia, Langerhans cell histiocytosis, T-cell large granular lymphocytosis, idiopathic hypereosinophilic syndrome, and adult T-cell leukemia (61)(62)(63)(64)(65)(66). CD52 is also expressed in plasma cell disorders including myeloma and Waldenstrom's macroglobulinemia but appears to be limited in expression in the latter and confined to the CD45 + plasma cells in the former (67)(68)(69)(70).…”

Section: Clinical Trials In Other Lymphoid Malignanciesmentioning

confidence: 95%

Alemtuzumab in CLL and Other Lymphoid Neoplasms

Ravandi

O’Brien

2006

Cancer Investigation

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The recent success of monoclonal antibodies in the treatment of various hematological and nonhematological cancers is the result of several decades of research in immune therapy of cancer. The identification of cancer-specific surface markers has led to the development of numerous monoclonal antibodies directed at these antigens, which have been associated with variable success in treating patients with different malignancies. Alemtuzumab, one such monoclonal antibody, is a humanized antibody directed against CD52. The target antigen is a small glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is highly expressed on normal T- and B-lymphocytes and on a large proportion of malignant lymphoid cells, but not on hematopoietic progenitor cells. A number of clinical trials have demonstrated the clinical activity of alemtuzumab in chronic lymphocytic leukemia (CLL), T-cell malignancies such as T-prolymphocytic leukemia (T-PLL) and cutaneous T-cell lymphoma (CTCL), and have examined its role as an immunosuppressive agent in transplantation and for the treatment of autoimmune disorders. Effective antibiotic prophylaxis can limit the incidence of infections, which are the major side effect associated with the profound lymphopenia occurring as a result of treatment with this agent.

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CD52 expression in hairy cell leukemia

Cited by 40 publications

References 23 publications

Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab

Effective Treatment of a Refractory Hairy Cell Leukemia Variant with Splenic Pre-Irradiation and Alemtuzumab

How I treat hairy cell leukemia

Alemtuzumab in CLL and Other Lymphoid Neoplasms

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