Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia

Alinari, Lapo; Lapalombella, Rosa; Andritsos, Leslie A.; Baiocchi, Robert A.; Lin, Thomas S.; Byrd, John C.

doi:10.1038/sj.onc.1210380

Cited by 108 publications

(92 citation statements)

References 74 publications

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“…CAMPATH-1H (Alemtuzumab), a humanized antibody against CD52, is used to deplete leukemia cells from patients with relapsed/refractory chronic lymphocytic leukemia. 15 Recent studies have suggested the effectiveness of CAMPATH-1H treatment in additional hematopoietic malignancies, including peripheral T-cell lymphoma, T-cell prolymphocytic leukemia and cutaneous T-cell lymphoma. [40][41][42] Although it has been reported that the majority of various subtypes of AML are negative for CD52 expression, a subset of acute myelomonocytic leukemias has been shown to exhibit CD52 expression.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] Although the function of CD52 is largely unknown, CD52 is a favored target for lymphoma therapy and immunosuppression before bone marrow transplantation. [12][13][14][15] Alemtuzumab (CAMPATH-1H; Genzyme, Cambridge, MA, USA) is a recombinant humanized monoclonal antibody targeting the CD52 antigen. 16,17 The binding of CAMPATH-1H to CD52 on lymphocytes induces complement-dependent cytotoxicity (CDC), 18,19 antibody-dependent cell-mediated cytotoxicity (ADCC) [20][21][22] and direct cytotoxicity.…”

Section: Therefore Identifying Novel Molecular Targets In Evi1mentioning

confidence: 99%

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CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression

et al. 2011

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Ecotropic viral integration site 1 (EVI1) is an oncogenic transcription factor in human acute myeloid leukemia (AML) with chromosomal alterations at 3q26. Because a high expression of EVI1 protein in AML cells predicts resistance to chemotherapy with a poor outcome, we have searched for molecular targets that will treat these patients with AML. In this study, we determined that CD52, which is mainly expressed on lymphocytes, is highly expressed in most cases of AML with a high EVI1 expression (EVI1 High ). CAMPATH-1H, a humanized monoclonal antibody against CD52, has been used to prevent graft-versus-host disease and treat CD52-positive lymphoproliferative disorders. Here, we investigated the antitumor effect of CAMPATH-1H on EVI1High AML cells. CAMPATH-1H significantly inhibited cell growth and induced apoptosis in CD52-positive EVI1High leukemia cells. Furthermore, CAMPATH-1H induced complement-dependent cytotoxicity and antibodydependent cellular cytotoxicity against CD52-positive EVI1 High leukemia cells. After an intravenous injection of CAMPATH-1H into NOD/Shi-scid/IL-2Rc;null mice with subcutaneous engraftment of EVI1High leukemia cells, tumor growth rates were significantly reduced, and the mice survived longer than those in the phosphate-buffered saline-injected control group. Thus, CAMPATH-1H is a potential therapeutic antibody for the treatment of patients with EVI1High leukemia.

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Section: Discussionmentioning

confidence: 99%

Section: Therefore Identifying Novel Molecular Targets In Evi1mentioning

confidence: 99%

CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression

et al. 2011

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“…6,23 Although the incidence of CMV reactivation was substantial, it was in line with earlier reports. 4,24 Furthermore, the patients with CMV reactivation showed no clinical signs of CMV disease and, once the CMV had been rapidly cleared be means of preemptive oral ganciclovir therapy, they could all safely resume taking alemtuzumab.…”

Section: Low-dose Sc Alemtuzumab In Refractory Cllmentioning

confidence: 99%

Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study

et al. 2009

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Alemtuzumab is active in chronic lymphocytic leukaemia (CLL) patients refractory to alkylators and fludarabine. The aim of this study was to determine the efficacy and safety of subcutaneous alemtuzumab at low dose (10 mg three times per week, for 18 weeks) to 49 patients with pre-treated CLL. The overall response rate was 53%, including 27% of complete responses; it was 42% in patients over 70 years, and 54% in the fludarabine-resistant patients. Forty-five percent of the patients with an unfavourable karyotype responded, including 60% of those with the 17p-aberration. After a median follow-up of 25 months, the median overall time to disease progression was 8 months (responders 12 months, non-responders 4 months). The median overall time to alternative treatment was 9 months (responders 17 months, non-responders 6 months) and median overall survival was 30 months. The treatment was well tolerated: grade IV neutropenia was observed in 17%, and cytomegalovirus (CMV) reactivation in 24% of the patients, with no CMV disease. We observed a total of 30 infections (50% during treatment and 50% during the 12-month follow-up), only one-third of which was severe. This study confirms that lowdose subcutaneous alemtuzumab is effective in poor prognosis CLL, and has a particularly favourable toxicity profile.

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“…Binding to leukemic cells leads to antibody-dependent cellular-mediated lysis [47], [48]. It is licensed for TP53 deleted/ mutated B-CLL, purine-analogue refractory B-CLL and T-prolymphocytic leukemia (T-PLL) [49].…”

Section: Yttrium-90 Ibritumomab Tiuxetanmentioning

confidence: 99%

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

Kyriazi

2016

IJMS

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Monoclonal antibodies (MoAbs) have been widely used in clinical hematology. As foreign macro-molecules, they can cause infusional reactions during the administration or within 24 hours after the infusion, which encompass a spectrum of mechanisms. Although most of these reactions are non-allergic, are often indistinguishable from true allergic reactions mediated by IgE immunoglobulins. The diagnosis is often challenging and relies mainly on clinical criteria. They occur during the first doses, soon after the initiation of treatment. The symptoms are usually well controlled by the immediate drug discontinuation or reduction of the infusion rate. The management remains largely supportive, consisting of oxygen, intravenous fluids, bronchodilators, antihistamines and steroids. Most of MoAb protocols recommend premedication with steroids and antihistamines and gradually escalating infusion rates. Increased medical and nursing vigilance is required and resuscitative equipment should always be readily available. These events affect patients' quality of life, leading to treatment delay or discontinuation and series of tests. The decision to rechallenge the treatment depends on severity grading, clinical parameters and treatment goals. This article provides an update of MoAbs used in clinical hematology. It summarizes the pathophysiology, the diagnostic approach, the preventive measures and treatment of MoAb-related reactions.

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Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia

Cited by 108 publications

References 74 publications

CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression

CD52 as a molecular target for immunotherapy to treat acute myeloid leukemia with high EVI1 expression

Low-dose subcutaneous alemtuzumab in refractory chronic lymphocytic leukaemia (CLL): results of a prospective, single-arm multicentre study

Immediate Reactions To Monoclonal Antibodies In Clinical Hematology

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