Low-dose intermittent alemtuzumab in the treatment of Sezary syndrome: clinical and immunologic findings in 14 patients

Bernengo, Maria Grazia; Quaglino, Pietro; Comessatti, Alessandra; Ortoncelli, Michela; Novelli, Mauro; Lisa, Francesco; Fierro, Maria Teresa

doi:10.3324/haematol.11127

Cited by 161 publications

(99 citation statements)

References 39 publications

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“…Similar results, with no infectious complications, were recently reported in a small cohort of patients treated with modified, low-dose, subcutaneous alemtuzumab for 6 weeks [321]. In addition to hematologic toxicity, conventionally dosed alemtuzumab in advanced-stage MF/SS is associated with a high incidence of infectious complications [319,320,[322][323][324][325]. Overall, infectious complications have been observed in twothirds of treated patients, most of which are bacterial, including sepsis.…”

Section: Monoclonal Antibodiessupporting

confidence: 81%

“…In a phase II study in 22 patients with advanced-stage MF/SS, overall and complete response rates of 55 and 32%, respectively, were observed, with a median time to treatment failure of 1 year [319]. Given the significant risk of infectious complications, low-dose subcutaneous alemtuzumab was investigated in 14 patients with SS, most of whom had relapsed/refractory disease [320]. Most patients in this study received 3 mg of subcutaneous alemtuzumab on day 1 followed by a 10 mg dose on alternating days until the Sé zary count was <1,000/mm 3 .…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

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Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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Section: Monoclonal Antibodiessupporting

confidence: 81%

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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“…[84][85][86][87][88] Trials of combination strategies in less-heavily pretreated patients are warranted. In general, outside the clinical trial setting, it has a very limited place in the treatment of MF/SS.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

How I treat mycosis fungoides and Sézary syndrome

Prince

Whittaker

Hoppe

2009

Blood

136

109

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The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a “stage-based” approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

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“…The dosing regimens reported so far are similar to those used for patients with chronic lymphocytic leukemia. However, a recent study conducted on patients with Sezary's syndrome showed that low-dose alemtuzumab was as effective as the standard dosing regimen (10 vs 15 mg on alternate days), with decreased toxicity [75]. Maintenance therapy was tailored for each patient on the basis of regular immunological monitoring of Sezary cell counts.…”

Section: Other Cytotoxic and Immunomodulatory Agentsmentioning

confidence: 99%