Article

Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study.

Hematology Department, Hematopoietic Transplantation Unit, Institute of Hematology and Oncology, Hospital Clinic, Barcelona, Spain.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (impact factor: 3.15). 06/2009; 15(5):639-42. DOI:10.1016/j.bbmt.2009.01.014 pp.639-42
Source: PubMed

ABSTRACT We conducted a phase II trial to investigate the safety and efficacy of alemtuzumab in treating steroid-refractory acute graft-versus-host disease (aGVHD) grade II or higher after stem cell transplantation. Ten adult patients (6 with aGVHD grade III and 4 with aGVHD grade IV) were included in the study. Nine patients had gastrointestinal tract involvement, 7 had skin involvement, and 5 had liver involvement. Five patients responded to treatment, 2 with complete response and 3 with partial response. Eight infectious events (4 of grade 3-4) and 7 cytomegalovirus (CMV) reactivations were observed. Six patients had grade 3-4 cytopenia. All 10 patients died (7 resulting from aGVHD progression, 2 from severe infection, and 1 from to leukemia relapse), at a median of 40 days (range, 4 to 88 days) after alemtuzumab treatment. Overall, our findings suggest that steroid-refractory aGVHD may be improved by treatment with alemtuzumab, but that this treatment does not overcome the dismal prognosis of patients with severe aGVHD, demonstrating the need for alternative therapies to treat this complication.

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    Article: Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease.
    Daniel Wolff, Michael Schleuning, Stephanie von Harsdorf, Ulrike Bacher, Armin Gerbitz, Michael Stadler, Francis Ayuk, Alexander Kiani, Rainer Schwerdtfeger, Georgia B Vogelsang, Guido Kobbe, Martin Gramatzki, Anita Lawitschka, Mohamad Mohty, Steven Z Pavletic, Hildegard Greinix, Ernst Holler
    [show abstract] [hide abstract]
    ABSTRACT: Steroid refractory chronic graft-versus-host disease (cGVHD) is associated with a significant morbidity and mortality. Although first-line treatment of cGVHD is based on controlled trials, second-line treatment is almost solely based on phase II trials or retrospective analyses. The consensus conference on clinical practice in cGVHD held in Regensburg aimed to achieve a consensus on the current evidence of treatment options as well as to provide guidelines for daily clinical practice. Treatment modalities are the use of steroids and calcineurin inhibitors as well as immunomodulating modalities (photopheresis, mTOR-inhibitors, thalidomide, hydroxychloroquine, vitamin A analogs, clofazimine), and cytostatic agents (mycophenolate mofetil, methotrexate, cyclophosphamide, pentostatin). Recent reports showed some efficacy of rituximab, alemtuzumab, and etanercept in selected patients. Moreover, tyrosine kinase inihibitors such as imatinib came into the field because of their ability to interfere with the platelet-derived growth factor (PDGF-R) pathway involved in fibrosis. An other treatment option is low-dose thoracoabdominal irradiation. Although different treatment options are available, the "trial-and-error system" remains the only way to identify the drug effective in the individual patient, and valid biomarkers are eagerly needed to identify the likelihood of response to a drug in advance. Moreover, the sparse evidence for most treatment entities indicates the urgent need for systematic evaluation of second-line treatment options in cGVHD.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2011; 17(1):1-17. · 3.15 Impact Factor
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Keywords

10 patients
 
adult patients
 
aGVHD grade III
 
aGVHD grade IV
 
aGVHD progression
 
alemtuzumab treatment
 
alternative therapies
 
cell transplantation
 
complete response
 
dismal prognosis
 
efficacy
 
grade 3-4
 
infectious events
 
leukemia relapse
 
partial response
 
phase II trial
 
severe aGVHD
 
severe infection
 
steroid-refractory acute graft-versus-host disease
 
steroid-refractory aGVHD