Alemtuzumab for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

Gómez‐Almaguer, David; Ruíz‐Argüelles, Guillermo J.; Tarín-Arzaga, Luz del Carmen; González-Llano, Óscar; Gutiérrez-Aguirre, Homero; Cantú-Rodrı́guez, Olga Graciela; Jaime‐Pérez, José Carlos; Carrasco-Yalán, Antonio A.; Giralt, Sergío

doi:10.1016/j.bbmt.2007.08.052

Cited by 72 publications

(40 citation statements)

References 36 publications

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“…The colleagues from Houston have reported effectiveness of subcutaneous alemtuzumab in acute as well as chronic GVHD. 11,12 In conclusion, in this difficult to treat patient population, low doses of alemtuzumab applied every 2 weeks may lead to relevant GVHD responses with a more favourable benefit-risk ratio. This schedule should be evaluated in a prospective randomized trial.…”

Section: Discussionmentioning

confidence: 95%

“…Licensed for the treatment of fludarabine-refractory B-cell CLL, 2 alemtuzumab was also used in T-cell tumors [3][4][5] and due to its known immunosuppressive activity in autoimmune diseases 6 and for GVHD prevention. 7,8 Although alemtuzumab in the treatment of acute and chronic GVHD in small studies and case reports has already shown therapeutic responses, [9][10][11][12][13] very recently Schnitzler et al 14 reported 20 patients with severe intestinal acute GVHD treated successfully with alemtuzumab. Here, we show the efficacy of alemtuzumab for intestinal and liver grade III and IV acute GVHD in 18 steroid-refractory patients and support the idea that smaller doses may be preferable.…”

Section: Introductionmentioning

confidence: 99%

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Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective

Schub

Günther

Schrauder

et al. 2010

Bone Marrow Transplant

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The efficacy and safety of CD52 antibody alemtuzumab to treat severe acute GVHD in 18 consecutive patients refractory to standard high-dose corticosteroid therapy is reported. Patients (age range 13-68 years) had developed acute GVHD grade III and IV with gut and/or liver involvement after stem cell transplantation from family donors (n ¼ 7) or HLA-matched unrelated donors (n ¼ 11), including five donors with one or two HLA mismatches. Initially, in three patients, start doses of alemtuzumab in the range of 70-80 mg were applied and repeated after 3 to 4 weeks. Impressive responses were seen, but virus reactivation and bacterial infections were frequent. In an attempt to reduce this complication, the next nine patients received a reduced starting dose of 20-33 mg, and the last six patients received 3-13 mg repeated every 2-3 weeks. Seventeen of 18 patients responded to alemtuzumab, six patients are alive with a median followup of 108 weeks. Chronic GVHD was observed frequently. Although pronounced lymphocyte depletion requiring close monitoring for signs of infections seems inevitable for efficacy, alemtuzumab given in moderate doses has a substantial activity not only in intestinal but also in severe acute GVHD of the liver.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective

Schub

Günther

Schrauder

et al. 2010

Bone Marrow Transplant

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“…On day 28 of treatment 15 patients had responses and 10 out of the 15 patients were alive at 11 months. Fourteen patients developed infections including 11 who developed CMV reactivation [90]. In another phase II trial of 10 patients with grade III and IV aGVHD, 5 responded to treatment but all 10 died with a median period of 40 days [91].…”

Section: Alemtuzumab (Campath)mentioning

confidence: 99%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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“…[1][2][3][4][5] Although several different agents have been proposed as therapy for steroid-refractory aGVHD, there remains no consensus as to optimal management following failure of corticosteroids. At our institution, steroid-refractory aGVHD is routinely treated with antithymocyte globulin (ATG), etanercept ± mycophenolate mofetil.…”

mentioning

confidence: 99%

“…5 Although this approach is able to salvage a significant proportion of patients, prognosis is historically dismal in those patients refractory to second-line therapy. Given the reports of steroid-refractory aGVHD responding to alemtuzumab, [1][2][3][4]6,7 we have incorporated this agent as third-line therapy in patients failing the above strategies. Herein, we report the outcome of 13 patients with steroid and ATG/etanercept-refractory aGVHD treated with alemtuzumab as third-line therapy at our institution.…”

mentioning

confidence: 99%

Alemtuzumab as salvage therapy for steroid and ATG/etanercept-refractory acute GVHD

Jackson

Curley

Leach

et al. 2011

Bone Marrow Transplant

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Alemtuzumab for the Treatment of Steroid-Refractory Acute Graft-Versus-Host Disease

Cited by 72 publications

References 36 publications

Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective

Therapy of steroid-refractory acute GVHD with CD52 antibody alemtuzumab is effective

State-of-the-art acute and chronic GVHD treatment

Alemtuzumab as salvage therapy for steroid and ATG/etanercept-refractory acute GVHD

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