The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children

Rovelli, Attilio; Arrigo, C; Nesi, Francesca; Balduzzi, Adriana; Nicolini, Benedetta; Locasciulli, Anna; Vassallo, Elena; Miniero, R; Uderzo, C

doi:10.1038/sj.bmt.1701138

Cited by 75 publications

(49 citation statements)

References 19 publications

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“…This effectiveness of thalidomide in children with chronic GVHD has also been noted by others. 11,18,19 Earlier introduction of thalidomide may be important, particularly in adults with aggressive disease. The ultimate role of thalidomide in therapy of chronic GVHD remains to be defined.…”

Section: Discussionmentioning

confidence: 99%

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Response to thalidomide therapy in refractory chronic graft-versus-host disease

Browne

Weisdorf

DeFor

et al. 2000

Bone Marrow Transplant

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Summary:Chronic graft-versus-host disease (GVHD) refractory to standard immunosuppressive therapy remains a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Thalidomide may be effective in some patients with high-risk or refractory chronic GVHD. We report a single-institution study of thalidomide in 37 BMT patients with extensive chronic GVHD refractory to standard immunosuppressive therapy. Acute GVHD occurred in 34 (91%) of patients and evolved progressively into chronic GVHD in 23 (62%) patients. Thalidomide was added to standard immunosuppressive therapy a median of 11 months (range 0-105 months) after the diagnosis of chronic GVHD. Fourteen of 37 (38%) patients responded after introduction of thalidomide (one complete, 13 partial). Ten of 21 (46%) children and four of 16 (25%) adults responded. Responses were seen in eight of 17 (47%) recipients of related donor marrow and six of 20 (30%) recipients of unrelated donor marrow. Eight of 23 (34%) patients with progressive onset of chronic GVHD showed a response. There were no deaths among the responders. The remaining 23 patients (62%) did not respond and of these only two survive, one with progressive scleroderma, and the other with bronchiolitis obliterans. Chronic GVHD with associated infection (most commonly disseminated fungal infection) was a major contributor to mortality in all cases. Overall, after initiation of thalidomide, the 2-year Kaplan-Meier survival was 41% (95% C.I. 24%-59%). We conclude that thalidomide is a useful and well-tolerated therapy for patients with previously treated refractory chronic GVHD, including those with progressive onset of chronic GVHD, recipients of unrelated donor marrow, and children. Earlier introduction of thalidomide as an adjunct to standard immunosuppressive therapy may lead to more frequent responses and possible better survival. Bone Marrow Transplantation (2000) 26, 865-869.

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Section: Discussionmentioning

confidence: 99%

“…At the time of this study, several other institutions including ours initiated similar trials of thalidomide, some of which have been described recently. 10,11 We now report the University of Minnesota experience with thalidomide in related and unrelated transplant recipients with chronic GVHD refractory to intensive first-line immunosuppressive therapy.…”

mentioning

confidence: 99%

Response to thalidomide therapy in refractory chronic graft-versus-host disease

Browne

Weisdorf

DeFor

et al. 2000

Bone Marrow Transplant

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“…Twenty-nine subjects discontinued because of adverse effects, including sedation, constipation, neuritis, neutropenia and rash. Rovelli et al 64 used thalidomide, 3-12 mg/kg/day in 14 children with cGVHD. Six complete responses and four partial responses were reported.…”

Section: Imid-class Drugsmentioning

confidence: 99%

Chronic GVHD: Where are we? Where do we want to be? Will immunomodulatory drugs help?

Linhares

Pavletić

Gale

2012

Bone Marrow Transplant

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Chronic GVHD (cGVHD) is an important problem after allotransplants. Some risk factors for cGVHD are similar to those of acute GVHD (aGVHD) but others are distinct indicating sometimes overlapping but unique pathogeneses. Precise incidence and prevalence data of cGVHD are lacking because of diverse diagnostic criteria but a 50% risk is a reasonable estimate. Incidence and prevalence of cGVHD are probably growing because of increased use of unrelated donors, blood rather than bone marrow (BM) grafts, decreased early transplant-related mortality (TRM) and increasing frequency of allotransplants. Pathophysiology of cGVHD is complex and poorly understood. Notably, no reliable surrogate end point to predict mechanism(s) of cGVHD has been identified. Therapy of cGVHD is unsatisfactory. Corticosteroids are effective but other drugs are controversial and few are rigorously tested in randomized trials. Highly variable response rates are reported because of small sample sizes and inconsistencies in eligibility, diagnostic and response criteria. We focus on the possible role of immunomodulatory drugs (IMiDs), thalidomide lenalidomide and pomalidomide, in preventing and treating cGVHD. The data suggest activity of thalidomide but at doses not clinically practical in many instances. There are few data with lenalidomide. Trials of pomalidomide, which has immune activities like thalidomide but with fewer adverse effects, are beginning. Because cGVHD is not recently reviewed in Bone Marrow Transplantation, we give a brief background and discuss challenges in diagnosing, understanding and treating cGVHD including the recently proposed National Institutes of Health consensus criteria for cGVHD. 1-3 It occurs in about 50% of persons surviving 41 year post transplant and causes substantial morbidity and mortality. There has been little progress over the past 30 years in preventing and/or treating cGVHD. Moreover, incidence and prevalence are increasing because of several factors including: (1) increased use of blood cell rather than BM grafts; (2) increasing use of incompletely HLA-matched related and unrelated donors; (3) increased use of donor-lymphocyte infusions, especially in the context of reduced-intensity allotransplants; (4) increased number of transplants done each year; and (5) increased proportion of transplants in older persons. [4][5][6] The focus of our review is on the use and potential of IMiD-class drugs to prevent and/or treat cGVHD. These drugs have unique, complex immune regulatory activities. As a prelude, we review some relevant definitional, laboratory and clinical features of cGVHD.

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“…Encouraging results were obtained in children treated with thalidomide for refractory and/or high risk extensive cGVHD. 31 In this study six (42%) of 14 patients given thalidomide had complete clinical responses, four (28%) had a partial response and four (28%) failed treatment. The best responders had predominantly mucocutaneous involvement by cGVHD and most of them had a quiescent form of disease.…”

Section: Thalidomide (N-phatalidoglutarimide)mentioning

confidence: 97%