Thalidomide treatment for chronic graft‐versus‐host disease

Heney, David; Norfolk, D. R.; Wheeldon, John; Bailey, Chris; Lewis, Ian; Barnard, D. L.

doi:10.1111/j.1365-2141.1991.tb04377.x

Cited by 90 publications

(36 citation statements)

References 18 publications

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“…In this trial sedation and constipation were the major side-effects and four patients discontinued their medication for peripheral neuropathy. Heney et al 30 who treated six patients with refractory cGVHD reported similar results: four patients had a dramatic response and one a partial response. In two patients peripheral neuropathy was observed.…”

Section: Thalidomide (N-phatalidoglutarimide)supporting

confidence: 64%

Chronic graft-versus-host disease: is there an alternative to the conventional treatment?

Gaziev¹,

Galimberti²,

Lucarelli³

et al. 2000

Bone Marrow Transplant

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Section: Thalidomide (N-phatalidoglutarimide)supporting

confidence: 64%

Chronic graft-versus-host disease: is there an alternative to the conventional treatment?

Gaziev¹,

Galimberti²,

Lucarelli³

et al. 2000

Bone Marrow Transplant

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“…Studies on the pharmacokinetics of thalidomide are not available in the mouse; in a rabbit model, however, treatment of the animals with two or three doses of 150 mg/kg thalidomide improved absorption and accumulation of the drug in the serum (20). Peak serum levels obtained after three injections of 150 mg/kg thalidomide (20) are similar to those obtained in humans treated with thalidomide for graft-versus-host disease (21). In our experiments, the need to use two doses of 200 mg/kg thalidomide to achieve cytokine modulation may reflect the poor solubility and bioavailability of the drug (22).…”

Section: Discussionmentioning

confidence: 64%

Thalidomide protects mice against LPS-induced shock

Moreira

Wang

Sarno

et al. 1997

Braz J Med Biol Res

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Thalidomide has been shown to selectively inhibit TNF-α production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-α has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-α and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-α, IL-6, IL-10, IL-1ß, GM-CSF and IFN-γ were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-α levels were reduced by 93%, in a dose-dependent manner, and TNF-α mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-γ. The LD 50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.

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“…Main adverse effects were sedation, neuropathy and constipation. 58 Heney et al 61 reported responses in five of six persons receiving thalidomide, 100-200 mg/day. Response was best in skin cGVHD.…”

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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Thalidomide treatment for chronic graft‐versus‐host disease

Cited by 90 publications

References 18 publications

Chronic graft-versus-host disease: is there an alternative to the conventional treatment?

Chronic graft-versus-host disease: is there an alternative to the conventional treatment?

Thalidomide protects mice against LPS-induced shock

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

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