Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease

Kulkarni, Samar; Powles, R; Sirohi, Bhawna; Treleaven, J; Sašo, Radovan; Horton, C; Atra, Ayad; Ortín, Miguel; Rudin, C.; Goyal, Sagun D.; Sankpal, S.; Meller, S; Pinkerton, CR; Mehta, Jayesh; Singhal, Seema

doi:10.1038/sj.bmt.1704033

Cited by 41 publications

(26 citation statements)

References 28 publications

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“…50 Browne e cols 51 estudaram seu uso em 37 pacientes e observaram 38% de resposta global (78% nas articulações e 46% na pele) e sobrevida de 41% em dois anos. Estudo pré-vio 52 com amostra maior (n = 80) reportou 20% de resposta com alta taxa (36%) de efeitos adversos e suspensão da droga (CIa).…”

Section: Tratamento De Resgateunclassified

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

Bouzas¹,

Silva²,

Tavares³

et al. 2010

Rev. Bras. Hematol. Hemoter.

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Section: Tratamento De Resgateunclassified

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

Bouzas¹,

Silva²,

Tavares³

et al. 2010

Rev. Bras. Hematol. Hemoter.

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“…Responses were more common in children than in adults. Kulkarni et al 66 reported data on 59 subjects with advanced cGVHD using thalidomide, 600-1200 mg/day. Thirteen subjects had a complete and eight, a partial response.…”

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 is active in mouse models of cGvHD and tested for prevention and therapy of cGvHD in humans. [4][5][6][7][8] However, doses expected to be effective were poorly tolerated because of somnolence, neuropathy and constipation. Pomalidomide is a new immune-modulating drug with 4000-fold greater inhibition of TNF-α relative to thalidomide.…”

mentioning

confidence: 99%

Phase-1/-2 study of pomalidomide in chronic GvHD

Pusic

Rettig

DiPersio

et al. 2015

Bone Marrow Transplant

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Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease

Cited by 41 publications

References 28 publications

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

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

Phase-1/-2 study of pomalidomide in chronic GvHD

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