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

Browne, Paul; Weisdorf, Daniel J.; DeFor, Todd E.; Miller, Wesley J.; Davies, S. M.; Filipovich, A. H.; Mcglave, P. B.; Ramsay, N. K. C.; Wagner, John E.; Enright, H

doi:10.1038/sj.bmt.1702626

Cited by 67 publications

(37 citation statements)

References 17 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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“…Despite one case report of BO responding to thalidomide, 43 a recent study has shown no benefit in pulmonary chronic GVHD. 44 Intravenous immunoglobulin has not been shown to prevent the development of BO. 45 Cyclosporine may prevent the development of BO.…”

Section: Treatmentmentioning

confidence: 99%

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

Afessa

Tefferi

2001

Bone Marrow Transplant

274

308

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Summary:Pulmonary complications develop in 30-60% of hematopoietic stem cell transplants (HSCT). The main, late onset, non-infectious complications include Bronchiolitis obliterans (BO), Bronchiolitis obliterans organizing pneumonia (BOOP), and idiopathic pneumonia syndrome (IPS). BO and BOOP occur almost exclusively in allogeneic HSCT, and have 61% and 21% mortality rates, respectively. BOOP responds favorably to corticosteroids. IPS has less than 15% 1-year survival. Bone Marrow Transplantation (2001) 28, 425-434. Keywords: pulmonary complications; Bronchiolitis obliterans; Bronchiolitis obliterans organizing pneumonia; interstitial pneumonia; hematopoietic stem cell transplantation Despite the success in treating otherwise fatal diseases, HSCT is associated with multiple complications. Pulmonary complications develop in 30-60% of HSCT recipients. 1,2 Factors that influence the development of pulmonary complications in HSCT include previous infections, pre-transplant conditioning regimen, current or prior immunosuppressant and radiation treatment, type of stem cell transplant (autologous vs allogeneic), use of prophylactic antibiotics, and time elapsed since transplant. With the use of prophylactic antibiotics, the spectrum of pulmonary complications following HSCT has changed increasingly from infectious to non-infectious etiologies. The times of onset and distinguishing features of the main non-infectious pulmonary complications are shown in Figure 1 and Table 1. This review will focus on the late-onset, non-infectious pulmonary complications in HSCT recipients. An algorithmic approach is outlined in Figure 2. Since most of the treatable pulmonary complications in HSCT recipients are diagnosed non-invasively and by bronchoscopy, we rarely subject our patients to surgical lung biopsy. However, in patients with suspected BOOP and when bronchoscopy is contraindicated or non-diagnostic, we occasionally resort to video-assisted thoracoscopic surgical lung biopsy. Abnormal lung functionRestrictive and obstructive ventilatory defects, and gas transfer abnormalities occur frequently in HSCT recipients. 3,4 In a study of 52 young, asymptomatic HSCT recipients, 38% had abnormalities in pulmonary function tests (PFT): 23% restrictive defect with or without impaired gas transfer and 15% isolated impaired gas transfer. 3 An abnormal pulmonary function test is a risk factor for pulmonary complications. 5-9 However, the role of PFT in identifying HSCT recipients at risk for pulmonary complications needs further investigation. The PFT findings in BO, BOOP, and delayed pulmonary toxicity syndrome are listed in Table 2. Bronchiolitis obliterans (BO)GVHD is a frequent complication of allogeneic HSCT. 10 The pulmonary morphological manifestations of GVHD include diffuse alveolar damage, lymphocytic bronchitis/ bronchiolitis with interstitial pneumonitis, BOOP, and BO. 11 BO is a nonspecific inflammatory injury affecting

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“…Six complete responses and four partial responses were reported. Browne et al 65 treated 37 subjects with advanced cGVHD with thalidomide, 200-800 mg/day. In all, 1 subject had a complete and 13, partial responses.…”

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

Cited by 67 publications

References 17 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

Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation

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

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