Progressive interstitial fibrosis of the lung in sclerodermoid chronic graft-versus-host disease

Abstract

Summary:Sclerodermoid chronic graft-versus-host disease (sGVHD) is a well-known complication in patients with a long history of chronic GVHD. Pulmonary involvement in chronic GVHD presents typically as bronchiolitis obliterans (BO). Pulmonary fibrosis after allogeneic hematopoietic stem cell transplantation (HSCT) is presumed to be caused by the long-term toxicity of the conditioning regimen or the result of lung injury elicited predominantly by viral infections or GVHD. We present two patients with late onset pulmonary fibrosis associated with moderate sGVHD of the skin after HSCT. At the initial diagnosis of chronic GVHD both patients presented with symptoms of interstitial pneumonia. Years later both patients developed moderate to severe interstitial pulmonary fibrosis in association with sGVHD. One patient showed additional clinical and histological signs of BO. While one patient responded to increased immunosuppression including total nodal irradiation (1 Gy), the other patient died due to complications related to pulmonary fibrosis. Bone Marrow Transplantation (2002) 29, 357-360. DOI: 10.1038/sj/bmt/1703386 Keywords: bone marrow transplantation; lung fibrosis; graft-versus-host disease; progressive systemic sclerosis; bronchiolitis obliterans; total nodal irradiation Sclerodermoid chronic GVHD (sGVHD) is a well-known late complication in patients with chronic GVHD. 1 It resembles progressive systemic sclerosis and involves the skin, fasciae, as well as the gastrointestinal tract. Furthermore data on cutaneous microchimerism in females with progressive systemic sclerosis may indicate a related pathophysiology. Progressive systemic sclerosis typically affects the kidneys and the lungs with development of alveolitis and pulmonary fibrosis. 5 However, pulmonary or renal involvement have not been reported in sGVHD. In chronic GVHD pulmonary changes are well known. Bronchiolitis obliterans (BO) is the typical and threatening pulmonary manifestation of chronic GVHD with progressive obstruction of the small bronchioles due to proliferation of the peribronchiolar tissue. [6][7][8][9][10][11] The occurrence of pulmonary fibrosis is mainly considered a manifestation of late toxicity of total body irradiation or chemotherapy during conditioning for allogeneic stem cell transplantation or the result of interstitial pneumonitis (IP) mainly due to viral infections or acute GVHD. 12-13 Here, we report two patients with sGVHD and late onset progressive pulmonary fibrosis. Patients Patient 1A 32-year-old male with a 15 pack-year smoking history received a peripheral stem cell graft from his HLA-identical sister for T-ALL in 2nd CR, after conditioning with TBI (12 Gy in six fractions with shielding of the lung, total pulmonary dose 10 Gy) and cyclophosphamide 60 mg/kg once daily i.v. on days 1 and 2. Patient and donor were CMVnegative by serology. GVHD prophylaxis consisted of cyclosporine A (CsA), MTX and prednisone. On day 90, the patient developed primary extensive chronic GVHD of the skin, oral mucosa, salivary glands an...

Small Chronic Pneumothoraces and Pulmonary Parenchymal Abnormalities After Bone Marrow Transplantation

“…[6][7][8][9][10] The chance of recurrence suggests that bilateral pneumothoraces are more likely to occur metachronously than simultaneously. An important feature of these pneumothoraces is that they tend to be small or at most moderate in size, such that patients are asymptomatic or have only mild symptoms.…”

“…However, one patient who developed pneumothorax as a complication of OB after BMT without evidence of multiple bullae has previously been reported. 9 OB occurs more often after allogeneic BMTs, and its pathogenesis is complex and multifactorial, though most cases are though to be secondary to bronchial mucosal damage from GVHD with inflammation of the small airways and their subsequent obliteration. In most cases, OB after BMT develops within a few years after transplantation, but its diagnosis is not always straightforward.…”

Incidence, outcome, and risk factors of late-onset noninfectious pulmonary complications after unrelated donor stem cell transplantation

“…However, several studies in children and adults showed a strong association between LONIPCs and chronic GVHD. [2][3][4][5][6][7] These studies focused on patients reinfused mostly with marrow progenitors from HLA-identical sibling donors. Since the incidence of chronic GVHD may be increased by the disparity of HLA matching and by the use of peripheral blood stem cells, 8,9 which have largely replaced bone marrow because of their relative ease of collection and the quicker engraftment kinetics, it may be hypothesized that LONIPC associated with GVHD is enhanced in the unrelated setting.…”

Les complications pulmonaires non infectieuses de l’allogreffe de cellules souches hématopoïétiques

“…Le scanner thoracique montre des images variées. Le LBA retrouve le plus souvent une alvéolite lymphocytaire et la biopsie pulmonaire des lésions de DAD, de pneumopathie interstitielle non spécifique, de LIP ou de fibrose évoluée avec infiltrat interstitiel lymphocytaire [43,50].…”