Cyclosporine as Possible Prophylaxis for Obstructive Airways Disease After Allogeneic Bone Marrow Transplantation

Summary:Pulmonary function testing (PFT) is used to characterize non-infectious pulmonary complications after allogeneic BMT. Identifying high-risk patients could facilitate preventive or early therapeutic measures. The objectives of the study were first, to review available data on PFT changes after BMT and second, to validate a previously published predictive index for PFT obstruction in patients transplanted at one center. For the systematic review, frequency, severity and time course of PFT changes after BMT and for the validation study, retrospective cohort comparing predicted with observed PFT, and calculation of indices of predictive accuracy were summarized. The validation study involved 434 patients from Princess Margaret Hospital, Toronto, Canada, who received their first BMT between 1980 and 1997, survived for at least 6 months and had adequate PFT follow-up. The systematic review included 20 studies. After BMT, decreased diffusion and total lung capacity were common and partially reversible. Obstruction was less common. The validation study of a previously published index, performed in 434 patients, found a sensitivity and specificity of 48% and 68% for identifying patients who develop obstruction. We concluded that PFT changes after BMT are common. A published predictive index is not sufficiently accurate to identify high-risk patients for potential preventive or early therapeutic strategies. The lung is often a target organ for complications after allogeneic marrow transplantation (BMT), 1,2 with pulmonary complications including infection, neoplasia, and idiopathic and iatrogenic disorders such as pulmonary edema, diffuse alveolar hemorrhage and obliterative bronchiolitis (OB). In the latter process, bronchioles become progressively constricted and obliterated from intramural infiltration, fibrosis and scarring. 1 After BMT, pulmonary function testing (PFT) can be useful to help diagnose complications, and in routine follow-up, as PFT abnormalities correlate with non-relapse mortality. 3 There are three main categories of PFT abnormalities. Obstructive defects occur when there is small airway closure or obstruction on expiration, leading to diminished forced expiratory volumes (one second forced expiratory volume -FEV1), classically with a preserved forced vital capacity (FVC), resulting in a decrease in FEV1/FVC ratio. In the BMT population, the prototypical cause of obstruction is OB. Its occurrence has been linked to chronic graft-versus-host disease (cGVHD), 4-11 and its frequency has been estimated to range from 8 to 33%. 4,[6][7][8][12][13][14] Although defined histologically, the diagnosis is most often presumptive, made based on signs and symptoms, radiographic changes and PFT showing obstruction, hyperinflation and gas trapping.Restriction is a pattern of decreased lung volumes (TLC, best measured by body plethysmography), with a preserved FEV1/FVC ratio. Our group and others have identified a decrease in TLC post BMT which tends to improve over time, 3,11,[15][16][17] with a reported inc...

mentioning

confidence: 59%

Section: Bone Marrow Transplantationmentioning

confidence: 99%

Pulmonary function abnormalities after allogeneic marrow transplantation: a systematic review and assessment of an existing predictive instrument

Marras

Szalai

Chan

et al. 2002

“…Overall rates of cGVHD were not different between eras, although we did not study the severity and extent of cGVHD. Cyclosporine use has been postulated to decrease the rates of OB, 13 but we were unable to adequately study this. Confounding by era (essentially all patients in the recent cohort received cyclosporine) prevented studying cyclosporine as an explanatory variable in the analysis restricted to recent era patients.…”

Section: Discussionmentioning

confidence: 94%

Long-term pulmonary function abnormalities and survival after allogeneic marrow transplantation

Marras

Chan

Lipton

et al. 2004

Summary:We studied long-term pulmonary function testing (PFT) in a retrospective cohort of 6-month survivors of allogeneic marrow transplant (BMT) between 1980 and 1997. Of 593 patients, 73, 71 and 65% had adequate data to assess for obstruction, restriction and diffusion impairments respectively. Over 5 years, mean declines in 1-s forced expiratory volume/forced vital capacity (FEV1/FVC), total lung capacity (TLC) and diffusion were 4, 7 and 17%, respectively. TLC and diffusion tended to subsequently increase. In all, 6, 12 and 35% of patients met criteria for obstruction, restriction and impaired diffusion, respectively. Obstruction was less common in recent transplants (5 vs 15%, P ¼ 0.004), while restriction and diffusion impairment rates remained stable. There was significantly greater mortality with obstruction (HR 2.0 (1.04-3.95)), and a nonstatistically significant higher mortality rate with restriction (HR 1.6 (0.95-2.75)), but not with impaired diffusion (HR ¼ 0.99 (0.65-1.50)). cGVHD ) and busulfan (OR 2.9 (1.01-8.24)) were associated with obstruction. Marrow from nonsibling or mismatched donors (OR 4.9 (2.2-10.7)) was associated with restriction. In summary, after BMT, decreased diffusion capacity is common and benign; obstruction has decreased in frequency, is rare without cGVHD, and is associated with mortality; nonsibling and mismatched donor are risk factors for restriction. The lung is often a target organ for complications after allogeneic marrow transplantation (BMT), 1,2 with pulmonary complications including infection, neoplasia, and idiopathic and iatrogenic disorders. The latter group includes pulmonary edema, peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, idiopathic pneumonia syndrome and obliterative bronchiolitis (OB). 3 Pulmonary function testing (PFT) after BMT is useful for predicting survival, given that PFT abnormalities correlate with nonrelapse mortality, 4 and the diagnosis of BMT complications, where PFT abnormalities make up some of the diagnostic criteria. 3,5 There are three main categories of PFT abnormalities. Obstructive defects occur when there is small airway closure or obstruction on expiration, leading to diminished forced expiratory volumes (1-s forced expiratory volume -FEV1), classically with a preserved forced vital capacity (FVC), resulting in a decrease in FEV1/FVC ratio. In the BMT population, the prototypical cause of obstruction is OB. Its occurrence has been linked to cGVHD. 6 Restriction is a pattern of decreased lung volumes (including the total lung capacity -TLC) with a preserved FEV1/FVC ratio. Idiopathic pneumonia syndrome, a diffuse noninfectious pneumonitis is a prototypical cause of restriction and may be due to thoracic irradiation, chemotherapy or other causes. Pulmonary edema, infectious pneumonitis and bronchiolitis obliterans organizing pneumonia (BOOP) may also cause restriction post-BMT. The final PFT derangement is one of diminished diffusion capacity for carbon monoxide (DCO). A low DCO often reflects thickenin...

“…However, the mortality rate in these patients still ranges from 60 to 75%. 11,[34][35][36] Interestingly, two of our patients received pleural adhesion therapy along with immunosuppressive agents. These two patients had longer survival times than did the patients who did not receive pleural adhesion therapy, suggesting that pleural adhesion therapy is effective.…”

Section: Tablementioning

confidence: 99%

Mediastinal emphysema and bilateral pneumothoraces with chronic GVHD in patients after allogeneic stem cell transplantation

Toubai

Tanaka

Kobayashi

et al. 2004

Summary:It is difficult to treat lung complications caused by chronic graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). We retrospectively analyzed the characteristics of five patients with mediastinal emphysema (ME) and bilateral pneumothoraces (BP) caused by chronic lung GVHD after allo-SCT. Four of these patients had undergone unrelated SCT, and three had had HLA-identical unrelated donors. All patients received total body irradiation (TBI) during conditioning. Immunosuppressive agents were administered as GHVD prophylaxis, but two patients developed acute GVHD and all the five developed chronic GVHD. The onset of lung complications was 99-1915 days (median, 202 days) after SCT. The onset of ME and BP was 6-48 days (median, 23 days) after the onset of lung complications. Immunosuppressive agents were initially beneficial on the lung complications, but the patients later showed no response to therapy, and all died from respiratory failure 7-195 days (median, 28 days) after the development of ME and BP. The results suggest that these complications progress rapidly, are resistant to treatment, and have a poor prognosis. It is therefore important to start prophylaxis and treatment as early as possible.