PURPOSE: Pulmonary complications occur in 30-60% of patients after HSCT,contributing to significant morbidity and mortality.Advances in pre-transplant antimicrobial prophylaxis have shifted concerns among transplant physicians to non-infectious complications,where relatively less progress has been made over the years in improving transplant-related outcomes.In particular,late onset non-infectious pulmonary complications(LONIPCs)including Idiopathic Pneumonia Syndrome(IPS), Bronchiolitis Obliterans(BO)and Bronchiolitis Obliterans Organising Pneumonia(BOOP)may occur and are strongly associated with chronic pulmonary GVHD.
METHODS: We reviewed data from 283 post-transplant patients in our registry between January 2004 to March 2011 and identified 26 allogeneic HSCT recipients who underwent bronchoscopy for pulmonary complications.
RESULTS: Eleven of these patients were diagnosed with LONIPCs at a median time of 14.6 months from transplant.Median age of subjects was 42 years old.Mean baseline Lung Function Score (LFS) was I.Eight patients received matched sibling donor (MSD),two patients umbilical cord blood(UCB) and one matched unrelated donor (MUD)transplant.All MSD and MUD transplant recipients received PBSC,and five male patients received allograft from sex-mismatched donors.Five of eleven patients received reduced intensity conditioning (RIC).Tubular bronchiectasis was the most common post-transplant radiologic abnormality.Post-transplant spirometric defects included obstruction(46%),restriction(36%)and isolated reduction in diffusion capacity(18%).Five patients fulfilled National Institute of Health (NIH) definition of Bronchiolitis Obliterans Syndrome(BOS).Histology in six patients reported BOOP,BO and non-specific inflammation in equal numbers.Most patients had GVHD involving at least another organ.Treatment involved oral azithromycin and systemic steroids in all patients; selected cases involved mycophenolate mofetil,calcineurin inhibitors,sirolimus,imatinib,thalidomide and extracorporeal photopheresis.At a median follow-up of 24 months for surviving patients,the 2-year survival was 78%.Majority of deaths were attributed to GVHD(BOS).
CONCLUSIONS: A significant proportion of patients post allogeneic HSCT develop LONIPCS.Bronchoscopy remains an important modality to exclude infective etiologies and to establish a more definitive histological diagnosis.
CLINICAL IMPLICATIONS: Although at present only BOS is considered diagnostic of pulmonary GVHD,BOOP is often closely associated,with a better prognosis.
DISCLOSURE: The following authors have nothing to disclose: Felicia Teo, Michelle Poon, Lip Kun Tan, Liang Piu Koh, Dipika Agrawal
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