Severe Chronic Pulmonary Graft Versus Host Disease: Case Report

Abstract

Background: Graft-versus-host disease (GvHD) is an immunological disorder that affects many organ systems including the gastrointestinal tract, liver, skin and lungs. Chronic GVHD (cGVHD) is still a major complication of long-term survivors after allo-HSCT, it occurs in 20%-45% of patients who survive after 6 months of transplantation and pulmonary involvement is common. Pulmonary complications significantly contribute to late mortality after allo-HSCT, furthermore, late-onset non-infectious pulmonary complications can be present with restrictive lung function impairment (restrictive pulmonary function test (PFT) pattern, late interstitial pneumonitis (IP), cryptogenic organizing pneumonia (COP),or airway obstruction (obstructive PFT pattern, bronchiolitis obliteratans (BO). However, BO is the only pulmonary complication, which is currently considered diagnostic of cGVHD. Late IP as well as COP may occur in association with cGVHD and are regarded as 'associated' manifestations of cGVHD, being rare the cases that occur in isolation. Methods: Description of a clinical case. Results: A 49-year-old female diagnosed with Acute Myeloid Leukemia (NMP1 + and FLT3 +) in 1 RC after HOVON 132 arm A protocol, followed by consolidation with high dose cytarabine, is described. Allograft of bone marrow, from related donor (sister, HLA 10/10, Isogrupal, CMV IgG -) was performed in January 2017. Prophylaxis of GVHD was made with Methotrexate and Cyclosporine. In April 2017, the patient had an irritative cough and dyspnea with moderate efforts which deteriorated to dyspnea with minimal efforts motivating the hospitalization in July 2017. Patient denied dry eyes, dry skin or weight lost. A diagnostic study was carried out, excluding infections, cardiac, thromboembolic and other possible manifestations of GVHD. CT scan with evidence of depolyzed glass densification in the upper lobe of the right lung and several others with peri-bronchial distribution, suggestive of COP. Spirometry with mixed ventilatory alteration (FEV1-29.5%; CPT-60.4%), with no positive response with bronchodilation and decreased CO diffusion capacity. Pulmonary biopsy showed aspects suggestive of organizational pneumonia that may correspond to the manifestation of graft disease. Treatment with 1mg/ kg/ day of Prednisolone, nebulizations with Fluticazone, Aclidinium bromide and Formoterol was initiated with clinical and imaging improvement. Conclusions: COP is a rare presentation of cGVHD, which sometimes leads to a complex diagnosis leading to a delayed initiation of therapy. The majority of patients with COP have persistent, bothersome, and progressive symptoms, the initial therapy is with oral glucocorticoids (dose of prednisone of 0.75 to 1 mg/kg per day). Recovery, usually with complete resolution of symptoms and normalization of the chest film, occurs in two-thirds of patients. Symptomatic improvement is occasionally quite dramatic, occurring in one to two weeks, although most patients improve more gradually over several weeks to a few months.