Case Presentation: A 56 years old man with a history of CMV-negative hematopoietic stem cell transplant (HSCT) for acute lymphoblastic leukemia (ALL) six years previously, complicated by cutaneous graft versus host disease (GVHD) on mycophenolate presented to the emergency department after three months of progressively worsening shortness of breath that has significantly worsened in the previous week, leading to outpatient treatment with amoxicillin-clavulanic acid and clarithromycin without improvement. Regular screening pulmonary function tests three months previously revealed slightly impaired diffusion capacity of carbon monoxide, but no obstructive processes. On presentation, vital signs were notable for fever to 101.8 (38.8C) and exam revealed coarse crackles on lungs auscultation bilaterally. Laboratory studies were remarkable for leukocytosis to 12.8 and sodium of 129. Chest X-ray revealed bilateral opacities concerning for atypical pneumonia. The patient was started on broad spectrum intravenous antibiotics, however his respiratory status continued to worsen, at which time a chest CT revealed diffuse ground glass opacities. Subsequent viral testing, including PCR for SARS-CoV-2, was negative. Bronchoscopy was done with no evidence of malignancy or infection, including multiple negative fungal PCR studies and PJP DFA and culture. At this time, the patient’s lung disease burden with continuous high oxygen requirements by high flow nasal cannula and occasionally non rebreather mask were suggestive of markedly increased risk of both transbronchial and open lung biopsy. At this time, the decision was made to start empiric steroid therapy (1mg/kg prednisone) for presumed organizing pneumonia secondary to HSCT. The patient experienced subjective symptom improvement within 24 hours, and a decrease in supplemental oxygen requirement within 48 hours, though he was not able to be weaned off oxygen prior to discharge from the hospital.
Discussion: Pulmonary complications of HSCT are common, and are typically divided into peri-engrafment, early post-transplant, and late post-transplant complications. Both infectious and non-infectious etiologies of lung disease are possible at each stage. Late post-transplant pulmonary complications are defined as occurring >100 days after transplant. The predominant late pulmonary complications include cryptogenic organizing pneumonia (COP, formerly known as bronchiolitis obilterans organizing pneumonia, or BOOP), and bronchiolitis obliterans syndrome (BOS). Biopsy is gold-standard for diagnosis of late non-infectious pulmonary complications of HSCT, but, as in the case of our patient, may not be tolerated due to the extent of illness. In this case, the diagnosis may be made after exclusion of infectious etiologies, as treatment is pulse dose steroids (0.5mg-1mg/kg) for a prolonged period of time, followed by a slow taper. While “late onset” is defined as >100 days after transplant, our patient was six years post-transplant.
Conclusions: Pulmonary complications of HSCT can develop even years after illness. While diagnosis with biopsy is the gold standard, there is significant morbidity with open lung biopsy. As more patients survive longer from the time oF HSCT, there will be a great incidence of these patients treated in general wards and outside of highly specialized bone marrow centers, so the hospitalist should be aware of and vigilant for late-onset GVHD-associated lung disease.