Infectious and Non-Infectious Pulmonary Complications in HCT Patients Treated with Post Transplant Cyclophosphamide (PTCy) Based Gvhd Prophylaxis

Introduction: Pulmonary complications are a leading cause of mortality and morbidity amongst pts undergoing hematopoietic stem cell transplantation (HCT). Increasingly, allogeneic HCT recipients are undergoing HCT with PTCy based GVHD prophylaxis. While lower rates of severe GVHD has been reported with PTCy, increased infection and organ toxicity has also been seen compared with standard calcineurin inhibitor (CNI) prophylaxis. The incidence and outcomes of pulmonary complications, both infectious and non-infectious/immune in pts receiving PTCy remain poorly characterized. Therefore, we aimed to assess for these in this study.

Methods: We performed a retrospective review of pts between 2012-2022 who underwent 1st allogeneic BMT and received PTCy as part of GVHD prophylaxis. We identified pts requiring hospitalization for pulmonary complications. Infectious cases were categorized as bacterial, fungal, viral, or mixed. Bacterial pneumonia was defined as fever, cough, dyspnea, purulence sputum, and new or progressive radiographic evidence of infiltrate not explained by a non-infectious cause, treated with at least 5 days of antibiotics. Viral and fungal pneumonia were diagnosed based on identified organism. Noninfectious complications included idiopathic pulmonary syndrome (IPS), diffuse alveolar hemorrhage (DAH), cryptogenic organizing pneumonia (COP), and bronchiolitis obliterans syndrome (BOS). IPS was defined as radiographic evidence of alveolar infiltrates, dyspnea, cough, increased work of breathing or oxygen requirements, exclusion of infection or alternate pathology, and treated with high-dose systemic corticosteroids. DAH was defined as radiographic evidence of widespread alveolar injury, increased work of breathing or oxygen requirements, and persistent and progressive bloody return on BAL. COP was defined as pathologic evidence of organizing pneumonia on transbronchial lung biopsy in the absence of pathogens. BOS was defined as FEV1/FVC <0.7 and FEV1 <75% with a ≥10% decline over <2 years.

Results: A total of 224 pts were identified. Median age at HCT was 55 years (20-78) (Table 1). 138 (64%) were male. The median comorbidity index (HCT-CI) score was 3 and median Karnofsky Performance Score was 80. 56%(n=125) pts underwent HCT with nonmyoablative conditioning, 78% (n=157) underwent HCT with a haploidentical donor, and 65% (n=145) of grafts were peripheral blood. 4%(n=10) were current smokers at time of HCT, 38% (n=84) were former smokers. 16% (n=35) had an existing diagnosis of asthma or COPD.

72 (32%) pts were hospitalized for pneumonia at any point after HCT. There were 23 bacterial pneumonias (30%), 20 viral (27%), 13 fungal (18%), and 12 were mixed (17%) (Table 2). There were 4 pts (6%)with documented pneumonia of unknown etiology due to rapid progression to death or hospice.

10 pts (4%) developed IPS with a median onset of 153 days (20-354). 2 pts (1%) developed COP with a mean onset of 754 days (388 - 1119). 5 pts (2%) developed BOS with a median onset of 336 days (153-677). 8 pts (4%) developed DAH with a median onset of 48 days (20-152).

Among all patients, 57 pts (25%) required mechanical ventilation at any point post-HCT, and 18 pts (8%) were prescribed home oxygen at any point post-HCT. Overall, 80pts (77%) died due to non-relapse causes. 29 deaths (28%) were pulmonary related, (21 (20%) infectious and 8 (8%) noninfectious). Of the noninfectious pulmonary deaths, 3 pts died due to IPS, and 5 died due to DAH.

Conclusion: In our cohort of pts receiving PTCy based GVHD prophylaxis, significant infectious pulmonary complications were common and were fatal in 9.4% of pts. Infections were the major driver of pulmonary related mortality, however, we observed noninfectious/immunologic pulmonary complications at a rate within or only slightly below the previously reported ranges among transplanted pts predominantly receiving CNI based prophylaxis.