Early Hypoxemia With Diffuse Ground-glass Opacities After Allogeneic Hematopoietic Stem Cell Transplantation: Diagnostic Challenge Between Noninfectious Pneumonitis and Opportunistic Infection
Year: 2026
Type: article
Study design: Case Report
Abstract: Introduction Early pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT) are diagnostically challenging because opportunistic infection, inflammatory toxicity, diffuse alveolar injury, and noninfectious syndromes may overlap. Idiopathic pneumonia syndrome is a diagnosis of exclusion, defined by diffuse lung injury, hypoxemia, and absence of a predominant infectious, cardiogenic, or fluid-overload cause. Case report A 25-year-old woman with B-cell acute lymphoblastic leukemia underwent allogeneic haploidentical HSCT, after conditioning with fludarabine, melphalan, and total body irradiation. She received a peripheral blood stem cell graft containing 5.24 × 10⁶ CD34+ cells/kg. Around day +27, she developed cough, tachypnea, and new-onset hypoxemia. Chest computed tomography showed extensive bilateral confluent centrilobular ground-glass opacities with mild septal thickening, without pleural effusion or pneumothorax, and with a small pericardial effusion. An extensive infectious workup was performed. The molecular respiratory viral panel was negative for adenovirus, bocavirus, seasonal coronaviruses, SARS-CoV-2, enterovirus, metapneumovirus, rhinovirus, influenza A/B, parainfluenza, respiratory syncytial virus, Mycoplasma pneumoniae, and Bordetella spp. She was receiving acyclovir and letermovir prophylaxis, plus therapeutic-dose trimethoprim-sulfamethoxazole and levofloxacin for Stenotrophomonas maltophilia. CMV monitoring showed transient low-level positivity, subsequently below the lower limit of detection. She also received meropenem, liposomal amphotericin B, vancomycin, and polymyxin B, in the context of previous catheter-related bloodstream infection by Enterococcus faecium and S. maltophilia. Bronchoalveolar lavage bacterial culture was negative. BAL galactomannan index was 1.048, borderline and slightly above the positivity cutoff; however, the clinical-radiological pattern did not support a predominant invasive fungal disease, although antifungal coverage was maintained as a precaution. She required intensive care and sedation, with progressive hypoxemia and worsening PaO₂/FiO₂ ratio, consistent with severe acute respiratory distress syndrome, requiring lung-protective ventilation and prone positioning, with partial improvement after the maneuver. Discussion This case illustrates the complexity of classifying acute hypoxemia with diffuse pulmonary infiltrates early after HSCT. Timing, new hypoxemia, bilateral ground-glass pattern, negative extended viral panel, and absence of findings strongly suggestive of invasive fungal disease favored post-transplant noninfectious pneumonitis within the spectrum of idiopathic pneumonia syndrome. Borderline BAL galactomannan positivity required caution, since opportunistic infection and inflammatory lung injury may coexist. Management integrated ventilatory support, broad-spectrum antimicrobials, systemic antifungal therapy, exclusion of cardiogenic or fluid-overload causes, and early consideration of a noninfectious pulmonary complication. Conclusion In allogeneic HSCT recipients, early hypoxemia with diffuse ground-glass opacities requires broad investigation and integrated management. Noninfectious pneumonitis/idiopathic pneumonia syndrome should be considered when the initial infectious workup is inconclusive and the clinical-radiological pattern does not support a predominant infectious etiology.
Institution: Mater Dei Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223138215