A41-04 When Cure Turns Toxic: Melphalan-Associated Interstitial Pneumonitis After Autologous Transplant

Introduction Melphalan is an alkylating chemotherapeutic agent commonly used as conditioning therapy before autologous stem cell transplantation (ASCT). While generally well tolerated, high-dose melphalan has been associated with rare but serious pulmonary complications, including interstitial pneumonitis, diffuse alveolar damage, and progressive fibrosis. Onset may occur weeks to months after exposure, presenting with worsening dyspnea and hypoxemia that can mimic infection or exacerbation of interstitial lung disease (ILD). Given the nonspecific clinical and radiologic features, diagnosis requires careful exclusion of infectious, cardiogenic, and autoimmune etiologies. Case Presentation A 76-year-old woman with hypertension, hyperlipidemia, coronary artery disease, and multiple myeloma status post ASCT six months earlier (conditioned with high-dose melphalan) presented with progressive shortness of breath and bilateral lower extremity edema. She had a recent diagnosis of pulmonary fibrosis requiring 2 L of home oxygen. On admission, she was acutely hypoxic, requiring a non-rebreather mask. Laboratory studies revealed leukocytosis and acute kidney injury. Chest CT demonstrated diffuse honeycombing and reticulation consistent with fibrotic interstitial lung disease (usual interstitial pneumonia pattern), along with new bilateral ground-glass opacities and pleural effusions. The differential included pneumonia, ILD exacerbation, and congestive heart failure. She was started on empiric antibiotics, diuretics, and high-dose corticosteroids; however, her respiratory status worsened, necessitating high-flow nasal cannula support. Renal dysfunction limited further diuresis. During hospitalization, she developed thrombocytopenia, elevated LDH, indirect hyperbilirubinemia, and low fibrinogen, raising concern for disseminated intravascular coagulation and possible thrombotic thrombocytopenic purpura (TTP). She underwent plasmapheresis, but ADAMTS13 testing was negative, excluding TTP. Despite supportive measures, she progressed to multiorgan failure requiring vasopressors. Given her poor prognosis, goals of care were discussed, and she was transitioned to comfort measures. Discussion Melphalan-induced pulmonary toxicity is a rare but potentially fatal complication, with an estimated incidence below 1%. Reported cases describe onset of respiratory symptoms weeks to months after ASCT. The proposed mechanism involves melphalan-induced oxidative stress with depletion of antioxidant defenses such as glutathione, creating a redox imbalance that drives alveolar injury and fibrosis. Radiographically, bilateral ground-glass opacities and interstitial changes are typical. Diagnosis relies on clinical suspicion and exclusion of infection or other causes of ILD. Although corticosteroids may help, response is inconsistent and prognosis poor. Conclusion This case highlights that melphalan-induced lung injury, though uncommon, should be considered in patients with new or progressive respiratory failure after stem cell transplantation. Early recognition and multidisciplinary management are crucial for better outcomes.