title: Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation.
abstract: OBJECTIVE
  To report the outcome as well as the clinical, radiographic, and pathologic features of idiopathic pneumonia syndrome (IPS) following autologous peripheral blood stem cell transplantation (aPBSCT).
  
  
  RESULTS
  A total of 271 patients with a variety of underlying malignancies received busulfan-containing myeloablative chemotherapy prior to aPBSCT; none of these patients received total body irradiation. Ten individuals developed IPS, with a median time of onset of 102 days after stem cell infusion. The major clinical and radiographic findings included an acute or subacute onset of dyspnea, cough, hypoxemia, and bilateral or unilateral infiltrates with or without pleural effusion. Pathologic findings consisted mainly of diffuse interstitial pneumonitis, organizing alveolitis, and cellular atypia. Nine patients diagnosed with IPS were treated with high doses of glucocorticoids parenterally. Despite heroic measures, eight patients died of IPS. The two remaining individuals recovered without experiencing significant long-term pulmonary sequelae.
  
  
  CONCLUSIONS
  Chronic low-dose busulfan therapy results in lung injury in 4-6% of patients after several years of treatment and once the cumulative dosage begins to approach 3g. High-dose, short-course busulfan (16 mg/kg)-containing conditioning chemotherapy prior to aPBSCT can also be complicated by IPS. IPS differs from lung damage due to chronic busulfan therapy by its earlier onset, an acute or subacute rather than indolent presentation, characteristic clinical and radiographic features, and lack of multinucleated giant cells on pathologic review. The pathophysiology of IPS secondary to high-dose busulfan-containing myeloablative regimens is not known, but cell-mediated immune reactions and release of cytokines may contribute to the lung injury. Mortality is high (80%) despite the use of heroic measures, including mechanical ventilation. Some patients, however, can respond to high doses of parenteral corticosteroid therapy.
  
  
  CONCLUSIONS
  IPS following high-dose, short-course busulfan-containing regimens exhibits unique clinical, radiographic, and pathologic features that differ from lung damage characteristic of chronic, low-dose busulfan therapy. Mortality from this complication is 80%, but some patients survive without long-term pulmonary sequelae following early treatment with glucocorticoids.
authors.affiliation: University of Connecticut Health Center, Farmington 06030-1315, USA. bilgrami@nso.uchc.edu
authors.forename: S F
authors.initials: SF
authors.lastname: Bilgrami
authors.forename: M L
authors.initials: ML
authors.lastname: Metersky
authors.forename: D
authors.initials: D
authors.lastname: McNally
authors.forename: B H
authors.initials: BH
authors.lastname: Naqvi
authors.forename: D
authors.initials: D
authors.lastname: Kapur
authors.forename: D
authors.initials: D
authors.lastname: Raible
authors.forename: R D
authors.initials: RD
authors.lastname: Bona
authors.forename: R L
authors.initials: RL
authors.lastname: Edwards
authors.forename: J M
authors.initials: JM
authors.lastname: Feingold
authors.forename: J M
authors.initials: JM
authors.lastname: Clive
authors.forename: P J
authors.initials: PJ
authors.lastname: Tutschka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D002066:Busulfan / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002066:Busulfan