Outcomes of Lung Transplantation After Allogeneic Hematopoietic Stem Cell Transplantation

Background:  Pulmonary complications can cause considerable morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT).  Other than lung transplantation (LT), no specific therapies exist for end-stage lung disease resulting from HCT-related complications such as bronchiolitis obliterans syndrome.  Here we describe the indications and outcomes in patients who had LT after HCT for hematologic disease.  Methods:  Retrospective chart review of cases identified by the Long-Term Follow Up (LTFU) database at the Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance. This database captures information provided by patients, primary physicians and by LTFU clinical service via telemedicine or by medical evaluation on site.  Any patient who received a HCT at our institution with a reported history of LT was included.  Results:  We identified 9 recipients of allogeneic HCT between 1971 and 2006 who subsequently received LT between 1990 and 2010.  The median age at the time of HCT was 16 (range, 10-35) years, and the median age at the time of LT was 34 (range, 17-44) years.  The diagnosis at the time of HCT was acute leukemia (n=7), chronic myeloid leukemia (n=1) and aplastic anemia (n=1). The median interval between HCT and LT was 123 (range, 35-326) months. None of the patients had evidence of the original hematologic disorder at time of LT.  Indications for LT included pulmonary fibrosis related to any history of radiation or chemotherapy before or as part of the conditioning regimen for HCT (n=4), interstitial pneumonitis related to graft-versus-host-disease (n=1), bronchiolitis obliterans syndrome (n=3), and primary pulmonary hypertension (n=1).  All patients received unilateral (n=4) or bilateral cadaveric LT (n=5).  Survival at one and five years after LT was 89% and 37%, respectively.  Eight of the 9 patients died at a median of 49 months (range, 2 weeks to 87 months), and 1 is alive more than two years after LT.  Deaths were attributed to chronic graft rejection and/or pulmonary infectious complications in 6 patients and anoxic brain injury from cardiac and pulmonary arrest in 1 patient.  Information about the cause of death for 1 patient who died 2 weeks after LT was unavailable.  According to a nationwide registry of organ transplantation (2010 OPTN/STRT Annual Data Report), survival of all LT recipients at one year improved from 72% in 1990 to 85% in 2008; survival at five years improved from 39% in 1990 to 56% in 2004.  Conclusions:  LT can prolong survival in some adult and adolescent patients who suffer from end-stage pulmonary complications after HCT.  These results can help to inform HCT patients who are considering LT.  HCT patients with progressive pulmonary disease, but otherwise in good health, should be referred to an established LT center for evaluation, since early identification of good candidates for LT may result in better survival outcomes.