Lung Transplantation for Bronchiolitis Obliterans After Allogeneic Hematopoietic Stem Cell Transplantation (2013)

The number of allogeneic hematopoietic stem cell transplants (allo-HSCT) performed is increasing, and with it, the number of patients with respiratory failure due to chronic graft-versus-host disease–associated bronchiolitis obliterans syndrome (BOS), estimated to occur in about 6% of the cases after allo-HSCT. However, because there is no effective medical treatment for patients with this condition, the number of such patients referred to lung transplantation (LTx) is increasing. We therefore read with great interest the article “Lung transplantation for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation: a single-center experience” by Vogl et al. (1) who describe a cohort of seven patients who received LTx due to BOS after allo-HSCT in the period from 1996 to 2012. In this cohort, there was a case fatality rate of 57% and a median survival of 24 months after LTx. In a previously published multicenter study comprising 12 patients receiving LTx due to BOS after allo-HSCT, the case fatality rate was 33% (2). We recently published a report of 13 patients receiving LTx after allo-HSCT in the Nordic countries (3), with only 2 (15%) patients succumbing in the observation time. One of these died shortly after LTx due to septic infection, possibly related to his poor condition before LTx. The other died 1 year after LTx due to relapse of the hematologic malignancy (acute myelogenous leukemia), but notably, the interval from allo-HSCT to LTx was only about 1 year in this patient. Of note, no fungal infections were detected in any of these patients, although some Nordic LTx centers do not even use any antifungal prophylaxis. The apparent difference in case fatality rate between the cohort reported by Vogl et al. and our Nordic cohort may of course be a coincidence, considering the low numbers of cases observed. However, other possible explanations should be discussed. As we may assume that the follow-up after LTx is not very different between most LTx centers, the difference in case fatality rate may be the results of different patient selection. The International Society of Heart and Lung Transplantation recommends a 5-year interval between LTx and previous malignancy and considers less than 2 years a contraindication (4). However, it has been unclear whether these recommendations also apply for the interval between LTx and previous hematologic malignancies treated with allo-HSCT. Notably, whereas this interval was 18.1 months (range, 6–120 months) in the cohort reported by Vogl et al., it was 99 months (range, 8–198 months) in our cohort. It would be interesting to know how Vogl et al. have weighed this interval when listing these patients for LTx and also whether this issue may be related to the outcome in their patients. Although they apparently observed no relapse of the original hematologic malignancy, other factors related to the recent allo-HSCT may have had an influence, such as infections, microbial colonization, or breaches of infectious barriers. Finally, a more detailed description of the patients who died of other causes than infection might be of interest. The number of donor lungs available for transplantation is very limited. Therefore, when considering LTx, it is necessary to carefully evaluate not only the prognosis of each individual patient with or without LTx (“beneficence”) but also the therapeutic gain that may be expected in this patient compared with other patients in need of LTx (“utility”) (5). As illustrated by the article by Vogl et al., this evaluation of priority for LTx has to be done in close cooperation between hematologists and the LTx team. In the absence of larger studies, a discussion of the selection process, including what might be an appropriate interval between allo-HSCT and LTx, might help in clinical decision-making. Both the prevailing organ shortage and the high variation in reported case fatality rate in these patients add to the urgency of this issue. Are Martin Holm 1,2 Gerdt C. Riise3 Lorentz Brinch4 Øystein Bjørtuft1 Martin Iversen5 Svein Simonsen6 Yngvar Fløisand4 1Department of Respiratory Medicine Oslo University Hospital Rikshospitalet Oslo, Norway 2Faculty of Medicine University of Oslo Oslo, Norway 3 Department of Respiratory Medicine and Allergology Sahlgrenska University Hospital Gothenburg, Sweden 4 Department of Hematology Oslo University Hospital Rikshospitalet Oslo, Norway Oslo, Norway 5 Medical Department B, Rigshospitalet Copenhagen, Denmark 6 Department of Cardiology Oslo University Hospital Rikshospitalet Oslo, Norway