Lung transplantation for bronchiolitis obliterans after hematopoietic stem cell transplantation: a retrospective single-center study

Abstract

Background: Bronchiolitis obliterans (BO) is one of the most common late non-infectious pulmonary complications after hematopoietic stem cell transplantation (HSCT). Lung transplantation (LT) is the only cure for patients with end-stage BO, but the overall efficacy is rarely reported. Our study aims to conclude and elucidate the clinical experience of our single center and provide a reference for the current selection of treatment.Methods: We retrospectively analyzed the medical records of six patients with post-HSCT BO who received LT in our center from 2015 to 2019. The collected information included demographic data, surgery-related conditions, and postoperative follow-up data, which covered blood tests, infection status assessment, lung function assessment, anesthesia assessment, function assessment of other organs and so on. All patients were regularly followed up after discharge, which in the first year, was performed every 3 months. Over the next 2 years, patients were assessed every 6 months, and after 3 years, the frequency was once annually.Results: The mean age of patients at LT time was 28±13 years, with an interval of 72±48 months from HSCT. All patients developed hypercapnia with an average carbon dioxide partial pressure (pCO 2 ) of 71.1±20.8 mmHg. Preoperative pulmonary function tests showed the mean actual forced expiratory volume in 1 second (FEV1) was 16.7%±5.9% of the predicted value in four patients. After assessment, four patients adopted sequential bilateral LT and two adopted right-sided LT. Due to hemodynamic instability, five patients adopted intraoperative assistance of extracorporeal membrane oxygenation (ECMO). One patient died of septic shock 9 days after surgery, and the other five survived healthy for 53±23 months. The actual value of FEV1 at 3 months postoperatively accounted for 57.9%±15.3% of the predicted value. No patients had recurrence of BO.Conclusions: LT may be a treatment worthy of consideration in patients with post-HSCT end-stage BO because it can improve lung function, quality of life and prolong survival of these selected patients.

ERS/EBMT clinical practice guidelines on treatment of pulmonary chronic graft-versus-host disease in adults

“…In three of the four prospective studies [78][79][80], overall response rate varied between 0-27%, while one prospective study [81] had only two BOS patients who both achieved a partial response. Stabilisation or improvement of FEV1 was observed in the majority of patients in the retrospective studies, although some studies [87][88][89][90] showed no or a small effect. In addition, several of these studies reported that corticosteroids could be reduced or discontinued.…”

“…84 An update of the literature search resulted in one more BOS study (n=6) with similar findings. 89 Overall survival after lung transplantation for lung cGvHD-BOS was good, with reported 1-year survival ranging between 78-90% 81,84,89 and 5-year survival of 75-80% 81,83 . Other studies reported an overall survival of 50%, 67% and 100% at median follow-up of 20-24 months.…”

“…Next to this direct evidence, we identified four prospective [78][79][80][81] and 13 retrospective [82][83][84][85][86][87][88][89][90][91][92][93][94] cGvHD studies with subgroup analyses for BOS (2-23 BOS patients per study, 151 in total). In three of the four prospective studies [78][79][80], overall response rate varied between 0-27%, while one prospective study [81] had only two BOS patients who both achieved a partial response.…”

“…[88] Other common adverse events included thrombocytopenia, anemia, oedema, and hypotension, which were often mild and reversible. [79,89] It is important to keep in mind that ECP is very resource intensive and necessitates multiple points of contact with the healthcare facility. So, the beneficial effect of ECP might also come from regular contact with healthcare providers.…”

“…81,82,86,88 Cause of death after lung transplantation included infection/sepsis (n=10), lung graft failure/CLAD (n=5), malignancy/haematological relapse (n=5), and intracranial bleeding (n=1), accounting for an overall number of 20 reported deaths in 67 patients (30%). [81][82][83][84][87][88][89] Incidence of infections varied between 11-100%, depending on the type of infection. [81][82][83][84][85][86][87][88][89] The most prevalent types of infection were cytomegalovirus (range 11-42%) and fungal (range 14-29%).…”