Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Survey of the Late Effect Working Party EBMT.

Abstract

Aim and Scope: Substantial morbidity and mortality is caused by respiratory complications in 40–60% of patients after HSCT. Bronchiolitis obliterans syndrome (BOS) is reported in 2–13% of patients, occurring within 6–12 months post transplant. The LEWP launched a retrospective survey in 2003 to document the incidence, current practice for the diagnosis, clinical work-up and treatment of BOS after allogeneic HSCT.Patients&Method: Between 2003 – 2005, 31 centers reported 226 patients with BOS. Adjusted BOS criteria were accepted (normal spirometry pretransplant, respiratory symptoms in the absence of an infection and combination of 3/4 items at onset: FEV1 <80% predicted/measured; FEV1/FVC <80% and MMFR <50% predicted/measured and residual volume >120%; HR CAT scan of the thorax. FOB and BAL were used in 60% of centers, but open lung bx.was not recommended by 75%.Results: The median age of the patients was 30.9 years (1–62) and 19% was pediatric. The donors were 64.6% siblings. HSCT indication was hematological malignancy in 92.3% (37% AL, 21% CL). The graft source was BM in 60% and PBSC in 39%. The preparative regimen was myeloablation in 85.8%. The majority of the patients had antecedent GVHD (acute 66%, chronic 89%). The median interval from transplant to onset of BOS was 11.7 mo.s (1–260). Two third of the patients are still alive (22% in remission and 70% still receiving therapy). Median survival is 39.5 mo.s (1–277). The main reasons for high mortality rate are BOS (69%), relapse (15%) and GVHD (14%). The results of the univariate analysis on KM curves are summarized in Table 1.Conclusion: Univariate data showed a negative impact of male gender, early onset (<11.7 mo.s) and MUD transplants. BOS is still an important cause of non-relapse late morbidity and mortality. Diagnosis and treatment are difficult and heterogeneous. The final analysis with multivariate methods should validate current results.Variables tested in univariate analysesVariablesMed. OS, months (95% CI)PSibling/MUDNR75.9 (28.1–123.6)043Male/Female72.5 (47.6–97.4)NR0.038Onset: Early/Late59 (33.3–84.8)NR0.00001Ablative/Non Ablative102.8 (67.7–137.9)NR0.191NR: not reached