Incidence and Outcomes of Respiratory Failure after Nonmyeloablative Related Haploidentical Blood or Marrow Transplantation

Abstract

Respiratory failure is a devastating complication of allogenic blood or marrow transplantation (BMT). Prior data suggest that respiratory failure occurs in 20% of BMT recipients and acute respiratory distress syndrome (ARDS) occurs in 15%. Nonmyeloablative (NMA) haploidentical BMT allows donor pool expansion and may decrease complications. Incidence, outcomes, and risk factors for respiratory failure after NMA haploidentical BMT are unknown. This study aimed to determine the incidence of respiratory failure after NMA haploidentical BMT and explore outcomes and risk factors for respiratory failure. In this single-center, retrospective study of all patients age >18 years undergoing NMA haploidentical BMT between 2004 and 2016, the primary outcome was respiratory failure, marked by the use of high-flow nasal cannula oxygen, noninvasive ventilation (NIV), or invasive mechanical ventilation (IMV) within 2 years after BMT. Respiratory failure incidence is reported as incidence rate ratio (IRR) with 95% confidence interval (CI). Unadjusted and multivariable Cox proportional hazards models with adjustment for a priori identified patient-level characteristics were used. Results are presented as hazard ratio (HR) with 95% CI. A total of 520 patients underwent NMA haploidentical BMT, of whom 82 (15.8%) developed respiratory failure (IRR, 0.114/person-year) at a median of 0.34 year (interquartile range, 0.06 to 0.75 year) after BMT. Older age (HR, 1.04; 95% CI, 1.02 to 1.07), transplantation for myelodysplastic syndrome (MDS) (HR, 1.99; 95% CI, 1.07 to 3.72), and parent donor (HR, 3.49; 95% CI, 1.32 to 9.26) were associated with an increased risk of respiratory failure, whereas higher pretransplantation lung diffusion capacity of carbon monoxide (DLCO; % of predicted) was associated with lower risk (HR, 0.98; 95% CI, 0.77 to 0.99). Sixty-one patients (11.7%) required IMV, and 30 were successfully extubated. Only 37 patients (7%) had ARDS. Of the 82 patients with respiratory failure, 43 (52.4%) died during index hospitalization and 61 (77.2%) died by 2 years post-transplantation. Only 40 (49%) had nonrelapse mortality. The incidence of respiratory failure and ARDS after NMA haploidentical BMT is modest at 15% by 2 years post-transplantation. Despite successful extubation in >50% of patients, respiratory failure, regardless of cause, is associated with a high rate of death by 2 years from both relapse and nonrelapse causes. Age, BMT for MDS, parental donor, and pretransplantation DLCO are risk factors for respiratory failure.

Keywords: Acute hypoxemic respiratory failure; Acute respiratory distress syndrome; Bone marrow transplantation; Hematologic malignancies; Hematopoietic stem cell transplantation; Respiratory failure; Respiratory insufficiency.