How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation

Abstract

In past years, a diagnosis of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant (HCT) conferred nearly universal mortality secondary to lack of consensus for diagnostic criteria, poorly understood disease pathogenesis, and very few studies of therapeutic or supportive care interventions. Recently, however, progress has been made in these areas: revised consensus diagnostic guidelines are now available, supportive care has improved, there is greater understanding of potential mechanisms of disease, and prospective trials are being conducted. This article describes these advances and provides suggestions to optimize therapy for patients with BOS after HCT.

Figure 1.

Representative flow volume. (A) Representative flow volume loop of a patient with BOS (red) compared with a patient with normal exhalation (gray) (left). Spirogram representation of BOS (red) as compared with normal lung volumes (gray) and those of a patient with sclerotic GVHD (blue) or extrapulmonary restriction (right). Within the spirogram, the FEV1 is shown first, then the FVC and RV, and then the TLC (TLC = RV + VC). Below the spirogram are representative PFT parameters for each of the 3 groups of patients: normal in gray, BOS in red, and sclerotic GVHD in blue. (B) Representative flow volume showing the notch characteristic of tracheomegaly or tracheobronchomalacia. Panel A reprinted from Williams et al with permission.

Figure 2.

Algorithm for diagnosis, work-up, and treatment of BOS. Summary algorithm for diagnosis, work-up, supportive care considerations, and treatment of BOS. CI, confidence interval; cx, culture; IVIG, intravenous immunoglobulin G; PCP, pneumocystis jirovecci pneumonia; ppx, prophylaxis.

Figure 3.

Graph of FEV1 (mL) vs time (days) of patient 2. The time of cGVHD diagnosis (dx) and clinical symptoms (cough) as well as the time of BOS diagnosis are noted by arrows.

Figure 4.

Diagram of the proposed immune mechanisms linked to BOS pathogenesis, the current treatments in BOS, and the pathways blocked by these treatments. Cytokine/chemokine indicates TNF α for etanercept and multiple activating chemokines and cytokines for ECP.