Chest

Chest

Volume 144, Issue 6, December 2013, Pages 1913-1922
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Recent Advances in Chest Medicine
An Update on Pulmonary Complications of Hematopoietic Stem Cell Transplantation

https://doi.org/10.1378/chest.12-1708Get rights and content

The indications for hematopoietic stem cell transplantation (HSCT) continue to expand. However, the risk for pulmonary complications post-HSCT continues to be high. Early recognition and treatment of pulmonary complications may improve outcomes. This is an overview of diagnosis, manifestations, and treatment of the most common infectious and noninfectious pulmonary complications post-HSCT. Knowing the patient's timeframe post-HSCT (preengraftment, postengraftment, late), type of HSCT (allogeneic vs autologous), radiographic findings, and clinical presentation can help to differentiate between the many pulmonary complications. This article will also address pretransplantation evaluation and infectious and noninfectious complications in the patient post-HSCT. While mortality post-HSCT continues to improve, respiratory failure continues to be the leading cause of ICU admissions for patients who have undergone HSCT. Mechanical ventilation is a predictor of poor outcomes in these patients, and further research is needed regarding their critical care management, treatment options for noninfectious pulmonary complications, and mortality prediction models posttransplantation.

Section snippets

Pretransplant Pulmonary Evaluation

Evaluating the patient who has undergone HSCT for pulmonary complications begins prior to bone marrow transplantation. A recent study in the autologous HSCT population showed that the strongest predictors of pulmonary complications were low Karnofsky scores and underlying malignancy.3

The choice of preparatory regimen, dose of total body irradiation, and source of HSCT can also influence early pulmonary complications. For example, patients undergoing myeloablative regimens, in contrast to RIT

Infectious Complications in HSCT

Despite prophylactic strategies and advances in diagnosis and treatment of pulmonary infections, pneumonia remains an important cause of nonrelapse mortality after HSCT.12 Infectious complications are more common in patients undergoing allogeneic transplants due to prolonged immunosuppressive therapy and graft vs host disease (GVHD) (complication in which the newly transplanted donor hematopoietic bone marrow attacks the recipient's body). Additionally, chemotherapeutic agents such as rituxan

Viral Infections

The occurrence of cytomegalovirus (CMV) pneumonia infection has decreased with CMV monitoring and prophylaxis.19 While ganciclovir for CMV prophylaxis has benefits, the myelosuppressive toxicity has limited its use as routine prophylaxis. Instead, many institutions opt for preemptive treatment of CMV based on plasma pp65 antigen or quantitative polymerase chain reaction (PCR) testing.20

In a recent small prospective trial, use of valganciclovir as preemptive therapy demonstrated equivalent viral

Fungal Infections

Invasive pulmonary aspergillosis is the most common invasive fungal infection among HSCT recipients with reported incidence of 5% to 30% in allogeneic and 1% to 5% in autologous HSCT.27 Incidence of aspergillosis continues to decrease with the increased use of Aspergillus prophylaxis. While a number of randomized controlled trials have shown that prophylaxis for Aspergillus infection is correlated with reduced all-cause mortality, long-term mortality (> 36 months) is unchanged.28

Prophylaxis

Noninfectious Pulmonary Complications

While the overall incidence of infectious pulmonary complications has decreased, the morbidity and mortality with noninfectious pulmonary complications remain relatively unchanged.41 A number of distinct acute lung injury syndromes have been described following HSCT: periengraftment respiratory distress syndrome, diffuse alveolar hemorrhage, and idiopathic pneumonia syndrome (Table 1).

Periengraftment respiratory distress syndrome (PERDS), previously referred to as engraftment syndrome, is a

Late Pulmonary Complications Post-HSCT

Late pulmonary complications (> 100 days posttransplant) occur most frequently in patients with chronic GVHD. The development of late-onset pulmonary complications is associated with reduced overall survival.55 Moreover, with the increasing use of RIT in older patients, there is a higher incidence of late pulmonary complications.4

These patients are often immunosuppressed and at risk for pulmonary infections such as fungal, viral, and encapsulated bacterial organisms. Additionally, patients with

Other Pulmonary Complications

Pulmonary venoocclusive disease is rare but fatal in the patient who has undergone HSCT if not recognized. The typical triad includes dyspnea, pulmonary arterial hypertension with normal pulmonary artery occlusion pressure, and radiographic imaging suggestive of pulmonary edema.68 Treatment with high-dose steroids and heparin have been anecdotally beneficial.56 Pulmonary venoocclusive disease rarely responds to therapy and lung transplantation should be considered for these patients.

Evaluating Suspected Pulmonary Complications

Evaluating the patient who has undergone HSCT with a suspected pulmonary complication can be challenging. Determining the time course, type of HSCT, and course of illness is the first step in narrowing the differential of potential pulmonary complications.

HRCT scanning can provide information to narrow the differential of pulmonary complications and localize an area for biopsy or sampling.71 Characteristic findings for late HSCT pulmonary complications include mosaic lung attenuation as seen in

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: We express gratitude to Deborah D. Poutsiaka, MD, PhD, for her assistance in reviewing the pulmonary complications related to infectious diseases.

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