Key Point

Impaired pretransplant lung function, particularly impaired DLCO and FEV1, is a significant risk factor for early respiratory failure and mortality after allogeneic stem cell transplantation.

SEATTLE—Pulmonary function tests are often performed before hematopoietic stem cell transplantation to screen for underlying respiratory problems. Recent research has suggested that pretransplant pulmonary function tests—particularly a measurement combining FEV₁ and the diffusing capacity of carbon dioxide (DLCO)—can predict posttransplant respiratory failure and mortality.¹

Jason Chien, MD, and colleagues retrospectively studied the pretransplant pulmonary function and arterial blood gasses of 2,852 cancer patients who received allogeneic stem cell transplants during a 12-year period. FEV₁, FVC, total lung capacity, DLCO, and alveolar-arterial oxygen tension difference (PaO₂) were measured. Patients in the nonmyeloablative group received 2Gy total body irradiation. Those in the myeloablative group received either total-body-irradiation-based or non-total-body-irradiation-based regimens. According to Dr. Chien, an Assistant Professor of Pulmonary and Critical Care Medicine at the Fred Hutchinson Cancer Center, “Assessment of pretransplant pulmonary function tests is very important, given their relationship with mortality risk. We would like to see every transplant center in the world screen their patients with pretransplant pulmonary function tests.”

LOW PULMONARY FUNCTION SPELLS BAD NEWS

The majority of patients (80%) had normal pretransplant pulmonary function tests. Similarly, among the 1,135 patients who had blood gas measurements, 85% had a normal PaO₂. The median PaO₂ was 5.4 mm Hg (range, 0 to 52.9 mm Hg). However, early respiratory failure (defined as respiratory failure that necessitated mechanical ventilation within 120 days after transplant) occurred in 14% of patients—within a median of 21 days. This is important, the researchers pointed out, because 91% of the patients who received ventilation died.

Multivariable analyses revealed that FVC, TLC, and DLCO less than 80%, PaO₂ more than 30 mm Hg, and pretransplant FEV₁ less than 70% were significantly associated with occurence of early respiratory failure after the transplant procedure. A significant increase in mortality was observed when the pulmonary function test values were less than 70% or the oxygen tension difference was above 20 mm Hg. It is possible that “the lungs injured prior to transplant had less reserve, such that the patient [was] unable to compensate for any significant damage to the lungs after transplant,” explained Dr. Chien. Alternatively, he suggested that pulmonary function tests could serve as a “nonspecific measure of the patient’s overall health status.”

NEW LUNG FUNCTION CATEGORY A BETTER PREDICTOR

The researchers reported that pulmonary function test values were not independent predictors of patient outcomes and that there were significant correlations between the individual pulmonary function test values. Given the correlation between some values, but not between DLCO and FEV₁, Dr. Chien and his colleagues found that FEV₁ and DLCO measured together represented a stronger indicator of risk for early respiratory failure and mortality. A separate score, called the “lung function score” was developed to measure these values together.

A lung function score of greater than 80% was ranked as category 1, 70% to 80% category 2, 60% to 70% 3, and less than 60% category 4. Each successively higher lung function score category was associated with a significantly increased risk for respiratory failure and death. The hazard ratio (HR) for respiratory failure in category 2 was 1.4. Categories 3 and 4 were associated with doubled and tripled risks of respiratory failure. The risks of death were similar (category 2 HR, 1.2; category 3 HR, 2.2; category 4 HR, 2.7). The survival probability was particularly grim for patients in category 4 who received total- body irradiation: No patients in this group survived beyond two years posttransplant.

The authors acknowledge that they did not diagnose the causes of the impaired pretransplant lung function. However, they noted that advanced malignancy, radiation treatment, and chemotherapy can damage the lungs, which could have contributed to the abnormal lung function. Because patients with poor lung function may not benefit from a transplant, clinicians need to help them weigh the transplant decision. “It is our hope that the lung function score and the associated mortality risk will be used in discussions with transplant candidates to help them decide if the potential mortality risk of transplantation outweighs the benefits,” explained Dr. Chien.

He cautioned that “pulmonary function tests need to be interpreted in light of other pretransplant risk factors for death.” He added that his team has developed a tool to assess this risk, called the Pretransplant Assessment of Mortality Score. This tool can help determine which patients are the best candidates for stem cell transplantation and which ones should forego transplantation and opt for palliative care instead.

—Tamara Gibb

Reference
1. Parimon T, Madtes DK, Au DH, et al. Pretransplant lung function, respiratory failure, and mortality after stem cell transplantation. Am J Respir Crit Care Med. 2005;172:384-390.

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