Predictive value of pulmonary function tests before marrow transplantation

Abstract

Objective: To evaluate association between pulmonary function tests (PFT) performed before marrow transplantation and mortality after transplant.

Setting: A single marrow transplantation research center.

Design: Case-series review.

Patients: All patients between January 1986 and July 1990 who performed PFT before a first marrow transplant for the treatment of malignancy (n = 1297) were included in study. Six hundred twenty-eight (48 percent) patients had morphologically or cytologically active malignant neoplasms at the time of transplant. Allogeneic marrow transplants were performed in 1,056 (82 percent) and autologous transplants were performed in 235 (18 percent). Three hundred seventy-two (29 percent) patients received HLA-nonidentical donor marrow. Graft-vs-host disease prophylaxis was methotrexate and cyclosporine in 901 (85 percent) of the allogeneic recipients. Most patients were prepared for transplant with total body irradiation in addition to cyclophosphamide (n = 1,059, 82 percent), while 230 (18 percent) were conditioned with busulfan and cyclophosphamide.

Measurements and main results: The overall mortality during the first six months of follow-up was 44 percent. Respiratory failure requiring assisted mechanical ventilation occurred in 23 percent (n = 298) of patients. A proportional hazards regression analysis was used to evaluate the predictive value of PFT results: (1) FEV1/FVC; (2) P(A-a)O2 gradient; (3) TLC; and (4) Dcosb (the latter two presented a percent of predicted). Abnormalities in TLC, Dcosb, and P(A-a)O2 were found to be significantly associated with death in univariate analysis. Next, the value of PFT for prediction above and beyond other baseline covariates was evaluated by first using the step-up stepwise proportional hazards model to select predictive variables other than the PFT variables. Then each of the PFT variables was tested in the presence of these other variables. The factors of age, primary diagnosis, relapse status, and donor-recipient HLA nonidentity were found to be risks for death and were entered as covariates. Each of the variables of PFT were entered stepwise into the model. Dcosb (RR = 1.43 for a value 80 percent of predicted) and P(A-a)O2 (RR = 1.28 for a value of 20 mm Hg) were found to be independent risk factors for death. The use of assisted mechanical ventilation appeared to increase proportionately with the increase in mortality among patients with abnormal Dcosb or P(A-a)O2.

Conclusions: Decreased Dcosb and increased P(A-a)O2 gradient before marrow transplant carry significantly increased risk of death after marrow transplant. The risk associated with abnormal PFT is less than that associated with other recognized risk factors, such as relapse status and donor-recipient HLA nonidentity. Respiratory failure does not appear to account entirely for the increased mortality associated with abnormal pretransplant PFT. PFT should be used in assessing fully the risks to recipients of marrow transplants for malignancy, but should not be used as absolute exclusion criteria for transplantation.