Longitudinal Changes in Pulmonary Function Following Bone Marrow Transplantation: Discussion
Also unlikely is a synergistic action of prior busulfan exposure with cyclophosphamide and TBI given at the time of transplant. Only six of 14 patients with CML received busulfan and cyclophosphamide as a preparative regimen. Radiation sensitization by busulfan and synergy between busulfan and other alkylating agents have been described in anecdotal reports only. Why patients with CML were more susceptible to a fall in Dsb is unclear. Other indicators of toxicity such as venoocclusive disease of the liver and interstitial pneumonia are not more prevalent in patients with CML. Age cannot be used to account for these findings in CML patients. The mean age of patients with CML (28.5 years; range, 18 to 44 years) was comparable to those with other diagnoses (27 years; range, 18 to 55 years). Further study is needed to determine the etiology of the progressive fall in Dsb seen in patients with CML.
Analysis of the effect of preparative regimen on rate of change of pulmonary function was most significant for the fact that patients who received cyclophosphamide alone showed a 15.7 percent increase in mean percent predicted Dsb. This result might be accounted for by the less intensive bone marrow transplantation preparative regimen and also possibly the fact that all four patients receiving cyclophosphamide alone had a pretransplant diagnosis of AP and thus had received no exposure to chemotherapeutic agents prior to transplantation. There was no significant difference in rate of change of pulmonary function between patients receiving cyclophosphamide and busulfan vs those receiving TBI and cyclophosphamide.
CGVHD predisposed patients to the development of a progressive obstructive ventilatory defect. The development of CGVHD was associated with a mean loss of 4.4 percent in percent predicted FEV! per year, in contrast to patients without GVHD who had a net gain in percent FEV! predicted of 4.3 percent. There were no significant differences in change in percent predicted FVC. In both the presence and absence of CGVHD, there was an associated loss of percent predicted Dsb of 13.5 and 11.2 percent per year, respectively. These were not significantly different. This is in keeping with the well described association of obstructive airway disease with CGVHD in multiple case reports. In the literature, the majority of these patients presented with progressive, severe and refractory dyspnea rapidly leading to deterioration and death due to respiratory failure. Postmortem examinations typically revealed evidence of bronchiolitis obliterans.