Pulmonary Changes in Myeloma Patients Following High Dose Melphalan.

Background: Eligibility for high dose chemotherapy and autologous stem cell rescue often includes adequate pulmonary function. While high dose melphalan has been noted to cause significant pulmonary toxicity in a small percentage of patients with adequate pulmonary function, there are little published data on risk factors and use in lung impaired patients. We retrospectively reviewed the charts of 50 patients with myeloma who received a fixed dose of melphalan (200 mg/m²) and who had pre-melphalan and at least one post-melphalan spirometry (FVC and FEV1) and diffusing capacity (DLco) measurement. Comparisons were made with Pearson correlations and one-way ANOVA. Patients receiving melphalan showed no significant differences in mean FVC (p=0.40), FEV1 (p=0.48) or hemoglobin corrected DLco (p=0.40) comparing baseline to 3-month and 1-year results with 1-way ANOVA. There was a consistent increase in mean FVC(L), FEV1(L) and DLco (ml CO/min/mmHg) from pre to 3 months post (3m) and to one-year post (1y): FVC: pre=3.89, 3m= 4.02, 1y=4.24; FEV1: pre=2.92, 3m=2.95, 1y=3.14; DLco: pre=24.3, 3m=25.1, 1y=26.5. However, individual changes in DLco showed a wide distribution. Therefore, we examined a number of potential risk factors for change in DLco at 3 months. No detrimental effects were discernable for age, gender, history of prior pulmonary disease including smoking, pre-melphalan lung function, the use of high dose cyclophosphamide in the mobilization regimen, amount of prior chemotherapy or chest radiation, disease stage or response, or renal function. CD34+ cell dose (p=0.017, r = −0.344) and immunoglobulin type (IgA worse than IgG) (p=0.029, r = 0.316) were correlated and were independent factors on regression analysis (p<0.0018, r²=0.36). We conclude that on average, high dose melphalan produces little pulmonary toxicity and may be considered for selected patients with impaired baseline pulmonary function. It may be of value to avoid higher CD34+ cell doses in patients with a low pre-melphalan DLco. More work should be directed at identifying the factors that contribute to pulmonary function compromise following high dose regimens.