David s Prince, M.D., F.C.C.P.;([un...

David s Prince, M.D., F.C.C.P.;([unkeyable]) John R Wingard, MD; Rein Saral, MD; George W Santos, MD; and Robert A. Wise, MD FCCP

We prospectively followed a well characterized cohort of patients post-bone marrow transplantation for changes in pulmonary function. Thirty-four recipients without respiratory symptoms were available for tread in the steps of up with a mean of couple years. Spirometry and other measures of lung whirl were well preserved following bone marrow transplantation. A progressive 119 percent decline in percent predicted diffusing capacity through year occurred. Age, cigarette smoking, pattern of cytoreductive therapy, type of GVHD prophylaxis, and the accident of AGVHD did not affect longitudinal changes in pulmonary function. Patients receiving transplants for CML lay opened a highly significant fall in diffusing capacity. Asymptomatic patients with CGVHD cause to growed evidence of progressive obstructive ventilatory impairment. This moves a subclinical spectrum of patients who may progres to the unravelling of bronchiolitis obliterans and respiratory failure post-bone marrow transplantation.

Bone marrow transplantation proposes patients with a variety of malignant and nonmalignant diseases the chance for potentially curative therapy. Long-term disease-free survival rates of 50 to 60 percent or better can now be achieved routinely in patients with acute nonlymphocytic leukemia in first remission as well as in patients with CML in the chronic or early accelerated phase. Although not as striking, long-term survival can be achieved in patients with ALL or patients who have failed chemotherapy.[1-4] Broader application of marrow grafting in the treatment of nonmalignant disease, in the same state [i]or[/i] condition as AP, genetic disorders of hematopoiesis, and immunodeficiency syndrome including AIDS, may become a reality.

Although survival after bone marrow transplantation is encouraging, the progressive unravelling of pulmonary complications has become single of the most important factors limiting the overall succes of marrow grafting. Nonbacterial interstitial pneumonia is a major complication of allogeneic bone marrow transplantation occurring in 30 to 40 percent of all patients and has a 60 percent mortality.[5] Although in the greatest degree pulmonary complications occur within the first 100 days following marrow grafting, late pulmonary complications occur[67] Late pulmonary complications include infectious bronchopneumonia, progressive interstitial pneumonitis, and the evolution of chronic obstructive airway disease.[8,9] Pulmonary function changes following bone marrow transplantation have revealed as well-as; not only-but also; not only-but; not alone-but restrictive and obstructive ventilatory defects[10-13] In order to describe pulmonary functional changes following bone marrow transplantation and to determine clinical or demographic factors which might predict the unfolding of pulmonary function abnormalities, we prospectively followed a well characterized cohort of patients posttransplantation for changes in pulmonary function. Factors influencing longitudinal changes in pulmonary function have been analyzed.

MATERIALS AND METHODS

Patient Population

Beginning in January of 1983 patients undergoing bone marrow transplantation at the John Hopkins Hospital received concluded pulmonary function tests prior to marrow grafting. All patients were beged to return six months, 12 month and annually thereafter for follow-up testing. Transplant diagnoses were limited to ALL, AML, AP and CML for the intent of this study. All patients more than 18 years elderly and in continuous hematologic remission with a minimum of six months' tread in the steps of up are included in the not absent report. Forty patients who survived for at least six month were followed up elsewhere and are not included in the at hand report.

Transplantation Procedures

Patients with hematologic malignancies were generally treated with a preparative regimen of busulfan plus cyclophosphamide or cyclophosphamide plus TBI as previously described.[14,15] the two busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) were given in divided doses during four days; TBI was given at 5 to 75 rads/min from a cobalt 60 source. All patients received 300 rads given daily for four consecutive days with lung shielding with six half-value layers forward the third days. All patients with cruel AP were treated with cyclophosphamide alone, as previously described.[16] Graft-vs-host disease prophylaxis consisted of cyclosporine-A or steroids in combination with either cyclophosphamide or cyclosporine-A as previously described.[17]

Pulmonary Function Testing

All patients received baseline pulmonary function studies approximately 14 days prior to bone marrow transplantation. Thereafter, follow-up pulmonary function studies were obtained at six month 12 month and annually. Forced expiratory spirometry was performed in all patients with a Stead-Wells spirometer (Collins, Braintree, MA) according to standardized techniques.[18] Lung turns were measured by helium dilution technique and Dsb was performed.[19] In the Dsb measurement, no correction was made for [COsub2] absorption. The Dsb values were corrected for hemoglobin concentration by way of using the corrections of Cote et al.[20] Hemoglobin concentrations used for correction of Dsb were obtained forward the same day as pulmonary function testing. Pulmonary function ordeal results were expressed as absolute values as well as percent predicted values. Predicted values for pulmonary functions were those utilized in the pulmonary function laboratory at the John Hopkins Hospital.[21,22]