Low Incidence of Pulmonary Graft-Versus-Host Disease in Older Patients After Reduced Toxicity Conditioning with FBM Prior to Hematopoietic Stem Cell Transplantation.

Abstract 4660

Allogeneic hematopoietic stem cell transplantation (HSCT) of older or comorbid patients has become feasible due to new protocols for reduced toxicity/intensity conditioning. Particularly using fludarabine, BCNU and melphalan (FBM) as preparative regimen confers reduced toxicity with substantial anti-leukemic activity, therefore allowing allogeneic HSCT in patients up to ages well above 70. Nevertheless, chronic Graft-versus-Host disease (cGvHD) of the lung remains a serious non infectious, late onset pulmonary complication, contributing to treatment related morbidity and mortality of the older patients. Since the clinical entity of pulmonary cGvHD in an older population after reduced toxicity/intensity conditioning has not yet been well characterized, we performed a retrospective analysis of patients, who were transplanted after FBM conditioning at the University Hospital Freiburg between 2003 and 2005 and were alive at least 100 days after HSCT. 92 patients were enrolled in this study (median age of 60 years (range 29-71)). All patients received conditioning with fludarabin (4-5 × 30 mg/m²), BCNU (or carmustin, patients> 55 years: 2×150 mg/m², <55 years: 2×200 mg/m²) and melphalan (patients >55 years 1×110mg/m², <55 years: 1×140 mg/m², fo). Peripheral stem cell grafts were used in most of the cases together with cyclosporin based GvHD prophylaxis. Seven patients (8.2%) developed a pulmonary cGvHD as defined by NIH criteria with a median time after HCT of 13.3 months (range 7-19m). In those patients, pulmonary function tests prior to HCT and on day +100 (prior to pulmonary GvHD) revealed a significant reduction in mean % of predicted value in FEV1 (88 v. 71 %), and of absolute values in MEF50 (3.33 v. 1.91) and MEF25 (0.96 v. 0.42) as characteristic changes. The patients with pulmonary GvHD showed at the time of diagnosis in comparison to values before HSCT a mixed pattern of obstruction (% of predicted FEV1 71 v. 50 %), restriction (mean % of predicted VCmax 78 v. 64 %) and changes in diffusions capacity (% of predicted TLCOc SB 79 v. 62%). In univariate analysis, risk factors for developing pulmonary cGvHD were: unrelated donor, chronic GvHD, smoking and lung disease (e.g. infections) after HCT. The latter emphasizes the importance of infections due to immunosuppression for the development of pulmonary GvHD in this patients. Interestingly, uncontrolled disease status or pre-existing lung disease per se did not increase the risk for the development of pulmonary GvHD. In conclusion, we found several risk factors and changes in pulmonary function test associated with developing pulmonary GvHD in HCT after reduced toxicity conditionig. These findings might help to identify a risk population in older patients and therefore result in personalized measures for GvHD prophylaxis.