Treatment with mesenchymal stromal cells is a risk factor for pneumonia-related death after allogeneic hematopoietic stem cell transplantation.

We performed a retrospective cohort study to find out whether the use of reduced-intensity conditioning (RIC) might reduce the risk of early death from pneumonia. Pneumonia-associated deaths were evaluated in 691 hematopoietic stem cell transplantation (HSCT) patients. The majority had a hematological malignancy (n = 504) and an HLA-matched donor (n = 584). RIC was given to 336 patients and myeloablative conditioning (MAC) to 355. Data concerning radiology, culture and autopsy results were evaluated together with risk factors for death related to pneumonia within or after 100 d after HSCT (early and overall pneumonia). In 60 patients, pneumonia contributed to death (early n = 17). The cumulative incidence of early pneumonia-related death was 2.8% and 2.1% in MAC and RIC patients, respectively. The cumulative incidence of overall pneumonia-related death was 8.2% and 10.5%, respectively. In 40 patients, (67%) an etiology could be established, with 19 patients having proven or probable mold infection. In the multivariate analyses, acute graft-versus-host disease (GVHD) grades II-IV, cytomegalovirus (CMV) infection and having received mesenchymal stromal cells (MSCs) were factors associated with overall pneumonia-related death. Bacteremia and a previous HSCT were associated with early pneumonia-related death. RIC did not reduce the incidence of early death associated with pneumonia. Acute GVHD II-IV, CMV infection and MSC treatment were factors associated with pneumonia-related death. Mold infection was the most common contributor to pneumonia-related death in HSCT patients.

Donor lymphocyte infusion may reduce the incidence of bronchiolitis obliterans after allogeneic stem cell transplantation.

Bronchiolitis obliterans (BO) is a serious pulmonary complication after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the diagnostic methods used, the incidence of BO, risk factors, and outcome in patients with BO at our center. The study included 527 HSCT patients transplanted between 1995 and 2003. Lung function tests (n = 1177) and risk factor analyses were performed in all patients. Chest X-rays and high-resolution tomographies were investigated in patients with BO. The incidence of BO was 4.8%, as the diagnosis was established in 25 patients (4 children). Median time between HSCT and diagnosis of BO was 356 (84-1823) days. Eight patients (32%) had radiologic changes consistent with BO. Forced expiratory volume for 1 second (FEV(1)) and forced expiratory flow at 50% (FEF(50)) and 75% (FEF(75)) of forced vital capacity (FVC) produced median values that were 49%, 25%, and 18% of the reference values at the time of BO diagnosis. FEF(75) was reduced before BO diagnosis in 7 patients (28%). In a multivariate risk factor analysis, chronic graft-versus-host disease (cGVHD) was found to be associated with BO (P < .001), whereas donor lymphocyte infusion (DLI) diminished the risk (P = .02). For 10 patients with late BO (>1 year after HSCT), 80% survived 5 years after diagnosis, compared to 38% survival in 15 patients with early-onset BO (P = .06). We conclude that lung function tests with a persistent decrease in FEV(1) were more important than radiographic methods to recognize and monitor BO, that FEF(75) may serve as an early warning of BO, and that late-onset BO appears to be associated with better outcome. Chronic GVHD was confirmed as a risk factor, and administration of DLI may diminish the risk.

Decreasing mortality rate in early pneumonia following hematopoietic stem cell transplantation.

Pulmonary complications after allogeneic hematopoietic stem-cell transplantation (HSCT) remain 1 of the most important causes of morbidity and mortality. This study evaluates the change over time of incidence, aetiology and risk factors for death related to pneumonia within 3 months after HSCT. 997 patients who underwent HSCT were studied retrospectively. Most patients (83%) had a haematological malignancy. The majority (89%) had an HLA-A, -B, and -DR matched related or unrelated donor. Conditioning consisted of cyclophosphamide and total-body irradiation or busulfan and graft-versus-host disease prophylaxis of cyclosporin and methotrexate in most cases. Death related to pneumonia occurred in 56 (5.6%) patients. Cytomegalovirus (37%) was the main pathogen involved, especially during the first 2 decades studied. In the multivariate risk factor analysis, we found that death from pneumonia was significantly associated with receiving a T-cell depleted graft (p<0.001), bacteraemia (p=0.001), and y of transplantation (p<0.001). In patients receiving a transplant during the last decade, the incidence of death related to pneumonia was 2.8% compared to 8.9% during the first decade. We conclude that the rate of mortality related to pneumonia has decreased over time, possibly as a result of improved diagnostic, prophylactic and therapeutic methods and treatment.