Diffuse Alveolar Hemorrhage Syndrome Research Articles

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome.

Autopsies Post Hematopoietic Stem Cell Transplant: A Reassessment of Their Role in Patient Management.

Introduction: An autopsy is considered the gold standard for establishing a cause of death, but autopsies are rarely performed on general medicine and surgical services despite documentation of missed diagnoses (Shojania K.G. et al, 2003). The only recent autopsy study (Al-Saidi, F. et al, 2002) of stem cell transplant patients that compared premortem and postmortem diagnoses reviewed 28 autopsies, showed 10 discrepancies, and found that in two, management would have been different. We present a larger review of post stem cell transplant patients to better define the clinical utility of the autopsy as a method of improving patient care.Results: Of 1,780 stem cell transplants (1268 autologous, 512 allogeneic) performed from 1986–2003 at our center, 125 autopsies were performed out of which 105 charts were available for review. We compared the cause of death as charted by the attending or fellow on service with data obtained from chart review and autopsy reports. Transplant indications were as follows: 28% NHL, 14% AML, 11% ALL, 11% CML, 9% metastatic ovarian cancer, 6% MDS, 5% breast cancer, and 5% Hodgkin's lymphoma. Causes of death were disseminated fungal disease in 19%, multi-drug resistant bacteria in 16%, progressive disease in 11%, uncontrolled GVHD in 10%, regimen-related toxicities in 9%, diffuse alveolar hemorrhage or engraftment syndrome in 7%, CMV in 6%, IPS in 5%, viruses in 4%, PCP in 4%, and VOD in 3%. The pre-mortem clinical diagnosis agreed with the retrospective post-mortem diagnosis 83% of the time. The 18 discrepancies were grouped as shown in the table below.Most discrepancies were seen in patients with overwhelming systemic fungal infection despite the best available antifungal medications or rapidly progressive disease in patients that could not have tolerated chemotherapy. Data obtained from this group of patients would have led to a change in management that could have prevented death only once. In 1993 that patient was admitted one year after autologous transplant with relapsed diffuse large B-cell lymphoma and, while undergoing salvage ESHAP chemotherapy, died of what was thought to be toxic hepatitis and bleeding diathesis from chemotherapy. Autopsy revealed systemic candidiasis in a patient that was not receiving systemic antifungal therapy.# of patientsActual cause of deathCauses of death from treating team's perspective8Disseminated aspergillus or candidaCHF, culture positive bacteremia, DAH, IPS, biopsy proven disease, and bleeding diathesis4Progressive diseaseFungi, pulmonary emboli4Bacterial sepsisProgressive disease, fungi, regimen-related toxicity1CMVCulture-positive bacteremia1Regimen-related toxicityDAHDAH = diffuse alveolar hemorrhage, IPS = idiopathic pneumonia syndrome, CHF = congestive heart failureConclusion: Considering available therapies at the time of their deaths, only one of the 105 autopsies reviewed provided data that might have prevented the patient's death. While autopsies may provide diagnostic confirmation that may alter the management of subsequent patients and be a psychological benefit to the patient's family, improved non-invasive methods for diagnosing disease relapse and occult infections may continue to erode their benefit in this clinical situation.

Airway inflammation predicts diffuse alveolar hemorrhage during bone marrow transplantation in patients with Hodgkin disease.

We determined risk factors present in patients with Hodgkin disease that predicted the development of diffuse alveolar hemorrhage syndrome (DAH) during autologous bone marrow transplantation (BMT). One hundred twenty-three patients with Hodgkin disease prospectively underwent bronchoscopy with bronchoalveolar lavage (BAL) before receiving BMT. The bronchitis index (BI) of the airways and bronchial and alveolar cell counts and differentials were determined in all patients and compared with 20 normal nonsmoking volunteers. Logistic regression analysis was used to determine factors that predicted for the development of DAH. Visual evidence of bronchial injury was observed regardless of smoking history (BI = 7.8 +/- 0.5 for BMT versus 2.3 +/- 0.5 for volunteers, p = 0.001). BMT patients who developed DAH (n = 14) had significantly greater numbers of bronchial neutrophils and eosinophils compared with DAH-negative (n = 109) patients (bronchial polymorphonuclear leukocytes (PMN), 33 +/- 7% versus 14 +/- 2%, p = 0.006; bronchial eosinophils, 0.9 +/- 0.3% versus 0.4% +/- 0.07%, p = 0.02). Logistic regression analysis revealed that the presence of bronchial PMN > 20% or bronchial eosinophils > zero% were predictive of DAH (p = 0.005 and 0.05, respectively). When both predictors were positive, the rate of DAH was 10 times greater than when both predictors were negative (43% versus 4% DAH occurrence). Survival was also significantly reduced when these predictors were positive. This study demonstrates that bronchial inflammation is present with or without intraluminal inflammatory cells in the majority of patients with Hodgkin disease before BMT. The subgroup of these patients with increased bronchial inflammatory cells are at greatly increased risk for development of DAH and death.