A histopathological scoring and grading system to predict outcome for patients with AA amyloidosis.

PURPOSE: Renal involvement is associated with significant morbidity and mortality in AA amyloidosis. Extend of amyloid deposition in kidney biopsies may be predictive for clinical manifestations and outcomes. The aim of our study is to assess clinical features of patients with biopsy-proven renal AA amyloidosis and to evaluate the relationship between histopathological scoring and grading of renal amyloid deposition with clinical findings and outcomes. METHODS: The study included 86 patients who were diagnosed with renal AA amyloidosis. The demographic and clinical features at the time of biopsy and follow-up data were retrospectively collected. Amyloid deposition in glomeruli, interstitium, vessels and tubulointerstitial findings were scored and renal amyloid prognostic score (RAPS) was assigned by adding all scores. RAPS was further divided into three grades (RAPS grade I, II, III). RESULTS: Median age was 50 (36-59) years. Familial Mediterranean fever was the leading cause. RAPS grade and interstitial inflammatory infiltration were associated with baseline eGFR and glomerular amyloid deposition was associated with proteinuria. During the follow-up period (median 50 months), 39 patients developed ESRD. Extensive (involving > 50%) glomerular amyloid deposition, baseline eGFR and proteinuria were independent risk factors for progression to end stage renal disease. Death censored renal survival was significantly lower among patients with RAPS grade III compared to those with RAPS grade I and II. Patient survival rate was not different according to RAPS grade. CONCLUSIONS: Degree of renal amyloid accumulation is associated with renal function and outcome. The scoring and grading system may be predictive in clinical outcome and contribute to understanding of disease mechanism.

Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regimen toxicity, and engraftment kinetics.

Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation is a frequently fatal complication with no standard therapy. Although significant changes in supportive and intensive care measures for patients undergoing hematopoietic stem cell transplantation have been made over the past decades, the impact of these changes on the incidence and outcome of patients with diffuse alveolar hemorrhage has not been examined. We analyzed 1228 patients who underwent allogeneic hematopoietic stem cell transplantation between 2008-2015 at the University of Minnesota to study the incidence, risk factors, and outcomes of diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage developed in 5% of allogeneic hematopoietic stem cell transplant recipients, at a median of 30 days (range +3 to +168 days) after transplantation. The incidence of diffuse alveolar hemorrhage was significantly greater in recipients of umbilical cord blood than peripheral blood or bone marrow grafts (HR: 2.08, 95% CI: 1.16-3.74; P=0.01). In multivariate analysis, delayed neutrophil engraftment or primary graft failure was a risk factor for diffuse alveolar hemorrhage following peripheral blood or bone marrow hematopoietic stem cell transplants (HR: 5.51, 95% CI: 1.26-24; P=0.02) and delayed platelet engraftment was associated with significantly increased diffuse alveolar hemorrhage in umbilical cord blood transplant recipients (HR: 6.96, 95% CI: 2.39-20.29; P<0.05). Myeloablative regimens including total body irradiation were also risk factors for diffuse alveolar hemorrhage (HR: 1.8, 95% CI: 1.03-3.13, P=0.05) in both peripheral blood or bone marrow and umbilical cord blood hematopoietic stem cell transplants (HR: 1.87, 95% CI: 0.95-3.71). Patients with diffuse alveolar hemorrhage had an inferior 6-month treatment-related mortality (HR: 6.09, 95% CI: 4.33-8.56, P<0.01) and 2-year overall survival (HR: 4.16, 95% CI: 3.06-5.64; P<0.01) using either graft source. The etiology of diffuse alveolar hemorrhage is multifactorial, involving lung injury influenced by high-dose total body irradiation, graft source, and delayed engraftment or graft failure. The survival of patients with diffuse alveolar hemorrhage after hematopoietic stem cell transplantation remains poor. Clinical interventions or experimental studies (e.g., cell expansion for umbilical cord blood transplants or thrombopoietin use) that modulate these risk factors may limit the incidence and improve the outcomes of diffuse alveolar hemorrhage.

Toxic epidermal necrolysis associated with radiotherapy and phenytoin in a patient with non-Hodking's lymphoma: A case report.

Toxic epidermal necrolysis (TEN) is a disease which is characterized by fever and desquamation of the skin and mucosal membranes. It is usually related with drugs, especially aromatic anticonvulsants which are recognized as the most common cause of this disorder. Cranial irradiation may act as a precipitating factor along with anticonvulsants for the development of TEN. We report a 28-year-old patient with central nervous system (CNS) relapsed non-Hodgkin lymphoma (NHL) who developed TEN after cranial radiotherapy and concurrent phenytoin treatment.