Community-acquired respiratory infections are common in patients with non-Hodgkin lymphoma and multiple myeloma.

PURPOSE: Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis. METHODS: Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed. RESULTS: One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age < 60 years, MM diagnosis, and autologous SCT increased the respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated. CONCLUSIONS: Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

Development of multifocal leukoencephalopathy in patients undergoing allogeneic stem cell transplantation-can preemptive detection of John Cunningham virus be useful?

Therapeutic options for progressive multifocal leukoencephalopathy (PML) caused by reactivation of John Cunningham virus (JCV) are limited and inefficient in preventing neurological progression and death. The current study investigated the course of JCV reactivation resulting in PML in patients undergoing allogeneic stem cell transplantation (allo-SCT) and assessed the feasibility and potential significance of preemptive JCV detection in peripheral blood, enabling early cessation of immunosuppressive therapy and immune restoration. Two allografted patients were diagnosed with PML at 188 and 808 days post-allo-SCT. Stored DNA samples of both patients, originally obtained for quantitative cytomegalovirus PCR analysis since transplantation, were evaluated for JCV. JCV reactivation in peripheral blood was found to precede the appearance of neurological symptoms by 126 and 105 days. JCV blood levels were found to be highly correlated with the steroid dosage administered for treating graft-versus-host disease (GVHD). In one patient, the cessation of immunosuppression, including steroids, led to the disappearance of JCV in peripheral blood, with a remarkable improvement in neurological symptoms. In conclusion, the current study suggests the feasibility of early detection of JCV reactivation in blood. Immune restoration at that point may prevent PML development; however prospective studies are warranted to elucidate these issues.

Acute cytomegalovirus infection associated with the onset of inflammatory bowel disease.

A 29-year-old man was admitted with high-grade fever, crampy abdominal pain, and watery diarrhea that had persisted for 2 weeks before his admission. Symptomatic treatment (acetaminophen only) was of no benefit. On physical examination, there was diffuse abdominal tenderness. Laboratory tests showed a leukomoid reaction with atypical lymphocytosis, and serology tests revealed acute cytomegalovirus infection. Abdominal computed tomography and colonoscopy revealed an inflammatory process involving the large intestine. On histologic examinations of intestinal biopsy samples, there was an active inflammation with no inclusion bodies. The patient was treated with ganciclovir with only mild improvement. Adding 5-aminosalicylic acid caused little further improvement. Repeated colonoscopy performed 2 months later showed severe chronic ulcerative colitis. Only the addition of systemic steroids caused complete resolution of the symptoms. On review of the literature (Medline search for cytomegalovirus colitis in immunocompetent patients), 18 cases were found. On follow-up, 10 of these patients were found to have inflammatory bowel disease.

Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients.

Preemptive ganciclovir therapy has reduced the occurrence of early cytomegalovirus (CMV) disease after hematopoietic stem cell (HSC) transplantation. However, late disease is increasingly reported. We describe 2 patients who developed late CMV central nervous system (CNS) disease after haploidentical HSC transplantation. Direct genotypic analysis was used to examine the presence of ganciclovir resistance. One patient had a mixed viral population in the cerebrospinal fluid (CSF), with coexistent wild-type and mutant UL97 sequences. The presence of 2 different strains was confirmed by subclone sequencing of the UL54 gene. One of the strains was different from the concurrent blood strain. The second patient had resistant variant in the lungs. These cases raise concern about the changing natural history of CMV disease in HSC transplantation, with emergence of previously uncommon manifestations following prolonged prophylaxis. Under these circumstances the CNS may be a sanctuary site, where viral persistence and antiviral drug resistance could result from limited drug penetration.

High glucose-induced replicative senescence: point of no return and effect of telomerase.

Primary human cells enter senescence after a characteristic number of population doublings (PDs). In the current study, human skin fibroblasts were propagated in culture under 5.5mM glucose (normoglycemia); addition of 16.5mM D-glucose to a concentration of 22 mM (hyperglycemia); and addition of 16.5mM L-glucose (osmotic control). Hyperglycemia induced premature replicative senescence after 44.42+/-1.5 PDs compared to 57.9+/-3.83 PDs under normoglycemia (p<0.0001). L-Glucose had no effect, suggesting that the effect of hyperglycemia was not attributed to hyperosmolarity. Activated caspase-3 measurement showed a significantly higher percentage of apoptotic cells in high glucose medium. Telomerase overexpression circumvented the effects of hyperglycemia on replicative capacity and apoptosis. The "point of no return," beyond which hyperglycemia resulted in irreversible progression to premature replicative senescence, occurred after exposure to hyperglycemia for as few as 20 PDs. These results may provide a biochemical basis for the relationship between hyperglycemia and those complications of diabetes, which are reminiscent of accelerated senescence.

The expression of hepatitis-C virus antigen by immunohistochemical stain and polymerase chain reaction in corneas of seropositive corneal donors.

Background: Of the donor corneas rejected for transplantation, the largest group is that from donors testing seropositive for hepatitis C virus (HCV). In situations of severe shortage in supply of donor corneal tissue, we may consider the use of seropositive donors for transplantation if we can prove with high certainty the absence of HCV RNA in the donor corneal tissue. Polymerase chain reaction (PCR) is a highly sensitive and specific technique for direct detection of HCV RNA and can be used for this purpose. Nevertheless, it is not applicable for routine clinical use in most eye departments due to its unavailability and cost effectiveness. Purpose: To study the possible use of immunohistochemical method for detection of HCV antigen in corneal tissue of seropositive donors and correlate the results with those of PCR. Immunohistochemical methods have not yet been studied in donor corneal tissue. Materials and methods: Eight corneas of 4 seropositive and 8 corneas of 4 seronegative corneal donors were studied by immunohistochemical and PCR methods for the presence of HCV antigen in their corneal tissue and sera. Results: HCV RNA was not detected in the sera and corneal tissue of all seropositive and seronegative corneal donors by either PCR and immunohistochemical methods. Conclusion: Although the study is too small for conclusive results, the correlation between the immunohistochemical and PCR studies for direct detection of HCV antigen in corneal tissue of seropositive donors may raise the possibility of using the immunohistochemical method for screening of donor corneas for the detection of HCV antigen. A larger prospective study investigating the sensitivity, specificity and clinical applicability of the immunohistochemical method is warranted.