Cytomegalovirus Status and the Outcome of T Cell-Replete Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) serostatus of donor and recipient are frequently used in algorithms of donor selection, whereas the impact of CMV reactivation on transplantation-related mortality, leukemia control, and overall survival (OS) remains controversial. Therefore, we retrospectively studied the impact of latent or active CMV infections on the outcome and occurrence of graft-versus-host disease (GVHD) after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (SCT) in 294 patients during the period from 2004 to 2010. CMV viral load was routinely monitored in plasma using a quantitative PCR. Preemptive antiviral therapy was initiated when the viral load in plasma exceeded a predefined threshold. In a proportional hazards model, a seropositive recipient was significantly associated with increased occurrence of acute GVHD. However the CMV serostatus of both recipient and donor and the presence of active CMV infection was not associated with the occurrence of relapses, chronic GVHD, or OS. We conclude that in the presence of viral load monitoring and preemptive treatment, latent or active CMV infection does not substantially affect the OS after T cell-replete RIC allogeneic SCT.

High level of aneuploidy of chromosome 6 by FISH analysis of head and neck squamous cell carcinoma: limited applicability of LOH analysis to define HLA loss.

Human Leukocyte Antigen (HLA) class I molecules are essential for tumor cell recognition by cytotoxic T cells of the adaptive immune system. Loss of HLA expression provides tumor cells with an escape mechanism to evade the immune system and thus immune therapy. Therefore, HLA loss, and in particular loss of heterozygosity (LOH), is frequently studied in tumors using microsatellite marker LOH analysis. Because LOH analysis detects any allelic imbalance and not just allelic loss, we evaluated the LOH analysis in nine head and neck squamous cell carcinomas (HNSCCs) using fluorescence in situ hybridization (FISH). These tumors were selected from 53 HNSCCs based upon the HLA class I immunohistochemical staining and LOH data. FISH analysis showed that only two tumors with LOH and one without LOH indeed had loss and a normal chromosome 6 copy number, respectively. Strikingly, for the remaining six tumors, LOH analysis did not reflect the genome HLA copy number. We demonstrated that LOH analysis cannot distinguish loss from gain and that the HLA region is not homogeneously affected within a tumor. Tumor heterogeneity and complex aneuploidy in tumors hinder a straightforward interpretation of microsatellite marker analysis. For immune therapy strategies in cancer patients, knowledge of the HLA expression on tumor cells is essential, to which LOH analysis has a limited contribution.