Additional chromosomal abnormalities in core-binding factor acute myeloid leukemia.

Despite sharing a similar genetic abnormality, patients with core binding factor acute myeloid leukemia (CBF-AML), which is characterized by the presence of t(8;21) or inv(16)/t(16;16), show heterogeneous survival. Other molecular or cytogenetic factors are supposed to have an impact on the prognosis. We enrolled 24 CBF-AML patients to determine the impact of cytogenetic abnormality, and c-KIT, FLT3, NPM1, and CEBPA mutations on the prognosis. Only three patients had the c-KIT mutation (3/24, 12.5%) and one had the FLT3 mutation. However, over half of the patients (14/24) harbored additional cytogenetic changes, including ten with loss of sexual chromosomes (LOS) [all in the t(8;21) group], and six had additional abnormalities (two cases had both LOS and additional abnormalities). From this small-number study, no association was found between c-KIT mutation and survival and relapse rate. However, additional chromosome abnormalities had a significant association with relapse of the disease (P = 0.027). Stem cell transplant had a trend of benefitting patients after relapse (P = 0.065). This implies that chromosome abnormalities occur in CBF-AML and might take part in the heterogeneous nature of CBF-AML.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Prognostic implication of molecular aberrations in cytogenetically normal acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation.

Different molecular aberrations can be discriminated into certain prognostic subgroups in cytogenetically normal acute myeloid leukemia (CN-AML) patients but their impact on allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains controversial and studies from Asian populations are lacking. Forty-two adult non-M3 AML patients receiving allo-HSCT from 2002 to 2009 in southern Taiwan were retrospectively reviewed for survey, 23 (54.7%) of whom were CN-AML. NPM1, FLT3-ITD, and CEBPA were analyzed. After a median follow-up of 104 weeks (range, 8 to 384), patients in the good risk group (harboring either NPM1 or CEBPA mutation without concurrent FLT3-ITD) showed a borderline worse overall survival (OS) compared with the intermediate/poor risk group (P = 0.08). Interestingly, a poorer OS was found in patients with the CEBPA mutation (P = 0.003) but not the NPM1 mutation (P = 0.96). No OS difference was found between patients with or without FLT3-ITD (P = 0.15). In patients receiving allo-HSCT at first remission, there was no significant OS benefit in the good risk group (P = 0.33). In patients receiving allo-HSCT beyond first remission, disease status played a major role (P = 0.006), irrespective of molecular aberrations. Allo-HSCT in good risk patients should be carefully evaluated in Taiwanese, especially in patients with the CEBPA mutation. Conversely, allo-HSCT should be considered in first remission in patients with an intermediate/poor risk, where it may overcome the adverse impact of FLT3-ITD. Disease status remained a main issue in patients receiving allo-HSCT beyond first remission.

Formaldehyde-treated, heat-inactivated virions with increased human immunodeficiency virus type 1 env can be used to induce high-titer neutralizing antibody responses.

The lack of success of subunit human immunodeficiency virus (HIV) type 1 vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses.

Induction of humoral immune responses following vaccination with envelope-containing, formaldehyde-treated, thermally inactivated human immunodeficiency virus type 1.

The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

An enzyme-linked immunosorbent assay (ELISA) for measurement of heterophile antibody.

An enzyme-linked immunosorbent assay (ELISA) test has been developed for measurement of heterophile antibody. The microtiter test utilizes a bovine erythrocyte monolayer as antigen and anti-human IgM antiserum conjugated with horseradish peroxidase to measure the degree of binding of the heterophile antibody in the test serum with the erythrocytes. A single serum dilution yields quantitative results when read in a spectrophotometer. The ELISA test showed a sensitivity comparable with the immune adherence hemagglutination assay (IAHA) and other heterophile tests, good reproducibility, and high specificity.