Hematopoietic Stem-Cell Transplantation in the Resource-Limited Setting: Establishing the First Bone Marrow Transplantation Unit in Bangladesh.

Purpose: Treatment of malignant and nonmalignant hematologic diseases with hematopoietic stem-cell transplantation (HSCT) was first described almost 60 years ago, and its use has expanded significantly over the last 20 years. Whereas HSCT has become the standard of care for many patients in developed countries, the significant economic investment, infrastructure, and health care provider training that are required to provide such a service have prohibited it from being widely adopted, particularly in developing countries.

Methods: Over the past two decades, however, efforts to bring HSCT to the developing world have increased, and several institutions have described their efforts to establish such a program.

Building Specialized Nursing Practice Capacity in Bangladesh: An Educational Program to Prepare Nurses to Care for Oncology and Bone Marrow Transplant Patients in Dhaka, Bangladesh.

In 2012, the Minister of Health and other leaders in the Bangladesh government approached Massachusetts General Hospital to establish the country's first bone marrow transplant program at Dhaka Medical College Hospital to serve the needs of the people of Bangladesh. Stated goals of this collaboration included a broad focus on the care of oncology patients with a specific emphasis on care of patients with hematologic malignancies and of women with gynecologic cancers. The purpose of this article is to describe the international nursing collaboration between Massachusetts General Hospital, Simmons College, the AK Khan Healthcare Trust in Dhaka, and Dhaka Medical College Hospital that was established to share nursing knowledge and to build specialized professional nursing capacities to deliver high-quality cancer care in the public sector.

Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses.

Background: The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined.

Methods: HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence.

Results: The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.

The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: implications for vaccine design.

Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HIV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2.

Defective immune function of primary effusion lymphoma cells is associated with distinct KSHV gene expression profiles.

Primary effusion lymphomas (PEL) are uniformly infected with Kaposi's sarcoma-associated herpesvirus (KSHV), and thus likely present both tumor and viral antigens to the immune system. In order to grow unrestricted and cause disease, multiple immune evasion strategies may be utilized by PEL to evade immune surveillance. Using six well-established PEL cell lines and comparing these to Epstein-Barr virus-transformed B cell lines and peripheral blood B cells, significant differences were found in the surface expression of molecules involved in antigen presentation, T cell activation and cell-cell adhesion.

Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences.

The antigenic diversity of human immunodeficiency virus type 1 (HIV-1) represents a significant challenge for vaccine design as well as the comprehensive assessment of HIV-1-specific immune responses in infected persons. In this study we assessed the impact of antigen variability on the characterization of HIV-1-specific T-cell responses by using an HIV-1 database to determine the sequence variability at each position in all expressed HIV-1 proteins and a comprehensive data set of CD8 T-cell responses to a reference strain of HIV-1 in infected persons. Gamma interferon Elispot analysis of HIV-1 clade B-specific T-cell responses to 504 overlapping peptides spanning the entire expressed HIV-1 genome derived from 57 infected subjects demonstrated that the average amino acid variability within a peptide (entropy) was inversely correlated to the measured frequency at which the peptide was recognized (P = 6 x 10(-7)).

Determinant of HIV-1 mutational escape from cytotoxic T lymphocytes.

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to study in vivo. Here we used a controlled in vitro system to evaluate the ability of HIV-1 to escape from CTL clones, finding that virus replicating under selective pressure rapidly can develop phenotypic resistance associated with genotypic changes.

HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted.