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Douglas E Joshua

Publications and source records attributed to Douglas E Joshua.

4 recordsLinked to original sources
PubMed2006

Transformation and progression of Waldenström's macroglobulinemia following cladribine therapy in two cases: natural evolution or iatrogenic causation?

We report two cases of Waldenström's macroglobulinemia with an unusual aggressive transformation following treatment with cladribine (2-chlorodeoxyadenosine, 2-CdA), a purine analogue. The first patient developed transformation to a diffuse large-cell non-Hodgkin lymphoma, while the second developed extensive extramedullary involvement. Both patients displayed rapid progression following transformation and were refractory to chemotherapy. Both patients were pretreated with multiple courses of prednisone and chlorambucil, and transformation occurred shortly after therapy with cladribine. We propose that immune suppression from alkylating agents and purine analogues may have contributed to the unusual progression, resulting in a dismal outcome.

Aged↗
PubMed2003

Clonal cytotoxic T cells in myeloma.

Multiple myeloma (MM) is a malignant disease characterized by accumulation of morphologically recognizable plasma cells producing immunoglobulin (Ig) in the bone marrow. The occurrence of clonal T cells in MM, as defined by the presence of rearrangements in the T-cell receptor (TCR)-beta chains detected on Southern blotting, is associated with an improved prognosis. This review aims to describe the various ways in which we have demonstrated the presence of such T cell clones, and to describe the phenotype of these cells. Finally, the specificities of these clinically important CD8+ T cell populations will be discussed in the context of immunotherapy.

Bone Marrow↗
PubMed2003

Prediction of high affinity class I-restricted multiple myeloma idiotype peptide epitopes.

Idiotypic determinants are potential patient-specific tumor antigens in multiple myeloma (MM). In this study, we have determined the DNA sequence of the variable region of the tumor immunoglobulin (Ig) in 6 patients with MM. We then selected high affinity class I-restricted T-cell peptide epitopes in tumor Ig using two different internet-based epitope prediction programs. High affinity binding peptides were identified by at least one program in 4 out of 6 patients. Of these 35 peptides, only 3 scored high by both analyses. Given that all 6 patients had expanded T-cell clones with a cytotoxic (CD57+CD8+CD28-perforin+) phenotype, known to be associated with a longer survival and postulated to recognise tumor epitopes, this analysis indicates that such clones are unlikely to be exclusively directed towards tumor immuoglobulin, and suggests the need to expand the scope of the search for tumor epitopes with the ability to stimulate cytotoxic T cells in vivo.

Adult↗