Cytogenetic aberrations identified by metaphase cytogenetics (MC) have important diagnostic, prognostic and therapeutic roles in myelodysplastic syndromes (MDS). Fluorescence in situ hybridization (FISH) complements MC by the ability to evaluate large numbers of both interphase and metaphase nuclei. However, clinically practical FISH strategies are limited to detection of known lesions.
View Article and Find Full Text PDFThe development of laboratory tests for the diagnosis and monitoring of graft-vs-host disease (GVHD) is hampered by a lack of knowledge of minor histocompatibility Ags triggering alloresponses. We hypothesized that the unique molecular structure of the TCR could be used as a marker for the unidentified Ags and exploited for molecular monitoring of GVHD posttransplant. To identify alloreactive T cell clones, we performed in vitro allostimulation cultures for a cohort of patients undergoing hemopoietic stem cell transplantation and determined the sequence of the CDR3 of immunodominant alloreactive clones; 10 corresponding clonotypes restricted to activated T cells were identified.
View Article and Find Full Text PDFThe non-relapse mortality of autologous stem cell transplant is low enough that the procedure has been extended to older patients with non-Hodgkin's lymphoma. We treated 537 non-Hodgkin's lymphoma patients with high-dose chemotherapy consisting of busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. Sixteen patients were identified who died of pulmonary complications at a five-year incidence of 3.
View Article and Find Full Text PDFPurpose: The risk factors for treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (AML) after autologous stem-cell transplantation (ASCT) are similar to those that increase the risk of difficult stem-cell harvests. We reviewed our experience in 526 patients with lymphoma treated by ASCT to determine whether difficult stem-cell harvests predict for an increased risk of t-MDS/AML.
Patients And Methods: Autologous peripheral stem cells were initially mobilized with granulocyte colony-stimulating factor (G-CSF; or granulocyte-macrophage colony-stimulating factor) alone (n = 334), etoposide and G-CSF (n = 166), or cyclophosphamide and G-CSF with or without etoposide (n = 26).
Objective: In allogeneic hematopoietic stem cell (HSCT) transplantation, recovery of the T cell receptor (TCR) repertoire depends upon the composition of the graft and is modulated by peri-transplant immunosuppression, viral infections, and graft-vs-host disease (GVHD). We hypothesized that after allogeneic HSCT, molecular analysis of the TCR repertoire can be used to identify and quantitate immunodominant T cell clones that may play a role in GVHD or other clinical events.
Methods: We utilized a rational strategy for the analysis of the expanded CTL clones.