We report the development of a double-cycle elutriation (DCE) technique separating 3 or greater logs of T cells from a stem-cell-enriched marrow fraction and the results of phase I T-cell depletion studies with HLA-disparate related bone marrow transplantation (BMT) donors in two patient groups. In group 1, 10 patients with refractory hematopoietic malignancies received combination chemotherapy, total body irradiation (TBI), and immunosuppression (pre- and post-BMT), and hematopoietic rescue with a marrow transplant, depleted of T cells by elutriation. Potentially to promote engraftment and a graft-versus- leukemia (GVL) effect, 0.5 to 0.75 x 10(5) T cells/kg were added back. All 10 patients engrafted. Five patients developed acute graft-versus- host disease (GVHD; four grade II, one grade III) and two subsequently developed chronic GVHD. Two patients have relapsed (median follow-up, 206 days; range, 46 to 1,035). Four patients died of BMT-related complications (three of infection, one of veno-occlusive disease [VOD]). Four patient are disease-free survivors (median follow-up, 960 days; range, 670 to 1,035). Group 2 included five infants, four with congenital lymphohematopoietic deficiencies and one with refractory acute lymphocytic leukemia (ALL). In these infants, busulfan and increased cyclophosphamide were substituted for TBI. Only the ALL patient received added T cells. Three patients engrafted: one has stable mixed chimerism, one relapsed with ALL, and one rejected the marrow. One patient had primary autologous recovery, while another failed to engraft. None developed GVHD. We conclude that, in this setting of HLA-disparate BMT with post-BMT antithymocyte globulin (ATG) and corticosteroids, DCE significantly depletes T cells from the marrow and that a defined number of T cells can be added without the occurrence of severe GVHD.
Background: Bone marrow necrosis (BMN) affects both stromal tissue and hematopoietic precursors and its prevalence ranges from 0.3–37%, being the hematologic malignancies the most frequent cause. Aim: To describe the clinical and pathological characteristics of 30 patients with BMN diagnosed and treated at our institution. Methodology: We included all adult patients diagnosed during the last 8 years (2000– 2007) via bone marrow aspiration and biopsy. Results: Median age was 44 years (range 14–78); 53.3% were females. 42.2% of the patients died within a month mainly due to adult respiratory distress syndrome (ARDS) and septic shock. Just 5 (16.7%) of them are still alive. In all cases, BMN was of coagulative type, and extense in 23 (76.6%) of the patients. The main symptoms were: bone pain (53%), anemia (53%) and fever (50%), whereas the main underlying diseases were: acute lymphoblastic leukemia (ALL) in 26.7%, non-Hodgkin lymphoma (NHL) in 13.3% and multiple myeloma (MM) in 10% of the patients. Conclusions: BMN is associated to a fatal course and to hematologic malignancies in most of our patients.
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