High-dose therapy and autologous peripheral blood stem cell transplantation for patients with lymphoma

Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.     

Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy

From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved. No manipulations to increase the number of stem cells circulating in the blood were used during the collections. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous cells were thawed and infused intravenously (IV). WBCs reappeared in the circulation at a median of eight days (range seven to 11 days) after stem cell infusion. Two patients died early, whereas the other eight reached normal numbers of circulating granulocytes that have persisted for up to greater than 20 months. These eight patients became independent of RBC transfusions (hemoglobin concentration greater than 10 g/dL) at a median of 27 days (range 11 to 58 days) after transplantation. One patient received platelet transfusions for counts less than 50 x 109)/L, one patient developed a clinical picture of idiopathic thrombocytopenic purpura, and six patients maintained a platelet count greater than 20 x 10(9)/L at a median of 23 days (range 14 to 25 days) following stem cell infusion. This technique allows patients ineligible for autologous bone marrow transplantation due to unacceptable anesthetic risks, prior pelvic irradiation, or bone marrow metastases to receive marrow ablative therapy.     

In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I- [Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA- octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.