Proliferative kinetics of human hematopoietic cells during different growth phases in vitro.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to B D Clarkson.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Nineteen recently diagnosed patients with acute leukemias received prophylactic platelet transfusions when thrombocytopenic. Platelet concentrates were always transfused within eight hours of collection. The result of each transfusion was carefully monitored for the posttransfusion platelet increment. One patient died four days after admission to the present study. Seven patients died 1 to 14 months after the institution of antileukemic chemotherapy. Four patients received marrow transplants 1 to 2 months after starting chemotherapy and, therefore, were longer evaluated in this study. One patient was lost to follow-up after seven months of observation. The remaining six patients are alive and have been followed for 9 to 18 months. During the period of observation, none of the patients developed any evidence of refractoriness to platelet transfusion therapy. Although this series does not permit any firm conclusions to be made, it appears that the magnitude of the problem of alloimmunization to platelet transfusion therapy may be overemphasized.
Because hematopoietic stem cells circulate in the peripheral blood (PB), the possibility exists for using leukocytaphereses in place of marrow for autologous transplantation. Normal stem cells, measured by the colony forming unit-culture (CFU-C) assay, usually in extremely small numbers in PB, are increased after aggressive chemotherapy. Patients with small-cell undifferentiated carcinoma of the lung had PB assayed for CFU-C numbers during induction chemotherapy. The median blood CFU-C concentration increased as much as 13.3-fold compared to pretreatment values following the third cycle of chemotherapy. The CFU-C peaks occurred at the same time as a relative monocytosis in the PB, with monocytosis percentages often 30 percent or higher. Compared to an average CFU-C dose obtained from a typical marrow procedure done under general anesthesia (4.0 X 10(4) CFU-C/kg), the anticipated CFU-C yield obtained from a single cytapheresis performed at the CFU-C peak after the third course of chemotherapy (2.9 X 10(4) CFU-C/kg) suggests that as few as two-cytaphereses could provide sufficient stem cells to reconstitute hematopoiesis following lethal myelosuppression.
The results of two intensive combination chemotherapy trials for heavily pretreated patients with Hodgkin's disease were markedly different. Only one of 27 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) achieved a complete remission (CR), while a CR was attained by 50% of the patients (nine of 18) treated with ABVD alternating with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP/ABVD). There was a significantly longer survival for patients on MOPP/ABVD. Characteristics of patients in the two trials which might have at least partially explained these differing results were identified. The patients treated with ABVD all had prior histories of multiple relapses or continuous disease activity, while the majority of responding patients treated with MOPP/ABVD had few prior relapses and long disease-free intervals immediately prior to treatment. In the MOPP/ABVD trial, a trend toward a higher CR rate was found for patients with relapses confined to lymph nodes, compared with patients who had extranodal disease, although the difference lacked statistical significance. The characteristics of the patient population undergoing treatment must be considered in the interpretation of the results of chemotherapy salvage regimens for Hodgkin's disease.
To investigate the possibility that a significant kinetic basis exists for the improved clinical response often obtained using drug combinations, Chinese hamster ovary cells were exposed to cytarabine and daunorubicin in combination. Cell survival was determined by a colony-counting assay; kinetic perturbations were monitored by flow cytometry. No major synergistic effects of the conditions, each drug appeared to provide some protection against the lethal effects of the other. By pairing a moderately toxic concentration of one drug with a nontoxic concentration of the other, we observed sequence-dependent differences in survival. These differences could not be attributed simple to alteration of the cell cycle phase positions by the nontoxic drug, combined with phase-specific lethality of the toxic drug. It is likely, however, that daunorubicin provided partial protection from cytarabine-related cytotoxicity through its effect on the DNA synthesis rate.
A group of 49 patients with advanced non-Hodgkin's lymphoma were entered in a combination-chemotherapy protocol (cyclophosphamide L2). Of 14 patients with diffuse poorly differentiated lymphocytic lymphoma (DPDL), 64% responded with two partial remissions (PR) and seven complete remissions (CR). Both PRs are stable at 17+ months while six of the CR group are free of disease at 3+-23+ months. Fifty-three percent of 30 patients with diffuse histiocyctic lymphoma (DHL) responded with 23% attaining CR status. Of the nine PR patients, six are stable at 11+-23+ months while six of the seven CR group are without disease at 9+-27+ months. The major toxic effect was bone marrow suppression with two deaths during periods of neutropenia; one of these deaths was definitely drug related. The encouraging results in the DPDL category have led to a continuation of this protocol for patients with this histologic type. In patients with DHL other approaches are being explored.