PubMed Health⌕ Search

Biomedical subjects

K Imrie

Publications and source records attributed to K Imrie.

24 records · Page 2Linked to original sources
PubMed1996

Acute leukemia in adults.

Several trends are emerging in the treatment and investigation of acute leukemia in adults; in this review both of these aspects are addressed. Chemotherapy forms the mainstay of treatment for acute myeloblastic leukemia. In the past year, groups reported on the value of dose intensification in patients with acute myeloblastic leukemia under the age of 60 years and on the role of intensive chemotherapy combined with growth factors in the treatment of elderly patients. Similarly, the role of autologous bone marrow transplantation for older patients has been studied. Improvements in the treatment of patients with acute leukemia are likely to come from a recognition and understanding of the biologic attributes of the leukemic cell. Failure to cure leukemia is likely due to failure to eradicate the leukemic clone. Mechanisms of drug resistance acting before the drug reaches its target (proximal resistance) and after the drug interacts with its target (distal resistance) are gaining greater importance in understanding treatment failures. Advances have been made in identifying new mechanisms that are involved in proximal as well as distal drug resistance. Genetic changes both at the cytogenetic and the molecular level identify different FAB subgroups and groups of patients with good and bad prognostic features. Finally, reports are reviewed of two new factors that stimulate the growth of acute myeloblastic leukemia cells (thrombopoietin and Flt3 ligand) and a factor that inhibits the autocrine growth characteristics of acute myeloblastic leukemia cells (interleukin-10). The results of these interface and basic studies offer the hope of identifying groups of patients with different therapeutic needs and suggest ways to develop therapies aimed at the biology of the leukemic cell.

Adult↗
PubMed1995

Optimizing the CD34+ and CD34+Thy-1+ stem cell content of peripheral blood collections.

We have previously described a sensitive and specific CD34 enumeration assay and report here a prospective analysis of 25 myeloma patients undergoing PBSC mobilization using this assay to determine the optimal days for collection of CD34+ and CD34+Thy-1+ cells after chemotherapy and growth factor mobilization. Correlations between frequency of peripheral blood CD34+ cells, circulating white blood cell (WBC) count, apheresis CD34+ cell count, nucleated cell count (NCC), and numbers of apheresis colony-forming units granulocyte/macrophage (CFU-GM) were determined. To assess levels of the more primitive subsets of CD34+ cells in the PBSC collections, coexpression of the Thy-1 antigen (CDw90) on CD34+ cells was also assessed. Marked heterogeneity was noted between patients with apheresis samples containing a median NCC of 4.2 x 10(8)/kg (range 1.3-8.1), median CFU-GM 17 x 10(4)/kg (range 0.15-32 x 10(4)/kg), and median CD34+ cell count of 1.39 x 10(6)/kg (range 0.02-6.6). The frequency of CD34+ cells in PBSC collections coexpressing Thy-1 was also heterogenous (6.2-50% of CD34+ cells), median 21.6%, mean 24.7 +/- 2%. The apheresis CD34+ cell count correlated with the peripheral blood CD34+ cell percentage (r = 0.71, p < 0.0001) but only weakly with the peripheral WBC. Apheresis CD34+Thy-1+ cell numbers correlated strongly with the circulating CD34+ cell numbers (r = 0.80), but no correlation was noted between these candidate stem cells and the peripheral WBC. In contrast, apheresis CFU-GM levels correlated most strongly with the peripheral WBC count (r = 0.61, p < 0.0001). The apheresis CD34+ cell count correlated with apheresis CFU-GM (r = 0.75, p < 0.0001) but not with the apheresis NCC. Apheresis CD34+Thy-1+ counts significantly correlated only with the apheresis CD34+ cell count and not with the apheresis CFU-GM or NCC. A higher percentage of circulating and apheresis CD34+ cells expressing Thy-1 were found on day 1 of collection, and the percentage of CD34+ cells expressing Thy-1 decreased on each subsequent day of measurement: median of 22% day 1 vs. 16.6% day 4, p = 0.04. This study therefore confirms that accurate quantitation of circulating CD34+ cells best predicts the optimal day for apheresis collection of CD34+ and CD34+Thy-1+ cells and is superior to the WBC count in this regard. Furthermore, the candidate stem cell (CD34+Thy-1+) subset is most prevalent during the earliest phases of CD34+ cell mobilization.

Blood Component Removal↗
PubMedDate not supplied

Blood stem cell collection: factors influencing the recovery of granulocyte-macrophage colony forming cells.

We evaluated data from all blood cell (BC) collections performed in our institution between 1989 and 1995 to determine factors influencing the outcome of collection. One hundred and thirty-three collections were performed on 106 patients. Malignant diagnoses were: non-Hodgkins lymphoma (NHL) in 35%, multiple myeloma in 31%, breast cancer in 26%, and Hodgkin's disease in 8%. Collections were obtained routinely in myeloma and breast cancer and due to bone marrow involvement with malignancy or inaspirable bone marrow in lymphoma patients. Collections were obtained on a Cobe Spectra or Baxter-Fenwall CS3000+. Engraftment potential was determined by methylcellulose colony assay (CFU-GM), with a target of > 10 x 10(4) CFU-GM/kg. Apheresis nucleated cell count correlated significantly, albeit weakly (r = 0.26), with CFU-GM with a cell count of > 5 x 10(8)/kg resulting in an adequate number of CFU-GM in 78% of patients. In univariant analysis outcome of collection was significantly influenced by the patients age (p = 0.01), malignant diagnosis (p < 0.001), reason for collection (p = 0.002), and the mobilization regimen (p = 0.01). The nature of the apheresis device used did not influence outcome. Only malignant diagnosis was significant (p < 0.001) in multivariate analysis. We conclude that the outcome of BC is most strongly influenced by patient factors such as malignant diagnosis. These factors must be considered when comparing the outcome of different mobilization regimens and when planning collection strategies.

Adolescent↗
PubMedDate not supplied

Bone marrow mononuclear cell count does not predict neutrophil and platelet recovery following autologous bone marrow transplant: value of the colony-forming unit granulocyte-macrophage (CFU-GM) assay.

The common use of the marrow autograft mononuclear cell (MNC) count derives from positive correlative studies following allogeneic transplantation and from earlier conflicting data regarding the value of the bone marrow autograft colony-forming unit granulocyte-macrophage (CFU-GM) assay for prediction hematologic recovery after ABMT. We conducted a retrospective analysis at our institution to determine whether autograft CFU-GM levels predict engraftment of neutrophils and platelets after ABMT in heavily pretreated patients with hematologic malignancies. Between 1 January 1993 and 1 March 1995, 58 heavily pretreated patients received only marrow cells as the autograft product. Patients with Hodgkin's disease (n = 25), acute myeloid leukemia (n = 19), and non-Hodgkin's lymphoma (n = 14) underwent intensive therapy with etoposide and melphalan. Unpurged marrow containing a minimum of 1.5 x 10(8)/kg (range: 1.5-4.8) was infused. Median time to an absolute neutrophil count > or = 0.5 x 10(9)/L was 21 days (range 10-270) and median time to a platelet count > or = 20 x 10(9)/L independent of transfusions was 44 days (range 13-317). There was no correlation between autograft MNC count and neutrophil or platelet engraftment. However, a correlation between autograft CFU-GM and both platelet and neutrophil recovery was demonstrated with a threshold CFU-GM of 3 x 10(4)/kg; delayed neutrophil recovery was observed in 79% of patients below this threshold compared to only 9% in those with an autograft CFU-GM level of more than 3 x 10(4)/kg (p = 0.0001). Similarly, platelet recovery was delayed in 76% of patients below, and 20% of those above this threshold (p = 0.003). We conclude that marrow autograft CFU-GM is predictive of engraftment of both platelets and neutrophils in heavily pretreated patients after ABMT for hematological malignancies.

Adolescent↗