PubMed Health⌕ Search

Biomedical subjects

S Tindle

Publications and source records attributed to S Tindle.

9 recordsLinked to original sources
PubMed1998

Collection, tumor contamination, and engraftment kinetics of highly purified hematopoietic progenitor cells to support high dose therapy in multiple myeloma.

Unfractionated peripheral blood stem cell (PBSC) grafts contain measurable quantities of myeloma cells and are therefore a potential source of relapse posttransplantation. In contrast, fluorescence-activated cell sorting (FACS)-sorted CD34+ Thy1+ Lin- peripheral blood cells are substantially enriched for stem cell activity, yet contain virtually no clonal myeloma cells. A study was performed in patients with symptomatic myeloma, who had received 12 months or less of preceding standard chemotherapy, to evaluate the feasibility of large scale purification of primitive hematopoietic stem cells in order to study engraftment kinetics posttransplantation and the degree of tumor cell contamination of this cell population, based on polymerase chain reaction (PCR) analysis for the patient-specific complementarity-determining region III (CDR III). PBSC were mobilized with high dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor (GM-CSF). A combination of elutriation and chemical lysis was used to deplete PBSC collections of monocytes, granulocytes, erythrocytes, and platelets. Subsequently, CD34+ Thy1+ Lin- progenitor cells were purified with high speed cell sorting. Of the 10 evaluable patients, nine met the required minimum criteria of >/=7.2 x 10(5) cells/kg to support tandem transplants. After high dose melphalan (200 mg/m2) eight engrafted successfully, although granulocyte (absolute neutrophil count [ANC] >0.5 x 10(9)/L, 16 days) and platelet recovery (platelets > 50 x 10(9)/L, 39 days) was substantially delayed when compared with unmanipulated PBSC grafts; one patient required infusion of a reserve graft because of lack of evidence of engraftment by day +28. Three patients proceeded to a second graft with high dose melphalan and total body irradiation; two required infusion of a reserve graft and both died of infectious complications; one showed delayed, but complete, engraftment after this myeloablative regimen. Two of the nine evaluable patients attained a clinical complete remission (CR). The grafts from three patients were tested for tumor contamination and contained no detectable clonal myeloma cells. Larger quantities of purified cells may be required to resolve the problem of delayed engraftment.

Adult↗
PubMed1998

Comparable engraftment kinetics following peripheral-blood stem-cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma.

PURPOSE: To compare, in the setting of tandem autotransplantations for multiple myeloma (MM), two established methods of peripheral-blood stem-cell (PBSC) procurement with chemotherapy or hematopoietic growth factor alone. PATIENTS AND METHODS: Between June 1994 and July 1995, 44 patients with MM were randomized to PBSC mobilization with either granulocyte colony-stimulating factor (G-CSF) 16 microg/kg (group 1; n = 22) or high-dose cyclophosphamide (HDCTX) 6 g/m2 plus G-CSF 5 microg/kg (group 2; n = 22). All 44 patients received melphalan 200 mg/m2 with their first autograft and 32 patients proceeded to a second transplantation. RESULTS: Group 2 required a significantly longer time interval for completion of PBSC collection than group 1 (median, 22 v 8 days; P = .0001), greater frequency of hospitalization (100% v 32%; P = .0001), and increased transfusion of platelets (86% v 18%; P = .0001) and packed RBCs (86% v 55%; P = .02). Likewise, the incidence of fever and pneumonia/sepsis were higher in group 2 (P = .02 and P = .04, respectively). Surprisingly, despite greater CD34 cell quantities infused in group 2, median recovery times of granulocytes (both > 500/microL and 2,500/microL) and platelets (both > 50,000/microL and > 100,000/microL) were similar (all P > .7). Posttransplant toxicities were also similar. CONCLUSION: Compared with HDCTX plus G-CSF, high-dose G-CSF alone is associated with lower morbidity, shorter duration of PBSC mobilization, and comparable hematopoietic recovery after transplantation, which should result in significant cost reduction. Considering the relatively limited antitumor activity of HDCTX (10% with > or = 50% tumor cytoreduction), PBSC mobilization with HDCTX should be limited to selected patients with persistent MM despite induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients.

Transfusion of autologous peripheral blood stem cells (PBSCs) of good quality ensures fast hematopoietic engraftment after myeloablative therapy with a decrease in procedure-related morbidity and mortality. We have analyzed variables influencing the kinetics of engraftment, and therefore reflecting the quality of PBSC collections, in 225 patients with newly diagnosed or refractory multiple myeloma (MM) who received an autotransplant in support of high dose melphalan (200 mg/m2); 132 of these patients also completed a second transplant. All PBSCs were collected before the first transplant after high-dose cyclophosphamide (6 g/m2) and hematopoietic growth factors, mainly granulocyte-macrophage colony-stimulating factor. PBSCs were administered either alone (91 patients) or with bone marrow (134 patients). A highly significant correlation was observed between the number of CD34+ cells per kilogram infused and prompt recovery of both granulocytes (P = .0001) and platelets (P = .0001). After correction for the proportion of patients with > or = 2 x 10(6)/kg CD34 PBSCs infused and with < or = 12 months of prior therapy, no difference in engraftment kinetics was seen between patients receiving PBSCs only and those also receiving bone marrow. Exposure to chemotherapy, even to < or = 6 months of alkylating agents, significantly delayed hematopoietic recovery posttransplantation. The threshold dose of CD34 cells necessary for prompt engraftment was > or = 2.0 x 10(6)/kg for patients with < or = 24 months of chemotherapy before the first transplant, whereas greater than 5 x 10(6)/kg CD34 cells were required to assure rapid recovery also in those with longer exposure. Such quantities, easily collected in the large majority of patients with shorter exposure (91%), were obtained in only 28% of patients with more than 24 months of prior chemotherapy. Rapid platelet recovery within a narrow range of time (before day 14) was almost invariably seen (94%) when greater than 5 x 10(6)/kg CD34 cells were infused, irrespective of the duration of prior therapy, whereas the range widened progressively when less CD34 cells were infused. In the absence of CD34 measurements, fast recovery of platelets to greater than 50 x 10(9)/L within 14 days after high-dose cyclophosphamide and < or = 12 months of prior chemotherapy were the best predictors of early engraftment. Prudent use of stem cell-damaging agents, such as melphalan and nitrosoureas, is recommended in MM patients who might be candidates for autotransplantation. Alternatively, PBSCs should be collected early after diagnosis.

Adult↗
PubMed1987

Magnetic affinity colloid (MAC) cell separation of leukemia cells from autologous bone marrow aspirates.

A colloidal suspension of Co2B with avidin irreversibly adsorbed to the surface has been used with biotinylated antibodies and lectins to eliminate specific cell populations from mixtures with peripheral blood or bone marrows. Using the monoclonal antibodies CF-1 and PM-81 with this magnetic affinity colloid (MAC), we can eliminate five logs of K562 cells from mixtures with peripheral blood or marrow cells as determined by a linear limiting dilution clonogenic assay. We have also used this separation to eliminate clonogenic leukemia cells from fresh samples of peripheral blood and bone marrow from relapsed acute leukemia patients. Using CF-1 alone or in combination with PM-81, we eliminated two logs of colonies and clusters of leukemia cells from the fresh samples. The same antibodies used with MAC separation of hematologically normal marrows allow recovery of greater than 30% of the hematopoietic progenitors.

Bone Marrow Cells↗
PubMed1987

Clinical application of Percoll gradient-separated bone marrow.

We have evaluated the transplantation potential of bone marrow stem cell concentrates isolated from the 40/60% interface of discontinuous Percoll gradients. This mononuclear fraction is free from platelets and depleted of granulocytes, and contains the majority of granulocyte-macrophage colony-forming cells (GM-CFC), erythroid burst-forming units (BFU-E), and granulocyte, erythroid, macrophage, megakaryocyte colony-forming cells (GEMM-CFC) in less than 10% of the cell number of the original buffy coat. This preparation allows further manipulation without the clumping and cell loss associated with buffy coat cell preparations. Cells isolated by this technique were evaluated for hematopoietic restoration potential in 14 patients who received allogeneic bone marrow transplants as supportive therapy after high dose cytoreduction to treat leukemias or lymphoma. The number of nucleated cells infused varied from 1.6-5.5 X 10(7)/kg, and the number of GM-CFC infused ranged from 0.4 to 3.7 X 10(5)/kg. There was an inverse relationship between the time to recovery of granulocytes and platelets and the number of GM-CFC infused when fewer than 10(5) GM-CFC/kg were transplanted. Above this dose, there was recovery within 10-15 days after transplantation. The stem cell-enriched fraction contained 30-40% of the original number of T lymphocytes, and acute graft-versus-host disease was observed in seven of these patients.

Adolescent↗
PubMed1987

Limiting-dilution analysis of the effects of colony-stimulating factors, phytohemagglutinin, and hydrocortisone on hematopoietic progenitor cell growth.

The effects of colony-stimulating factors (CSFs), phytohemagglutinin (PHA), and hydrocortisone on the growth of human bone marrow hematopoietic progenitor cells (granulocyte-macrophage; GM) were analyzed in a limiting-dilution assay (LDA). Both low-density bone marrow cells separated by discontinuous Percoll gradients and a T cell-depleted and progenitor-enriched cell fraction obtained by the combination of counterflow elutriation centrifugation and Percoll gradients were examined in LDA. GCT (monocytoid cell line-conditioned medium containing GM-CSF), human placenta-conditioned medium, bladder carcinoma cell line 5637-conditioned medium (containing GM- and G-CSF), and recombinant CSF (G-CSF) directly induced proliferation of progenitors with single-hit kinetics. In some instances, however, PHA-stimulated lymphocyte-conditioned medium (containing G- and GM-CSF) showed deviation from single-hit kinetics, which demonstrated the presence of factor(s) suppressive to progenitor growth. In a T cell-depleted, progenitor-enriched fraction, PHA alone was found to suppress progenitor growth at a level as low as 100 ng/mL. The addition of hydrocortisone (10(-6) mol/L) increased the progenitor frequency but suppressed progenitor growth at 10(-4) mol/L. LDA appears to be a valuable method for exploring mechanisms of factors regulating hematopoietic cell growth.

Bone Marrow Cells↗
PubMed1981

Human myeloid leukaemic cell interactions in vitro with normal myeloid colonies.

To determine whether myeloid leukaemic cells could inhibit normal myeloid colony formation, leukaemic cells at concentrations ranging from 0.5 to 8 X 10(6)/ml were co-cultured in agar but separated by a 1 ml underlayer from 10(5) low-density (less than 1.077 g/ml) nonadherent normal marrow cells. Inhibition of normal-marrow myeloid colony formation occurred regularly at high cell concentrations (8 X 10(6)) at a leukaemic:normal cell ratio of 80:1. This suppression persisted with addition of indomethacin (10(-6)M). On the other hand, both low leukaemic cell numbers and irradiated leukaemic cells frequently stimulated normal colony growth. No inhibitor of colony growth could be detected in leukaemic-conditioned media, and absorption of colony-stimulating activity (CSA) with leukaemic cells improved CSA activity. These experiments point to the difficulty in unravelling the effect of leukaemic cells on normal haemopoiesis (both inhibitory and stimulatory) by in vitro agar culture.

Cell Count↗
PubMed1980

Adherent cell-mediated inhibition of human leukemic myelopoiesis.

We investigated the possibility that the control of leukemic growth by autologous adherent marrow cells may explain the indolent behavior of oligoleukemia. Leukemic cluster growth was measured by in vitro agar culture. The following marrow fractions (Fr) were examined from 13 patients for leukemic growth: Fr I: ficollisopaque interface cells (density less than 1.077 g/ml); Fr II: adherent-cell depleted Fr I (4.8% +/- 2.1 (SE) monocytes); Fr III: adherent and phagocytic cell depleted Fr I (0.3% +/- 0.2 monocytes); and Fr IV: adherent cells removed from plastic surfaces by lidocaine plus EDTA (74% +/- 10.9 monocytes). Two patient groups were recognized: Group A showed cluster growth in Fr IV with no absolute increase in Fr III and no suppression of Fr III cluster growth with addition of Fr IV. In Group B, Fr III showed an absolute increase in cluster growth. Fr IV did not show cluster growth and addition of Fr IV to Fr III suppressed growth. This suggested that in Group B, monocytes may suppress leukemic growth, the failure to observe this in Group A indicated the possible leukemic nature of the adherent cell fraction and the absence of residual normal monocytes. Other possible explanations are discussed.

Bone Marrow↗