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T R Chauncey

Publications and source records attributed to T R Chauncey.

30 records · Page 2Linked to original sources
PubMed1997

Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is likely caused by donor T lymphocytes. Because unmodified blood stem cell grafts contain one log more T lymphocytes than unmodified marrow grafts, we evaluated the incidence of chronic GVHD in previously reported 37 blood stem cell recipients and 37 computer-matched historical control marrow recipients (Bensinger et al, Blood 88:2794, 1996). All patients have been followed until death, relapse, or occurrence of chronic GVHD or for a minimum of 2 years. In a univariable proportional hazards regression model, the relative risk of developing clinical chronic GVHD (includes clinical limited and clinical extensive disease) by 2 years posttransplant among the peripheral blood stem cell recipients compared with the marrow recipients was 2.22 (95% confidence interval, 1.04 to 4.74; P = .039). For clinical extensive chronic GVHD, the relative risk was 2.37 (95% confidence interval, 1.07 to 5. 29; P = .035). In multivariable analyses, considering also the covariables of patient age, patient cytomegalovirus serostatus, and donor cytomegalovirus serostatus, the relative risks of clinical chronic GVHD and clinical extensive chronic GVHD were also greater than 2 (P < .05). We conclude that the transplantation of unmanipulated filgrastim-mobilized blood stem cells may result in a relatively high incidence of chronic GVHD.

Chronic Disease↗
PubMed1997

Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose.

Transplantation of hematopoietic stem cells from an HLA-compatible unrelated volunteer is an option for patients with acute leukemia lacking a family match. However, criteria for patient and donor selection and the most effective transplant procedures, including the number of hematopoietic cells, remain to be defined. We tested factors influencing outcome of 174 patients with primary acute leukemia receiving non-T-cell depleted marrow from unrelated donors. Median patient age was 20 years (range, 0.5 to 54 years). A multivariable analysis found that leukemia in remission at the time of transplantation was associated with improved leukemia-free survival (relative risk [RR] of treatment failure: 0.5, confidence interval [CI]: 0.3 to 0.7), and presence of blasts in the peripheral blood, as opposed to marrow involvement only or isolated extramedullary relapse, was associated with impaired outcome (RR of treatment failure: 2.5, CI: 1.7 to 5.0). The use of donors with a limited HLA-mismatch was associated with decreased leukemic relapse (RR: 0.5, CI: 0.3 to 0.9) but no improvement in leukemia-free survival compared with HLA-matched unrelated donors. Transplantation of a marrow cell dose above the median value of 3.65 x 10(8)/kg was associated with faster neutrophil (RR: 1.5, CI: 1.1 to 2.0) and platelet (RR: 4.5, CI: 2.7 to 7.5) engraftment, and decreased incidence of severe acute graft-versus-host disease (RR: 0.6, CI: 0.4 to 0.9). In patients transplanted in remission, the use of a marrow cell dose above the median translated into less nonleukemic death (RR: 0.2, CI: 0.1 to 0.4) and better leukemia-free survival (RR of treatment failure: 0.3, CI: 0.2 to 0.6). Transplant in remission with a high dose of marrow cells was associated with the best outcome in both children and adults.

Acute Disease↗
PubMed1997

Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial.

Patients with a lymphohematopoietic malignancy considered to be at high risk for posttransplant relapse were enrolled in a study to compare the use of cyclosporine (CSP) as a single agent with a combination of methylprednisolone (MP) and CSP for graft-versus-host disease (GVHD) prophylaxis after marrow transplantation from an HLA-identical sibling donor. Sixty patients were randomized to receive CSP only and 62 were randomized to receive CSP plus MP. Daily CSP was started on day -1 (5 mg/kg/d intravenously) and administered at gradually reduced doses until day 180. MP was started on day 7 at 0.5 mg/kg/d, increased to 1.0 mg/kg/d on day 15, started on a taper schedule on day 29, and discontinued on day 72. All 104 evaluable patients (surviving > or =28 days) had sustained engraftment. The incidence rates of grades II-IV acute GVHD were 73% and 60% for patients receiving CSP and CSP plus MP, respectively (P = .01). No difference was seen for grades III-IV GVHD. However, chronic GVHD occurred somewhat more frequently in patients receiving CSP plus MP (44%) than in patients receiving only CSP (21%; P = .02). The incidence of de novo chronic GVHD was marginally higher in patients receiving CSP plus MP (P = .08). No significant differences in the risk of infections were observed. There was a suggestion that the risk of relapse was lower in patients receiving CSP plus MP (P = .10) and, although the overall survival in the two groups was not different (P = .44), there was a slight advantage in favor of CSP plus MP-treated patients for relapse-free survival (P = .07). These results suggest that prophylactic MP, when combined with CSP, has only limited efficacy in acute GVHD prevention and may increase the probability of chronic GVHD.

Adolescent↗
PubMed1997

Allogeneic marrow transplantation for primary myelofibrosis and myelofibrosis secondary to polycythaemia vera or essential thrombocytosis.

Primary myelofibrosis is a clonal haemopoietic disorder, incurable with conventional therapy, and associated with a median survival of 4-5 years. Patients with polycythaemia vera and essential thrombocytosis who progress into a myelofibrotic picture also have a poor prognosis. Between 1980 and 1996, 13 patients with myelofibrosis due to one of these three myeloproliferative disorders (primary myelofibrosis [n=8], essential thrombocytosis [n=3], polycythaemia vera [n=2]) underwent allogeneic marrow transplantation in Seattle. The median age was 40 years (range 18-49). The median time from myeloproliferative diagnosis to transplantation was 39 months (range 5-192). Three patients received preparative regimens containing total body irradiation and 10 received busulphan-cyclophosphamide regimens. Nine patients received marrow from HLA-matched related donors, one from a one antigen mismatched related donor, and three from HLA-matched unrelated donors. The median time to both granulocyte and platelet engraftment was 21 d. Nine patients survive between 1.2 and 7.1 years post-transplant. Two patients relapsed at 1 year post-transplant, both of whom survive in a chronic myeloproliferative state. Four patients died of transplant-related complications between 43 d and 2.2 years post-transplant. At 1 year post-transplant the majority of the disease-free survivors have normal peripheral blood counts and none-to-minimal marrow fibrosis. These preliminary results are encouraging, and suggest that stem cell transplantation can be curative therapy for selected patients with myelofibrosis.

Adolescent↗
PubMed1996

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors.

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3-year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.

Actuarial Analysis↗
PubMed1983

The catalytic mechanism of yeast thiosulfate reductase.

Thiosulfate reductase catalyzes the desulfuration of thiosulfonates while oxidizing GSH to GSSG. Kinetic studies of the enzyme-catalyzed reaction between GSH and benzenethiosulfonate have been carried out, and direct evidence for the occurrence of glutathione persulfide as an immediate product of the reaction has been obtained. The formal mechanism of this enzymic reaction has been shown to be rapid equilibrium-ordered with GSH as the leading substrate.

Glutathione↗
PubMed1983

On the mechanism of transfer of cholesterol between human erythrocytes and plasma.

The kinetics of transfer of [3H]cholesterol between human erythrocytes and plasma at 37 degrees C in physiological buffer had these features. 1) Cholesterol transfer was strikingly similar in both directions. 2) Transfer progressed to isotopic equilibrium in a monotonic, apparently first order fashion, except for a minor rapid component (approximately 15%) observed in the transfer of cholesterol from cells to plasma. 3) The mechanism of transfer was not via transient collisions in that the rate of the reaction was quite insensitive to the concentration of reactants over a wide range. 4) The mechanism of transfer did not involve specific, stable complex formation in that there was little difference in the behavior of erythrocytes and inside-out plasma membrane vesicles derived therefrom or between plasma and sonicated liposomes as acceptors. Furthermore, transfer was not affected by vigorous proteolysis of either the cells or the plasma. 5) The kinetics of transfer were fully compatible with diffusion of cholesterol through the aqueous compartment. This was shown by fitting our data to a rigorous model for diffusion equilibrium between three compartments. 6) The partition coefficient of [3H]cholesterol between red cells and buffer was shown to be 10(7). 7) The rate constants for cholesterol release from both red cells and plasma were approximately 1 X 10(-4) s-1 (t 1/2 approximately 2 h). The rate constant for cholesterol uptake into red cells was approximately 1 X 10(3) s-1 (t 1/2 approximately 1 ms). 8) The similarity of the corresponding kinetic constants among red cells, plasma, and liposomes suggests that phospholipids in a variety of physical forms are equivalent solvents for cholesterol. We conclude that despite its extremely low solubility in water, cholesterol moves between lipid compartments by aqueous diffusion.

Biological Transport↗
PubMed1983

Improved purification and sulfhydryl analysis of thiosulfate reductase.

Thiosulfate reductase purified 900-fold from an extract of baker's yeast by a new procedure consisted of three charge-isomeric species, all with catalytic activity. Amino acid analysis of thiosulfate reductase and titrations with 5,5'-dithiobis(2-nitrobenzoate) and iodo[14C]acetate indicated only one cysteine residue per enzyme molecule. Alkylation of this cysteine with either iodoacetate or iodoacetamide did not inactivate the enzyme, indicating that sulfur-sulfur bond cleavage in the thiosulfate substrate does not require an enzymic sulfhydryl group as attacking nucleophile.

Alkylation↗