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Biomedical subjects

R Paquette

Publications and source records attributed to R Paquette.

9 recordsLinked to original sources
PubMed2003

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission.

In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission therapy in 129 patients aged 18-71 years (median 49 years) with newly diagnosed acute myelogenous leukemia (AML) in first complete remission (CR1). The median follow-up from remission for surviving patients was 62.2 months (range 3.7-127.9 months). A total of 57 patients were alive and leukemia free at the end of the study. The LFS and overall survival 5 years from remission were 40.2% (+/-9.2%) and 41.4% (+/-9.4%), respectively. The median LFS and overall survival are 17.3 and 23.3 months, respectively. Multivariate analysis identified age as the most significant predictor for both LFS and overall survival. Karyotype was also found to be predictive of outcome. Our results show that autologous transplantation of PBPC procured after a single cycle of high-dose cytarabine-based consolidation chemotherapy for a population of adult patients with AML in CR1 produces a high likelihood of long-term LFS, offering a state of clinical minimal residual disease for the investigation of future therapeutic approaches.

Adolescent↗
PubMed2001

Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification.

Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of BCR-ABL signal transduction in all cases examined. In six of nine patients, resistance was associated with a single amino acid substitution in a threonine residue of the Abl kinase domain known to form a critical hydrogen bond with the drug. This substitution of threonine with isoleucine was sufficient to confer STI-571 resistance in a reconstitution experiment. In three patients, resistance was associated with progressive BCR-ABL gene amplification. These studies provide evidence that genetically complex cancers retain dependence on an initial oncogenic event and suggest a strategy for identifying inhibitors of STI-571 resistance.

Amino Acid Sequence↗
PubMed2001

Transplantation of IL-2-mobilized autologous peripheral blood progenitor cells for adults with acute myelogenous leukemia in first remission.

In order to improve leukemia-free survival we evaluated the feasibility and efficacy of autologous transplantation of interleukin-2 (IL-2)-mobilized peripheral blood progenitor cells for adult patients with acute myelogenous leukemia in first remission. Forty-nine consecutive patients (median age 49, range 21-70) with acute myelogenous leukemia in first remission were enrolled on a study of high-dose cytarabine/mitoxantrone consolidation chemotherapy with post-recovery IL-2 used as a method of in vivo purging for the purpose of autologous peripheral blood progenitor cell transplantation. A median of 2.08 x 10(6) CD34+ peripheral blood progenitor cells/kg were infused 1 day after preparative conditioning with 11.25 Gy total body irradiation and cyclophosphamide (120 mg/kg). Forty-one patients received myeloablative chemoradiotherapy followed by the infusion of IL-2-mobilized autologous peripheral blood progenitor cells. The median times to both neutrophil and platelet recovery were 16 days (range, 2-43) and 23 days (8-318+ days), respectively. Twenty-seven patients remain alive with 24 in continued first complete remission. Median remission duration for all eligible patients is 8 months, and actuarial leukemia-free survival is 49+/-15%. The actuarial risk of relapse is 43+/-16%. Toxicity of autologous peripheral blood progenitor cell transplant included treatment-related death in three patients and serious organ toxicity in 12. Advanced age was a negative prognostic factor for leukemia-free survival. Results were compared to an age-matched historical control treated with autologous transplantation of chemotherapy-mobilized progenitor cells; no significant difference in favor of IL-2 mobilization could be demonstrated. Our results demonstrate that autologous transplantation of IL-2-mobilized peripheral blood progenitor cells is feasible in an unselected population of adult patients with acute myelogenous leukemia in first remission with minimal toxicity but no clear evidence of benefit in leukemia-free survival.

Adult↗
PubMed1999

Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with secondary acute myelogenous leukemia in first remission.

Patients with acute myelogenous leukemia secondary to an antecedent hematologic disturbance or cytotoxic chemotherapy are considered to have a very low likelihood of leukemia-free survival regardless of the form of post-remission therapy. The purpose of this study is to evaluate, on the basis of intention to treat, the feasibility and efficacy of high-dose cytarabine/anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for seventeen adult patients (median age 63, range 27 to 68) with secondary acute myelogenous leukemia in first remission. Ten eligible patients underwent autologous transplantation of peripheral blood progenitor cells procured following high-dose cytarabine/mitoxantrone consolidation chemotherapy used as a method of in vivo purging. A median of 5 collections (range 2 to 13) were required to procure a median of 9.27 x 10(8) total mononuclear cells/kg (range 2.35 to 21.44 x 10(8) per kg). The median number of CD34-positive progenitor cells was 1.18 x 10(6) kg (range 0.34 to 30.9 x 10(6) kg). After preparative conditioning with 11.25 Gy total body radiation and cyclophosphamide (120 mg/kg) and autologous transplantation, the median time to neutrophil and platelet recovery were 18 days (range 12 to 29 days) and 25 days (range 8 to 158+ days), respectively. After a median follow-up for surviving patients of 33.4 months (range 7.5 to 54 months), 9 of 17 patients (53%) remain alive with 7 in continued first remission. The median remission duration is 13 months (3 to 53 months) and actuarial leukemia-free survival at 3 years is 51+/-25%. Toxicity of autologous peripheral blood progenitor cell transplant included serious liver and pulmonary toxicity in 2 and 1 patient, respectively. Our results demonstrate that a postremission program of high-dose cytarabine-based consolidation chemotherapy followed by autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible for patients with secondary acute myelogenous leukemia producing prolonged leukemia-free survival with minimal toxicity.

Adult↗
PubMed1997

Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with acute myelogenous leukemia in first remission.

The purpose of the study was to evaluate the feasibility and efficacy of high-dose cytarabine-anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for adult patients with acute myelogenous leukemia in first remission. Fifty-nine consecutive patients (median age 45, range 18-69) with acute myelogenous leukemia in first remission were enrolled on a study of high-dose cytarabine-mitoxantrone consolidation chemotherapy used as a method of in vivo purging for the purpose of autologous peripheral blood progenitor cell transplantation. A median of 7 x 10(8) peripheral blood mononuclear cells/kg were infused 1 day after preparative conditioning with 11.25 Gy total body irradiation and cyclophosphamide (120 mg/kg). Forty-six patients received myeloablative chemo-radiotherapy followed by the infusion of chemotherapy/rHu-G-CSF-mobilized autologous peripheral blood progenitor cells. The median time to both neutrophil and platelet recovery from transplant was 15 days (range, 11-36 and 5-253+ days, respectively). After a median follow-up of 27 months, 31 patients remain alive with 27 in complete remission. Median remission duration for all eligible patients is 12 months, and actuarial leukemia-free survival at 3 years is 42 +/- 14%. The actuarial risk of relapse is 54 +/- 15%. Toxicity of autologous peripheral blood progenitor cell transplant included treatment-related death in two patients and grade III/IV organ toxicity in six. Advanced age was a negative prognostic factor for leukemia-free survival. Our results demonstrate that autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible in an unselected population of adult patients with acute myelogenous leukemia in first remission producing improved leukemia-free survival with minimal toxicity.

Adult↗
PubMed1990

[A space to construct desire...].

It is a matter of being woman or simply of being? Is there actually a feminine way to be? Here, women put psychoanalysis into question. This article suggests a return to the notion of castration and to the developments surrounding the significance of the phallus. The castration experience is presented as being closely likely to the process of sexualization and to the individual's self-realization. The authors advance the woman's point of view, which questions castration. They find that psychoanalysis does not provide an answer, but imposes a limit: that of a symbolic order in which the individual must fit. Within the limiting phenomenon of castration, there remains the need for every man and woman in contemporary Québec society to share a sense of desire.

Anxiety, Castration↗