References of "BARON, Frédéric"
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See detailImpact of Imatinib on immune function in vitro
Pirson, Laurence ULg; Baron, Frédéric ULg; Gothot, André ULg et al

Poster (2006)

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See detailCurrent status of hematopoietic stem cell transplantation after nonmyeloablative conditioning
Baron, Frédéric ULg; Sandmaier, B. M.

in Current Opinion in Hematology (2005), 12(6), 435-443

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See detailHigh doses of transplanted CD34(+) cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation
Baron, Frédéric ULg; Maris, M. B.; Storer, B. E. et al

in Leukemia (2005), 19(5), 822-828

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood ... [more ▼]

This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) ( n = 116) or marrow ( n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/ kg. Higher numbers of grafted CD14(+) ( P = 0.0008), CD3(+) ( P = 0.0007), CD4(+) ( P = 0.001), CD8(+) ( P = 0.004), CD3 - CD56(+) ( P = 0.003), and CD34(+) ( P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) ( P = 0.01) and CD34(+) ( P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) ( P = 0.005) and CD34(+) ( P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism ( P = 0.01), rapid achievement of complete donor T-cell chimerism ( P = 0.02), and a trend for lower risk for graft rejection ( P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning. [less ▲]

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See detailHLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with chronic myeloid leukemia
Baron, Frédéric ULg; Maris, M. B.; Storer, B. E. et al

in Biology of Blood and Marrow Transplantation (2005), 11(4), 272-279

We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m(2) and 2 Gy of total body irradiation as ... [more ▼]

We evaluated 10/10 HLA antigen-matched unrelated hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with fludarabine 3 x 30 mg/m(2) and 2 Gy of total body irradiation as treatment for patients with chronic myeloid leukemia who were ineligible for conventional HCT. Data from 21 consecutive patients in first chronic phase (CP1; n = 12), accelerated phase (AP; n = 5), second CP (CP2; n = 3), and blast crisis (n = 1) were analyzed. Stem cell sources were bone marrow (n = 4) or granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells (G-PBMCs; n = 17). The patient who underwent transplantation in blast crisis died on day 21 (too early to be evaluated. for engraftment) from progressive disease. Sustained engraftment was achieved in 5 of 12 patients who underwent transplantation in CP1, 4 of 5 patients who underwent transplantation in AP, and 2 of 3 patients who underwent transplantation in CP2, whereas 9 patients rejected their grafts between 28 and 400 days after HCT. Specifically, I of 4 marrow recipients and 10 of 17 G-PBMC recipients achieved sustained engraftment. Graft rejections were nonfatal in all cases and were followed by autologous reconstitution with persistence or recurrence of chronic myeloid leukemia. Seven of 11 patients with sustained engraftment-including all 5 patients in CP 1, 2 of 4 patients in AP, and neither of the 2 patients in CP2-were alive in complete cytogenetic remissions 118 to 1205 days (median, 867 days) after HCT. Two of the remaining 4 patients died of nonrelapse causes in complete (n = 1) or major (n = 1) cytogenetic remissions, and 2 died of progressive disease. Further efforts are directed at reducing the risk of graft rejection by exclusive use of G-PBMC and increasing the degree of pretransplantation immunosuppression. (c) 2005 American Society for Blood and Marrow Transplantation. [less ▲]

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See detailGraft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning
Baron, Frédéric ULg; Maris, M. B.; Sandmaier, B. M. et al

in Journal of Clinical Oncology (2005), 23(9), 1993-2003

Purpose We have used a nonmyelorablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell ... [more ▼]

Purpose We have used a nonmyelorablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy. Patients and Methods We analyzed GVT effects in 322 patients given grafts from HILA-matched related (n = 192) or unrelated donors (n = 130). Results Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD, P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003). Conclusion New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning. (c) 2005 by American Society of Clinical Oncology. [less ▲]

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See detailAssessing donor chimerism level among CD3 T, CD4 T, CD8 T, and NK cells predicts subsequent graft rejection, GVHD, and relapse after allogeneic HCT with nonmyeloablative conditioning
Baron, Frédéric ULg; Storb, R.; Gooley, T. et al

in Biology of Blood & Marrow Transplantation (2005), 11(2), 11

We previously showed that low levels of day-14 CD3 T and NK (CD56) cells donor chimerism predicted graft rejection, whereas high levels of day-28 CD3 T-cell donor chimerism predicted acute graft-versus ... [more ▼]

We previously showed that low levels of day-14 CD3 T and NK (CD56) cells donor chimerism predicted graft rejection, whereas high levels of day-28 CD3 T-cell donor chimerism predicted acute graft-versus-host disease (GVHD) after HCT with nonmyeloablative conditioning. Here we investigate whether assessing chimerism levels among CD4 T cells and CD8 T cells, and also the absolute number of lymphocyte subsets of donor and host origins, would lend greater precision to our initial observations. We analyzed data from 157 patients receiving HCT after conditioning with 2 Gy TBI +/− fludarabine as treatment for AML (n= 22), ALL (n= 4), CML (n= 13), CLL (n= 19), MDS (n= 26), MM (n= 24), NHL (n= 30), HD (n= 14), RCC (n= 4), and WASP deficiency (n= 1). Postgrafting immunosuppression included MMF and CSP. A total of 97 patients received grafts from HLA-identical siblings, and 60 patients received grafts from HLA-matched unrelated donors. Lymphocyte subsets were isolated from peripheral blood by flow cytometry on days 14, 28, and 42. The proportion of cells of donor origin (chimerism levels) were assessed by VNTR-PCR and quantified by phosphor imaging. Eighteen patients (11%) had graft rejection. Day-14 donor chimerism levels< 50% among CD3 T (P =.0007), CD4 T (P =.03), and NK cells (P =.003) but not CD8 T cells predicted graft rejection. High absolute numbers of CD3 T (P =.002) and NK cells (P= .002) of host origin on day 14 were each associated with increased risks of graft rejection when treated as continuous linear variables. Grades 2, 3, and 4 acute GVHD were seen in 40%, 9%, and 5% of patients, respectively. High donor chimerism levels on day 14 among CD3 T (P= .02), CD4 T (P =.03), and CD8 T cells (P =.02) but not NK cells were each associated with increased risks of grades 2–4 acute GVHD. High absolute numbers of CD4 T (P =.04) and CD8 T cells (P =.04) of donor origin on days 14–42 were each associated with increased risks of grade 2–4 acute GVHD when treated as continuous linear variables, whereas high donor CD3 T (P= .002), CD8 T (P= .006), and NK cell (P= .002) chimerism levels from days 14–42 were associated with decreased risks of relapse. No statistically significant correlations between absolute numbers of donor cells and risks of relapse were found. These data suggest that assessing CD3, CD4, CD8, and NK cell donor chimerism levels and determining absolute numbers of CD3 and NK cells of host and donor origins are useful for predicting HCT outcomes after nonmyeloablative conditioning. [less ▲]

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See detailEfficacy of recombinant human erythropoietin therapy started one month after autologous peripheral blood stem cell transplantation.
Vanstraelen, Gaetan; Baron, Frédéric ULg; Frere, Pascale ULg et al

in Haematologica (2005), 90(9), 1269-70

On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment ... [more ▼]

On day 30 after autologous peripheral blood stem cell transplantation (PBSCT), 20 patients were randomized to receive either erythropoietin at a dose of 500 U/kg/week s.c. (Epo group) or no treatment (control group). After 3 weeks, hemoglobin (p<0.0001) and serum transferrin receptor (p<0.0001) concentrations were higher in the Epo group. Hb response (+2 g/dL) was achieved in 100% vs 28% (p<0.0001) and Hb correction (> or =13 g/dL) in 70% vs 10% (p=0.0238) of the patients, respectively. This is the first randomized study showing an efficacy of erythropoietin therapy on Hb levels after autologous PBSCT. [less ▲]

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See detailKinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning.
Baron, Frédéric ULg; Little, Marie-Terese; Storb, Rainer

in Blood Reviews (2005), 19(3), 153-64

Nonmyeloablative or reduced-intensity conditioning regimens have been used to condition elderly or ill patients with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT ... [more ▼]

Nonmyeloablative or reduced-intensity conditioning regimens have been used to condition elderly or ill patients with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT). Initial mixed donor/host chimerism (i.e. the coexistence of hematopoietic cells of host and donor origin) has been observed in most patients after such transplants. Here, we describe both factors affecting engraftment kinetics in patients given a nonmyeloablative or a reduced-intensity conditioning, and associations between peripheral blood cell subset chimerism levels and HCT outcomes. [less ▲]

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See detailWhat role is there for antithymocyte globulin in allogeneic nonmyeloablative canine hematopoietic cell transplantation?
Diaconescu, Razvan; Little, Marie-Terese; Leisenring, Wendy et al

in Biology of Blood & Marrow Transplantation (2005), 11(5), 335-44

We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit ... [more ▼]

We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit engraftment of canine dog leukocyte antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum levels of ATG peaked on days 4 to 6 after initiation of therapy and became undetectable by day 13 as a result of canine antibody responses to ATG. ATG prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days in control dogs (P = .0003). Five dogs were given marrow transplants after ATG (3.5-5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained engraftment, and 4 rejected their grafts. The duration of engraftment ranged from 8 to > or = 36 weeks (median, 11 weeks), and this is comparable to that in 6 historical controls not given ATG (range, 3-12 weeks; median, 10 weeks; P = .20). The total nucleated cell doses in the marrow grafts had the highest correlation coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI failed to secure uniform stable hematopoietic engraftment. [less ▲]

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See detailHematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT.
Sorror, Mohamed L; Maris, Michael B; Storb, Rainer et al

in Blood (2005), 106(8), 2912-9

We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of ... [more ▼]

We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of patients with scores of 1 or more, captured by the CCI, did not exceed 35%. Further, some comorbidities were rarely found among patients who underwent HCT. Therefore, the current study was designed to (1) better define previously identified comorbidities using pretransplant laboratory data, (2) investigate additional HCT-related comorbidities, and (3) establish comorbidity scores that were suited for HCT. Data were collected from 1055 patients, and then randomly divided into training and validation sets. Weights were assigned to individual comorbidities according to their prognostic significance in Cox proportional hazard models. The new index was then validated. The new index proved to be more sensitive than the CCI since it captured 62% of patients with scores more than 0 compared with 12%, respectively. Further, the new index showed better survival prediction than the CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561, respectively, P < .001). In conclusion, the new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival. This index will be useful for clinical trials and patient counseling before HCT. [less ▲]

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See detailCurrent roles for allogeneic hematopoietic cell transplantation following nonmyeloablative or reduced-intensity conditioning.
Baron, Frédéric ULg; Storb, Rainer

in Clinical Advances in Hematology & Oncology (2005), 3(10), 799-819

Nonmyeloablative and reduced-intensity conditioning regimens followed by allogeneic hematopoietic cell transplantation (HCT) have been evaluated in patients with hematologic malignancies who were not ... [more ▼]

Nonmyeloablative and reduced-intensity conditioning regimens followed by allogeneic hematopoietic cell transplantation (HCT) have been evaluated in patients with hematologic malignancies who were not considered candidates for conventional HCT because of age or medical comorbidities and in selected patients with metastatic renal cell carcinoma. The regimens have relied more on graft-versus-tumor effects than on chemoradiation therapy to facilitate engraftment and eradicate malignant cells. While nonmyeloablative HCT has been associated with reduced regimen-related toxicities and has been curative for a number of patients with hematologic malignancies, challenges have remained in regard to graft-versus-host disease, infections, and disease progression. In this article, we review data from a number of published phase I and II studies that describe the results of allogeneic HCT after nonmyeloablative conditioning. [less ▲]

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See detailImmunotherapie du cancer par minigreffe de cellules souches hematopoietiques.
Willems, Evelyne ULg; Baron, Frédéric ULg; Vanstraelen, Gaëtan et al

in Revue Médicale Suisse (2005), 1(30), 1973-7

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected haematological malignancies. Its curative potential is based on two different mechanisms, i.e. the ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected haematological malignancies. Its curative potential is based on two different mechanisms, i.e. the conditioning regimen and the graft-versus-host immunologic reactions. However, because of its toxicity, it is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols. These transplants are called nonmyeloablative HSCT or minitransplants. These are feasible with a relatively low transplant-related mortality even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several haematological malignancies. [less ▲]

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See detailGraft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning
Baron, Frédéric ULg; Maris, Michael; Sandmaier, Brenda et al

in Blood (2004), 104

We have used a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation +/– fludarabine, 30 mg/m²/day x 3 days, to condition elderly or ill patients (pts) with hematological ... [more ▼]

We have used a nonmyeloablative conditioning regimen consisting of 2 Gy total body irradiation +/– fludarabine, 30 mg/m²/day x 3 days, to condition elderly or ill patients (pts) with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT). This approach relies almost exclusively on graft-versus-tumor (GVT) effects for control of malignancy. Here, we analyzed GVT effects in 322 pts with hematological malignancies given grafts from HLA-matched related (n=192) or unrelated (n=130) donors. Grades I, II, III and IV acute GVHD were seen in 26 (8.1%), 141 (43.8%), 34 (10.6%) and 11 (3.4%) pts, respectively. Extensive chronic GVHD was seen in 181 (56.2%) pts and of these, 64 (19.9%) cases had de novo chronic GVHD. Putative GVT effects were evaluated using time-dependent Cox regression models. Of the 221 pts with measurable disease at HCT, 126 (57%) achieved complete (n=98) or partial (n=28) remissions. Multivariate analysis identified chemosensitivity for B-cell malignancies (p=.02), and tandem autologous/allogeneic HCT (p=.04) as pre-transplant factors associated with higher probabilities of achieving complete remissions (CR) after HCT. After adjusting for these factors, acute GVHD of any grade was not found to be associated with an increased probability of achieving CR. There was a trend for a higher probability of achieving CR in pts with chronic GVHD (p=.07). Progression/relapse was observed in 108 pts. Multivariate analysis identified that lower disease-risk (p=.0004), tandem autologous/allogeneic HCT (p=.02) and adapted Charlson comorbidity index (CCI) score at transplant < 3 (p=.002) resulted in significantly decreased risk of progression/relapse. After correcting for these factors, extensive chronic GVHD was associated with a decreased risk of progression/relapse (p=.006). Pts with grade 1 acute GVHD tended to have less progression/relapse (p=.07). Conversely, grade II–IV acute GVHD did not significantly affect the risk of progression/relapse. Nonrelapse mortality was observed in 70 pts. Multivariate analysis showed that lower disease-risk (p=. 001), tandem autologous/allogeneic HCT (p=.002) and CCI score at transplant < 3 (p<.0001) significantly decreased nonrelapse mortality. After adjusting for these variables, grade II (p=.04) and grade III–IV (p<.0001) acute GVHD increased nonrelapse mortality while extensive chronic GVHD did not. The 3-year probability of progression-free survival (PFS) was 38.5%. In multivariate analysis, lower disease-risk (p<.0001), tandem autologous/allogeneic HCT (p=.0008) and CCI score at transplant < 3 (p<.0001) resulted in significantly better PFS. After adjusting for theses variables, grade 1 acute GVHD (p=.02) and chronic extensive GVHD (p=.003) were both associated with significantly better PFS, while grade III–IV acute GVHD (p<.0001) was associated with decreased PFS. In summary, chronic GVHD in pts given nonmyeloablative conditioning was associated with substantial GVT effects which led to improved PFS. Conversely, any potential GVT benefits from grade II–IV acute GVHD were offset by higher nonrelapse mortality resulting in worse PFS. Efforts should be directed at reducing the risk of grade II–IV acute GVHD while allowing de novo chronic GVHD for best PFS after allogeneic HCT with nonmyeloablative conditioning. [less ▲]

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See detailCD34+ cell dose predicts costs after autologous peripheral blood stem cell transplantation for breast cancer.
Baron, Frédéric ULg; Copizza, Sandra; Baudoux, Etienne ULg et al

in Haematologica (2004), 89(9), 1146-8

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for ... [more ▼]

We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for patients receiving a CD34+ cell dose <5 x 10(6) cells/kg versus 22,339.4+/- 5471.1 for those receiving >5 x 10(6) CD34+ cells/kg (p=0.0065). [less ▲]

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See detailAllogeneic hematopoietic cell transplantation as treatment for hematological malignancies: a review.
Baron, Frédéric ULg; Storb, Rainer

in Springer Seminars in Immunopathology (2004), 26(1-2), 71-94

Allogeneic hematopoietic cell transplantation (HCT) was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient ... [more ▼]

Allogeneic hematopoietic cell transplantation (HCT) was originally developed as a form of rescue from high-dose chemoradiotherapy, which is given both to eradicate malignancy and provide sufficient immunosuppression for allogeneic engraftment. The first attempts of allogeneic HCT in humans met with little success. However, a better understanding of the complexities of the human leukocyte antigen (HLA) system has allowed selecting compatible sibling donors, and the development of postgrafting immunosuppressive regimens has helped prevent serious graft-versus-host disease, thereby changing the role of allogeneic HCT from a desperate therapeutic maneuver to a curative treatment modality for many patients with malignant hematological diseases. In addition, the establishment of large registries of HLA-typed volunteers has permitted finding suitable unrelated donors for many patients without family donors. Further advances in the immunogenetics of HLA, especially typing by molecular techniques, have improved results after unrelated HCT, which have begun resembling those obtained with HLA-identical sibling grafts, at least in young patients. Important advances have also been made in the prevention and treatment of infectious complications and in other areas of supportive care. Since the late seventies, it has been recognized that allogeneic immunocompetent cells transplanted with the stem cells, or arising from them, mediated therapeutic anti-tumor effects independent of the action of the high-dose therapy, termed graft-versus-tumor (GVT) effects. This has prompted the recent development of non-myeloablative conditioning regimens for allogeneic HCT that have opened the way to include elderly patients and those with comorbid conditions. Remaining challenges include further advances in the prevention and treatment of both severe graft-versus-host disease and infections. Also, progress in adoptive transfer of T cells with relative tumor specificity and disease-targeted therapy with agents such as Imatinib, Rituximab or radiolabeled monoclonal antibodies would make allogeneic HCT even more effective. [less ▲]

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See detailKinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning.
Baron, Frédéric ULg; Baker, Jennifer E.; Storb, Rainer et al

in Blood (2004), 104(8), 2254-62

We analyzed the kinetics of donor engraftment among various peripheral blood cell subpopulations and their relationship to outcomes among 120 patients with hematologic malignancies given hematopoietic ... [more ▼]

We analyzed the kinetics of donor engraftment among various peripheral blood cell subpopulations and their relationship to outcomes among 120 patients with hematologic malignancies given hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning consisting of 2 Gy total body irradiation (TBI) with or without added fludarabine. While patients rapidly developed high degrees of donor engraftment, most remained mixed donor/host chimeras for up to 180 days after HCT. Patients given preceding chemotherapies and those given granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts had the highest degrees of donor chimerism. Low donor T-cell (P = .003) and natural killer (NK) cell (P = .004) chimerism levels on day 14 were associated with increased probabilities of graft rejection. High T-cell chimerism on day 28 was associated with an increased probability of acute graft-versus-host disease (GVHD) (P = .02). Of 93 patients with measurable malignant disease at transplantation, 41 achieved complete remissions a median of 199 days after HCT; 19 of the 41 were mixed T-cell chimeras when complete remissions were achieved. Earlier establishment of donor NK-cell chimerism was associated with improved progression-free survival (P = .02). Measuring the levels of peripheral blood cell subset donor chimerisms provided useful information on HCT outcomes and might allow early therapeutic interventions to prevent graft rejection or disease progression. [less ▲]

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See detailHematopoietic cell transplantation: five decades of progress.
Baron, Frédéric ULg; Storb, Rainer; Little, Marie-Terese

in Archives of Medical Research (2003), 34(6), 528-44

During the past 50 years, the role of allogeneic hematopoietic cell transplantation (HCT) has changed from a desperate therapeutic maneuver plagued by apparently insurmountable complications to a curative ... [more ▼]

During the past 50 years, the role of allogeneic hematopoietic cell transplantation (HCT) has changed from a desperate therapeutic maneuver plagued by apparently insurmountable complications to a curative treatment modality for thousands of patients with hematologic diseases. Now, cure rates following human leukocyte antigen (HLA) allogeneic HCT with matched siblings exceed 85% for some otherwise lethal diseases, such as chronic myeloid leukemia, aplastic anemia, or thalassemia. In addition, the recent development of non-myeloablative conditioning and stem cell transplantation has opened the way to include elderly patients with a wide variety of hematologic malignancies. Further progress in adoptive transfer of T cell populations with relative tumor specificity would make the transplant procedure more effective and would extend the use of allogeneic HCT for treatment of non-hematopoietic malignancies. [less ▲]