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Barry E Storer - One of the best experts on this subject based on the ideXlab platform.
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total body irradiation dose escalation decreases risk of progression and graft rejection after Hematopoietic Cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Haematologica, 2019Co-Authors: Federico Monaco, Barry E Storer, Thomas R Chauncey, Bart L Scott, F B Petersen, Frederic Baron, Mary E D FlowersAbstract:A non-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic Hematopoietic Cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed Hematopoietic Cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by Hematopoietic Cell transplantation with total body irradiation dose escalation for excessive Hematopoietic Cell transplantation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: myelodysplastic syndrome high-risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem Cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 Hematopoietic Cell transplant failure, with the objective of reducing the incidence to
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inosine monophosphate dehydrogenase pharmacogenetics in Hematopoietic Cell transplantation patients
Biology of Blood and Marrow Transplantation, 2018Co-Authors: Jeannine S Mccune, Barry E Storer, Sushma S Thomas, Jožefa S Mckiernan, Rohan Gupta, Brenda M SandmaierAbstract:Abstract We evaluated inosine monophosphate dehydrogenase ( IMPDH) 1 and IMPDH2 pharmacogenetics in 247 recipient–donor pairs after nonmyeloablative Hematopoietic Cell transplant (HCT). Patients were conditioned with total body irradiation + fludarabine and received grafts from related or unrelated donors (10% HLA mismatch), with postgraft immunosuppression of mycophenolate mofetil (MMF) with a calcineurin inhibitor. Recipient and donor IMPDH genotypes (rs11706052, rs2278294, rs2278293) were not associated with day 28 T Cell chimerism, acute graft-versus-host disease (GVHD), disease relapse, cytomegalovirus reactivation, nonrelapse mortality, or overall survival. Recipient IMPDH1 rs2278293 genotype was associated with a lower incidence of chronic GVHD (hazard ratio, .72; P = .008) in nonmyeloablative HCT recipients. Additional studies are needed to confirm these results with the goal of identifying predictive biomarkers to MMF that lower GVHD.
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lung function trajectory in bronchiolitis obliterans syndrome after allogeneic Hematopoietic Cell transplant
Annals of the American Thoracic Society, 2016Co-Authors: Madan Jagasia, Barry E Storer, Guang Shing Cheng, Jason W Chien, Jesse Hubbard, Linda J Burns, Joseph Pidala, Jeanne Palmer, Laura JohnstonAbstract:Rationale: The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic Hematopoietic Cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.Objectives: To describe the longitudinal trajectory of lung function parameters, including FEV1, in patients with BOS after Hematopoietic Cell transplant.Methods: Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV1 for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6–18 months after diagnosis. The effect of treatment o...
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factors associated with outcomes in allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning after failed myeloablative Hematopoietic Cell transplantation
Journal of Clinical Oncology, 2006Co-Authors: Frederic Baron, Barry E Storer, Michael B Maris, Thomas R Chauncey, Judith A. Shizuru, Rainer Storb, Stephen J Forman, Dietger Niederwieser, Benedetto Bruno, Peter A McsweeneyAbstract:Purpose Several studies have investigated the feasibility of allogeneic Hematopoietic Cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches. Patients and Methods We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Results Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients wi...
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graft versus tumor effects after allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning
Journal of Clinical Oncology, 2005Co-Authors: Frederic Baron, Barry E Storer, Brenda M Sandmaier, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Thomas R Chauncey, Mohamed L Sorror, Razvan Diaconescu, Marco MielcarekAbstract:Purpose We have used a nonmyeloablative 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.
Thomas R Chauncey - One of the best experts on this subject based on the ideXlab platform.
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total body irradiation dose escalation decreases risk of progression and graft rejection after Hematopoietic Cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Haematologica, 2019Co-Authors: Federico Monaco, Barry E Storer, Thomas R Chauncey, Bart L Scott, F B Petersen, Frederic Baron, Mary E D FlowersAbstract:A non-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic Hematopoietic Cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed Hematopoietic Cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by Hematopoietic Cell transplantation with total body irradiation dose escalation for excessive Hematopoietic Cell transplantation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: myelodysplastic syndrome high-risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem Cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 Hematopoietic Cell transplant failure, with the objective of reducing the incidence to
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fibrosing cholestatic hepatitis c after Hematopoietic Cell transplantation report of 3 fatal cases
The American Journal of Surgical Pathology, 2015Co-Authors: Ashley T Evans, Thomas R Chauncey, Howard M. Shulman, Keith R Loeb, Sajida Hassan, David M Hockenbery, George N Ioannou, David R Gretch, George B. McdonaldAbstract:Development of liver disease after Hematopoietic Cell transplantation is common and the causes diverse. Infection by hepatitis C virus (HCV) can be seen in patients who are chronically infected before transplant or from passage of virus from an infected donor; the normal 10-year course of hepatitis
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non myeloablative conditioning with allogeneic Hematopoietic Cell transplantation for the treatment of high risk acute lymphoblastic leukemia
Haematologica, 2011Co-Authors: Rainer Storb, Thoralf Lange, Brenda M Sandmaier, David G Maloney, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Ginna G Laport, Thomas R Chauncey, Amelia LangstonAbstract:Background Allogeneic Hematopoietic Cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia. Design and Methods Fifty-one patients (median age 56 years) underwent allogeneic Hematopoietic Cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib. Results With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft- versus -host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft- versus -host disease was 44%. Hematopoietic Cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival ( P =0.005 and P =0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%. Conclusions For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic Hematopoietic Cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival. ([Clinicaltrials.gov][1] identifier: NCT0036738) [1]: http://ClinicalTrials.gov
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factors associated with outcomes in allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning after failed myeloablative Hematopoietic Cell transplantation
Journal of Clinical Oncology, 2006Co-Authors: Frederic Baron, Barry E Storer, Michael B Maris, Thomas R Chauncey, Judith A. Shizuru, Rainer Storb, Stephen J Forman, Dietger Niederwieser, Benedetto Bruno, Peter A McsweeneyAbstract:Purpose Several studies have investigated the feasibility of allogeneic Hematopoietic Cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches. Patients and Methods We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Results Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients wi...
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graft versus tumor effects after allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning
Journal of Clinical Oncology, 2005Co-Authors: Frederic Baron, Barry E Storer, Brenda M Sandmaier, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Thomas R Chauncey, Mohamed L Sorror, Razvan Diaconescu, Marco MielcarekAbstract:Purpose We have used a nonmyeloablative 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.
Mary E D Flowers - One of the best experts on this subject based on the ideXlab platform.
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total body irradiation dose escalation decreases risk of progression and graft rejection after Hematopoietic Cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Haematologica, 2019Co-Authors: Federico Monaco, Barry E Storer, Thomas R Chauncey, Bart L Scott, F B Petersen, Frederic Baron, Mary E D FlowersAbstract:A non-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic Hematopoietic Cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed Hematopoietic Cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by Hematopoietic Cell transplantation with total body irradiation dose escalation for excessive Hematopoietic Cell transplantation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: myelodysplastic syndrome high-risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem Cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 Hematopoietic Cell transplant failure, with the objective of reducing the incidence to
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non myeloablative conditioning with allogeneic Hematopoietic Cell transplantation for the treatment of high risk acute lymphoblastic leukemia
Haematologica, 2011Co-Authors: Rainer Storb, Thoralf Lange, Brenda M Sandmaier, David G Maloney, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Ginna G Laport, Thomas R Chauncey, Amelia LangstonAbstract:Background Allogeneic Hematopoietic Cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia. Design and Methods Fifty-one patients (median age 56 years) underwent allogeneic Hematopoietic Cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib. Results With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft- versus -host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft- versus -host disease was 44%. Hematopoietic Cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival ( P =0.005 and P =0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%. Conclusions For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic Hematopoietic Cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival. ([Clinicaltrials.gov][1] identifier: NCT0036738) [1]: http://ClinicalTrials.gov
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long term acyclovir for prevention of variCella zoster virus disease after allogeneic Hematopoietic Cell transplantation a randomized double blind placebo controlled study
Blood, 2006Co-Authors: Michael Boeckh, Mary E D Flowers, Joel D Meyers, Raleigh A BowdenAbstract:VariCella-zoster virus (VZV) disease occurs in 30% of allogeneic Hematopoietic Cell transplant recipients who had a history of VZV infection. A safe and effective prevention strategy has not been established. In a double-blind controlled trial, 77 Hematopoietic Cell transplant recipients at risk for VZV reactivation were randomized to acyclovir 800 mg twice daily or placebo given from 1 to 2 months until 1 year after transplantation. VZV disease at 1 year was the primary end point; VZV disease after discontinuation of prophylaxis, VZV-specific T-Cell immunity, herpes simplex virus (HSV) infection, cytomegalovirus (CMV) disease, survival, and safety were secondary end points. Acyclovir significantly reduced VZV infections at 1 year after transplantation (HR, 0.16; 95% CI, 0.035-0.74; P = .006). In the postintervention observation period, this difference was not statistically significant (2 years: HR, 0.52; 95% CI, 0.21-1.3; 5 years: HR, 0.76; 95% CI, 0.36-1.6). There was no statistically significant difference in reconstitution of VZV-specific T-helper Cell responses, HSV infections, CMV disease, chronic graft-versus-host disease, and overall survival between the groups. Acyclovir was well tolerated. Post-study VZV disease predominantly occurred in patients with continued need for systemic immunosuppression. In conclusion, acyclovir effectively and safely prevents VZV disease during the first year after Hematopoietic Cell transplantation. Periods of prophylaxis longer than 12 months may be beneficial for those Hematopoietic Cell transplant recipients on continued immune suppression.
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graft versus tumor effects after allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning
Journal of Clinical Oncology, 2005Co-Authors: Frederic Baron, Barry E Storer, Brenda M Sandmaier, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Thomas R Chauncey, Mohamed L Sorror, Razvan Diaconescu, Marco MielcarekAbstract:Purpose We have used a nonmyeloablative 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.
Brenda M Sandmaier - One of the best experts on this subject based on the ideXlab platform.
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inosine monophosphate dehydrogenase pharmacogenetics in Hematopoietic Cell transplantation patients
Biology of Blood and Marrow Transplantation, 2018Co-Authors: Jeannine S Mccune, Barry E Storer, Sushma S Thomas, Jožefa S Mckiernan, Rohan Gupta, Brenda M SandmaierAbstract:Abstract We evaluated inosine monophosphate dehydrogenase ( IMPDH) 1 and IMPDH2 pharmacogenetics in 247 recipient–donor pairs after nonmyeloablative Hematopoietic Cell transplant (HCT). Patients were conditioned with total body irradiation + fludarabine and received grafts from related or unrelated donors (10% HLA mismatch), with postgraft immunosuppression of mycophenolate mofetil (MMF) with a calcineurin inhibitor. Recipient and donor IMPDH genotypes (rs11706052, rs2278294, rs2278293) were not associated with day 28 T Cell chimerism, acute graft-versus-host disease (GVHD), disease relapse, cytomegalovirus reactivation, nonrelapse mortality, or overall survival. Recipient IMPDH1 rs2278293 genotype was associated with a lower incidence of chronic GVHD (hazard ratio, .72; P = .008) in nonmyeloablative HCT recipients. Additional studies are needed to confirm these results with the goal of identifying predictive biomarkers to MMF that lower GVHD.
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conditioning regimens for Hematopoietic Cell transplantation one size does not fit all
Blood, 2014Co-Authors: Brenda M Sandmaier, Boglarka GyurkoczaAbstract:An essential component of allogeneic and autologous Hematopoietic Cell transplantation (HCT) is the conditioning regimen administered before the Hematopoietic Cell infusion. Early regimens relied on dose intensity, assuming that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion of the graft would then restore hematopoiesis. However, as the contribution of graft-versus-tumor effects to the success of allogeneic HCT was recognized over time, in an effort to exploit these, many investigators lowered the dose of radiation and chemotherapeutic agents in the preparative regimen. This resulted in a major paradigm shift, and consequently, the pool of eligible patients underwent a remarkable expansion. In this article, we provide a review of the definition of high-dose, reduced-intensity, and nonmyeloablative conditioning regimens, the most commonly used agents and combinations, and the evolution of some early regimens. We also provide a brief review of the toxicities associated with these regimens.
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non myeloablative conditioning with allogeneic Hematopoietic Cell transplantation for the treatment of high risk acute lymphoblastic leukemia
Haematologica, 2011Co-Authors: Rainer Storb, Thoralf Lange, Brenda M Sandmaier, David G Maloney, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Ginna G Laport, Thomas R Chauncey, Amelia LangstonAbstract:Background Allogeneic Hematopoietic Cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults with acute lymphoblastic leukemia are not candidates for myeloablative conditioning regimens. A non-myeloablative preparative regimen is a reasonable treatment option for this group. We sought to determine the outcome of non-myeloablative conditioning and allogeneic transplantation in patients with high-risk acute lymphoblastic leukemia. Design and Methods Fifty-one patients (median age 56 years) underwent allogeneic Hematopoietic Cell transplantation from sibling or unrelated donors after fludarabine and 2 Gray total body irradiation. Twenty-five patients had Philadelphia chromosome-positive acute lymphoblastic leukemia. Eighteen of these patients received post-grafting imatinib. Results With a median follow-up of 43 months, the 3-year overall survival was 34%. The 3-year relapse/progression and non-relapse mortality rates were 40% and 28%, respectively. The cumulative incidences of grades II and III-IV acute graft- versus -host disease were 53% and 6%, respectively. The cumulative incidence of chronic graft- versus -host disease was 44%. Hematopoietic Cell transplantation in first complete remission and post-grafting imatinib were associated with improved survival ( P =0.005 and P =0.03, respectively). Three-year overall survival rates for patients with Philadelphia-negative acute lymphoblastic leukemia in first remission and beyond first remission were 52% and 8%, respectively. For patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first remission who received post-grafting imatinib, the 3-year overall survival rate was 62%; for the subgroup without evidence of minimal residual disease at transplantation, the overall survival was 73%. Conclusions For patients with high-risk acute lymphoblastic leukemia in first complete remission, non-myeloablative conditioning and allogeneic Hematopoietic Cell transplantation, with post-grafting imatinib for Philadelphia chromosome-positive disease, can result in favorable long-term survival. ([Clinicaltrials.gov][1] identifier: NCT0036738) [1]: http://ClinicalTrials.gov
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graft versus tumor effects after allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning
Journal of Clinical Oncology, 2005Co-Authors: Frederic Baron, Barry E Storer, Brenda M Sandmaier, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Thomas R Chauncey, Mohamed L Sorror, Razvan Diaconescu, Marco MielcarekAbstract:Purpose We have used a nonmyeloablative 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.
Frederic Baron - One of the best experts on this subject based on the ideXlab platform.
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total body irradiation dose escalation decreases risk of progression and graft rejection after Hematopoietic Cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Haematologica, 2019Co-Authors: Federico Monaco, Barry E Storer, Thomas R Chauncey, Bart L Scott, F B Petersen, Frederic Baron, Mary E D FlowersAbstract:A non-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allogeneic Hematopoietic Cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed Hematopoietic Cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently performed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloablative conditioning followed by Hematopoietic Cell transplantation with total body irradiation dose escalation for excessive Hematopoietic Cell transplantation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syndrome low risk (n=36); and Arm B: myelodysplastic syndrome high-risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of peripheral blood stem Cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 Hematopoietic Cell transplant failure, with the objective of reducing the incidence to
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factors associated with outcomes in allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning after failed myeloablative Hematopoietic Cell transplantation
Journal of Clinical Oncology, 2006Co-Authors: Frederic Baron, Barry E Storer, Michael B Maris, Thomas R Chauncey, Judith A. Shizuru, Rainer Storb, Stephen J Forman, Dietger Niederwieser, Benedetto Bruno, Peter A McsweeneyAbstract:Purpose Several studies have investigated the feasibility of allogeneic Hematopoietic Cell transplantations (HCTs) after reduced-intensity conditioning in patients who experienced relapse after myeloablative HCT. Although most studies showed relatively low nonrelapse mortality (NRM) rates and encouraging short-term results, it has yet to be defined which patients would benefit most from these approaches. Patients and Methods We analyzed data from 147 patients with hematologic malignancies who experienced treatment failure with conventional autologous (n = 135), allogeneic (n = 10), or syngeneic (n = 2) HCT and were treated with HLA-matched related (n = 62) or unrelated (n = 85) grafts after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Results Three-year probabilities of NRM, relapse, and overall survival were 32%, 48%, and 27%, respectively, for related recipients, and 28%, 44%, and 44%, respectively, for unrelated recipients. The best outcomes were observed in patients wi...
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graft versus tumor effects after allogeneic Hematopoietic Cell transplantation with nonmyeloablative conditioning
Journal of Clinical Oncology, 2005Co-Authors: Frederic Baron, Barry E Storer, Brenda M Sandmaier, Ann E Woolfrey, Mary E D Flowers, Michael B Maris, Thomas R Chauncey, Mohamed L Sorror, Razvan Diaconescu, Marco MielcarekAbstract:Purpose We have used a nonmyeloablative 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.