Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning

Ho, A Y L; Pagliuca, Antonio; Kenyon, Michelle; Parker, Jane E.; Mijović, Aleksandar; Devereux, Stephen; Mufti, Ghulam J.

doi:10.1182/blood-2003-12-4207

Cited by 193 publications

(127 citation statements)

References 49 publications

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“…RI regimens have been reported to reduce the cytokine release and damage to mucosal tissues and result in less aGVHD compared with MA, which can contribute to a lower TRM. The TRM using RI regimens has been reported from 5% [25] to nearly 20% [20,22,26]. TRM varies with the patient population, the time point at which it is assessed following HSCT, and the intensity of the RI regimen.…”

Section: Discussionmentioning

confidence: 99%

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

et al. 2007

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We evaluated the efficacy of hematopoietic stem cell transplantation (HSCT) using reduced intensity (RI) vs. myeloablative (MA) conditioning for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome. Thirty two patients (median age 54) who underwent a RI HSCT (2000HSCT ( -2003 were compared with 187 patients (median age 39) who received a MA transplant (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003). Neutrophil engraftment was more rapid in the RI group (median 11.5 vs. 21 days). Platelet recovery was similar and graft failure was infrequent. The incidence of graft-versus-host disease (GVHD) and treatment-related mortality was similar though relapse was more frequent after RI conditioning (RR 2.2 [95% CI 5 1.1-4.6] P 5 0.03). At 2 years, disease-free survival (DFS) (31% vs. 30%, P > 0.1) and overall survival (33% vs. 35%, P > 0.1) were comparable between RI and MA groups, respectively. We suggest that RI allografts can yield satisfactory DFS both for older as well as younger patients with pre-existing comorbidities, who are ineligible for MA allografts. Advances in GVHD management and new approaches for relapsed or refractory disease are necessary to improve these outcomes. Am. J. Hematol. 82:867-872, 2007. V

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Section: Discussionmentioning

confidence: 99%

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

et al. 2007

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“…Standard nursing care and post-transplant prophylaxis were administered as described earlier. 6 Comorbidity score The HCT-CI was used to assign a pretransplant comorbidity score to all patients. 19 A score of 0 was identified in 40 (31%), score 1 in 23 (18%), score 2 in 22 (17%) and X3 in 43 (34%) patients.…”

Section: Conditioning Regimenmentioning

confidence: 99%

“…More recently, a significant reduction in regimen-related toxicity and non-relapse mortality (NRM) with reduced-intensity conditioning (RIC) regimens has enabled allogeneic transplantation to be extended to this group of patients. [1][2][3][4][5][6] Despite these advances, transplant-related morbidity and mortality, particularly in elderly patients with advanced disease, remain significant.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, in patients with high-risk disease MDS or AML undergoing RIC HSCT, patients with an HCT-CI of X3 had a 2-year OS of only 29%. 20 Various groups have used in vivo T-cell depletion with either alemtuzumab (Campath-1H) or anti-thymocyte globulin to lower the incidence of both acute GVHD (aGVHD) and chronic GVHD (cGVHD) 6,[21][22][23][24][25] with the aim of reducing NRM.…”

Section: Introductionmentioning

confidence: 99%

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Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML

Lim

Ingram

Brand

et al. 2009

Bone Marrow Transplant

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We report a retrospective analysis of 128 consecutive patients with high-risk myelodysplastic syndrome (MDS) and AML who received an alemtuzumab-based reducedintensity conditioning hematopoietic SCT (RIC HSCT). The median recipient age was 53 years (range 21-72 years). A total of 49 (38%) recipients had a sibling donor and 79 (62%) had a volunteer-unrelated donor. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was assigned to all patients with a score of 0 in 40 (31%), of 1-2 in 45 (35%) and X3 in 43 (34%) patients. The 3-year non-relapse mortality (NRM) was 31%, disease-free survival (DFS) was 41% and overall survival (OS) was 46%. The 3-year NRM for patients with a HCT-CI score of 0, 1-2 or X3 was 16, 24 and 42%, respectively. The 3-year DFS and OS by HCT-CI was 58 and 69% (score 0), 39 and 39% (score 1-2) and 24 and 32% (score X3), respectively. On multivariate analysis, HCT-CI was an independent variable affecting 3-year NRM, DFS and OS (P-value ¼ 0.04, 0.01 and o0.01, respectively). Although the disease stage at the time of transplant was an additional independent predictive variable on transplant outcomes, recipient age (4/o50 years) did not have a significant predictive impact. In MDS or AML patients with advanced disease receiving alemtuzumab-based RIC HSCT, the HCT-CI provides an important means of stratifying patients with a high risk of inferior transplant outcomes.

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“…Similar improved results using RIC-HSCT have also been reported recently in older patients with myelodysplastic syndromes. [16][17][18] Due to this improved results, older age may no more further impact on outcome after HSCT 18 .…”

Section: Impact Of Conditioning Regimen Modifications In Older Patientsmentioning

confidence: 99%

Management of adult patients older than 40 years refractory to at least one immunosuppressive course: HLA-identical sibling HSCT using fludarabine-based conditioning

Maury

Aljurf

2012

Bone Marrow Transplant

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Allogeneic hematopoietic SCT (HSCT) from an HLA-identical sibling donor is the recommended upfront therapeutic option for young patients with SAA. The outcome of allogeneic sibling HSCT has remarkably improved during the last decade as a function of improvement in transplantation supportive care. However, there is still much debate concerning the upper age limit for sibling HSCT in SAA, particularly in patients who are refractory to at least one immunosuppressive course. Recent studies suggest that fludarabine-based conditioning may improve HSCT outcome in older patients with SAA. This review discusses available data about the use of fludarabine-based conditioning in transplantation of older patients with SAA. More definitive conclusions are needed from larger studies before the wide adoption of fludarabine-based conditioning as an alternative to the standard CY and ATG-based conditioning. (2013) 48, 196-197; doi:10.1038/bmt.2012.251; published online 10 December 2012 Bone Marrow TransplantationKeywords: aplastic anemia; sibling donor; conditioning regimen; impact of age HLA-IDENTICAL SIBLING HSCT IN OLDER PATIENTSAllogeneic hematopoietic SCT (HSCT) from an HLA-identical sibling donor is the first line treatment of choice for newly diagnosed patients with severe acquired idiopathic aplastic anemia (SAA) younger than 40 years.However, for older patients X40 years, the decision whether to treat with immunosuppressive therapy (IST), namely antithymocyte globulin (ATG) and cyclosporine, or to transplant upfront from an HLA-identical sibling donor remains a key question. Two large studies from Seattle 1 and the European Group for Blood and Marrow Transplantation (EBMT) SAA Working Party 2 that examined survival by age group did not show an advantage for either HSCT or IST in older patients. This was notably related to a lower long-term survival after HSCT for older patients, that is, 440 years in the Seattle cohort 1 and 420 years in the European study. 2 The negative impact of older age at transplant has been confirmed in several other studies. 3-5 A recently published large study from the CIBMTR performed on 1307 patients analyzed the impact of age on outcome after sibling donor HSCT for SAA. 6 Patients older than 40 years were more likely to (i) have had immunosuppressive therapy before HSCT, (ii) have a poor performance status, (iii) have an interval from diagnosis to HSCT of43 months and (iv) have received a PBSC graft. The mortality risk was higher in patients over 40 years than in patients 20-40 years (P ¼ 0.008) and patients less than 20 years old (Po0.0001). IMPACT OF CONDITIONING REGIMEN MODIFICATIONS IN OLDER PATIENTSThe standard conditioning regimen for HLA identical sibling HSCT relies on CY, with or without ATG. In order to improve survival in patients older than 40 years, the use of less cytotoxic but more immunosuppressive regimens including lowered dose of CY (below the standard dose of 200 mg/kg) in combination with ATG, while adding fludarabine, might be an option to explore with the aim of reducin...

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Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning

Cited by 193 publications

References 49 publications

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

Impact of pretransplant comorbidities on alemtuzumab-based reduced-intensity conditioning allogeneic hematopoietic SCT for patients with high-risk myelodysplastic syndrome and AML

Management of adult patients older than 40 years refractory to at least one immunosuppressive course: HLA-identical sibling HSCT using fludarabine-based conditioning

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