The impact of center experience on results of reduced intensity: allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

Giebel, Sebastian; Labopin, Myriam; Mohty, Mohamad; Mufti, Ghulam J.; Niederwieser, Dietger; Cornelissen, Jan J.; Janssen, Jeroen; Milpied, Noël; Vindeløv, Lars L.; Petersen, Eefke; Arnold, R; Bacigalupo, Andrea; Blaise, Didier; Craddock, Charles; Nagler, Arnon; Frassoni, Francesco; Saduś-Wojciechowska, Maria; Rocha, Vanderson

doi:10.1038/bmt.2012.131

Cited by 27 publications

(21 citation statements)

References 23 publications

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“…Another strategy used to prevent AML relapse after alemtuzumab-based RIC has been based on the pre-emptive administration of azacitidine which can likely favor the GVT effect without excessive GVHD. 36,37 Besides the impact of in vivo T-cell depletion on outcomes, this study also confirmed the negative impact of poor risk cytogenetics, 23,38,39 of being transplanted with a female donor in case of male recipients, 40 and of being transplanted in low-activity centers 18,22 on OS and PFS, as previously observed by our group 18,22,38,41 and by other groups of investigators. 39,40 Further, in contrast to what was observed in a recent CIBMTR study, 39 current data suggest that older patient age at transplantation is associated with higher NRM translating to worse LFS and OS in multivariate analyses.…”

Section: Discussionsupporting

confidence: 77%

“…We did not have complete data on the use of pre-emptive DLI in the registry but at least 15 (5%) control patients, 39 (14%) ATG patients and 66 (36%) alemtuzumab patients received pre-emptive DLI (defined as DLI given before/without AML relapse). Finally, there were a higher proportion of patients transplanted in low-activity centers 22 (arbitrarily defined as centers that contributed for p10 patients in the current study) among control patients (55%) than among ATG (43%) or alemtuzumab (44%) patients (Po0.001).…”

Section: Patients and Conditioningmentioning

confidence: 99%

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Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

Baron

Labopin

Blaise³

et al. 2014

Bone Marrow Transplant

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The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (Po0.001).In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (Po0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of o6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR ¼ 1.1), whereas there was a suggestion for higher relapse risk in patients given X6 mg/kg ATG (HR ¼ 1.4, P ¼ 0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC. INTRODUCTIONThe use of PBSC instead of BM in patients receiving grafts from HLA-matched donors after myeloablative conditioning has been associated with faster hematological recovery, lower relapse risk in patients with advanced disease (due to higher immune-mediated graft-versus-tumor (GVT) effects), but also higher incidence extensive chronic GVHD. 1-4 These observations prompted several groups of investigators to study in vivo T-cell depletion of the graft with antithymocyte globulin (ATG) or alemtuzumab as a way to reduce severe GVHD in patients given PBSC after highdose myeloablative conditioning regimen. [5][6][7] These studies demonstrated that the use of ATG or alemtuzumab was successful at preventing severe GVHD without apparently increasing the relapse incidence (RI). [5][6][7] In contrast to patients given grafts after myeloablative conditioning who benefit from both the high-dose chemo/radiotherapy given as part of the conditioning regimen and the GVT effect for tumor eradication,

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Section: Discussionsupporting

confidence: 77%

Section: Patients and Conditioningmentioning

confidence: 99%

Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

Baron

Labopin

Blaise³

et al. 2014

Bone Marrow Transplant

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“…Current results are in accordance with a recent study from the CIBMTR analyzing data from 1676 patients given grafts after RIC as treatment for various hematological malignancies demonstrating that the use of alemtuzumab and/or ATG was associated with higher risk of relapse, that translated into worse disease-free survival. 30 Patients transplanted in high-activity centers had higher incidence of chronic GVHD and better outcomes owing to both lower relapse risk and lower NRM than those transplanted in lower-activity centers, as previously observed by Giebel et al 27 The higher incidence of chronic GVHD in patients transplanted in high-activity centers (even after adjusting for the use of ATG or alemtuzumab) could be due in part at a better recognition of signs of chronic GVHD in larger transplant centers, or to different modulation strategies of postgrafting immunosuppression according to disease risk and minimal residual disease data after transplantation in patients transplanted in high-activity centers (leading to both lower risk of relapse and higher incidence of chronic GVHD). Interestingly, NRM in patients diagnosed with extensive chronic GVHD was similar in patients transplanted in centers with high or low activity, stressing that treatment of extensive chronic GVHD has remained a difficult challenge even in large transplant centers.…”

Section: Discussionsupporting

confidence: 53%

“…Associations of patient and graft characteristics with other outcomes (chronic GVHD, relapse, NRM, LFS and OS) were evaluated in multivariable analyses, using Cox proportional hazards. Factors included in the models for acute and chronic GVHD included donor type, patient age 456 years, female donor to male recipient versus other gender combinations, donor and recipient cytomegalovirus serostatus, disease status at the time of transplant, cytogenetic risk group, TBI-versus chemotherapy-based RIC, the use of antithymocyte globulin (ATG) in the conditioning, the use of alemtuzumab in the conditioning, center activity 27 (arbitrarily defined as center that performed por X20 first allo-SCT with RIC conditioning as treatment for AML between 2000 and 2009) and prior grade II-IV acute GVHD (for chronic GVHD). The same factors as well as acute, limited chronic and extensive chronic GVHD were included in the models for NRM, relapse, LFS and OS ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

et al. 2012

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This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR) ¼ 0.7, P ¼ 0.02) translating into a trend for better overall survival (OS; HR ¼ 1.3; P ¼ 0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR ¼ 0.4, Po0.0.001) owing to high risk of nonrelapse mortality (NRM; HR ¼ 5.2, Po0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR ¼ 0.72; P ¼ 0.07) translating into a better OS (HR ¼ 1.8; Po0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR ¼ 0.65; P ¼ 0.02) but also with higher NRM (HR ¼ 3.5; Po0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (Po0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR ¼ 0.65; P ¼ 0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD.

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“…Superior leukemia-free survival (LFS) after myeloablative alloHCT for acute myeloid leukemia (AML) was observed in countries with very high HDI values. On the other hand, individual center activity and organization also strongly influence the results of alloHCT [5][6][7][8]. In particular, increased nonrelapse mortality (NRM) after alloHCT with reduced-intensity conditioning was observed in centers with very little experience [8].…”

Section: Introductionmentioning

confidence: 99%

Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT

et al. 2016

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Acute lymphoblastic leukemia x Non-relapse mortality ABSTRACT Purpose. From a global perspective, the rates of allogeneic hematopoietic cell transplantation (alloHCT) are closely related to the economic status of a country. However, a potential association withoutcome hasnot yet been documented.The goal ofthis study was to evaluate effects of health care expenditure (HCE), Human Development Index (HDI),team density, and center experience on nonrelapsemortality(NRM)afterHLA-matchedsiblingalloHCTfor adults with acute lymphoblastic leukemia (ALL). Patients and Methods. A total of 983 patients treated with myeloablative alloHCT between 2004 and 2008 in 24 European countries were included. Results. In a univariate analysis, the probability of day 100 NRM was increased for countries with lower current HCE (8% vs. 3%; p 5 .06), countries with lower HDI (8% vs. 3%; p 5 .02), and centers with less experience (8% vs. 5%; p 5 .04). In addition, the overall NRM was increased for countries with lower current HCE (21% vs. 17%; p 5 .09) and HDI (21% vs. 16%; p 5 .03) and for centers with loweractivity (21% vs. 16%;p 5 .07). In a multivariate analysis,the strongest predictive model for day 100 NRM included current HCE greater than the median (hazard ratio [HR], 0.39; p 5 .002).The overall NRM was mostly predicted by HDI greater than the median (HR, 0.65; p 5 .01). Both lower current HCE and HDI were associated with decreased probability of overall survival. Conclusion. Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. The Oncologist 2016;21:377-383 Implications for Practice: Results of allogeneic hematopoietic cell transplantation (alloHCT) and other advanced oncological procedures may vary among countries and be related to various economic factors.This study, which included a homogenous population of patients with acute lymphoblastic leukemia, demonstrated significant associations of health care expenditure and the Human Development Index with nonrelapse mortality and overall survival after transplantation.The findings should be taken into account when clinical studies in the field of alloHCT are interpreted. The study should be followed by further investigation in other fields of oncology.

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The impact of center experience on results of reduced intensity: allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

Cited by 27 publications

References 23 publications

Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT

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