0
selected
-
1.
Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT
Poire, X., Labopin, M., Polge, E., Forcade, E., Ganser, A., Volin, L., Michallet, M., Blaise, D., Yakoub-Agha, I., Maertens, J., et al
Haematologica. 2019
-
-
-
Free full text
-
Editor's Choice
Abstract
Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia is a common high-risk feature referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with acute myeloid leukemia harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified 4 different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the 4 groups were active disease, age, monosomal karyotype and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
PICO Summary
Population
Adult patients with acute myeloid leukemia harboring deletion 5q or monosomy 5 (-5/5q-) (n=501)
Intervention
First allogeneic transplantation between 2000 and 2015
Comparison
None
Outcome
The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.
-
2.
The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA-matched allogeneic stem cell transplantation
Poire, X., Labopin, M., Polge, E., Volin, L., Finke, J., Ganser, A., Blaise, D., Yakoub-Agha, I., Beelen, D., Forcade, E., et al
American journal of hematology. 2019
Abstract
Monosomy 7 or deletion 7q (-7/7q-) is the most frequent adverse cytogenetic features reported in acute myeloid leukemia (AML) and is a common indication for allogeneic stem cell transplantation (SCT). Nevertheless, -7/7q- occurs frequently with other high-risk cytogenetic abnormalities such as complex karyotype (CK), monosomal karyotype (MK), monosomy 5 or deletion 5q (-5/5q-), 17p abnormalities (abn(17p)) or inversion of chromosome 3 (inv(3)), the presence of which may influence the outcomes after SCT. A total of 1,109 patients has been allocated to this study. Two-year probability of leukemia-free survival (LFS) and overall survival (OS) were 30% and 36%, respectively. Two-year probability of non-relapse mortality (NRM) was 20%. We defined 5 different cytogenetic subgroups: the "-7/7q- +/- CK group- designated group1", the "MK group-designated group 2", the "-5/5q- group- designated group 3", the 'abn(17p) group- designated group 4" and the "inv(3) group- designated group 5". The 2-year probability of LFS in first remission was 48% for group 1, 36.4% for group 2, 28.4% for group 3, 19.1% for group 4 and 17.3% for group 5, respectively (p<0.001). Multivariate analysis confirmed those significant differences across groups. SCT in -7/7q- AML provides durable response in one third of the patients. The presence of -7/7q- with or without CK in the absence of MK, abn(17p) or inv(3) is associated with a better survival after SCT. On the contrary, addition of MK, -5/5q-, abn(17p) or inv(3) identifies a sub-group of patients with poor prognosis even after SCT. This article is protected by copyright. All rights reserved.
-
3.
Impact of antithymocyte globulin on outcomes of allogeneic hematopoietic cell transplantation with TBI
Nagler, A., Labopin, M., Dholaria, B., Niittyvuopio, R., Maertens, J., Poire, X., Cornelissen, J., Remenyi, P., Bourhis, J. H., Beguin, Y., et al
Blood advances. 2019;3(13):1950-1960
-
-
Free full text
-
Abstract
The impact of the use of antithymocyte globulin (ATG) following a total body irradiation (TBI)-based myeloablative conditioning regimen has been poorly explored. We retrospectively analyzed 724 patients who underwent a first allogeneic hematopoietic cell transplantation (allo-HCT) following a TBI-based conditioning regimen for acute myeloid leukemia (AML) and compared the outcomes of 251 (35%) patients who received ATG (ATG group) with 473 (65%) patients who did not (non-ATG group). Median follow-up of surviving patients was 59 months (interquartile range, 28-83). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) for non-ATG and ATG groups in the first 100 days was 33% vs 24%, respectively (P = .0098). The 2-year cumulative incidence of chronic graft-versus-host disease (cGVHD) was reduced significantly in the ATG group in comparison with the non-ATG group (46% vs 34%, P = .003). Using multivariate analysis, in vivo T-cell depletion (ATG group) was independently associated with a decreased incidence of grade II-IV aGVHD (hazard ratio [HR], 0.28; P < .001), grade III-IV aGVHD (HR, 0.21; P < .001), cGVHD (HR, 0.63; P = .02), and nonrelapse mortality (NRM) (HR, 0.54; P = .02). Relapse risk, overall survival, and leukemia-free survival were similar between the 2 groups. Our results suggest that the addition of ATG to TBI-based myeloablative conditioning for allo-HCT in AML patients results in a significant reduction in aGVHD and cGVHD, translating into a significant reduction in NRM without increasing the relapse rate.
-
4.
Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Poire, X., Labopin, M., Maertens, J., Yakoub-Agha, I., Blaise, D., Ifrah, N., Socie, G., Gedde-Dhal, T., Schaap, N., Cornelissen, J. J., et al
Journal of hematology & oncology. 2017;10(1):20
Abstract
BACKGROUND Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. METHODS To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. RESULTS One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients' age. CONCLUSIONS In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.
-
5.
Allogeneic stem cell transplantation benefits for patients >= 60 years with acute myeloid leukemia and FLT3-ITD; a study from the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT)
Poire, X., Labopin, M., Polge, E., Passweg, J., Craddock, C., Blaise, D., Cornelissen, J. J., Volin, L., Russell, N. H., Socie, G., et al
Haematologica. 2017
Abstract
Intermediate-risk cytogenetic acute myeloid leukemia with an internal tandem duplication of FLT3 (FLT3-ITD) is associated with a high risk of relapse and is now a standard indication for allogeneic stem cell transplantation. Nevertheless, most studies supporting this strategy have been performed in young patients. To address the benefit of allogeneic transplantation in elderly patients, we selected from the EBMT registry de novo intermediate-risk cytogenetic acute myeloid leukemia harboring FLT3-ITD in patients with an age equal or over the age of 60 years and transplanted from a related or unrelated donor between January 2000 and December 2015. Two hundred and ninety-one patients were identified. Most patients received a reduced-intensity conditioning (82%) and donor consisted of an unrelated donor in 161 (55%) patients. Two hundred twelve patients received their transplantation in first remission, 37 in second remission and 42 in more advanced stage of the disease. The 2-year leukemia-free survival was 56% in patients in first remission, 22% in those in second remission and 10% in patients with active disease, respectively (p<0.005). Non-relapse mortality for the entire cohort was 20%. In multivariate analysis, disease status at transplantation was the most powerful predictor of worse leukemia-free survival, graft-versus-host disease and relapse-free survival and overall survival. In this advanced age population, age was not associated with outcome. Based on the current results, allogeneic transplantation translates into a favorable outcome in fit patients >= 60 patients with FLT3-ITD acute myeloid leukemia in first remission, similarly to current treatment recommendation in younger patients.