Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study

Sengsayadeth, Salyka; Gatwood, Katie S.; Boumendil, Ariane; Labopin, Myriam; Finke, Jürgen; Ganser, Arnold; Stelljes, Matthias; Ehninger, Gerhard; Beelen, Dietrich; Niederwieser, Dietger; Blaise, Didier; Dreger, Peter; Mufti, Ghulam J.; Chevallier, Patrice; Mailhol, Audrey; Gilleece, Maria; Gorin, Norbert Claude; Esteve, Jordi; Ciceri, Fabio; Baron, Frédéric; Schmid, Christoph; Giebel, Sebastian; Mohty, Mohamad; Savani, Bipin N.; Nagler, Arnon

doi:10.1182/bloodadvances.2018019976

Cited by 36 publications

(36 citation statements)

References 31 publications

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“…Indeed, while it did not reach statistical significance perhaps because of an insufficient study power, the incidence of relapse in patients transplanted in CR1 was 11% higher in patients given RIC than in those given MAC (29% vs. 18% at 2 years). This is consistent with a prior study in patients with de novo AML demonstrating more relapses in patients given CBT following RIC than in those given MAC regimens [21], and with a recent study showing lower risk of relapse and better OS in sAML patients given MAC (versus RIC) conditioning before HLA-identical sibling or HLAmatched unrelated donor transplantation [34]. Besides increasing the antileukemic activity of the conditioning regimens, further approaches to prevent relapse after CBT might consist of posttransplant administration of disease-targeted medications [35][36][37].…”

Section: Discussionsupporting

confidence: 91%

“…Two-year incidences of relapse and of NRM were 29% (95% CI, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 39% (95% CI, 31-48), respectively. The figures were 25% (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and 35% (95% CI, 25-45), respectively, in patients in CR1, versus 36% (95% CI, 22-49, P = 0.06) and 49% (95% CI, 33-62, P = 0.03), respectively, in patients with active disease at transplantation ( Fig. 1).…”

Section: Relapse and Nonrelapse Mortalitymentioning

confidence: 99%

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Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

et al. 2019

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Israel). Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission. J Intern Med 2019; 285: 446-454.Background. We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML).Methods. Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT.Results. One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. Conclusions.We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.

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Section: Discussionsupporting

confidence: 91%

Section: Relapse and Nonrelapse Mortalitymentioning

confidence: 99%

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

et al. 2019

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“…Furthermore, the results may contribute to the design of optimized transplant protocols. Previous studies have suggested comparable outcomes after RIC and MAC in sAML, however, with a trend for better outcome after MAC 11,29 . Hence, a myeloablative, but reduced toxicity conditioning regimen such as the combination of Fludarabine and Treosulfan 30 might be of particular value in patients with sAML.…”

Section: Discussionmentioning

confidence: 79%

“…Allogeneic stem cell transplantation (alloSCT) is regarded as the treatment option for sAML with the best chance of achieving a long-term remission. Considering the transplant setting 8,9 , patients with sAML tend to have less available HLA identical siblings, and the majority receive reduced intensity conditioning (RIC) 10,11 . However, it is not clear whether having sAML per se is a risk factor for outcome after alloSCT, when all wellknown risk factors are controlled for 8 .…”

Section: Introductionmentioning

confidence: 99%

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

et al. 2020

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Following chemotherapy, secondary acute myeloid leukemia (sAML), occurring after antecedent hematologic diseases, previous chemotherapy or radiation, has an inferior prognosis compared with de novo AML. To define the outcome of sAML in the context of allogeneic stem cell transplantation (alloSCT), a retrospective, registry-based comparison was performed, including 11,439 patients with de novo and 1325 with sAML. Among transplants in first complete remission (CR1) (n = 8,600), the 3-year cumulative incidence of relapse (RI) and non-relapse mortality (NRM) was 28.5% and 16.4% for de novo, and 35% and 23.4% for sAML. Three-year overall survival (OS), leukemia-free survival (LFS) and Graft-versus-Host Disease/relapse-free survival (GRFS) was 60.8%, 55.1%, and 38.6% for de novo, and 46.7%, 41.6%, and 28.4% for sAML, respectively. In multivariate analysis, sAML was associated with a lower OS (HR = 1.33 [95% CI = 1.21–1.48]; p < 10−5), LFS (HR = 1.32 [95% CI = 1.19–1.45]; p < 10−5) and GRFS (HR = 1.2 [95% CI = 1.1–1.31]; p < 10−4) and higher NRM (HR = 1.37 [95% CI = 1.17–1.59]; p < 10−4) and RI (HR = 1.27 [95% CI = 1.12–1.44]; p < 10−3). Results of the Cox model were confirmed in a matched-pair analysis. In contrast, results did not differ between de novo and sAML after alloSCT in induction failure or relapse. Hence, this analysis identified sAML as an independent risk factor for outcome after alloSCT in CR1.

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“…Data on transplant related factors of importance and outcome specific for s-AML has historically been scarce. However, during 2018-2019 the European Society for Blood and Marrow Transplantation (EBMT), mostly through the work of the Acute Leukemia Working Party, published a series of reports on various aspects of allogeneic transplantation based on large numbers of s-AML patients [149][150][151][152][153][154][155][156]. They show that s-AML, compared to de novo AML, is a risk factor for relapse and survival after HCT [150,154].…”

Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Nilsson

Hulegårdh

Garelius

et al. 2019

Biology of Blood and Marrow Transplantation

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Secondary acute myeloid leukemia (s-AML) refers to patients with either therapy-related AML (t-AML), that is, AML after treatment with chemo-and/or radiation for a prior disease, or AML progressing from an antecedent hematologic disorder (AHD-AML), typically a myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm. Patients with s-AML present with higher rates of adverse cytogenetic aberrations and higher frequencies of adverse mutations and, subsequently, respond worse to therapy, and have poorer outcome compared to de novo AML. To identify clinical and molecular factors that may improve prognostication is therefore of importance to guide clinical decision-making. The general aim of this thesis was to broaden the real-world knowledge of s-AML, regarding disease properties and outcome, using population-based registries, and additionally to investigate the importance of mutations in the transformation from MDS to AML. The research papers presented herein cover mutational screening in MDS and s-AML (study I), general characteristics and outcome of s-AML (study II), the role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML (study III), and the epidemiology and treatment outcome specifically for t-AML (study IV). långtidsöverlevare utan transplantation. Att genomgå transplantation i s.k. första remission var överlägset behandling med enbart cytostatika. Studie IV fokuserade på patienter med terapirelaterad AML. Data från svenska AMLregistret på 686 patienter kombinerades med data från Socialstyrelsens cancerregister och Svensk Reumatologis Kvalitetsregister. Huvudsakliga fynd var att incidensen av t-AML tydligt ökar över tid och att andelen terapirelaterad AML av AML-fallen totalt blev allt större. Överlevnaden vid terapirelaterad AML var generellt mycket dyster, men i vissa genetiska undergrupper var den bättre och jämförbar med patienter med motsvarande genetisk riskprofil som nyinsjuknat i AML. Sammanfattningsvis är sekundär-AML en ovanlig sjukdom som är mycket svårbehandlad. Nya läkemedel kommer att krävas för att förbättra överlevnaden, men förhoppningsvis kommer sådana att utvecklas hand i hand med den ökade förståelsen av sjukdomsbiologin. Behandlingen av AML har i stort sett varit oförändrad i årtionden, men nyligen har läkemedel som bl.a. utnyttjar specifika genetiska avvikelser introducerats. Inom andra cancerformer har immun-och cellterapi fått stort genomslag och dessa är potentiellt användbara även mot AML. För gruppen med sekundär-AML är det därför av stor betydelse att sjukdomshistorik, hög ålder och samsjuklighet inte utgör hinder för deltagande i kommande läkemedelsstudier. LIST OF SCIENTIFIC PAPERS I. High-throughput mutational screening adds clinically important information in myelodysplastic syndromes and secondary or therapy-related acute myeloid leukemia.

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Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study

Cited by 36 publications

References 31 publications

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

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