Outcomes of UCB transplantation are comparable in FLT3+ AML: Results of CIBMTR, eurocord and EBMT collaborative analysis.

Ustun, C.; Giannotti, F.; Zhang, M.-J.; Wang, H.-L.; Brunstein, C.; Labopin, M.; Rocha, V.; de Lima, M.; Baron, Frédéric; Sandmaier, B. M.; Eapen, M.; Gluckman, E.; Nagler, A.; Weisdorf, D. J.; Ruggeri, A.

doi:10.1038/leu.2017.42

Article (Scientific journals)

Outcomes of UCB transplantation are comparable in FLT3+ AML: Results of CIBMTR, eurocord and EBMT collaborative analysis.

Ustun, C.; Giannotti, F.; Zhang, M.-J. et al.

2017 • In Leukemia, 31, p. 1408-1414

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https://hdl.handle.net/2268/206005

DOI
10.1038/leu.2017.42

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28119528

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Keywords :

AML; FLT3; umbilical cord blood HCT

Abstract :

[en] Allogeneic hematopoietic cell transplantation (HCT) from siblings or unrelated donors (URD) during complete remission (CR) may improve leukemia-free survival (LFS) in FLT3+ acute myeloid leukemia (AML) that has poor prognosis due to high relapse rates. Umbilical cord blood (UCB) HCT outcomes are largely unknown in this population. We found that compared with sibling HCT, relapse risks were similar after UCB (n=126), (HR 0.86, P=0.54) and URD (n=91) (HR 0.81, P=0.43). UCB HCT was associated with statistically higher non-relapse mortality compared with sibling HCT (HR 2.32, P=0.02), but not vs URD (HR 1.72, P=0.07). All three cohorts had statistically not significant 3-year LFS: 39% (95% CI 30-47) after UCB, 43% (95% CI 30-54) after sibling, and 50% (95% CI 40-60) after URD. Chronic GVHD rates were significantly lower after UCB compared with either sibling (HR 0.59, P=0.03) or URD (HR 0.49, P=0.001). Adverse factors for LFS included high leukocyte count at diagnosis and HCT during CR2. UCB is a suitable option for adults with FLT3+AML in the absence of an HLA-matched sibling and its immediate availability may be particularly important for FLT3+ AML where early relapse is common thus allowing HCT in CR1 when outcomes are best.Leukemia accepted article preview online, 25 January 2017. doi:10.1038/leu.2017.42.

Disciplines :

Hematology

Author, co-author :

Ustun, C.

Giannotti, F.

Zhang, M.-J.

Wang, H.-L.

Brunstein, C.

Labopin, M.

Rocha, V.

de Lima, M.

Baron, Frédéric ; Université de Liège > GIGA-R : Hématologie

Sandmaier, B. M.

More authors (5 more)

Language :

English

Title :

Outcomes of UCB transplantation are comparable in FLT3+ AML: Results of CIBMTR, eurocord and EBMT collaborative analysis.

Publication date :

2017

Journal title :

Leukemia

ISSN :

0887-6924

eISSN :

1476-5551

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Pages :

1408-1414

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 26 January 2017

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Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002; 99: 4326-4335.
Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 2001; 97: 2434-2439.
Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002; 100: 1532-1542.
Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001; 98: 1752-1759.
Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008; 111: 2776-2784.
Meshinchi S, Alonzo TA, Stirewalt DL, Zwaan M, Zimmerman M, Reinhardt D et al. Clinical implications of FLT3 mutations in pediatric AML. Blood 2006; 108: 3654-3661.
Whitman SP, Ruppert AS, Radmacher MD, Mrozek K, Paschka P, Langer C et al. FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cyto-genetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood 2008; 111: 1552-1559.
Brunet S, Labopin M, Esteve J, Cornelissen J, Socie G, Iori AP et al. Impact of FLT3 internal tandem duplication on the outcome of related and unrelated hemato-poietic transplantation for adult acute myeloid leukemia in first remission: a retrospective analysis. J Clin Oncol 2012; 30: 735-741.
Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE. Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood 2014; 124: 273-276.
Whitman SP, Maharry K, Radmacher MD, Becker H, Mrozek K, Margeson D et al. FLT3 internal tandem duplication associates with adverse outcome and gene-and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 2010; 116: 3622-3626.
Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML 10 and 12 trials. Blood 2005; 106: 3658-3665.
Meshinchi S, Arceci RJ, Sanders JE, Smith FO, Woods WB, Radich JR et al. Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood 2006; 108: 400.
Bornhauser M, Illmer T, Schaich M, Soucek S, Ehninger G, Thiede C. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood 2007; 109: 2264-2265.
DeZern AE, Sung A, Kim S, Tsai HL, Kowalski J, Smith BD et al. Patients with FLT3/ITD AML may benefit from allogeneic transplant in first remission: outcomes from a consecutive series of patients at a single institution. Blood 2010; 116: 896-897.
Sengsayadeth SM, Jagasia M, Engelhardt BG, Kassim A, Strickland SA, Goodman S et al. Allogeneic stem cell transplantation for Flt3/Itd positive acute myeloid leukemia in CR1 implication for personalized therapy to prevent early relapses. Biol Blood Marrow Transplant 2012; 18: S332-S333.
Kayser S, Dohner K, Krauter J, Kohne C, Horst HA, Held G et al. Allogeneic transplantation from matched related and unrelated donors in first complete remission in younger adult AML patients with FLT3 internal tandem duplications. Bone Marrow Transplant 2011; 46: S40-S41.
Hemmati P, Terwey TH, Vuong LG, le Coutre PD, Dorken B, Arnold R, Allogeneic Stem. Cell transplantation for cytogenetically normal acute myeloid leukemia: impact of FLT3 and NPM1 mutational status. Blood 2013; 122: 2104.
Liegel J, Courville E, Sachs Z, Ustun C. Use of sorafenib for post-transplant relapse in FLT3/ITD-positive acute myelogenous leukemia: maturation induction and cytotoxic effect. Haematologica 2014; 99: e222-e224.
Deol A, Sengsayadeth S, Ahn K, Wang H, Aljurf M, Antin J et al. ADoes FLT3 mutation impact survival after hematopoietic cell transplant for AML? CIBMTR Anal Cancer 2016; 122: 3005-3014.
Laboure G, Dulucq S, Vigouroux S, Lippert E, Pigneux A, Tabrizi R et al. Potent graft-versus-leukemia effect after reduced intensity (RIC) allogeneic stem-cell transplantation (asct) as post-remission therapy for intermediate-risk de-novo acute myeloid leukemia (AML) with FLT3-ITD genotype or wild-type (WT) NPM1 and CEBPA without FLT3-ITD. Blood 2011; 118: 1766.
Schmid C, Labopin M, Socie G, Daguindau E, Volin L, Huynh A et al. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. Blood 2015; 126: 2062-2069.
DeZern AE, Sung A, Kim S, Smith BD, Karp JE, Gore SD et al. Role of allogeneic transplantation for FLT3/ITD acute myeloid leukemia: outcomes from 133 consecutive newly diagnosed patients from a single institution. Biol Blood Marrow Transplant 2011; 17: 1404-1409.
Bejanyan N, Oran B, Shanley R, Warlick E, Ustun C, Vercellotti G et al. Clinical outcomes of AML patients relapsing after matched-related donor and umbilical cord blood transplantation. Bone Marrow Transplant 2014; 49: 1029-1035.
Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA et al. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood 2010; 116: 4693-4699.
Ruggeri A, Labopin M, Sormani MP, Sanz G, Sanz J, Volt F et al. Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen. Haematologica 2014; 99: 1509-1515.
Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001; 97: 2962-2971.
Eapen M, Klein JP, Ruggeri A, Spellman S, Lee SJ, Anasetti C et al. Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. Blood 2014; 123: 133-140.
Barker JN, Weisdorf DJ, Wagner JE. Creation of a double chimera after the transplantation of umbilical-cord blood from two partially matched unrelated donors. N Engl J Med 2001; 344: 1870-1871.
Sandhu KS, Brunstein C, DeFor T, Bejanyan N, Arora M, Warlick E et al. Umbilical cord blood transplantation outcomes in acute myelogenous leukemia/myelo-dysplastic syndrome patients aged X70 years. Biol Blood Marrow Transplant 2015; 22: 390-393.
Weisdorf D, Eapen M, Ruggeri A, Zhang MJ, Zhong X, Brunstein C et al. Alternative donor transplantation for older patients with acute myeloid leukemia in first complete remission: a center for International Blood and Marrow Transplant Research-Eurocord Analysis. Biol Blood Marrow Transplant 2014; 20: 816-822.
de Latour RP, Brunstein CG, Porcher R, Chevallier P, Robin M, Warlick E et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant 2013; 19: 1355-1360.
Eckfeldt CE, Randall N, Shanley RM, Yohe S, Bejanyan N, Dolan M et al. Umbilical cord blood transplantation is a suitable option for consolidation of acute myeloid leukemia with FLT3-ITD. Haematologica 2016; 101: e348-e351.
Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075-4083.
Mrozek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol 2012; 30: 4515-4523.
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642-4649.
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 2009; 15: 1628-1633.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825-828.
Flowers ME, Kansu E, Sullivan KM. Pathophysiology and treatment of graft-versus-host disease. Hematol Oncol Clin N Am 1999; 13: 1091-1112, viii-ix.
Zhang X, Zhang MJ. SAS macros for estimation of direct adjusted cumulative incidence curves under proportional subdistribution hazards models. Comput Methods Programs Biomed 2011; 101: 87-93.
Zhang X, Loberiza FR, Klein JP, Zhang MJ A. SAS macro for estimation of direct adjusted survival curves based on a stratified Cox regression model. Comput Methods Programs Biomed 2007; 88: 95-101.
de Latour RP, Brunstein C, Porcher R, Chevallier P, Robin M, Warlick E et al. Equivalent outcome between siblings, unrelated donors and cord blood after reduced intensity allogeneic haematopoietic cell transplantation for patients older than 50 years with acute myeloid leukaemia in complete remission. Bone Marrow Transplant 2013; 48: S379-S380.
Ustun C, Courville E, DeFor T, Dolan M, Randall N, Yohe S et al. Myeloablative, but not reduced-intensity, conditioning overcomes the negative effect of flow-cytometric evidence of leukemia in acute myeloid leukemia. Biol Blood Marrow Transplant 2015; 22: 669-675.
Ponce DM, Hilden P, Devlin SM, Maloy M, Lubin M, Castro-Malaspina H et al. High disease-free survival with enhanced protection against relapse after double-unit cord blood transplantation when compared with t cell-depleted unrelated donor transplantation in patients with acute leukemia and chronic myelogenous leukemia. Biol Blood Marrow Transplant 2015; 21: 1985-1993.
Sato T, Yang X, Knapper S, White P, Smith BD, Galkin S et al. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood 2011; 117: 3286-3293.
Rocha V, Gluckman E, Eurocord-Netcord R, European B, Marrow Transplant G. Improving outcomes of cord blood transplantation: HLA matching, cell dose and other graft-and transplantation-related factors. Br J Haematol 2009; 147: 262-274.
Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947-1954.
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276-2285.
Grewal SS, Barker JN, Davies SM, Wagner JE. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood 2003; 101: 4233-4244.
Sugimoto K, Narimatsu H, Kawase T, Iida H, Watanabe M, Kohno A et al. Clinical characteristics of chronic graft-versus-host disease following umbilical cord blood transplantation for adults. Bone Marrow Transplant 2008; 41: 729-736.
Lazaryan A, Weisdorf DJ, DeFor T, Brunstein CG, MacMillan ML, Bejanyan N et al. Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biol Blood Marrow Transplant 2015; 22: 134-140.
Narimatsu H, Miyakoshi S, Yamaguchi T, Kami M, Matsumura T, Yuji K et al. Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan. Blood 2008; 112: 2579-2582.
Pratz KW, Sato T, Murphy KM, Stine A, Rajkhowa T, Levis M. FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML. Blood 2010; 115: 1425-1432.
Schlenk RF, Kayser S, Bullinger L, Kobbe G, Casper J, Ringhoffer M et al. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood 2014; 124: 3441-3449.
Pratcorona M, Brunet S, Nomdedeu J, Ribera JM, Tormo M, Duarte R et al. Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy. Blood 2013; 121: 2734-2738.
Oran B, Cortes J, Beitinjaneh A, Chen HC, de Lima M, Patel K et al. Allogeneic transplantation in first remission improves outcomes irrespective of FLT3-ITD allelic ratio in FLT3-ITD-positive acute myelogenous leukemia. Biol Blood Marrow Transplant 2016; 22: 1218-1226.
Versluis J, In 't Hout FE, Devillier R, van Putten WL, Manz MG, Vekemans MC et al. Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio. Leukemia 2016; 31: 26-33.
de Jonge HJ, Valk PJ, de Bont ES, Schuringa JJ, Ossenkoppele G, Vellenga E et al. Prognostic impact of white blood cell count in intermediate risk acute myeloid leukemia: relevance of mutated NPM1 and FLT3-ITD. Haematologica 2011; 96: 1310-1317.
Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res 2001; 61: 7233-7239.
Sorror ML, Giralt S, Sandmaier BM, De Lima M, Shahjahan M, Maloney DG et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 2007; 110: 4606-4613.
Chen YB, Li S, Lane AA, Connolly C, Del Rio C, Valles B et al. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant 2014; 20: 2042-2048.