Allogeneic hematopoietic cell transplantation improves outcome of adults with t(6;9) acute myeloid leukemia: results from an international collaborative study
Jazyk angličtina Země Itálie Médium print-electronic
Typ dokumentu časopisecké články, multicentrická studie, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
P50 CA100632
NCI NIH HHS - United States
13371
Cancer Research UK - United Kingdom
P30 CA008748
NCI NIH HHS - United States
16484
Cancer Research UK - United Kingdom
K12 CA184746
NCI NIH HHS - United States
PubMed
31004014
PubMed Central
PMC6939530
DOI
10.3324/haematol.2018.208678
PII: haematol.2018.208678
Knihovny.cz E-zdroje
- MeSH
- akutní myeloidní leukemie * diagnóza terapie MeSH
- cytarabin MeSH
- dospělí MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- přežití bez známek nemoci MeSH
- retrospektivní studie MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- cytarabin MeSH
Acute myeloid leukemia (AML) with t(6;9)(p22;q34) is a distinct entity accounting for 1-2% of AML cases. A substantial proportion of these patients have a concomitant FLT3-ITD. While outcomes are dismal with intensive chemotherapy, limited evidence suggests allogeneic hematopoietic cell transplantation (allo-HCT) may improve survival if performed early during first complete remission. We report on a cohort of 178 patients with t(6;9)(p22;q34) within an international, multicenter collaboration. Median age was 46 years (range: 16-76), AML was de novo in 88%, FLT3-ITD was present in 62%, and additional cytogenetic abnormalities in 21%. Complete remission was achieved in 81% (n=144), including 14 patients who received high-dose cytarabine after initial induction failure. With a median follow up of 5.43 years, estimated overall survival at five years was 38% (95%CI: 31-47%). Allo-HCT was performed in 117 (66%) patients, including 89 in first complete remission. Allo-HCT in first complete remission was associated with higher 5-year relapse-free and overall survival as compared to consolidation chemotherapy: 45% (95%CI: 35-59%) and 53% (95%CI: 42-66%) versus 7% (95%CI: 3-19%) and 23% (95%CI: 13-38%), respectively. For patients undergoing allo-HCT, there was no difference in overall survival rates at five years according to whether it was performed in first [53% (95%CI: 42-66%)], or second [58% (95%CI: 31-100%); n=10] complete remission or with active disease/relapse [54% (95%CI: 34-84%); n=18] (P=0.67). Neither FLT3-ITD nor additional chromosomal abnormalities impacted survival. In conclusion, outcomes of t(6;9)(p22;q34) AML are poor with chemotherapy, and can be substantially improved with allo-HCT.
Cardiff University School of Medicine Cardiff UK
Clinical Research Division Fred Hutchinson Cancer Research Center Seattle WA USA
Department of Epidemiology University of Washington Seattle WA USA
Department of Haematology Nottingham University Hospitals NHS Trust Nottingham UK
Department of Internal Medicine 1 University Hospital Carl Gustav Carus Dresden Germany
Department of Internal Medicine 5 University Hospital of Heidelberg Heidelberg Germany
Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA
Department of Medicine University of Maryland School of Medicine Baltimore MD USA
Division of Hematology Department of Internal Medicine Mayo Clinic Rochester MN USA
Division of Hematology Department of Medicine University of Washington Seattle WA USA
Laboratory of Hematology André Mignot Hospital Le Chesnay France
Massachusetts General Hospital Boston MA USA
Medical Clinic 3 for Oncology Hematology and Rheumatology University Hospital Bonn Bonn Germany
NCT Trial Center National Center for Tumor Diseases Heidelberg Germany
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University Baltimore MD USA
Université Paris Saclay Gustave Roussy Villejuif France
University of Maryland Greenebaum Comprehensive Cancer Center Baltimore MD USA
Zobrazit více v PubMed
Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues, revised 4th edition. WHO Press, Geneva, Switzerland, 2017.
Slovak ML, Gundacker H, Bloomfield CD, et al. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare ‘poor prognosis’ myeloid malignancies. Leukemia. 2006;20(7):1295–1297. PubMed
Rowley JD, Potter D. Chromosomal banding patterns in acute nonlymphocytic leukemia. Blood.1976;47(5):705–721. PubMed
von Lindern M, Fornerod M, van Baal S, et al. The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA. Mol Cell Biol. 1992;12(4):1687–1697. PubMed PMC
Scandura JM, Boccuni P, Cammenga J, Nimer SD. Transcription factor fusions in acute leukemia: variations on a theme. Oncogene. 2002;21(21):3422–3444. PubMed
Ageberg M, Drott K, Olofsson T, et al. Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis. Genes Chromosomes Cancer. 2008;47(4):276–287. PubMed
Boer J, Bonten-Surtel J, Grosveld G. Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis. Mol Cell Biol. 1998;18(3):1236–1247. PubMed PMC
Oancea C, Rüster B, Henschler R, et al. The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation. Leukemia. 2010; 24(11):1910–1919. PubMed
Oyarzo MP, Lin P, Glassman A, et al. Acute myelogenous leukemia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of FLT3 gene mutations. Am J Clin Pathol. 2004;122(3):348–358. PubMed
Thiede C, Steudel C, Mohr B, 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(12):4326–4335. PubMed
Chi Y, Lindgren V, Quigley S, Gaitonde S. Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. Arch Pathol Lab Med. 2008;132(11):1835–1837. PubMed
Gupta M, Ashok Kumar J, Sitaram U, et al. The t(6;9)(p22;q34) in myeloid neoplasms: a retrospective study of 16 cases. Cancer Genet Cytogenet. 2010;203(2):297–302. PubMed
Sandahl JD, Coenen EA, Forestier E, et al. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients. Haematologica. 2014;99(5):865–872. PubMed PMC
Tarlock K, Alonzo TA, Moraleda PP, et al. Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is associated with poor outcome in childhood AML regardless of FLT3-ITD status: a report from the Children’s Oncology Group. Br J Haematol. 2014;166(2):254–259. PubMed PMC
Grimwade D, Hills RK, Moorman AV, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–365. PubMed
O’Donnell MR, Tallman MS, Abboud CN, et al. Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(7):926–957. PubMed
Ishiyama K, Takami A, Kanda Y, et al. Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis. Leukemia. 2012;26(3):461–464. PubMed
Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N Engl J Med. 2017;377(5):454–464. PubMed PMC
Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103(4):620–625. PubMed
Cheson BD, Bennett JM, Kopecky KJ, 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(24):4642–4649. PubMed
Mitelman F: ISCN: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S. Karger; 1995.
Yokota S, Kiyoi H, Nakao M, et al. Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia. 1997;11(10):1605–1609. PubMed
Schaich M, Röllig C, Soucek S, et al. Cytarabine dose of 36 g/m2 compared with 12 g/m2 within first consolidation in acute myeloid leukemia: results of patients enrolled onto the prospective randomized AML96 study. J Clin Oncol. 2011; 29(19):2696–2702. PubMed
Schaich M, Parmentier S, Kramer M, et al. High-dose cytarabine consolidation with or without additional amsacrine and mitoxantrone in acute myeloid leukemia: results of the prospective randomized AML2003 trial. J Clin Oncol. 2013;31(17):2094–2102. PubMed
Wheatley K, Brookes CL, Howman AJ, et al. Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials. Br J Haematol. 2009;145(5):598–605. PubMed
Burnett AK, Russell NH, Culligan D, et al. The addition of the farnesyl transferase inhibitor, tipifarnib, to low dose cytarabine does not improve outcome for older patients with AML. Br J Haematol. 2012;158(4):519–522. PubMed
Burnett AK, Russell NH, Hills RK, et al. A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients. Blood. 2015;125(25):3878–3885. PubMed PMC
Pautas C, Merabet F, Thomas X, et al. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010;28(5):808–814. PubMed
Thomas X, Elhamri M, Raffoux E, et al. Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study. Blood. 2011;118(7):1754–1762. PubMed
Thomas X, de Botton S, Chevret S, et al. Randomized phase II study of clofarabine-based consolidation for younger adults with acute myeloid leukemia in first remission. J Clin Oncol. 2017;35(11):1223–1230. PubMed
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343–346. PubMed
Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457–481.
Cox DR. Regression models and life tables (with discussion). J R Stat Soc. 1972; 34(2):187–220.
Mantel N, Byar D. Evaluation of response-time data involving transient states: An illustration using heart transplant data. J Am Stat Assoc. 1974;69(345):81–86.
Andersen P, Gill RD. Cox’s regression model for counting processes: A large sample study. Ann Stat. 1982;10(4):1100–1120.
Simon R, Makuch RW. A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med. 1984;3(1):35–44. PubMed
Gray RJ. A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 1988;16(3):1141–1154.
Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York: Springer; 2001.
R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing; Vienna, Austria, 2014.
Knapper S, Russell N, Gilkes A, et al. A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML. Blood. 2017;129(9):1143–1154. PubMed PMC
Perl AE, Altman JK, Cortes J, et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol. 2017; 18(8):1061–1075. PubMed PMC
Beya MD, Labopin M, Maertens J, et al. Allogeneic stem cell transplantation in acute myeloid leukemia with t(6;9)(p23;q34);dek-NUP214 is followed by a low relapse risk and favorable outcome in early phase- a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Blood. 2017; 130(Suppl 1):596.
Heinssmann M, Drangmeister L, Schmid K, et al. T(6;9)-DEK/CAN-positive leukemia: role of FLT3-ITD for the determination of the leukemic phenotype. Blood. 2012; 120(21):1316.
Kayser S, Levis MJ. FLT3 tyrosine kinase inhibitors in acute myeloid leukemia: clinical implications and limitations. Leuk Lymphoma. 2014;55(2):243–255. PubMed PMC
Thiede C, Bloomfield CD, Lo Coco F, et al. The high prevalence of FLT3-ITD mutations is associated with the poor outcome in adult patients with t(6;9)(p23;q34) positive AML - results of an international meta-analysis. Blood. 2007;110(11):761.
Visconte V, Shetty S, Przychodzen B, et al. Clinicopathologic and molecular characterization of myeloid neoplasms with isolated t(6;9)(p23;q34). Int J Lab Hematol. 2017; 39(4):409–417. PubMed PMC
Wattad M, Weber D, Döhner K, et al. Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia. 2017;31(6):1306–1313. PubMed
Schlenk RF, Frech P, Weber D, et al. Impact of pretreatment characteristics and salvage strategy on outcome in patients with relapsed acute myeloid leukemia. Leukemia. 2017;31(6):1306–1313. PubMed PMC
Willemze R, Suciu S, Meloni G, et al. High-dose cytarabine in induction treatment improves the outcome of adult patients younger than age 46 years with acute myeloid leukemia: results of the EORTC-GIMEMA AML-12 trial. J Clin Oncol. 2014;32(3):219–228. PubMed
Prebet T, Bertoli S, Delaunay J, et al. Anthracycline dose intensification improves molecular response and outcome of patients treated for core binding factor acute myeloid leukemia. Haematologica. 2014;99(10):e185–e187. PubMed PMC
Luskin MR, Lee JW, Fernandez HF, et al. Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood. 2016; 127(12): 1551–1558. PubMed PMC
Röllig C, Bornhäuser M, Thiede C, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol. 2011; 29(20):2758–2765. PubMed