Sequential Intensified Conditioning Regimen Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Intermediate- or High-Risk Acute Myeloid Leukemia in Complete Remission: A Study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

被引:34
作者
Malard, Florent [1 ,2 ,3 ]
Labopin, Myriam [1 ]
Stuhler, Gernot [4 ]
Bittenbring, Joerg [5 ]
Ganser, Arnold [6 ]
Tischer, Johanna [7 ]
Michallet, Mauricette [8 ]
Kroeger, Nicolaus [9 ]
Schmid, Christoph [10 ]
Anne Huynh [11 ]
Hallek, Michael [12 ]
Savani, Bipin N. [13 ]
Mohty, Mohamad [1 ,2 ,3 ,14 ]
Nagler, Arnon [14 ,15 ]
机构
[1] St Antoine Hosp, Dept Haematol, Paris, France
[2] INSERM, UMRs 938, Paris, France
[3] Pierre & Marie Curie Univ, Paris, France
[4] ZMT Ctr, German Diagnost Clin, Wiesbaden, Germany
[5] Univ Saarland, Univ Hosp, BMT Unit, Dept Internal Med, Homburg, Germany
[6] Hannover Med Sch, Dept Haematol Hemostasis Oncol & Stem Cell Transp, Hannover, Germany
[7] Ludwig Maximilians Univ Hosp Munich, BMT Unit, Dept Internal Med 3, Campus Grosshadern, Munich, Germany
[8] Univ Hosp Lyon Sud, Dept Haematol, Lyon, France
[9] Univ Hosp Eppendorf, Bone Marrow Transplantat Ctr, Hamburg, Germany
[10] Augsburg Hosp, Dept Internal Med, Augsburg, Germany
[11] IUCT Oncopole, Dept Hematol, Toulouse, France
[12] Univ Cologne, Dept Med, Cologne, Germany
[13] Vanderbilt Univ, Haematol & Transplantat, 221 Kirkland Hall, Nashville, TN 37235 USA
[14] CEREST TC, EBMT Paris Study Off, Paris, France
[15] Chaim Sheba Med Ctr, Div Hematol, Tel Hashomer, Israel
关键词
Acute myeloid leukemia; Complete remission; Allogeneic hematopoietic stem cell transplantation; Sequential conditioning regimen; Intermediate intensity conditioning regimen; 1ST COMPLETE REMISSION; REDUCED-INTENSITY; MYELODYSPLASTIC SYNDROME; BUSULFAN; CHEMOTHERAPY; FLUDARABINE; SURVIVAL; TRIAL; OLDER; EBMT;
D O I
10.1016/j.bbmt.2016.11.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Post-transplant relapse is the leading cause of treatment failure in acute myeloid leukemia (AML) patients after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT). To improve their outcome, we evaluated the outcome of a sequential intermediate-intensity conditioning regimen combining fludarabine, cytosine arabinoside, amsacrine, cyclophosphamide, and either total body irradiation or busulfan (FLAMSA) in patients with intermediate or high-risk AML in first or second complete remission (CR). A total of 265 patients (median age, 55 years; range, 19 to 76) with AML who underwent allo-HSCT using a FLAMSA regimen were included. At the time of transplant, 216 (81.5%) were in CR1 and 49 (18.5%) in CR2. Cytogenetic was intermediate in 114 (43%) and poor in 42 (15.8%) patients, whereas 109 patients (41.1%) had a secondary AML. With a median follow-up of 46 months (range, 1 to 145), the Kaplan-Meier estimate of overall and leukemia-free survival at 2 years were 56.1% (95% CI, 49.7% to 62.6%) and 52.8% (95% CI, 46.4% to 59.2%), respectively. At 2 years, the cumulative incidences of relapse and nonrelapse mortality were 22.8% (95% CI, 17.6% to 28.4%) and 24.0% (95% CI, 18.8% to 29.5%), respectively. In multivariate analysis, patient age and cytogenetics were the only parameters with a significant impact on overall survival. These data suggest that the FLAMSA sequential intermediate conditioning regimen provides an efficient disease control in intermediate- and high-risk AML patients, including those in CR2 and with secondary AML (C) 2017 American Society for Blood and Marrow Transplantation.
引用
收藏
页码:278 / 284
页数:7
相关论文
共 25 条
[1]   Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT) [J].
Aoudjhane, M ;
Labopin, M ;
Gorin, NC ;
Shimoni, A ;
Ruutu, T ;
Kolb, HJ ;
Frassoni, F ;
Boiron, JM ;
Yin, JL ;
Finke, J ;
Shouten, H ;
Blaise, D ;
Falda, M ;
Fauser, AA ;
Esteve, J ;
Polge, E ;
Slavin, S ;
Niederwieser, D ;
Nagler, A ;
Rocha, V .
LEUKEMIA, 2005, 19 (12) :2304-2312
[2]   Correlation of somatic mutations with outcome after FLAMSA-busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes [J].
Christopeit, Maximilian ;
Badbaran, Anita ;
Alawi, Malik ;
Zabelina, Tatjana ;
Zeck, Gaby ;
Wolschke, Christine ;
Ayuk, Francis ;
Kroeger, Nicolaus .
EUROPEAN JOURNAL OF HAEMATOLOGY, 2016, 97 (03) :288-296
[3]   Acute Myeloid Leukemia [J].
Doehner, Hartmut ;
Weisdorf, Daniel J. ;
Bloomfield, Clara D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (12) :1136-1152
[4]   Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet [J].
Doehner, Hartmut ;
Estey, Elihu H. ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Burnett, Alan K. ;
Dombret, Herve ;
Fenaux, Pierre ;
Grimwade, David ;
Larson, Richard A. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel A. ;
Sierra, Jorge ;
Tallman, Martin S. ;
Loewenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2010, 115 (03) :453-474
[5]   Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML) [J].
Goodyear, Oliver C. ;
Dennis, Mike ;
Jilani, Nadira Y. ;
Loke, Justin ;
Siddique, Shamyla ;
Ryan, Gordon ;
Nunnick, Jane ;
Khanum, Rahela ;
Raghavan, Manoj ;
Cook, Mark ;
Snowden, John A. ;
Griffiths, Mike ;
Russell, Nigel ;
Yin, John ;
Crawley, Charles ;
Cook, Gordon ;
Vyas, Paresh ;
Moss, Paul ;
Malladi, Ram ;
Craddock, Charles F. .
BLOOD, 2012, 119 (14) :3361-3369
[6]  
HOROWITZ MM, 1990, BLOOD, V75, P555
[7]   Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome [J].
Kroeger, Nicolaus .
BLOOD, 2012, 119 (24) :5632-5639
[8]   Randomized Trial of Myeloablative Conditioning Regimens: Busulfan Plus Cyclophosphamide Versus Busulfan Plus Fludarabine [J].
Lee, Je-Hwan ;
Joo, Young-Don ;
Kim, Hawk ;
Ryoo, Hun Mo ;
Kim, Min Kyoung ;
Lee, Gyeong-Won ;
Lee, Jung-Hee ;
Lee, Won-Sik ;
Park, Jae-Hoo ;
Bae, Sung-Hwa ;
Hyun, Myung Soo ;
Kim, Dae-Young ;
Kim, Sung-Doo ;
Min, Young Joo ;
Lee, Kyoo-Hyung .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (06) :701-709
[9]   Effect of Age on Outcome of Reduced-Intensity Hematopoietic Cell Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission or With Myelodysplastic Syndrome [J].
McClune, Brian L. ;
Weisdorf, Daniel J. ;
Pedersen, Tanya L. ;
Tunes da Silva, Gisela ;
Tallman, Martin S. ;
Sierra, Jorge ;
DiPersio, John ;
Keating, Armand ;
Gale, Robert P. ;
George, Biju ;
Gupta, Vikas ;
Hahn, Theresa ;
Isola, Luis ;
Jagasia, Madan ;
Lazarus, Hillard ;
Marks, David ;
Maziarz, Richard ;
Waller, Edmund K. ;
Bredeson, Chris ;
Giralt, Sergio .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (11) :1878-1887
[10]   High-Dose Total Body Irradiation and Myeloablative Conditioning before Allogeneic Hematopoietic Cell Transplantation: Time to Rethink? [J].
Mohty, Mohamad ;
Malard, Florent ;
Savani, Bipin N. .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2015, 21 (04) :620-624