Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report

被引：22

作者：

Zhou, Zheng ^{[1
]}

Nath, Rajneesh ^{[2
]}

Cerny, Jan ^{[3
]}

Wang, Hai-Lin ^{[4
]}

Zhang, Mei-Jie ^{[4
,5
]}

Abdel-Azim, Hisham ^{[6
]}

Agrawal, Vaibhav ^{[7
]}

Ahmed, Gulrayz ^{[8
]}

Al-Homsi, A. Samer ^{[9
]}

Aljurf, Mahmoud ^{[10
]}

Alkhateeb, Hassan B. ^{[11
]}

Assal, Amer ^{[12
]}

Bacher, Ulrike ^{[13
]}

Bajel, Ashish ^{[14
]}

Bashir, Qaiser ^{[15
]}

Battiwalla, Minocher ^{[16
]}

Bhatt, Vijaya Raj ^{[17
]}

Byrne, Michael ^{[18
]}

Cahn, Jean-Yves ^{[19
]}

Cairo, Mitchell ^{[20
]}

Choe, Hannah ^{[21
]}

Copelan, Edward ^{[22
]}

Cutler, Corey ^{[23
]}

Damlaj, Moussab B. ^{[24
]}

DeFilipp, Zachariah ^{[25
]}

De Lima, Marcos ^{[26
]}

Diaz, Miguel Angel ^{[27
]}

Farhadfar, Nosha ^{[28
]}

Foran, James ^{[29
]}

Freytes, Cesar O. ^{[30
]}

Gerds, Aaron T. ^{[31
]}

Gergis, Usama ^{[32
]}

Grunwald, Michael R. ^{[22
]}

Gul, Zartash ^{[33
]}

Hamadani, Mehdi ^{[4
]}

Hashmi, Shahrukh ^{[34
,35
]}

Hertzberg, Mark ^{[36
]}

Hildebrandt, Gerhard C. ^{[37
]}

Hossain, Nasheed ^{[38
]}

Inamoto, Yoshihiro ^{[39
]}

Isola, Luis ^{[40
]}

Jain, Tania ^{[41
]}

Kamble, Rammurti T. ^{[42
]}

Khan, Muhammad Waqas ^{[43
]}

Kharfan-Dabaja, Mohamed A. ^{[44
]}

Kebriaei, Partow ^{[15
]}

Kekre, Natasha ^{[45
]}

Khera, Nandita ^{[46
]}

Lazarus, Hillard M. ^{[47
]}

Liesveld, Jane L. ^{[48
]}

机构：

[1] Lahey Hosp & Med Ctr, Beth Israel Lahey Hlth, Burlington, MA 01805 USA

[2] Banner MD Anderson Canc Ctr, Gilbert, AZ USA

[3] Univ Massachusetts, Med Ctr, Dept Med, Div Hematol Oncol, Worcester, MA USA

[4] Med Coll Wisconsin, Dept Med, Div Hematol Oncol & Blood & Marrow Transplantat, Milwaukee, WI 53226 USA

[5] Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI 53226 USA

[6] Univ Southern Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90007 USA

[7] Indiana Univ Sch Med, Div Hematol Oncol, Indianapolis, IN 46202 USA

[8] Med Coll Wisconsin, Internal Med, Milwaukee, WI 53226 USA

[9] NYU, Langone Med Ctr, New York, NY USA

[10] King Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh, Saudi Arabia

[11] Mayo Clin, Bone Marrow Transplant Program, Rochester, MN USA

[12] NYPH Columbia Univ Med Ctr, New York, NY USA

[13] Univ Bern, Bern Univ Hosp, Dept Hematol, Inselspital, Bern, Switzerland

[14] Royal Melbourne Hosp, City Campus, Parkville, Vic, Australia

[15] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Div Canc Med, Houston, TX 77030 USA

[16] Sarah Cannon Blood Canc Network, Nashville, TN USA

[17] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE USA

[18] Vanderbilt Univ, Med Ctr, Nashville, TN USA

[19] Ctr Hosp Univ Grenoble Alpes, Dept Hematol, Grenoble, France

[20] New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA

[21] Ohio Univ, Wexner Med Ctr, James Comprehens Canc Ctr, Columbus, OH USA

[22] Atrium Hlth, Dept Hematol Oncol & Blood Disorders, Levine Canc Inst, Charlotte, NC USA

[23] Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA

[24] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

[25] Massachusetts Gen Hosp, Blood & Marrow Transplant Program, Boston, MA 02114 USA

[26] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Med, Cleveland, OH USA

[27] Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain

[28] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA

[29] Mayo Clin, Bone Marrow Transplant Program, Jacksonville, FL 32224 USA

[30] Texas Transplant Inst, San Antonio, TX USA

[31] Cleveland Clin, Taussig Canc Inst, Hematol & Med Oncol, Cleveland, OH 44106 USA

[32] New York Presbyterian Hosp, Dept Med Oncol, Hematol Malignancies & Bone Marrow Transplant, Weill Cornell Med Ctr, New York, NY USA

[33] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA

[34] Mayo Clin, Dept Internal Med, Rochester, MN USA

[35] King Faisal Specialist Hosp & Res Ctr, Oncol Ctr, Riyadh, Saudi Arabia

[36] Prince Wales Hosp, Dept Haematol, Randwick, NSW, Australia

[37] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA

[38] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Stem Cell Transplant Program,Div Hematol Oncol, Maywood, IL USA

[39] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan

[40] Mt Sinai Med Ctr, New York, NY 10029 USA

[41] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA

[42] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[43] Louisiana State Univ, Bone Marrow Transplant Program, Div Hematol Oncol, Baton Rouge, LA 70803 USA

[44] Mayo Clin, Blood & Marrow Transplantat Program, Div Hematol Oncol, Jacksonville, FL 32224 USA

[45] Ottawa Hosp Blood & Marrow Transplant Program, Ottawa, ON, Canada

[46] Mayo Clin, Dept Hematol Oncol, Phoenix, AZ USA

[47] Case Western Reserve Univ, Cleveland, OH 44106 USA

[48] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

[49] Mayo Clin Rochester, Div Hematol & Transplant Ctr, Rochester, MN USA

[50] Univ Chicago Med, Chicago, IL USA

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 13期

基金：

美国国家卫生研究院;

关键词：

STEM-CELL TRANSPLANTATION; EUROPEAN-GROUP; WORKING PARTY; FLUDARABINE/MELPHALAN; OLDER; RELAPSE; BLOOD; AML;

D O I：

10.1182/bloodadvances.2019001266

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

引用

页码：3180 / 3190

页数：11

共 21 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] What is the impact of hematopoietic cell transplantation (HCT) for older adults with acute myeloid leukemia (AML)? [J].

Appelbaum, Frederick R. .

BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY, 2008, 21 (04) :667-675

[3] Defining the Intensity of Conditioning Regimens: Working Definitions [J].

Bacigalupo, Andrea ;

Ballen, Karen ;

Rizzo, Doug ;

Giralt, Sergio ;

Lazarus, Hillard ;

Ho, Vincent ;

Apperley, Jane ;

Slavin, Shimon ;

Pasquini, Marcelo ;

Sandmaier, Brenda M. ;

Barrett, John ;

Blaise, Didier ;

Lowski, Robert ;

Horowitz, Mary .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2009, 15 (12) :1628-1633

[4] Reduced-Intensity Conditioning With Fludarabine and Busulfan Versus Fludarabine and Melphalan for Patients With Acute Myeloid Leukemia: A Report From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation [J].

Baron, Frederic ;

Labopin, Myriam ;

Peniket, Andy ;

Jindra, Pavel ;

Afanasyev, Boris ;

Sanz, Miguel A. ;

Deconinck, Eric ;

Nagler, Arnon ;

Mohty, Mohamad .

CANCER, 2015, 121 (07) :1048-1055

[5] Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents [J].

Barrett, A. J. ;

Savani, B. N. .

LEUKEMIA, 2006, 20 (10) :1661-1672

[6] Medical progress: Hematopoietic stem-cell transplantation [J].

Copelan, EA .

NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (17) :1813-1826

[7] Fludarabine-Busulfan Reduced-Intensity Conditioning in Comparison with Fludarabine-Melphalan Is Associated with Increased Relapse Risk In Spite of Pharmacokinetic Dosing [J].

Damlaj, Moussab ;

Alkhateeb, Hassan B. ;

Hefazi, Mehrdad ;

Partain, Daniel K. ;

Hashmi, Shahrukh ;

Gastineau, Dennis A. ;

Al-Kali, Aref ;

Wolf, Robert C. ;

Gangat, Naseema ;

Litzow, Mark R. ;

Hogan, William J. ;

Patnaik, Mrinal M. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (08) :1431-1439

[8] Myeloablative busulfan/cytoxan conditioning versus reduced-intensity fludarabine/melphalan conditioning for allogeneic hematopoietic stem cell transplant in patients with acute myelogenous leukemia [J].

Dhere, Vishal ;

Edelman, Scott ;

Waller, Edmund K. ;

Langston, Amelia ;

Graiser, Michael ;

Connolly, Erin C. ;

Switchenko, Jeffrey M. ;

Esiashvili, Natia ;

Khan, Mohammad K. .

LEUKEMIA & LYMPHOMA, 2018, 59 (04) :837-843

[9] Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: Harnessing graft-versus-leukemia without myeloablative therapy [J].

Giralt, S ;

Estey, E ;

Albitar, M ;

vanBesien, K ;

Rondon, G ;

Anderlini, P ;

OBrien, S ;

Khouri, I ;

Gajewski, J ;

Mehra, R ;

Claxton, D ;

Andersson, B ;

Beran, M ;

Przepiorka, D ;

Koller, C ;

Kornblau, S ;

Korbling, M ;

Keating, M ;

Kantarjian, H ;

Champlin, R .

BLOOD, 1997, 89 (12) :4531-4536

[10] Conditioning regimens for hematopoietic cell transplantation: one size does not fit all [J].

Gyurkocza, Boglarka ;

Sandmaier, Brenda M. .

BLOOD, 2014, 124 (03) :344-353

← 1 2 3 →