Ex Vivo CD34+-Selected T Cell-Depleted Peripheral Blood Stem Cell Grafts for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia and Myelodysplastic. Syndrome Is Associated with Low Incidence of Acute and Chronic Graft-versus-Host Disease and High Treatment Response

被引：35

作者：

Barba, Pere ^{[1
,2
]}

Hilden, Patrick ^{[3
]}

Devlin, Sean M. ^{[3
]}

Maloy, Molly ^{[1
]}

Dierov, Djamilia ^{[1
]}

Nieves, Jimmy ^{[1
]}

Garrett, Matthew D. ^{[1
]}

Sogani, Julie ^{[1
]}

Cho, Christina ^{[1
]}

Barker, Juliet N. ^{[1
,4
]}

Kernan, Nancy A. ^{[5
]}

Castro-Malaspina, Hugo ^{[1
]}

Jakubowski, Ann A. ^{[1
,4
]}

Koehne, Guenther ^{[1
,4
]}

Papadopoulos, Esperanza B. ^{[1
,4
]}

Prockop, Susan ^{[5
]}

Sauter, Craig ^{[1
,4
]}

Tamari, Roni ^{[1
,4
]}

van den Brink, Marcel R. M. ^{[1
,4
]}

Avecilla, Scott T. ^{[6
]}

Meagher, Richard ^{[6
]}

O'Reilly, Richard J. ^{[5
]}

Goldberg, Jenna D. ^{[1
,4
]}

Young, James W. ^{[1
,4
]}

Giralt, Sergio ^{[1
,4
]}

Perales, Miguel-Angel ^{[1
,4
]}

Ponce, Doris M. ^{[1
,4
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplant Serv, Div Hematol Oncol, Box 259,1275 York Ave, New York, NY 10065 USA

[2] Univ Autonoma Barcelona, Dept Hematol, Hosp Univ Vall dHerbon, E-08193 Barcelona, Spain

[3] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA

[4] Weill Cornell Med Coll, New York, NY USA

[5] Mem Sloan Kettering Canc Ctr, Dept Pediat, Bone Marrow Transplant Serv, 1275 York Ave, New York, NY 10021 USA

[6] Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2017年 / 23卷 / 03期

基金：

美国国家卫生研究院;

关键词：

T cell-depleted transplantation; Acute graft-versus-host disease; Chronic graft-versus-host disease; ACUTE MYELOID-LEUKEMIA; CLINICAL-TRIALS NETWORK; 1ST COMPLETE REMISSION; MARROW-TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; UNMODIFIED ALLOGRAFTS; UNRELATED DONORS; GVHD PROPHYLAXIS; FREE SURVIVAL; BONE-MARROW;

D O I：

10.1016/j.bbmt.2016.12.633

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Ex vivo CD34(+)-selected T cell depletion (TCD) has been developed as a strategy to reduce the incidence of graft-versus-host disease (GVHD) after allogeneic (allo) hematopoietic stem cell transplantation (HSCT). Clinical characteristics, treatment responses, and outcomes of patients developing acute (aGVHD) and chronic GVHD (cGVHD) after TCD allo-HSCT have not been well established. We evaluated 241 consecutive patients (median age, 57 years) with acute leukemia (n = 191, 79%) or myelodysplastic syndrome (MDS) (n = 50, 21%) undergoing CD34+-selected TCD allo-HSCT without post-HCST immunosuppression in a single institution. Cumulative incidences of grades II-IV and III-IV aGVHD at 180 days were 16% (95% confidence interval [CI], 12 to 21) and 5% (95% CI, 3 to 9), respectively. The skin was the most frequent organ involved, followed by the gastrointestinal tract. Patients were treated with topical corticosteroids, poorly absorbed corticosteroids (budesonide), and/or systemic corticosteroids. The overall day 28 treatment response was high at 82%. The cumulative incidence of any cGVHD at 3 years was 5% (95% CI, 3 to 9), with a median time of onset of 256 days (range, 95 to 1645). The 3-year transplant-related mortality, relapse, overall survival, and disease-free survival were 24% (95% CI, 18 to 30), 22% (95% CI, 17 to 27), 57% (95% CI, 50 to 64), and 54% (95% CI, 47 to 61), respectively. The 1-year and 3-year probabilities of cGVHD-free/relapse-free survival were 65% (95% CI, 59 to 71) and 52% (95% CI, 45 to 59), respectively. Our findings support the use of ex vivo CD34(+)-selected TCD allograft as a calcineurin inhibitor-free intervention for the prevention of GVHD in patients with acute leukemia and MDS. (C) 2017 American Society for Blood and Marrow Transplantation.

引用

页码：452 / 458

页数：7

共 42 条

[1] Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network [J].

Alousi, Amin M. ;

Weisdorf, Daniel J. ;

Logan, Brent R. ;

Bolanos-Meade, Javier ;

Carter, Shelly ;

DiFronzo, Nancy ;

Pasquini, Marcelo ;

Goldstein, Steven C. ;

Ho, Vincent T. ;

Hayes-Lattin, Brandon ;

Wingard, John R. ;

Horowitz, Mary M. ;

Levine, John E. .

BLOOD, 2009, 114 (03) :511-517

[2] Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors [J].

Anasetti, Claudio ;

Logan, Brent R. ;

Lee, Stephanie J. ;

Waller, Edmund K. ;

Weisdorf, Daniel J. ;

Wingard, John R. ;

Cutler, Corey S. ;

Westervelt, Peter ;

Woolfrey, Ann ;

Couban, Stephen ;

Ehninger, Gerhard ;

Johnston, Laura ;

Maziarz, Richard T. ;

Pulsipher, Michael A. ;

Porter, David L. ;

Mineishi, Shin ;

McCarty, John M. ;

Khan, Shakila P. ;

Anderlini, Paolo ;

Bensinger, William I. ;

Leitman, Susan F. ;

Rowley, Scott D. ;

Bredeson, Christopher ;

Carter, Shelly L. ;

Horowitz, Mary M. ;

Confer, Dennis L. .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (16) :1487-1496

[3] Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation [J].

Armand, Philippe ;

Kim, Haesook T. ;

Logan, Brent R. ;

Wang, Zhiwei ;

Alyea, Edwin P. ;

Kalaycio, Matt E. ;

Maziarz, Richard T. ;

Antin, Joseph H. ;

Soiffer, Robert J. ;

Weisdorf, Daniel J. ;

Rizzo, J. Douglas ;

Horowitz, Mary M. ;

Saber, Wael .

BLOOD, 2014, 123 (23) :3664-3671

[4] Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation [J].

Arora, Mukta ;

Cutler, Corey S. ;

Jagasia, Madan H. ;

Pidala, Joseph ;

Chai, Xiaoyu ;

Martin, Paul J. ;

Flowers, Mary E. D. ;

Inamoto, Yoshihiro ;

Chen, George L. ;

Wood, William A. ;

Khera, Nandita ;

Palmer, Jeanne ;

Duong, Hien ;

Arai, Sally ;

Mayer, Sebastian ;

Pusic, Iskra ;

Lee, Stephanie J. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (03) :449-455

[5] Ex Vivo T Cell-Depleted versus Unmodified Allografts in Patients with Acute Myeloid Leukemia in First Complete Remission [J].

Bayraktar, Ulas D. ;

de Lima, Marcos ;

Saliba, Rima M. ;

Maloy, Molly ;

Castro-Malaspina, Hugo R. ;

Chen, Julianne ;

Rondon, Gabriela ;

Chiattone, Alexander ;

Jakubowski, Ann A. ;

Boulad, Farid ;

Kernan, Nancy A. ;

O'Reilly, Richard J. ;

Champlin, Richard E. ;

Giralt, Sergio ;

Andersson, Borje S. ;

Papadopoulos, Esperanza B. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2013, 19 (06) :898-903

[6] A scheme for defining cause of death and its application in the T cell depletion trial [J].

Copelan, Edward ;

Casper, James T. ;

Carter, Shelly L. ;

van Burik, Jo-Anne H. ;

Hurd, David ;

Mendizabal, Adam M. ;

Wagner, John E. ;

Yanovich, Saul ;

Kernan, Nancy A. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2007, 13 (12) :1469-1476

[7] Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT [J].

Cutler, Corey ;

Logan, Brent ;

Nakamura, Ryotaro ;

Johnston, Laura ;

Choi, Sung ;

Porter, David ;

Hogan, William J. ;

Pasquini, Marcelo ;

MacMillan, Margaret L. ;

Hsu, Jack W. ;

Waller, Edmund K. ;

Grupp, Stephan ;

McCarthy, Philip ;

Wu, Juan ;

Hu, Zhen-Huan ;

Carter, Shelly L. ;

Horowitz, Mary M. ;

Antin, Joseph H. .

BLOOD, 2014, 124 (08) :1372-1377

[8] National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report [J].

Filipovich, AH ;

Weisdorf, D ;

Pavletic, S ;

Socie, G ;

Wingard, JR ;

Lee, SJ ;

Martin, P ;

Chien, J ;

Przepiorka, D ;

Couriel, D ;

Cowen, EW ;

Dinndorf, P ;

Farrell, A ;

Hartzman, R ;

Henslee-Downey, J ;

Jacobsohn, D ;

McDonald, G ;

Mittleman, B ;

Rizzo, JD ;

Robinson, M ;

Schubert, M ;

Schultz, K ;

Shulman, H ;

Turner, M ;

Vogelsang, G ;

Flowers, MED .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2005, 11 (12) :945-956

[9] CLINICAL MANIFESTATIONS OF GRAFT VERSUS HOST DISEASE IN HUMAN RECIPIENTS OF MARROW FROM HL-A-MATCHED SIBLING DONORS [J].

GLUCKSBERG, H ;

STORB, R ;

FEFER, A ;

BUCKNER, CD ;

NEIMAN, PE ;

CLIFT, RA ;

LERNER, KG ;

THOMAS, ED .

TRANSPLANTATION, 1974, 18 (04) :295-304

[10] T Cell-Depleted Stem Cell Transplantation for Adults with High-Risk Acute Lymphoblastic Leukemia: Long-Term Survival for Patients in First Complete Remission with a Decreased Risk of Graft-versus-Host Disease [J].

Goldberg, Jenna D. ;

Linker, Alex ;

Kuk, Deborah ;

Ratan, Ravin ;

Jurcic, Joseph ;

Barker, Juliet N. ;

Castro-Malaspina, Hugo ;

Giralt, Sergio ;

Hsu, Katharine ;

Jakubowski, Ann A. ;

Jenq, Robert ;

Koehne, Guenther ;

Papadopoulos, Esperanza B. ;

van den Brink, Marcel R. M. ;

Young, James W. ;

Boulad, Farid ;

Kernan, Nancy A. ;

O'Reilly, Richard J. ;

Prockop, Susan E. ;

Yahalom, Joachim ;

Heller, Glenn ;

Perales, Miguel-Angel .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2013, 19 (02) :208-213

← 1 2 3 4 5 →