Coinfusion of Mesenchymal Stromal Cells Facilitates Platelet Recovery Without Increasing Leukemia Recurrence in Haploidentical Hematopoietic Stem Cell Transplantation: A Randomized, Controlled Clinical Study

被引：49

作者：

Liu, Kaiyan ^{[1
]}

Chen, Yuhong ^{[1
]}

Zeng, Yang ^{[2
]}

Xu, Lanping ^{[1
]}

Liu, Daihong ^{[1
]}

Chen, Huan ^{[1
]}

Zhang, Xiaohui ^{[1
]}

Han, Wei ^{[1
]}

Wang, Yu ^{[1
]}

Zhao, Ting ^{[1
]}

Wang, Jing ^{[1
]}

Wang, Jingzhi ^{[1
]}

Han, Qin ^{[2
]}

Zhao, Chunhua ^{[2
]}

Huang, Xiaojun ^{[1
]}

机构：

[1] Peking Univ, Peking Univ Inst Hematol, Peoples Hosp, Beijing 100044, Peoples R China

[2] Chinese Acad Med Sci, Basic Inst, Ctr Tissue Engn, Basic Med Dept,Peking Union Med Coll, Beijing 100730, Peoples R China

来源：

STEM CELLS AND DEVELOPMENT | 2011年 / 20卷 / 10期

关键词：

VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCY PATIENTS; PROLIFERATION IN-VITRO; CD34(+) CELLS; NOD/SCID MICE; G-CSF; COTRANSPLANTATION; VIVO; ENGRAFTMENT; RESISTANT;

D O I：

10.1089/scd.2010.0447

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Previous studies have suggested that mesenchymal stromal cells (MSCs) enhance the engraftment of hematopoietic stem cells and modulate the host's immune response. However, there are no randomized studies to confirm these results. Moreover, there are some concerns about the risk of tumor recurrence because of the immunosuppressive property of MSCs. We conducted an open-label, randomized phase II clinical study to assess the outcome of MSC coinfusion (3-5x10(5) cells/kg) during haploidentical hematopoietic stem cell transplantation. From June 2007 to June 2008, a total of 55 patients who were diagnosed with leukemia in complete remission entered the study (27 in the treatment group and 28 in the control group). No immediate or long-term toxic side effects related to MSC infusion were noted, and the median times of white blood cell and platelet engraftment were comparable between the 2 groups. However, within 100 days, the time to a platelet concentration of >50x10(9) cells/L was markedly faster in the treatment group compared with the control group (22 days vs. 28 days; P=0.036). Stromal-derived factor-1 alpha (SDF-1 alpha) reached a peak concentration more rapidly in the treatment group compared with the control group (8th vs. 16th day). The concentrations of SDF-1 alpha, thrombopoietin (TPO), and interleukin-11 were also elevated in the MSC-treated group compared with the control group. The accumulative occurrence rate of acute graft-versus-host disease greater than grade 2 was 51.8% and 38.9% in the treatment and control groups (P=0.422), respectively, whereas the occurrence rate of chronic graft-versus-host disease was 51.4% and 74.1% (P=0.261), respectively. Through March 2010, which marked 2 years, the overall survival rate was 69.7% for the MSC-treated group and 64.3% for the control group (P=0.737). Three patients in the treatment group and 2 patients in the control group experienced a hematological relapse and died of leukemia.

引用

页码：1679 / 1685

页数：7

共 27 条

[1] Cotransplantation of ex vivo-expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation [J].

Ball, Lynne M. ;

Bernardo, Maria Ester ;

Roelofs, Helene ;

Lankester, Arjan ;

Cometa, Angela ;

Egeler, R. Maarten ;

Locatelli, Franco ;

Fibbe, Willem E. .

BLOOD, 2007, 110 (07) :2764-2767

[2] Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo [J].

Bartholomew, A ;

Sturgeon, C ;

Siatskas, M ;

Ferrer, K ;

McIntosh, K ;

Patil, S ;

Hardy, W ;

Devine, S ;

Ucker, D ;

Deans, R ;

Moseley, A ;

Hoffman, R .

EXPERIMENTAL HEMATOLOGY, 2002, 30 (01) :42-48

[3]

Cheng LZ, 2000, J CELL PHYSIOL, V184, P58, DOI 10.1002/(SICI)1097-4652(200007)184:1<58::AID-JCP6>3.0.CO

[4]

2-B

[5]

Frassoni F, 2002, BONE MARROW TRANSPL, V29, pS2

[6] Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies [J].

Huang, X. -J. ;

Liu, D. -H. ;

Liu, K. -Y. ;

Xu, L. -P. ;

Chen, H. ;

Han, W. ;

Chen, Y. -H. ;

Wang, J. -Z. ;

Gao, Z. -Y. ;

Zhang, Y. -C. ;

Jiang, Q. ;

Shi, H. -X. ;

Lu, D. -P. .

BONE MARROW TRANSPLANTATION, 2006, 38 (04) :291-297

[7] Maintaining hyporesponsiveness and polarization potential of T cells after in vitro mixture of G-CSF mobilized peripheral blood grafts and G-CSF primed bone marrow grafts in different proportions [J].

Huang, Xiao-Jun ;

Chang, Ying Jun ;

Zhao, Xiang Yu .

TRANSPLANT IMMUNOLOGY, 2007, 17 (03) :193-197

[8] Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation [J].

Khoury, HJ ;

Loberiza, FR ;

Ringdén, O ;

Barrett, AJ ;

Bolwell, BJ ;

Cahn, JY ;

Champlin, RE ;

Gale, RP ;

Hale, GA ;

Urbano-Ispizua, A ;

Martino, R ;

McCarthy, PL ;

Tiberghien, P ;

Verdonck, LF ;

Horowitz, MM .

BLOOD, 2006, 107 (04) :1712-1716

[9] Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients [J].

Lazarus, HM ;

Koc, ON ;

Devine, SM ;

Curtin, P ;

Maziarz, RT ;

Holland, HK ;

Shpall, EJ ;

McCarthy, P ;

Atkinson, K ;

Cooper, BW ;

Gerson, SL ;

Laughlin, MJ ;

Loberiza, FR ;

Moseley, AB ;

Bacigalupo, A .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2005, 11 (05) :389-398

[10] Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells [J].

Le Blanc, K ;

Rasmusson, I ;

Sundberg, B ;

Götherström, C ;

Hassan, M ;

Uzunel, M ;

Ringdén, O .

LANCET, 2004, 363 (9419) :1439-1441

← 1 2 3 →