tceic.com
>> >>

23


ۧ 20 28

2016C07C01
www.CRTER.org

Chinese Journal of Tissue Engineering Research July 1, 2016 Vol.20, No.28



23
( 400016) . 23 [J].ۧ2016 20(28):4218-4225. DOI: 10.3969/j.issn.2095-4344.2016.28.017
23
(1)22 19 (2) 7 4 (3) 100 d 22%(5/23) (4) 100 d 2 14 2 2

ORCID: 0000-0001-8517-7750()

23





1990 2014 400016
:R394.2



:B :2095-4344 (2016)28-04218-08 2016-05-04


HLA 2007 11 2015 3 23 4 12 7 + ++ + ++ ++ A 22 19 7 4 100 d 22%(5/23) 100 d 2 14 2 2







(cstc2013jcyjA1007)(81502117)

4218

P.O. Box 10002, Shenyang

110180

www.CRTER.org

. 23
Jiang Qu, Master, Department of Hematology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

www.CRTER.org

Haploidentical hematopoietic stem cell transplantation for leukemia in 23 cases
Jiang Qu, Zhang Hong-bin, Yang Li, Luo Hong, Miao Qiao, Deng Xue-mei (Department of Hematology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China)

Abstract
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the effective methods in the treatment of leukemia. The haploidentical HSCT is an option for the patients who need a HSCT without a human leukocyte antigen (HLA)-matched donor. OBJECTIVE: To study the clinical efficacy of HLA-haploidentical HSCT on leukemia and its complications. METHODS: A total of 23 patients (4 cases of acute lymphoblastic leukemia, 12 of acute myelogenous leukemia, and 7 of chronic granulocytic leukemia) who had been treated with HLA-haploidentical HSCT from November 2007 to March 2015 were enrolled. Conditioning regimen I was set as cyclohexyl nitrosourea+cytarabine+busulfan+cyclophosphamide; regimen II as cyclophosphamide+total body irradiation; regimen III as fludarabine+cytarabine+busulfan+cyclophosphamide; and regimen IV as busulfan+cyclophosphamide. Cyclosporin A, mycophenlate mofetil, antithymocyte globulin and methotrexate were used to prevent graft-versus-host disease (GVHD). Hematopoietic remodeling, complications and prognosis were observed in all patients undergoing HLA-haploidentical HSCT. RESULTS AND CONCLUSION: Of the 23 patients, 22 achieved reconstitution of the granulocyte series, and 19 achieved reconstruction of the megakaryocyte series. Additionally, there were 7 cases of acute GVHD and 4 of chronic GVHD. Transplant-related mortality was 22% (5/23) within 100 days post transplantation including graft failure, acute GVHD, intracranial hemorrhage and disseminated infections. There were 14 cases of disease-free survival from 100 days to 24 months post transplantation, 2 cases of death due to GVHD and fungal infection, or recurrence and chronic GVHD, and 2 cases of recurrence under treatment. These findings indicate that HLA-haploidentical HSCT is an effective approach for the treatment of patients with leukemia, which is worth further investigation in clinical practice. Subject headings: Hematopoietic Stem Cell Transplantation; Leukemia; Graft vs Host Disease; Tissue Engineering Funding: the Natural Science Foundation of Chongqing Municipal Science and Technology Committee in China, No. cstc2013jcyjA1007; the National Natural Science Foundation of China, No. 81502117 Cite this article: Jiang Q, Zhang HB, Yang L, Luo H, Miao Q, Deng XM. Haploidentical hematopoietic stem cell transplantation for leukemia in 23 cases. Zhongguo Zuzhi Gongcheng Yanjiu. 2016;20(28):4218-4225.

Corresponding author: Zhang Hong-bin, Associate chief physician, Department of Hematology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

0 Introduction
(hematopoietic stem cell transplantation HSCT)() (allogeneic hematopoietic stem cell transplantation Allo-HSCT) / (human leukocyte antigen HLA)
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH

78.1% HLA HLA HLA-ABCDRDQ˦ 5 HLA100%50% 2007 11 2015 3 23
4219
[2] [1]

. 23

www.CRTER.org

1
1.1 1.2 1.3

Subjects and methods
2007 1120153 23

(6-8)10 /kg( ) CD34 (2-4)10 /kg( ) 1.4.3 (ATG)A(CsA)(MMF) (MTX)10 mg/kg3 d A 2.0-3.0 mg/(kg?d)2 4.0-6.0 mg/(kg?d)A 200-400 g/L +1 d 15 mg/m +3+6+11 d10 mg/m -1 d 3 () 1.4.4
9
-1

8

+

6



1.3.1

1013 14-4827.3(ALL)4 (AML)12(M1 1M2 4M4 2 M5 5)14 1 M5 1M2 (CML)7 5 2 15 8݌ 1 1.3.2 1.3.3
[3]

2

2





<0.5 10 L 1.4.5 E

1.3.4 1.3.5 1.4 1.4.1 GIAC(+ ( )

< 2010 L ^ < 70 g/L 1.5 a.
9
-1

9

-1

0.510 L 3 db. 5 d 2010 L ( [4]) 1.6 SPSS 21.0 Kaplan-Meier t =0.05
2 9
-1

++)CY+TBI(+ 9.0 Gy 2 d ) FLAG+BU+CY( + + + )BU+CY(+) 2 1.4.2 4 d(-4 d) 5 g/(kg?d) 2 d3 d 1 K K 800 mL
4220

2
2.1

Results

9
-1

231

22 0.510 L 11-33 d16.5 d19 2010 L 1427 d19 d3
P.O. Box 10002, Shenyang 110180 www.CRTER.org
9
-1

. 23

www.CRTER.org

^ 2.2 2.2.1 3 100 d

1 2.2.2 1 11 §108 d 2100 d 1 11 2.2.3 10 v 1 ݦ 2.3 100 d 78.3%(18/23) 5 100 d 2 60.9%(14/23) 4 17.4% 1254 8 Kaplan-Meier1
+ +

730%(7/23) -4 2 mg/(kg?d)- 1 CD25 1+8 d +15 d- CD25 117 d +31 d CD25100 d18 4 22%(4/18)2 2 1
1 23 Table 1 General data of 23 patients with leukemia
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 ALL-CR ALL-CR ALL-CR ALL-CR AML-CR AML-CR AML-CR AML AML-CR AML-CR AML-CR AML-CR AML-CR CML-CP CML-BP CML-BP CML-CP CML-CP CML-CP CML-CP AML-CR AML-CR AML-PR PBSC PBSC BMSC&PBSC PBSC PBSC PBSC BMSC&PBSC PBSC BMSC&PBSC PBSC BMSC&PBSC PBSC PBSC BMSC&PBSC PBSC BMSC&PBSC BMSC&PBSC PBSC BMSC&PBSC PBSC PBSC PBSC PBSC / (d) 16/19 17/15 11/14 27/19/24 12/20 13/15 33/19 21/27 21/28/12/17 12/17 16/21 -/13/19 20/25 16/24 20/26 15/15 16/15 17/22 18/20 HC TMA HC HC HC HC HC HC HC HC HC





aGVHD - aGVHD aGVHD aGVHD- cGVHD aGVHD aGVHD- cGVHD cGVHD aGVHD cGVHD

1+ 8+ 2+ 2 4+6+ 7+

AMLALLCMLCRPRCPBP BMSCPBSCHCaGVHDcGVHD -

ISSN 2095-4344 CN 21-1581/R

CODEN: ZLKHAH

4221

. 23

www.CRTER.org

A 1.0 0.8 0.6 0.4 0.2 0 0 10 20 30 40 50 60

B 1.0 0.8 0.6 0.4 0.2 0 0 10 20 30 40 50 60

1 Kaplan-Meier Figure 1 Kaplan and Meier survival analysis A B

()

()

2 Table 2 Conditioning regimen dose and time
GIAC -10-9 d4 g/(m2 d) -10 d250 mg/(m d)
2

3 Table 3 The incidence of transplant-related complications
- - 3 10 5 2 2 2 (%) 13 43(10/23) 30(7/23) 22 9 22(4/18) 11 11

-8-6 d0.8 mg/(kg )6 h/

CY+TBI

7

-5-4 d1.8 g/(m2 d) -5-4 d4.5 Gy/d

4

FLAG+ BU+CY BU+CY

-3-2 d60 mg/(kg d) -10-7 d30 mg/(m2 d) -10-7 d2 g/(m2 d) -6-4 d0.8 mg/(kg )6 h/ -3-2 d1.8 g/(m2 d) -7-4 d0.8 mg/(kg )6 h/ -3-2 d60 mg/(kg d)

30%(7/23) - 9%(2/23) 4 22%(4/18) 11%(2/18)

3

Discussion


(P 0.4890.4450.1140.762)
[10-11]

[9]

[12]

HLA
[5-6]

Funke CD25 23 1 CD25 CD25 2 - CD25 ਹ
[13-15]

HLA
[7-8]

23 11-33 d 16.5 d 14-27 d 19 d 1 1 1 ݼ A
4222
[7]

3


P.O. Box 10002, Shenyang
[16-18]


www.CRTER.org

110180

. 23

www.CRTER.org

23 100 d 9%(2/23) 1 1 § 100 d 2 1 1 § (3/23) (P=0.257) 23 10 43%
[19-20] [7]

1 ۨ / (DLI/DSI) (DC/CIK)
[32]



23 8
[33]




[34-39]


[25-26]

(BK )
[21-24]

10 E
[27]

23

100 d 1 210
[40]




[28]







2015 10 61% 52%23 100 d 22%1 1 1 1 2 1 81 d 1 2 1 108 d 1 4 1 1 1 2 4 17% 2
[29] + + + + + +

ݧ





p





CNKI
3

10%2
[30-31]

20%-30%5 20%






(CP2) 2 7 8 1
ISSN 2095-4344 CN 21-1581/R CODEN: ZLKHAH
+ +

է
֦p( )
4223

. 23

www.CRTER.org



[13] Bernardo ME, Ball LM, Cometa AM, et al. Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation. Bone Marrow Transplant. 2011;46(2):200-207. [14] Kuzmina LA, Petinati NA, Parovichnikova EN, et al. Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease-A Phase II Study. Stem Cells Int. 2012;2012:968213. [15] Wu Y, Wang Z, Cao Y, et al. Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells with a myeloablative regimen for refractory/relapsed hematologic malignancy. Ann Hematol. 2013;92(12):1675-1684. [16] Snchez-Guijo F, Caballero-Velzquez T, Lpez-Villar O, et al. Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(10): 1580-1585. [17] Introna M, Lucchini G, Dander E, et al. Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant. 2014;20(3): 375-381. [18] Zhao K, Lou R, Huang F, et al. Immunomodulation effects of mesenchymal stromal cells on acute graft-versus-host disease after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015; 21(1):97-104. [19] Batista CK, Mota JM, Souza ML, et al. Amifostine and glutathione prevent ifosfamide- and acrolein-induced hemorrhagic cystitis. Cancer Chemother Pharmacol. 2007;59(1):71-77. [20] ,,. [J]., 2011; 32(3):148-151. [21] ],,. [J].,2009:26(2): 132-134. [22] ,,. [J].,2010,18(4): 1007-1012. [23] Lee GW, Lee JH, Choi SJ, et al. Hemorrhagic cystitis following allogeneic hematopoietic cell transplantation. J Korean Med Sci. 2003;18(2):191-195. [24] Leung AY, Mak R, Lie AK, et al. Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation. Bone Marrow Transplant. 2002;29(6): 509-513.
P.O. Box 10002, Shenyang 110180 www.CRTER.org




4 References
[1] Chen XH, Gao L, Zhang X, et al. HLA-haploidentical blood and bone marrow transplantation with anti-thymocyte globulin: long-term comparison with HLA-identical sibling transplantation. Blood Cells Mol Dis. 2009;43(1):98-104. [2] [3] [4] [5] ,,.HLA [J].,2013,26(6):506-510. ,,[M].: ,2008:131-139. Thomas E,Storb R,Cliff RA,et al. Bone-marrow transplantation. N Engl J Med.1975;292:832-843. ,,,. [J].,2010, 19(12): 714-717. [6] ,,,. ল [J].?,2015,24(6):346-351. [7] Petersdorf EW. Genetics of graft-versus-host disease: the major histocompatibility complex. Blood Rev. 2013; 27(1):1-12. [8] Lazaryan A, Weisdorf DJ, DeFor T, et al. Risk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors. Biol Blood Marrow Transplant. 2016;22(1): 134-140. [9] ,,,.HLA [J].ۧ ,2011,15(27):5123-5126. [10] Champlin RE, Schmitz N, Horowitz MM, et al. Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2000; 95(12):3702-3709. [11] Lazarus HM, Vogelsang GB, Rowe JM. Prevention and treatment of acute graft-versus-host disease: the old and the new. A report from the Eastern Cooperative Oncology Group (ECOG). Bone Marrow Transplant. 1997;19(6):577-600. [12] Funke VA, de Medeiros CR, Setbal DC, et al. Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist. Bone Marrow Transplant. 2006;37(10): 961-965. 4224

. 23

www.CRTER.org

[25] Ruggeri A, Roth-Guepin G, Battipaglia G, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17(6):822-830. [26] ,,,. [J].?,2013, 22(7):410-414. [27] Qian L, Shen J, Zhao D, et al. Successful treatment of hemorrhagic cystitis after HLA-mismatched allogeneic hematopoietic stem cell transplantation by hyperbaric oxygen. Transplantation. 2014;97(7):e41-42. [28] ,,,. 8[J]., 2014,14(7):554-557. [29] Champlin R, Jabbour E, Kebriaei P, et al. Allogeneic stem cell transplantation for chronic myeloid leukemia resistant to tyrosine kinase inhibitors. Clin Lymphoma Myeloma Leuk. 2011;11 Suppl 1:S96-100. [30] Gratwohl A, Brand R, Apperley J, et al. Allogeneic hematopoietic stem cell transplantation for chronic myeloid leukemia in Europe 2006: transplant activity, long-term data and current results. An analysis by the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2006;91(4):513-521. [31] Nicolini FE, Mauro MJ, Martinelli G, et al. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation. Blood. 2009; 114(26):5271-5278. [32] ,,.G-CSF [J]., 2007,15(5):1121-1125.

[33] Holtick U, Albrecht M, Chemnitz JM, et al. Comparison of bone marrow versus peripheral blood allogeneic hematopoietic stem cell transplantation for hematological malignancies in adults - a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2015;94(2):179-188. [34] ,,,. [J].ۧ, 2011, 15(23):4251-4256. [35] ,,,.HLA [J]. ۧ ,2012, 16(32): 6076-6080. [36] Luo R, Wanming DA, Zhang X, et al. The safety and efficacy of hematopoietic stem cell transplantation for 22 children with high-risk hematologic malignancies. Journal of China Pediatric Blood & Cancer, 2013; 18(6): 255-258. [37] Yang K, Si Y, Chen H, et al. Comparative study of the efficacy of allogeneic hematopoietic stem cell transplantation from human leukocyte antigen-haploidentical related and unrelated donors in the treatment of leukemia. Acta Haematol. 2014;131(1): 37-44. [38] Di Stasi A, Milton DR, Poon LM, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transplant. 2014;20(12):1975-1981. [39] Piemontese S, Ciceri F, Labopin M, et al. A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia. 2015;29(5):1069-1075. [40] Wang Y, Chang YJ, Xu LP, et al. Who is the best donor for a related HLA haplotype-mismatched transplant. Blood. 2014;124(6):843-850.

ISSN 2095-4344 CN 21-1581/R

CODEN: ZLKHAH

4225


:


...C13_....pdf

Flud+Bu+CCNU+Ara-C13

HLA....pdf

HLA__... Hi.HSC T 23 ...

4.pdf

4 - ۧ 1

....pdf

- ,HLA...


40.pdf

40 - :(HSCT)(AML) :HSCT...

....pdf

- 4 O

1_.pdf

1 - (JMML)16JMML,...

Ly+AMLMy+ALL (24).doc

...19 5 , B 6 ,...

-.doc

-,,...

.doc

, ... ,... ...

HLAKIR....pdf

HLAKIR__... ,...

43:....pdf

43: - :,...

....pdf

(mixHSCT) (hiDLI) 2 (IL-2) ( AML) ...

.pdf

- 838

HLA....pdf

HLA - (HLA)...

89Aml1_Eto.pdf

89Aml1_Eto__... ...

64....pdf

64__...44HLA,20HLA ...

|
All rights reserved Powered by www.tceic.com
copyright ©right 2010-2021
zhit325@126.com