tceic.com
>> >>

CIK


546

www.tumorsci.org 2012 7 32 7 TUMOR Vol. 32, July 2012

?Clinical Experience

DOI: 10.3781/j.issn.1000-7431.2012.07. 012 Copyright? 2012 by TUMOR

CIK9/

400010 [ ] / allogeneic-peripheral hemopoietic stem cell transplantation Allo-PBSCT cytokine induced killerCIK 9 / Allo-PBSCT CIK 9 CIK 4 1 59 d 9.22 20 Allo-PBSCT CIK ߧ / [ ] []R733.71 []A []1000-7431 (2012) 07-0546-05

Allogeneic hematopoietic stem cell transplantation followed by sequential infusion of donor-derived cytokine induced killer cells for relapsed/ refractory hematologic malignancy: A preliminary study of 9 cases
LUO Yun, ZHANG Ping, ZHANG Ying, LOU Shi-feng, ZHOU Kang, DENG Jian-chuan, CHEN Shu, CHEN Lin
Department of Hematology, Second Af?liated Hospital, Chongqing Medical University, Chongqing 400010, China

[ABSTRACT] Objective: To explore the efficacy and complications of allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) followed by sequential infusion of donor-derived cytokine induced killer (CIK) cells for relapsed/refractory hematologic malignancy. Methods: Nine patients with relapsed/ refractory hematologic malignancy without complete remission received Allo-PBSCT. After hematopoietic reconstitution, the donor-derived peripheral blood mononuclear cells were collected by blood cell separator and cultured into CIK cells in vitro . The CIK cells were infused back into the patients. The therapeutic efficacy, adverse reactions and prognosis were observed. Results: All patients engrafted. Complete remission was also achieved in all patients. After infusion of CIK cells, four patients developed graft-versus -host disease (GVHD) which was relieved by reinforced immunosuppression therapy. One patient died of infection 59 days after Allo-PBSCT, and the other 8 patients survived at a median followup of 9.2 months (2-20 months). Conclusion: Allo-PBSCT followed by sequential infusion of donor-derived CIK cells can salvage the patients with relapsed/refractory hematologic malignancy and it is worthy of further large-scale study. [KEY WORDS] Leukemia; Hematopoietic stem cell transplantation; Graft versus host disease; Cytokineinduced killer cells [TUMOR , 2012, 32 (07): 546-550]

/ acute myeloid leukemiaAML

Correspondence to: LOU Shi-feng E-mail: loushifeng@hotmail.com Received2012-02-24Accepted2012-06-08

non-Hodgkin lymphomaNHL multiple myelomaMM autologous peripheral hemopoietic stem cell transplantationAuto-PBSCT

. CIK 9 /

547

allogeneic-peripheral hemopoietic stem cell transplantationAllo-PBSCT [1] ئ ݦ [2] Allo-PBSCT donor lymphocyte infusionDLI T 2010 6 2011 12 9 / Allo-PBSCT CIK ȧ 1 1.1 1
1 Table 1Characteristics of patients and donors
Case Gender/age Diagnosis (year) AML(M2) ALL(TLBL) MM (IgA, Kappa) NHL(SLL) AML(M2) NHL(ALCL) Chromosome analysis del(9)(q22,q34) Normal Normal

/ 2010 6 2011 12 k 9 5 4 15 64 41 AMLNHLMM CML chronic myeloid leukemia 1 Allo-PBSCT CIK 1.26 12 568 9 BUCY 30 mg/m2 9 6 4 -1 -1 mg?kg ?d 6 4 -1 -1 60 mg?kg ?d 3 2 2 6 2 200 mg/m2 4 2 6 MM 2 3 7 30 mg/m2 8 4 140 2 mg/m 3 2 2.5 mg?kg-1?d-1 2 1 1.3graft - versus - host disease GVHD 1 d 2.5 mg? -1? -1 kg d

N =9 Therapy Autologous-PBSCT Autologous-PBSCT Autologous-PBSCT Bortezomib, Lenalidomide Autologous-PBSCT DA Autologous-PBSCT Autologous-PBSCT DAImatinib DA Response NR NR PR Gender/age HLA Type of graft (year) of donor match Male/42 Female/44 Female/53 3/6 3/6 6/6 AllogeneicPBSCT+BMT AllogeneicPBSCT+BMT AllogeneicPBSCT+BMT Allogeneic-PBSCT AllogeneicPBSCT+BMT Allogeneic-PBSCT AllogeneicPBSCT+BMT AllogeneicPBSCT+BMT Allogeneic-PBSCT

No 1 Female/15 No 2 Male/21 No 3 Female/64

No 4 Male/57 No 5 Female/32 No 6 Female/42 No 7 Male/47 No 8 Male/45 No 9 Male/48

+11 t(8;21)(q22;q22) C-Kit(+) Normal

NR NR NR NR NR NR

Male/55 Female/38 Male/38 Female/42 Male/46 Male/52

6/6 5/6 6/6 6/6 6/6 6/6

MM Normal (IgG, Lambda) CML(AP) AML(M2) t(9;22)(q34;q11) Normal

AML: Acute myeloid leukemia; ALL: Acute lymphoplastic leukemia; MM: Multiple myeloma; CML: Chronic myeloid leukemia; NHL: Non-Hodgkin lymphoma; DLI: Donor lymphocyte infusion; Autologous-PBSCT: Autologous peripheral blood stem cell transplantation; BMT: Bone marrow transplantation; DA: Daunorubicin+cytarabina; HLA: Human leukocyt antigen; PR: Partial remission; NR: Non-remission.

548

. CIK 9 /

7 0.5 g 2 20 mg 15 mg/m2 1 10 mg/m2 3 7 1.4 ¦ ڨ cytomegavirus CMV EB Epstein-Barr virusEBV DNA Φ§ 5 2.0109/L 1.5 5 g?kg-1?d-14 5 d SPECTRA 6.0 Cobe 5 1.6CIK 80 120 mL 200 300 mL ] 1106 /L RPMI 1640 Gibco interferon-IFN- -2interleukin-2, IL-2 CD3 orthoclone3OKT3 ̦ [3] 37 CO2 5% 12 14 d CIK CIK 1.7 neutrophilic 9 granulocyteANC 0.510 /L 3 d 1 platelet PLT 20109/L

short tandem repeatsSTR DNA complete remission CR partial remissionPR non-remissionNR 1.8 SPSS 16.0 s P 0.05 ^ 2 2.1 9 8.58108/kg3.86 15.56 108/kg CD34 3.49106/kg 1.32 9.22106/kg 2.29 ANC 0.5109/L 11.8 d 9 13 PLT 2010 9/L 13 d 10 16 8 30 d STR 1 CIK 2.3 4 GVHD 4 212535 37 1 47 CMV CMV 4 1 307 2 1 54 § 59 2 2.4CIK 9 1 7 CIK 1106/kg 1109/kg CIK 1 chronic graft-versus-host diseasecGVHD 2 cGVHD 2.5CIK CD3 78.5 3.2%CD3 CD4 48.07.2%CD3

. CIK 9 /

549

2 Table 2Transplantation and complications of 9 cases
Engraft time Case ANC> GVHD Transplant-related complications PLT> 0.5109/L 20109/L No.1 No.2 d13 d9 d13 d11 0 0 Hemorrhagic cystitis (d25) Hemorrhagic cystitis (d21) Oral cavity fungal infection (d25), pneumonia (d232), activation of hepatitis B virus (d307), acute upper respir tract infection (d391) Degree stomatitis (d7) CMV infection (d47), steroid diabetes (d52)pneumonia (d6) Hemorrhagic cystitis (d37), enteritis, idiopathic interstitial pneumonia, Guillain-Barre syndrome (d54) Hemorrhagic cystitis (d35) Degree stomatitis (d7) Degree stomatitis (d8) Time of donor CIK cells infusion

(N =9) Current status Followup t /d 557 394

d25, d57, d85, d145 cGVHD (skin) d30, d74, d78, d367,d380 d430 cGVHD (skin)

No.3

d12

d16



CR

592

No.4 No.5 No.6 No.7 No.8 No.9

d13 d13 d12 d10 d13 d11

d13 d13 d15 d10 d13 d13

0

d165 d59 d52 d54, d57 d59 d31, d34

cGVHD 459 (oral cavityeye CR Died (d59) CR CR CR 229 94 91 61

0 0

ANC: Neutrophilic granulocyte; PLT: Platelet; GVHD: Graft-versus -host disease; CMV: Cytomegalovirus; CIK: Cytokine induced killer; cGVHD: Chronic graft-versus -host disease; CR: Complete response.

CD8 % % 29.06.4 CD3 CD56 1.50.2 CD3 CD19 20.62.4% 3 14 d CIK CD3 88.85.2%CD3 CD4 12.05.6%CD3 CD8 69.07.4% CD3 CD56 11.34.5% CD3 CD19 % % 0.60.2 NKG2D 90.02.6 8 CD8 CD56 2.6 CIK CIK CD3 71.304.30% CD4 76.143.22% CD8 5.431.41% CD56 8.324.56%5 1 CD3 80.612.43%CD4 48.36 2.82%CD8 35.233.44%CD56 21.48 6.22%5 CD4 CD8 CD56 P 0.05 2.7 2012 1 10 9.2 2 20 1 9 1 360 d 2 CIK 3 cGVHD

3 AlloPBSCT ħ [4] AML ڦ Allo-PBSCT CR NR 1 CD25 GVHD graft versus leukemiaGVL graft versus tumorGVT DLI GVHD

550

. CIK 9 /

Nishimura [5] CIK CIK GVHD GVT GVHD Allo-PBSCT 1 NR 40% 180 d NKG2A [6] CIK GVL GVT Barrett [7] GVL T Dellabona [8] Passweg [9] T Introna [10] CIK Allo-PBSCT CIK CIK CIK T DLI DLI T CIK GVHD Allo-PBSCT CIK Ȧ [ ]
[1] KLINGEBIEL T, CORNISH J, LABOPIN M, et al . Results and factors in?uencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk

acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group[J].

Blood , 2010, 115(17):3437C3446.
[2] W A N G Y , L I U D H , X U L P , et al . S u p e r i o r graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison [J]. Biol

Blood Marrow Transplant , 2011, 17(6):821-830.
[3] , , , . CIK [J]. , 2010, 30(8):700-705. [4] , , , . HLA [J]. , 2011, 32(3):141-143. [5] NISHIMURA R, BAKER J, BEILHACK A, et al . In vivo trafficking and survival of cytokine-induced killer cells resulting in minimal GVHD with retention of antitumor activity [J]. Blood , 2008, 112(6): 2563-2574. [6] GIEBEL S, DZIACZKOWSKA J, CZERW T, et al . Sequential recovery of NK cell receptor repertoire after allogeneic hematopoietic SCT[J]. Bone

Marrow Transplant , 2010, 45(6):1022-1030.
[7] BARRETT A J. Understanding and harnessing the graft-versus-leukaemia effect [J]. Br J Haematol , 2008, 142(6):877-888. [8] DELLABONA P, CASORAT G, LALLA C D E, et al . On the use of donor-derived iNKT cells for adoptive immunotherapy to prevent leukemia recurrence in pediatric recipients of HLA haploidentical HSCT for hematological malignancies[J]. Clin Immunol , 2010, 140(2):152-159. [9] PASSWEG J R, TICHELLI A, MEYER-MONARD S,

et al . Puri?ed donor NK-lymphocyte infusion to
consolidate engraftment after haploidentical stem cell transplantation[J]. Leukemia , 2004, 18(11): 1835-1838. [10] INTRONA M, BORLERI G, CONTI E, et al . Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase study[J].

Haematologica , 2007, 92(7):952-959.
[ ]


:

CIK....pdf

CIK M2 ...[26] ,,,.CIK 9...

DC_CIK.pdf

12 DC2CIK ...1 M4 , ( ) ...

().ppt

DC ? (... 50-60ml DCCIK d7 DC ...

.doc

,...,... CIK , ...


.pdf

, , 3 2 ALL2... (DL1) CML ...

_.ppt

...3. ...HLA ...

vod_.ppt

vod - ...

()_.ppt

(Allo-HSCT) ...( )...,(CIK)T...

_.pdf

,(, 100038) [] Ty,...

_.pdf

1981 (... (G-CSF)...(DLI) (CIK)...

_.ppt

/ /..., ...... 60 ...

DC_CIK....pdf

DC_CIK... ( auto 2PBSCT) ... ...

GM-CSF....doc

GVL)ASCT, ( donor lymphoctyes ...[16] CIK I ...

.pdf

8 ..., 1 HLA ...: PB SC B ...

DC-CIK6.doc

IgH, IgH...1.3 DC-CIK 3 ...HLA ,...

....pdf

(...IsGlgAIgD (AS...2.:45 d ...

_.ppt

HLA ? GVHD,...2004;103:1527) 304 ?...5-12 (IV), 400 mg/...

.doc

dc-cik ... ,..., ...

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