Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma

被引：159

作者：

Shah, Nina ^{[1
,10
]}

Li, Li ^{[1
]}

McCarty, Jessica ^{[1
]}

Kaur, Indreshpal ^{[1
]}

Yvon, Eric ^{[1
]}

Shaim, Hila ^{[1
]}

Muftuoglu, Muharrem ^{[1
]}

Liu, Enli ^{[1
]}

Orlowski, Robert Z. ^{[2
]}

Cooper, Laurence ^{[3
]}

Lee, Dean ^{[4
]}

Parmar, Simrit ^{[1
]}

Cao, Kai ^{[5
]}

Sobieiski, Catherine ^{[6
]}

Saliba, Rima ^{[1
]}

Hosing, Chitra ^{[1
]}

Ahmed, Sairah ^{[1
]}

Nieto, Yago ^{[1
]}

Bashir, Qaiser ^{[1
]}

Patel, Krina ^{[1
]}

Bollard, Catherine ^{[7
,8
,9
]}

Qazilbash, Muzaffar ^{[1
]}

Champlin, Richard ^{[1
]}

Rezvani, Katy ^{[1
]}

Shpall, Elizabeth J. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Unit 432, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA

[4] Nationwide Childrens Hosp, Dept Hematol & Oncol, Columbus, OH USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA

[6] Columbia Univ, Inst Human Nutr, Coll Phys & Surg, New York, NY 10032 USA

[7] Childrens Natl Hlth Syst, Dept Allergy & Immunol, Washington, DC USA

[8] Childrens Natl Hlth Syst, Dept Blood & Marrow Transplantat, Washington, DC USA

[9] George Washington Univ, Washington, DC USA

[10] Univ Calif San Francisco, Dept Med, 400 Parnassus Ave,4th Floor,Box 0324, San Francisco, CA USA

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2017年 / 177卷 / 03期

关键词：

myeloma; natural killer; cord blood; exvivo expansion; autologous transplant; REGULATORY T-CELLS; HLA CLASS-I; NK CELLS; DENDRITIC CELLS; HIGH-RISK; CYTOTOXICITY; LENALIDOMIDE; EXPRESSION; THERAPY; ACTIVATION;

D O I：

10.1111/bjh.14570

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Multiple myeloma (MM) is a disease with known immune dysregulation. Natural killer (NK) cells have shown preclinical activity in MM. We conducted a first-in-human study of umbilical cord blood-derived (CB) NK cells for MM patients undergoing high dose chemotherapy and autologous haematopoietic stem cell transplantation (auto-HCT). Patients received lenalidomide (10mg) on days -8 to -2, melphalan 200mg/m(2) on day -7, CB-NK cells on day -5 and auto-HCT on day 0. Twelve patients were enrolled, three on each of four CB-NK cell dose levels: 5x10(6), 1x10(7), 5x10(7) and 1x10(8) CB-NK cells/kg. Ten patients had either high-risk chromosomal changes or a history of relapsed/progressed disease. There were no infusional toxicities and no graft-versus-host disease. One patient failed to engraft due to poor autologous graft quality and was rescued with a back-up autologous graft. Overall, 10 patients achieved at least a very good partial response as their best response, including eight with near complete response or better. With a median follow-up of 21months, four patients have progressed or relapsed, two of whom have died. CB-NK cells were detected invivo in six patients, with an activated phenotype (NKG2D(+)/NKp30(+)). These data warrant further development of this novel cellular therapy.

引用

页码：457 / 466

页数：10