Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation

被引：39

作者：

Olson, Amanda ^{[1
]}

Lin, Ruitao ^{[2
]}

Marin, David ^{[1
]}

Rafei, Hind ^{[1
]}

Bdaiwi, Mustafa H. ^{[1
]}

Thall, Peter F. ^{[2
]}

Basar, Rafet ^{[1
]}

Abudayyeh, Ala ^{[3
]}

Banerjee, Pinaki ^{[1
]}

Aung, Fleur M. ^{[4
]}

Kaur, Indresh ^{[1
]}

Abueg, Glorette ^{[1
]}

Rao, Sheetal ^{[1
]}

Chemaly, Roy ^{[5
]}

Mulanovich, Victor ^{[5
]}

Al-Atrash, Gheath ^{[1
]}

Alousi, Amin M. ^{[1
]}

Andersson, Borje S. ^{[1
]}

Anderlini, Paolo ^{[1
]}

Bashir, Qaiser ^{[1
]}

Castro, Karla M. ^{[1
]}

Daher, May ^{[1
]}

Galvan, Isabel M. ^{[1
]}

Hosing, Chitra ^{[1
]}

Im, Jin S. ^{[1
]}

Jones, Roy B. ^{[1
]}

Kebriaei, Partow ^{[1
]}

Khouri, Issa ^{[1
]}

Mehta, Rohtesh ^{[1
]}

Molldrem, Jeffrey ^{[1
]}

Nieto, Yago ^{[1
]}

Oran, Betul ^{[1
]}

Popat, Uday ^{[1
]}

Qazilbash, Muzaffar ^{[1
]}

Rondon, Gabriela ^{[1
]}

Saini, Neeraj ^{[1
]}

Spencer, Bryan ^{[1
]}

Srour, Samer ^{[1
]}

Washington, Dominique ^{[1
]}

Barnett, Melissa ^{[1
]}

Champlin, Richard E. ^{[1
]}

Shpall, Elizabeth J. ^{[1
]}

Rezvani, Katayoun ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd,Unit 423, Houston, TX 77030 USA

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

[3] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Sect Nephrol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Div Pathol & Lab Med, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2021年 / 39卷 / 24期

基金：

美国国家卫生研究院;

关键词：

EPSTEIN-BARR-VIRUS; BLADDER IRRIGATION; CELLS; TRANSPLANTATION; CYTOMEGALOVIRUS; GENERATION; SURVIVAL;

D O I：

10.1200/JCO.20.02608

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS We performed a clinical trial (ClinicalTrials.gov identifier: ) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT. (C) 2021 by American Society of Clinical Oncology

引用

页码：2710 / +

页数：11

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