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Successful chimeric Ag receptor modified T cell therapy for isolated testicular relapse after hematopoietic cell transplantation in an acute lymphoblastic leukemia patient

Bone Marrow Transplantation volume 52, pages 1065–1067 (2017)Cite this article

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Primary disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a major cause of treatment failure in patients with ALL.1, 2 Bone marrow (BM) relapse is the most common type of relapse; extramedullary relapse occurs less commonly but usually refers to a poor prognosis.3 The testes, regarded as an immune sanctuary organ, are one of the most common sites of extramedullary relapse after allo-HSCT.4 For patients with isolated testicular relapse (ITR), current treatment modalities include local irradiation, orchiectomy, systemic chemotherapy, or a combination of these strategies.5, 6 However, side effects of such combination therapy impeded its clinical application and disease control. Thus, an appropriate treatment strategy for ITR is still urgently needed. Recently, chimeric Ag receptor-modified T cells against CD19 (CART19s) have shown promise as a novel therapy for relapsed/refractory (R/R) ALL patients in our own and other clinical trials.7, 8, 9 Most of these trials demonstrated data on BM relapse, as well as on tracing of CART19s to several extramedullary sites, including the liver, lymph nodes and the central nervous system (CNS). Although the blood-brain barrier (BBB) and blood-testis barrier (BTB), which consist primarily of a continuous endothelium with tight junctions,10 commonly inhibit immune cell migration and protect CNS or testis from cytotoxic cell attacks, in our trial, we have reported for the first time that CART19s penetrated BBB and eliminated CNS lymphoma in a patient with R/R ALL.11 Since BBB and BTB have similar anatomical structures and immunologic features, the consideration that CART19s might penetrate BTB and eradicate ITR as a potential therapy needs to be clarified.

The patient was followed up consistently and remained in CR for 153 days. During the follow-up, the patient had no CART-associated complications. CART19s still showed significant anti-leukemia activities. Testis mass size was evaluated weekly by ultrasound. As shown in Supplementary Table 1, the testis mass shrank gradually. On day 28 after CART19 infusion, the mass had almost disappeared. A fine-needle aspiration was performed on the testis mass 7 days after CART19 infusion; 3.74% of aspirated cells were CD3+ T cells, and 15.54% of T cells expressing the anti-CD19 CAR, while 2.98% of T cells expressing the anti-CD19 CAR in PB as measured by flow cytometry with a CAR-specific Ab (Figure 2b). A fine-needle aspiration was performed on the testis mass again 28 days after CART19 infusion and no leukemia cell was detected (Figure 1c). The patient was considered to have achieved CR from ITR.

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Acknowledgements

This work was supported by the grants from 973 Program (2015CB964900), Zhejiang Provincial Natural Science Foundation of China (LY14H080002), the Natural Science Foundation of China (81370647, 81570146), Zhejiang Medical Technology & Education (2014KYA064, 2014KYA066), Key Project of Science and Technology Department of Zhejiang Province (2015C03G2010091) and Beijing Municipal Administration of Hospitals' Youth Programme (QML20150506).

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  1. J Yu, Y Hu and C Pu: These authors contributed equally to this work.

Authors and Affiliations

  1. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    J Yu, Y Hu, Z Liang, H Zhang, Y Luo, J Shi, A Jin & H Huang

  2. Innovative Cellular Therapeutics Co., Ltd, Shanghai, China

    C Pu, L Xiao & Z Wu

  3. Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Q Cui

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Yu, J., Hu, Y., Pu, C. et al. Successful chimeric Ag receptor modified T cell therapy for isolated testicular relapse after hematopoietic cell transplantation in an acute lymphoblastic leukemia patient. Bone Marrow Transplant 52, 1065–1067 (2017). https://doi.org/10.1038/bmt.2017.64

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