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Case Reports
. 2010 Apr;18(4):666-8.
doi: 10.1038/mt.2010.31.

Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial

Renier Brentjens, Raymond Yeh, Yvette Bernal, Isabelle Riviere, Michel Sadelain
Case Reports

Treatment of chronic lymphocytic leukemia with genetically targeted autologous T cells: case report of an unforeseen adverse event in a phase I clinical trial

Renier Brentjens et al. Mol Ther. 2010 Apr.
No abstract available

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Figures

<b>Figure 1</b>
Figure 1
Clinical assessment of subject 4 on IRB no. 06-138, NIH-RAC no. 0507-721, NCT00466531. Assessment of patient from the time of admission to the hospital before cyclophosphamide chemotherapy (–48 hours), through time of modified T-cell infusion (0 hours), to time of death (44 hours). Clinical status was assessed by routine vital sign parameters, including (a) temperature and systolic blood pressure, as well as by laboratory chemistry measurements, including (b) renal function as measured by creatinine, potassium, phosphorus, and uric acid concentrations. Vital signs over time are consistent with a sepsis syndrome (fever with hypotension), whereas laboratory chemistry studies demonstrate an initial rise in creatinine coinciding with the patient's anuric state, followed by rising potassium, phosphorus, and uric acid at concentrations that are consistent with tumor lysis but confounded by the antecedent acute renal failure. The vertical arrow indicates the time of T-cell infusion.
<b>Figure 2</b>
Figure 2
Serum cytokine concentrations measured in subject 4. Serum samples were obtained 30 days before cyclophosphamide (–30 d), 2 hours before T-cell infusion (–2 h), and 4 and 26 hours after T-cell infusion (+4 h, +26 h, respectively). The –2-h sample is therefore post-cyclophosphamide but pre-T-cell infusion. Pretreatment tumor necrosis factor-α (TNF-α) serum values were 200, 50, and 59 ng/ml in subjects 1, 2, and 3, respectively. IFN-γ, interferon-γ IL, interleukin.
See this image and copyright information in PMC

Comment in

  • Safer CARS.
    Heslop HE. Heslop HE. Mol Ther. 2010 Apr;18(4):661-2. doi: 10.1038/mt.2010.42. Mol Ther. 2010. PMID: 20357776 Free PMC article. No abstract available.

References

    1. Sadelain M, Rivière I., and , Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer. 2003;3:35–45. - PubMed
    1. Brentjens RJ, Latouche JB, Santos E, Marti F, Gong MC, Lyddane C.et al.(2003Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15 Nat Med 9279–286. - PubMed
    1. Maher J, Brentjens R, Gunset G, Rivière I., and , Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002;20:70–75. - PubMed
    1. Brentjens RJ, Santos E, Nikhamin Y, Yeh R, Matsushita M, La Perle K.et al. (2007Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts Clin Cancer Res 135426–5435. - PubMed
    1. Sadelain M, Brentjens R., and , Rivière I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009;21:215–223. - PMC - PubMed

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