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01-04-2013 | Oncology | Article

T-cell therapy holds promise for ALL children


Free abstract

medwireNews: Two children with relapsed and chemotherapy-refractory pre-B-cell acute lymphoblastic leukemia (ALL) achieved complete remission after treatment with modified T cells, show study findings published in TheNew England Journal of Medicine.

Chimeric antigen receptor-modified T cell treatments that target the B-cell antigens CD19 and CD20, expressed in various hematological malignancies, have successfully treated adults with chronic lymphocytic leukemia (CLL) and B-cell lymphomas.

"However, the effects of chimeric antigen receptor T cells on ALL blasts, a more immature leukemia that progresses more rapidly, have not been fully investigated," write Stephan Grupp (University of Pennsylvania, Philadelphia, USA) and colleagues.

They report two cases of 7- and 10-year-old girls with pre-B-cell ALL who were treated with T cells transduced with an anti-CD19 antibody, as well as the T-cell signaling molecule. The two girls are the first patients enrolled in a phase 1 clinical trial to test the safety and feasibility of this type of therapy for patients with relapsed or refractory B-cell cancers.

The two girls went into complete remission (minimal residual disease <0.01%) 1 month after receiving the modified T-cell infusion.

The 7-year-old girl remains disease free at present, but the 10-year-old had a relapse that became apparent 2 months after she received the infusion. The new leukemia cells were positive for CD45+ and CD34 antigens, but not CD19.

"This study describes how these cells have a potent anticancer effect in children," commented Grupp in a press statement. "However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells," he conceded.

Regarding treatment related adverse events, both children experienced acute toxic effects from the treatment including fever and a cytokine-release syndrome, but these were managed successfully without affecting treatment efficacy.

Co-author of the study Carl June, also from the University of Pennsylvania, commented: "We're hopeful that our efforts to treat patients with these personalized cellular therapies will reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations.

"In the long run, if the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy."

By Helen Albert, Senior medwireNews Reporter

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