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Case Reports
. 2024 Nov;103(11):4811-4815.
doi: 10.1007/s00277-024-06011-4. Epub 2024 Sep 21.

CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase

Laura-Jane Kramp  1 , Christiane Heydrich-Karsten  1 , Stephanie Sembill  2   3 , Axel Karow  2   3 , Thomas Lion  4 , Guranda Chitadze  5   6 , Meinolf Suttorp  7 , Gunnar Cario  1   5 , Markus Metzler  8   9
Affiliations
Case Reports

CAR-T cells for the treatment of pediatric chronic myeloid leukemia in repeatedly relapsed lymphoid blast phase

Laura-Jane Kramp et al. Ann Hematol. 2024 Nov.

Abstract

Chronic myeloid leukemia presenting de novo in the blast phase (CML-BP) is a rare diagnosis among pediatric malignancies. We report on a 16-year-old male who presented with CML-BP lymphoid at diagnosis. He was treated with shortened acute lymphoblastic leukemia induction plus the tyrosine kinase inhibitor (TKI) imatinib followed by dasatinib. After achieving molecular remission (MR), hematopoietic stem cell transplantation (HSCT) was performed early after diagnosis. Despite prophylactic dasatinib, he relapsed 3 months later with the kinase domain mutation T315I. Multiple therapeutic approaches including ponatinib, blinatumomab, a 2nd HSCT from a different donor, donor lymphocyte infusions, and high-dose asciminib all resulted in subsequent relapse. Another molecular response was achieved by combining ponatinib plus asciminib with chemotherapy. In this situation, CD19-directed CAR-T cells (Kymriah®) were administered for compassionate use and tolerated without adverse events. Compared to all prior therapies, CAR T-cells maintained remission. After 12 months of follow-up, complete B-cell aplasia and low numbers of CAR-T cells are detectable in the peripheral blood, potentially mediating long-term disease control.

Keywords: Blast phase; CD19 CAR-T cells; Chronic myeloid leukemia; Refractory leukemia.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Time course of measurable residual disease (MRD) markers and therapy elements administered. (A) The markers for measurable residual disease (MRD) analyzed in peripheral blood (pB) included BCR::ABL1IS (green line) and CD19+/cyCD79a+/CD10+/CD34+/TdT + blasts measured by flow cytometry (FC, orange dots). (B) CAR vector copies were quantified by ddPCR in PB. Note the persistence of low numbers of CAR-T cells for >120 days post-infusion. (C) Sequence of tyrosine kinase inhibitors administered as monotherapy or combined with other therapies (see text). CD19-CAR-T cells, CD19-positive chimeric antigen receptor T cells; DLI, donor lymphocyte infusion; HSCT, hematopoietic stem cell transplantation; i.th., intrathecal
See this image and copyright information in PMC

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