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Wolfgang Miesbach: Gene Therapy-Associated Leukaemia With Clonal Persistence Over 16 Years

Wolfgang Miesbach, Michael Rothe/LinkedIn

Oct 30, 2026, 13:42

Wolfgang Miesbach: Gene Therapy-Associated Leukaemia With Clonal Persistence Over 16 Years

Wolfgang Miesbach, Head of Hemostasis/Hemophilia Center at Medical Clinic 2 at University Hospital Frankfurt, shared a post on LinkedIn:

“Four years old at gene therapy. Dead of the same clone sixteen years later.

ESGCT 2026.

Michael Rothe and colleagues from Hannover Medical School presented the full 16-year course of patient WAS4 from the Wiskott–Aldrich syndrome trial (Braun et al., Sci Transl Med 2014).

The therapy: autologous CD34+ cells transduced with C MMP.WASP, a gammaretroviral vector with an intact LTR driving the transgene. 24.9 × 10⁶ CD34+ cells/kg, vector copy number 3.2. Eight of nine treated patients later developed leukaemia through insertional mutagenesis.

WAS4 was four at infusion. MDS at 4.7 years, AML at 9.2 years, matched-unrelated transplant, then a haploidentical graft from his mother, fatal AML at 16.1 years.

The leukaemic cells are vector-positive and the dominant clones are defined by their integrations, PRDM16 among them.

The fatal clone was the one already detectable at 4.7 years. It survived both transplants.

Highest vector copy numbers in the CD34-enriched fractions. Dominant integrations in TLE3, PRDM16, CD300A and SNX12.

The earlier AML clone sat in the marrow only. Peripheral blood never showed it.

The authors’ conclusions are practical: integration site analysis on blood alone can miss what lives in the marrow, and clone-specific ddPCR belongs in follow-up once a vector-associated leukaemia has occurred.”

Wolfgang Miesbach: Gene Therapy-Associated Leukaemia With Clonal Persistence Over 16 Years