Evolutionary genomic analysis for ALL

Article Medicine, General & Internal

Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia

Inge M. van der Sluis et al.

Summary: Blinatumomab added to Interfant-06 chemotherapy appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged ALL as compared with historical controls from the Interfant-06 trial.

NEW ENGLAND JOURNAL OF MEDICINE (2023)

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Article Oncology

Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy

Tim H. H. Coorens et al.

Summary: Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment.

NATURE CANCER (2023)

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Article Hematology

KIR-favorable TCR-αβ/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial

Michael A. Pulsipher et al.

Summary: A prospective multicenter study was conducted to evaluate the use of TCR-alpha beta/CD19-depleted haploidentical donors in hematopoietic cell transplantation for children with acute leukemia and MDS. The study showed improved outcomes in terms of disease-free survival and overall survival, especially in younger patients, those treated with reduced toxicity conditioning, and children with minimal residual disease before transplantation.

BLOOD (2022)

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Meeting Abstract Hematology