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Undetectable leukemic blasts and absence of NOD/SCID leukemia-initiating cells in cord blood from a case of maternal AML

Bone Marrow Transplantation volume 36, pages 269–270 (2005)Cite this article

Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells in allogeneic transplantation for patients lacking HLA-matched donors. Widespread banking of UCB is increasing worldwide and has generated new issues in the assessment of graft adequacy. The presence of maternal cells in UCB has been previously documented although the ability to confer disease-related phenotypes in the infant is unknown.1 Transplantation of UCB containing maternal T-lymphocytes or malignant leukemic cells could increase the risk of graft-versus-host disease (GVHD) or leukemia in the recipient. We report a case of AML occurring in a pregnant female and our efforts to identify contaminating leukemic cells in the UCB are described. Our case illustrates an uncommon but important issue in the quality assurance of stem cell grafts.

A 21-year-old female patient developed AML (FAB subtype M0) at 35 weeks gestation. She developed peripheral pancytopenia associated with a bone marrow aspirate containing greater than 30% CD33(+)CD19(+) leukemic blasts. Cytogenetic studies revealed a normal female karyotype. Cytotoxic chemotherapy was withheld until spontaneous vaginal delivery occurred 2 weeks later. Initial bloodwork of the newborn boy revealed a normal complete blood count and differential. Immunophenotype analysis of the peripheral blood and UCB specimens was also normal with no detectable CD33(+)CD19(+) population. Cytogenetic analysis of 200 metaphase UCB cells revealed only normal male karyotype and no maternal (46, XX) cells. Tail vein injection of unfractionated UCB cells into seven irradiated (350 Gy) 11-week-old NOD/SCID mice (1.0–5.0 × 107 mononuclear cells (post-Ficoll) or 5.0 × 107 buffy coat cells per mouse) produced high levels of multilineage human engraftment (11–54% human cells in flushed bone marrow) in recipient animals killed 6 weeks after transplantation. No detectable human leukemic cells coexpressing CD33 and CD19, however, were detected. Transplantation of 3.0 × 105 lineage-depleted mononuclear UCB cells (StemSep 2a antibody cocktail, Stem Cell Technologies, Vancouver, Canada) likewise yielded significant multilineage human engraftment in two mice with no identifiable leukemic cells on flow cytometric analysis. The male child remains well at 22 months of age. The patient underwent successful allogeneic transplantation in CR2 with an HLA-matched unrelated donor.

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Authors and Affiliations

  1. Division of Hematology, London Health Sciences Centre, London, Ontario, Canada

    D S Allan, M Keeney, I Chin-Yee & A Xenocostas

  2. University of Western Ontario, London, Ontario, Canada

    M Bhatia, I Chin-Yee & A Xenocostas

  3. Robarts Research Institute, London, Ontario, Canada

    D S Allan, L Gallacher & M Bhatia

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  1. D S Allan
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  2. L Gallacher
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  3. M Keeney
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Allan, D., Gallacher, L., Keeney, M. et al. Undetectable leukemic blasts and absence of NOD/SCID leukemia-initiating cells in cord blood from a case of maternal AML. Bone Marrow Transplant 36, 269–270 (2005). https://doi.org/10.1038/sj.bmt.1705035

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