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Donor-derived constitutional chromosomal abnormalities after allogeneic hematopoietic cell transplantation: a single-center experience and a review of the literature

Bone Marrow Transplantation volume 50, pages 1388–1392 (2015)Cite this article

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Allogeneic hematopoietic cell transplantation (HCT) represents the only curative treatment modality for patients with hematological malignancies. Disease risk stratification in various hematological malignancies incorporates cytogenetic aberrations and novel molecular abnormalities to help discern those who are anticipated to have a more aggressive course. As a result, treatment algorithms have evolved that dictate offering front-line allogeneic HCT to eligible candidates. Periodic karyotypic analysis remains an important disease assessment tool coupled with engraftment chimerism analysis post-HCT. Comparison to pre-HCT karyotype allows for detection of early cytogenetic relapse or persistence of the malignant clone present at the time of allografting. Rarely, a novel karyotypic abnormality may be identified in the course of post-HCT assessment. Such incidental chromosomal changes pose a significant clinical challenge and a therapeutic dilemma given that they may indicate clonal evolution, laboratory error or an incidental finding of donor-derived constitutional chromosomal abnormalities. Here we present four allogeneic HCT recipients in whom donor-derived constitutional chromosomal aberrations were identified during post-transplant evaluation.

The patient population included those who underwent an allogeneic HCT at the Moffitt Cancer Center between 1 January 2004 and 31 December 2014 and those with constitutional chromosomal abnormalities following allogeneic HCT were identified. All recipients underwent periodic chimerism analysis at approximately 1, 3, 6 and 12 months after allogeneic HCT based on standard protocol. The baseline patient characteristics at allogeneic HCT are summarized (Table 1). This study was conducted with approval from the Liberty IRB Institutional Review Board and in compliance with the Declaration of Helsinki. We identified four cases of donor-derived constitutional chromosomal abnormalities discovered after receiving an allogeneic HCT, summarized in Table 1. The median ages of recipients and donors were 71 (range, 29–75) and 33 (range, 27–42) years, respectively. Indications for allogeneic HCT were myelodysplastic syndrome (refractory anemia with excess blasts-2: n=2), acute myeloid leukemia (n=1) and acute lymphoblastic leukemia (n=1). All four cases received peripheral blood stem cell grafts from HLA-matched unrelated donors. Preparative regimens were either busulfan/fludarabine or fludarabine/melphalan. Two patients received myeloablative preparative regimens. Three of the four patients received tacrolimus/sirolimus as GVHD prophylaxis regimen.

Table 1 Clinical characteristics of four cases of presumed donor-derived constitutional chromosomal abnormalities after allogeneic HCT
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Author notes

  1. T Nishihori and J El-Asmar: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA

    T Nishihori, J El-Asmar, C Anasetti & M A Kharfan-Dabaja

  2. Department of Oncologic Sciences, Moffitt Cancer Center/University of South Florida Morsani College of Medicine, Tampa, FL, USA

    T Nishihori, B Shah, M Hussaini, R Komrokji, A List, C Anasetti & M A Kharfan-Dabaja

  3. Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    J El-Asmar

  4. Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA

    B Shah, R Komrokji & A List

  5. Department of Hematopathology, Moffitt Cancer Center, Tampa, FL, USA

    M Hussaini

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  1. T Nishihori
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Correspondence to M A Kharfan-Dabaja.

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Nishihori, T., El-Asmar, J., Shah, B. et al. Donor-derived constitutional chromosomal abnormalities after allogeneic hematopoietic cell transplantation: a single-center experience and a review of the literature. Bone Marrow Transplant 50, 1388–1392 (2015). https://doi.org/10.1038/bmt.2015.168

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