Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

Abstract

A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML) which harbored del(11q23) in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT) from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14) and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23). Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity.In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.

Donor Cell–Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review

“…The status of the donor at the moment of DCHN diagnosis in the recipient was reported in 73 cases: 62 donors (85%) were healthy, 9 donors (12%) had developed hematologic malignancies, and 2 donors (3%) had nonhematologic cancers (breast cancer and bronchogenic carcinoma). Only a handful of DCHN cases reported (11/137) [11,12,15,16,[24][25][26][27][28][29] included detailed molecular studies in both donors and recipients (Table 2). Interestingly, in these cases at least 1 of the mutations detected in leukemic cells at the moment of DCHN diagnosis was also found in the donor.…”

Stem cell donors should be screened for CHIP

“…24 Even though the etiology of DCL is not entirely clear, the growing body of literature suggest that preexisting somatic or predisposing germline mutations play a key role in this process. [25][26][27][28][29][30][31] In addition to clinically apparent donor-derived malignancies, donor age was also associated with significantly higher rate of unexplained posttransplant cytopenias, particularly when donors with preexisting CHIP were used. 32 In both instances, low-level CHIP clones not only engrafted but also outcompeted nonclonal counterparts during early hematopoietic reconstitution.…”

Individual capacity for repair of DNA damage and potential uses of stem cell lines for clinical applications: a matter of (genomic) integrity

“…In patients with transplantations of HPSCs, there is always a risk of recurrence of the original tumour and for development of secondary malignancies, the risk being slightly higher in patients that have received autologous grafts [9]. There is already a report that grafts carrying variant alleles of genes coding for proteins of DNA repair (specifically, the rs1052559 polymorphism in the XPD (ERCC2) gene and rs861539 in the XRCC3 gene) may be associated with higher risk of development of secondary leukemia [25].…”