Twenty-Six-Year Follow-up of Donor-Derived Del(20q) after Allogeneic Hematopoietic Cell Transplantation

Deletion of the long arm of chromosome 20 (del(20q)) is the most prevalent large structural genetic abnormality in older adults and is associated with a potential for malignant transformation. While del(20q) has been reported in donor-derived cells after allogeneic hematopoietic cell transplantation (HCT), its long-term clinical impact remains unclear. Here we report 26-year follow-up of a patient with refractory angioimmunoblastic T cell lymphoma who received HCT from her HLA-identical sister, where the donor was subsequently diagnosed with early myelodysplastic syndrome with del(20q). Early analysis at 18 and 158 days post-HCT showed donor cell engraftment with del(20q) in the recipient (Mielcarek British J. Hematology 1999) (Fig 1). Subsequent analysis at 3 & 7 years post-HCT was previously reported (Mielcarek Blood 2006; Fig 1). In this current follow-up, recipient blood cells were analyzed at 20- and 26-years post-HCT using fluorescent in situ hybridization (FISH) with a del(20q) probe. We also conducted next-generation sequencing on donor DNA from time of HCT and recipient blood mononuclear cells at 20- and 26-years (Thermo Fisher Scientific Oncomine Myeloid MRD Assay). At 20 and 26-years post-HCT, FISH showed sustained high-level del(20q) positivity in myeloid cell fractions (CD14+/CD33+, CD33+/CD14-); lymphoid cell fractions (CD19+ and CD3+) showed lower levels of positivity (Figure 1). Despite the persistence of del(20q), the recipient remains clinically stable, in remission of lymphoma and without evidence of myeloid malignancy. Oncogenic and likely oncogenic variants detected include one DNMT3A and 4 TP53 variants in the donor baseline DNA; these were also detected in one or both post-HCT time points in the recipient at low levels (<2%). These subclones remained stable over 26 years and do not expand over time (Table 1). This case demonstrates that long-term donor-engrafted del(20q) may remain a cytogenetic abnormality without clinical significance, even in the presence of multiple donor-derived somatic mutations in TP53 and DNMT3A . To contextualize our findings, we conducted a literature review of del(20q) in donor-derived cells post-HCT, creating the largest collection of such cases to date (n=20) (Table 2). Seven (35%) cases of donor-cell myeloid malignancies were reported in recipients at a median of 1.8 (range, 0.6-7.4) years post-HCT. Although the duration of reported follow-up was limited, most patients followed a benign course, similar to our case. The risk of developing donor-derived myeloid malignancy in this setting is likely influenced by presence of concurrent mutations, but the mutation load at which myeloid malignancy develops is unclear. Further study of the clonal evolution of donor-engrafted del(20q) post-HCT is of interest.