Loss of D expression associated with hematologic disease progression: a case report and review of the literature

We report a case of a 61-year-old male patient with a complex hematologic history including pre-B acute lymphocytic leukemia, allogeneic stem cell transplant, and newly treated colon cancer followed by diagnosis of high-risk myelodysplastic syndrome (MDS), who exhibited abolishment of D antigen production. The patient’s red blood cells (RBCs), which originally typed as group A, D+, again typed as group A, D+, after receiving stem cells from a female donor with the same blood type. The reactivity of the patient’s RBCs was strong when tested with anti-D reagent until he was treated for colon cancer. Within 6 months of diagnosis of cancer, he developed a mixed-field D typing result followed by a complete D– phenotype over the course of a few weeks, coinciding with the new diagnosis of MDS and initiation of immunosuppressive therapy. Polymerase chain reaction (PCR) testing revealed no weak or partial D variants, and subsequent Sanger sequencing confirmed the presence of a conventional RHD gene. A more focused analysis by chromosomal microarray identified deletions involving the RHD locus, supporting the hypothesis that active MDS disrupted gene expression. The patient received another stem cell transplant, this time from a group AB, D+ male donor. In a short period of time, MDS re-emerged along with re-identification of microarray mutations encompassing RHD in female cells (from the first donor) even after the second stem cell transplant. However, D expression remained strong, underscoring the presence of enough male donor RHD expression to maintain the D+ phenotype.