Cytomegalovirus-driven early-onset lymphocytosis in hematopoietic allogeneic transplant mimicking a T-cell lymphoma progression

Hepatosplenic T-cell lymphoma (HSTCL) is an uncommon and highly aggressive subtype of peripheral T-cell lymphoma characterized by liver, spleen, and bone marrow involvement. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment for HSTCL, but it carries a significant risk of relapse. Cytomegalovirus (CMV) reactivation is a frequent complication after alloHSCT, particularly in patients undergoing lymphocyte-toxic therapies. A 27-year-old man diagnosed with HSTCL underwent an alloHSCT with active disease after six lines of therapy. A CMV reactivation was successfully treated with foscarnet. A sudden reappearance of symptomatic lymphocytosis (15,550/mu L) by day +20, prior to engraftment, raised suspicion of disease progression. A comprehensive diagnostic work-up revealed an oligoclonal expansion of donor lymphocytes along with complete donor chimerism, leading to an alternative diagnosis of a CMV-driven T-cell expansion. This was confirmed by an in vitro assay testing T-cell specificity against CMV. The patient achieved both complete response and complete donor chimerism despite persisting lymphocytosis, but ultimately relapsed. This case highlights the importance of diagnostic tools in understanding disease progression and guiding treatment decisions.