Autologous and allogeneic
hematopoietic stem cell transplantation (HSCT) has revolutionized the
therapy of hematolymphoid
malignancies. Yet, how to best detect or predict the emergence of HSCT-related complications remain unresolved. Here, we describe a case of donor-derived, transient Alpha Beta (αβ) T-cell large granular clonal
lymphocytosis and
cytopenia that emerged post-HSCT in a patient with a history of gamma delta (γδ)
T-cell large granular lymphocytic leukemia (T-LGLL). Clonal unrelatedness of post-transplant T-LGL
lymphocytosis to the patient's pretransplant T-LGLL was first identified by
T-cell receptor (TCR) PCR showing different sized fragments of rearranged gamma chains, in addition to shift from γδ to αβ TCR expression by flow cytometry analyses. Donor-derivation of the patient's post-transplant clonal
lymphocytosis was confirmed by serial chimerism analyses of recipient's blood specimens demonstrating 100% donor
DNA. Moreover, oncogenic DNMT3A and RUNX1 mutations were detected by next-generation sequencing (NGS) only in post-transplant specimens. Intriguingly, despite continued increase in DNMT3A and RUNX1 mutation load, the patient's clonal
lymphocytosis and
anemia eventually largely resolved; yet, the observed mutation profile with persistent
thrombocytopenia indicated secondary clonal cytopenia of undetermined significance (CCUS) in the absence of overt morphologic evidence of myeloid
neoplasm in the marrow. This case illustrates the utility of longitudinal chimerism analysis and NGS testing combined with flow cytometric immunophenotyping to evaluate emerging donor-derived hematolymphoid processes and to properly interpret partial functional engraftment. It may also support the notion that driver mutation-induced microenvironmental changes may paradoxically contribute to reestablishing tissue homeostasis.