T-Cell Large Granular Lymphocyte Leukemia of Donor Origin Following Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Myeloid Leukemia.
Authors: Rabinowits Guilherme , Herzig Roger H. , Herzig Geoffrey P. 
Published: October 2019

Abstract
Lymphoproliferative disorders are a recognized complication of allogeneic hematopoietic cell transplantation (HCT). Most are B-cell disorders, often associated with Epstein-Barr virus infection. We report the fourth case of T-cell, large granular lymphocyte leukemia. In May 2005, a 63-year-old woman with acute myeloid leukemia in first relapse underwent reduced intensity, myeloablative, allogeneic peripheral blood HCT from her HLA-genotypically matched brother. Three months later, she received a donor-lymphocyte infusion (DLI) for recurrent leukemia. She developed acute graft-versus-host disease (GvHD) and remission of leukemia. GvHD was controlled with high-dose steroids. Multiple episodes of asymptomatic cytomegalovirus viremia were treated with pre-emptive valganciclovir. In June 2006, 10 months post-DLI, PCR-based chimerism studies revealed 100% donor peripheral blood cells. One month later, immunophenotyping of peripheral blood to evaluate neutropenia and lymphocytosis, revealed expansion of CD3+, CD8+, CD2+, CD11c+ and HLA-DR+ lymphocytes with clonally rearranged T-cell receptor genes, consistent with the diagnosis of large granular lymphocyte (LGL) leukemia. Evaluation of her donor, including bone marrow aspiration and biopsy, showed normal hematopoiesis with no evidence of LGL expansion. PCR of donor peripheral blood mononuclear cells was negative for TCRγ rearrangements. During the year since diagnosis of T-cell LGL leukemia the CBC has been stable, without specific treatment, and AML remains in remission.
Discussion: lymphocytosis due to expansion of T-cell large granular lymphocytes is a rare occurrence after allogeneic HCT. Non-clonal expansion is more common, with 6 cases described in a series of 201 patients (Mohty et al. Leukemia2002; 16:2129–33). To our knowledge, this is the fourth documented case of donor-derived T-cell LGL leukemia (clonal expansion) after allogeneic HCT. The course of post-transplant LGL leukemia appears to resemble de novo disease. Of the previously reported cases, 2 patients were alive 6 and 18 months (Chang et al. Am J Clin Pathol2005; 123:196–9), and 1 died 7 months post-LGL leukemia diagnosis (Au et al. Am J Clin Pathol 2003; 120:626–30). Our patient is 12 months since diagnosis without therapy. Etiologic factors responsible for post-transplant LGL leukemia have not been identified. In all cases tested, the leukemia arose in donor cells, but was not transmitted from the donor. An association between long-term antigenic stimulation due to GvHD or viral infection has been proposed. Our patient had both GvHD and recurrent CMV viremia before developing T-cell LGL leukemia. Of interest, our patient experienced long-lasting complete remission of AML after DLI. Whether the T-cell LGL leukemia, which developed almost one year after DLI, has any impact on maintaining remission (graft-versus-leukemia effect) is unknown, but has been suggested by other authors.