# Hemopoietic stem cell transplantation for infectious mononucleosis-related aplastic anemia

**Authors:** Stefano Cordella, Andrea Gilioli, Valeria Pioli, Andrea Messerotti, Fabio Forghieri, Francesca Bettelli, Monica Morselli, Luca Cassanelli, Leonardo Potenza, Roberto Marasca, Paola Bresciani, Angela Cuoghi, Mario Luppi

PMC · DOI: 10.1007/s00277-026-06746-2 · Annals of Hematology · 2026-03-04

## TL;DR

A young woman with aplastic anemia following a mild Epstein-Barr virus infection was successfully treated with stem cell transplantation and rituximab.

## Contribution

This is the second reported case of EBV-related aplastic anemia successfully treated with HLA-matched sibling donor hematopoietic stem cell transplantation.

## Key findings

- The patient achieved transfusion independence and stable hematologic recovery two years post-transplantation.
- Pre-emptive rituximab administration effectively controlled EBV reactivation after HSCT.
- Mixed chimerism persisted with no signs of graft-versus-host disease.

## Abstract

We report the case of a young woman who developed aplastic anemia (AA), following a serologically confirmed primary Epstein–Barr virus (EBV) infection, occurring with fever and pharyngotonsillitis, in the absence of either palpable lymph nodes or enlarged spleen. Pancytopenia persisted after EBV DNA clearance, requiring multiple red blood cell and platelet transfusions. Given the availability of a human leukocyte antigen (HLA)-matched sibling donor (MSD), hematopoietic stem cell transplantation (HSCT) from bone marrow source was performed after a non-myeloablative conditioning regimen with cyclophosphamide and thymoglobulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and methotrexate. EBV reactivation occurred, one month post-HSCT, peaking at 28,838 DNA copies/ml in peripheral blood, without evidence of post-transplant lymphoproliferative disorder. Two pre-emptive doses of rituximab were administered, resulting in sustained EBV DNA negativity. Subsequent bone marrow evaluation showed normal cellularity and restoration of peripheral counts. After two years of follow-up, the patient remains transfusion-independent, with stable hematologic recovery, no signs of GVHD, and persistent mixed chimerism (70–75% host cells in peripheral blood; about 60% donor CD3 + lymphocytes). To our knowledge, this is the only second reported case of EBV-related AA successfully treated with MSD HSCT. This case underscores the importance of assessing EBV serology in all patients with AA, since EBV infection may be mild or subclinical, and highlights the efficacy of early rituximab administration in high-level EBV DNA reactivation after transplantation.

## Linked entities

- **Chemicals:** cyclophosphamide (PubChem CID 2907), cyclosporine A (PubChem CID 5284373), methotrexate (PubChem CID 4112)
- **Diseases:** aplastic anemia (MONDO:0013879), Epstein-Barr virus infection (MONDO:0005111), graft-versus-host disease (MONDO:0013730), post-transplant lymphoproliferative disorder (MONDO:0019088)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, CD34 (CD34 molecule) [NCBI Gene 947], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}
- **Diseases:** pernicious anemia (MESH:D000752), fever (MESH:D005334), Bone marrow failure syndromes (MESH:D000080983), hypofibrinogenemia (MESH:D000347), autoimmune thyroiditis (MESH:D013967), lymphadenopathies (MESH:D008206), infectious mononucleosis (MESH:D007244), PTLD (MESH:D008232), Bone marrow aplasia/hypoplasia (MESH:D019046), AA (MESH:D000741), coagulopathy (MESH:D001778), hepatosplenomegaly (MESH:C535727), graft failure (MESH:D051437), myeloid neoplasms (MESH:D009369), Pancytopenia (MESH:D010198), marrow hypoplasia (MESH:D001855), HS (MESH:C567159), GVHD (MESH:D006086), fibrosis (MESH:D005355), EBV infection (MESH:D020031), paroxysmal nocturnal hemoglobinuria (MESH:D006457), HLH (MESH:D051359), cytopenia (MESH:D006402), viral infections (MESH:D014777), dysplasia (MESH:D015792)
- **Chemicals:** acyclovir (MESH:D000212), cyclophosphamide (MESH:D003520), folate (MESH:D005492), RTX (MESH:C024353), steroids (MESH:D013256), prednisone (MESH:D011241), methotrexate (MESH:D008727), Vitamin B12 (MESH:D014805), rituximab (MESH:D000069283), triglyceride (MESH:D014280), anti (-), DEB (MESH:C007366), CsA (MESH:D016572)
- **Species:** Human parvovirus B19 (no rank) [taxon 10798], Cytomegalovirus (genus) [taxon 10358], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Homo sapiens (human, species) [taxon 9606], Leishmania (subgenus) [taxon 38568], Human immunodeficiency virus (species) [taxon 12721]

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12960299