Successful treatment of early onset Epstein-Barr virus-negative T-cell lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation with histone deacetylase inhibitor chidamide
Post-transplant lymphoproliferative disorder (PTLD) is one of the most life-threatening complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a 3-year survival rate as low as 20%. Most cases involve B cells, but T-cell PTLD—especially when it strikes early and is Epstein-Barr virus (EBV)-negative—is extremely rare. A case report from researchers at Zhejiang University School of Medicine highlights how a histone deacetylase inhibitor (HDACi) called chidamide helped a patient overcome this aggressive condition.
The patient, a 58-year-old man diagnosed with chronic myelomonocytic leukemia in June 2019, achieved complete bone marrow remission after five cycles of decitabine chemotherapy (35 mg/day for 5 days). In December 2019, he underwent allo-HSCT from his HLA-haploidentical daughter—both donor and recipient were EBV-negative before transplant. He received a myeloablative conditioning regimen (cytarabine, busulfan, cyclophosphamide, methyl-N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, anti-thymocyte globulin) and graft-versus-host disease (GVHD) prophylaxis with cyclosporin A (switched to tacrolimus on day +15 due to gastrointestinal side effects) and mycophenolate mofetil (MMF). Neutrophil and platelet engraftment occurred on days +12 and +18, respectively, with complete donor chimerism confirmed on day +26.
Trouble began early: on day +20, he developed recurrent fevers (peak 40°C) with no evidence of bacterial or viral infection. Labs showed elevated lactic dehydrogenase (LDH: 170 to 270 U/L) and slightly high hypersensitive C-reactive protein (19.1 mg/L), but normal procalcitonin and immunoglobulin M. Ferritin was mildly elevated (2069.6 ng/mL vs. 1795.3 ng/mL pre-transplant). A lung CT was normal. By day +25, he had left cervical lymphadenopathy that rapidly spread to both sides. Ultrasound revealed multiple enlarged nodes in the neck and axilla. Two cervical lymph node biopsies (days +30 and +40) confirmed EBV-negative T-cell PTLD: immunohistochemistry showed positive staining for T-cell markers (CD3, CD43, CD5, CD8) and T-cell intracellular antigen-1 (TIA-1), with a Ki-67 proliferation index of ~60%. T-cell receptor gene rearrangement was positive, and EBV in situ hybridization (using Epstein-Barr-encoded RNA, EBER) was negative. PET-CT on day +42 showed increased FDG uptake only in the neck and axillary nodes, with no other abnormalities.
Immunosuppressants (tacrolimus, MMF) were discontinued immediately. Dexamethasone (10 mg/day) and ruxolitinib (5 mg/day) were started to control fever and prevent GVHD—his temperature normalized, but lymphadenopathy persisted. Increasing ruxolitinib to 10 mg/day (day +45) had no effect. On day +49, he received the CHOPE chemotherapy regimen (etoposide 100 mg on days 1, 3, 5; dexamethasone 10 mg days 1–5; vindesine 4 mg day 1; cyclophosphamide 600 mg day 1; liposomal doxorubicin 20 mg day 1). The lymphoid lesions decreased, but he developed severe myelosuppression (white blood cells [WBC] dropped to 0.7 × 10⁹/L, platelets to 40 × 10⁹/L). Worse, by day +64, the lymphadenopathy returned.
That’s when the team turned to chidamide, a HDACi approved in China for relapsed/refractory peripheral T-cell lymphoma (PTCL). Starting on day +66, he received 30 mg of chidamide biweekly. Within three weeks, the enlarged nodes resolved completely. Chidamide was stopped after four weeks, and his WBC and platelet counts—briefly reduced to 2.8 × 10⁹/L and 38 × 10⁹/L—recovered within two weeks. As of 13 months post-transplant, he has had no recurrence.
PTLD typically develops 5 months after HSCT, but this patient’s onset at day +25 is unprecedented for T-cell PTLD. Most PTLDs are EBV-positive and B-cell derived; T-cell PTLD accounts for just 7–15% of cases. Chidamide, which targets histone deacetylation to regulate gene expression in cancer cells, has shown promise in relapsed/refractory PTCL: a 2015 phase II study in 79 Chinese patients found 14% achieved complete response (CR), with a median progression-free survival of 2.1 months and overall survival of 21.4 months.
This case highlights the challenge of early-onset EBV-negative T-PTLD post-HSCT—and the potential of chidamide as a treatment option. The patient achieved complete response with minimal, reversible side effects, even after chemotherapy failed. Timely lymph node biopsy was critical for diagnosis. While more research is needed to confirm chidamide’s long-term efficacy in this setting, this case offers hope for patients with this rare, aggressive complication.
This study was originally published in the Chinese Medical Journal (2021;134:2756–2758) by Hua-Rui Fu, Ting-Ting Yang, Yan-Min Zhao, Ya-Min Tan, Qi-Qi Gao, He Huang, and Ji-Min Shi from the First Affiliated Hospital, Institute of Hematology, and Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy at Zhejiang University School of Medicine, and Zhejiang University School of Medicine.
doi.org/10.1097/CM9.0000000000001488
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