Successful Treatment of Early Onset Epstein-Barr Virus-Negative T-Cell Lymphoproliferative Disorder After Allogeneic Hematopoietic Stem Cell Transplantation with Histone Deacetylase Inhibitor Chidamide

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-transplantation lymphoproliferative disorder (PTLD) is a rare but life-threatening complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While the majority of PTLD cases are associated with Epstein-Barr virus (EBV) and originate from B cells, T-cell PTLD (T-PTLD) is exceedingly rare, accounting for only 7% to 15% of all PTLD cases. This article presents a detailed case study of a 58-year-old male patient who developed early onset EBV-negative T-PTLD following allo-HSCT and was successfully treated with the histone deacetylase inhibitor (HDACi) chidamide.

The patient was initially diagnosed with chronic myelomonocytic leukemia in June 2019. After achieving complete bone marrow remission following five courses of chemotherapy with decitabine, he underwent allo-HSCT in December 2019. The donor was his human leukocyte antigen-haploidentical daughter, and both the donor and host were EBV serology-negative prior to transplantation. The myeloablative conditioning regimen included cytarabine, busulfan, cyclophosphamide, methyl-N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea, and anti-thymocyte globulin. The graft contained 12.23 x 10^8 mononuclear cells/kg and 7.57 x 10^8 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was managed with cyclosporin A (CSA) and mycophenolate mofetil (MMF), with CSA later switched to tacrolimus due to a gastrointestinal reaction on day +15.

Neutrophil and platelet engraftment occurred on days +12 and +18, respectively, and cytogenetic studies confirmed complete donor chimerism by day +26. However, on day +20, the patient developed recurrent fever with temperatures peaking at 40°C. Initial investigations ruled out bacterial and viral infections but revealed elevated lactic dehydrogenase levels (from 170 to 270 U/L) and a slightly increased hypersensitive C-reactive protein level (19.1 mg/L). A lung CT scan was normal, but by day +25, the patient exhibited left cervical lymphadenopathy that rapidly progressed to bilateral lymph nodes.

Ultrasound examinations identified multiple lymphadenopathies in the neck and axilla. Lymph node biopsies performed on days +30 and +40 suggested PTLD. Immunohistochemical studies showed positive staining for CD3, CD43, CD5, CD68, CD8, Bcl-2, Bcl-6, and T-cell intracellular antigen-1, with focal positivity for CD20, CD30, and CD4. Negative staining was observed for CD10, CD34, and CD56. The Ki-67 proliferation index was approximately 60%, and gene rearrangement studies of the T-cell receptor were positive. EBV in situ hybridization was negative in tumor cells, and TB and fungi were also ruled out. A PET-CT scan on day +42 confirmed increased fluorodeoxyglucose uptake in multiple enlarged lymph nodes of the neck and axilla, leading to a final diagnosis of EBV-negative PTLD, specifically peripheral T-cell lymphoma (PTCL).

Upon diagnosis, tacrolimus and MMF were discontinued. Given the patient’s poor tolerance to chemotherapy early post-HSCT, dexamethasone (10 mg/day) combined with ruxolitinib (5 mg/day) was initiated on day +40 to control fever and prevent GVHD. While the fever temporarily subsided, lymphadenopathy persisted. By day +45, the fever recurred, prompting an increase in ruxolitinib dosage to 10 mg/day, which proved ineffective. Subsequently, on day +49, the patient was treated with a CHOPE chemotherapeutic regimen, which included etoposide (100 mg on days 1, 3, and 5), dexamethasone (10 mg on days 1–5), vindesine (4 mg on day 1), cyclophosphamide (600 mg on day 1), and liposome doxorubicin (20 mg on day 1) over five days. This regimen led to a reduction in lymphoid lesions, but the patient experienced significant myelosuppression, with WBC and platelet counts dropping to 0.7 x 10^9/L and 40.0 x 10^9/L, respectively.

By day +64, lymphadenopathy recurred, and chidamide was introduced at a dose of 30 mg biweekly starting on day +66. The patient showed gradual improvement in lymph node enlargement, with complete resolution observed three weeks later. Chidamide was discontinued after four weeks, during which the patient maintained normal body temperature. Although temporary thrombocytopenia and leukopenia occurred, with platelet and WBC counts dropping to 38.0 x 10^9/L and 2.8 x 10^9/L, respectively, these counts normalized two weeks post-chidamide withdrawal. At the time of reporting, 13 months post-HSCT, the patient remained asymptomatic with no further lymphadenopathy.

This case highlights the rarity and complexity of early onset EBV-negative T-PTLD following allo-HSCT. The successful use of chidamide, an HDAC inhibitor, in this context is particularly noteworthy. Chidamide, approved in China for relapsed/refractory PTCL, demonstrated efficacy in achieving complete remission with manageable side effects. While the patient experienced transient myelosuppression, recovery was swift upon discontinuation of the drug. This case underscores the potential of chidamide as a therapeutic option for T-PTLD, especially in patients with limited tolerance to conventional chemotherapy early post-HSCT. However, further studies are needed to validate these findings and explore the broader applicability of HDAC inhibitors in treating PTLD.

doi.org/10.1097/CM9.0000000000001488

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