Umbilical cord blood transplantation induces a durable remission in hepatosplenic gamma‐delta T cell lymphoma with associated hemophagocytic lymphohistiocytosis
Authors: Ernesto Ayala, Jean Chalhoub, Mohamed A. Kharfan‐Dabaja
Journal: American Journal of Hematology (2014)

To the Editor: Umbilical cord blood transplantation is an alternative for hematopoietic cell allografting when Human Leukocyte Antigen compatible siblings or unrelated donors are unavailable1, 2. For adults, transplantation using two cord units is frequently necessary 3-5 and literature demonstrates that double umbilical cord blood transplantation (DUCT) yields durable remissions 1, 5, 6. Data on DUCT in hepatosplenic gamma-delta T-cell lymphoma with hemophagocytic lymphohistiocytosis (HLH) are limited to case reports 7, 8. We describe a 22-year-old woman with hepatosplenic gamma-delta lymphoma with hemophagocytosis treated with DUCT. She presented with B-symptoms, severe anemia, and thrombocytopenia. Bone marrow (BM) flow-cytometry showed an abnormal T-cell population of intermediate size expressing gamma-delta T-cell receptor (coexpression of CD45 and CD3, aberrant expression of CD16 and CD56, intermediate CD2 and CD7, decreased CD8 and aberrant loss of CD5 expression). Cytogenetics showed a female karyotype. She had hepatomegaly, splenomegaly (25 cms), but no radiologic evidence of lymphadenopathy. Splenectomy showed diffuse infiltration by atypical T-cells with identical BM phenotype. FISH of splenic cells showed rearrangement or extracopies of 7q31 but no Epstein–Barr virus. She had elevated liver enzymes and lactate dehydrogenase 2217 (range: 313–618) U/L. Serum ferritin level was 12100 (range: 6–137) ng/mL. Serology for hepatitis B, C, HIV I/II, and HTLV I/II were negative. BM biopsy showed hemophagocytosis. She received three cycles of etoposide, solumedrol, cytarabine, and cisplatinum; but due to persistent fevers, elevated ferritin, and elevated triglycerides, therapy was changed to ifosfamide, carboplatin, and etoposide, given for two cycles. Fevers persisted and repeat BM biopsies showed low-level (5%) persistent lymphoma. CT scans demonstrated persistent hepatomegaly with heterogeneous enhancement suggesting lymphomatous involvement. Serum ferritin level remained elevated (16400 ng/mL), prompting treatment with dexamethasone and etoposide with rapid resolution of fevers and improved performance 9. She started a conditioning regimen of fludarabine 30 mg/m2/day (days −6 to −2), cyclophosphamide 50 mg/kg (day −6), thiotepa 5 mg/kg (days −5, −4) and TBI 200 cGy/day (days −2, −1), followed by DUCT 10. Cord units were HLA-A, C, and DRB-1 antigen-mismatched (5/8) and CD34 cell dose/kg (recipient body weight) were: unit 1 = 13.5 × 104, unit 2 = 6.03 × 104. GVHD prophylaxis entailed cyclosporine and mycophenolate mofetil. Neutrophil and platelet engraftment occurred on days +32 and +43, respectively. Post-transplant course was complicated by HHV-6 reactivation resolving with foscarnet. On day +52, she was readmitted for steroid-responsive gastrointestinal acute GVHD. On day +56, she developed adenovirus and CMV viremia requiring cidofovir and valgancyclovir, later complicated by renal failure. BM analysis on days +96 and +251 showed resolution of lymphoma. Serial contrasted CT scans confirmed resolution of hepatomegaly and ferritin level decreased (1750 ng/mL) (Fig. 1). She remains in remission from her lymphoma and HLH 412 days later. Ferritin levels in ng/mL over time. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] DUCT is a promising therapy for hepatosplenic gamma-delta T cell lymphoma with associated HLH. There is reported increased risk of graft failure and transplant-related mortality from organ injury due to HLH 11. Notwithstanding the relatively short follow-up, the sustained response in our case is noteworthy considering that three lines of therapy were needed to achieve an objective response and had measurable disease before DUCT. Ernesto Ayala1,2, Jean Chalhoub1, AND Mohamed A. Kharfan-Dabaja1,2 1Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida; 2Department of Oncologic Sciences, Moffitt Cancer Center/University of South Florida College of Medicine, Tampa, Florida