Graft-versus-lymphoma effect in progressive hepatosplenic gamma/delta T-cell lymphoma
Graft-versus-lymphoma effect in progressive hepatosplenic gamma/delta T-cell lymphoma
复制标题
进行性肝脾 γ/δ T 细胞淋巴瘤的移植物抗淋巴瘤效应
作者：
Simon Z. He;A. Roberts;D. Ritchie;A. Grigg
肝脾γ/δ T细胞淋巴瘤（HSTCL）是一种罕见的临床病理实体，具有独特的特征，包括年轻男性为主、脾肿大、血小板减少和骨髓浸润[1]。 HSTCL 已被认为是实体器官移植和炎症性肠病长期免疫抑制治疗的并发症[2,3]。由于完全缓解 (CR) 率低于 50%，且早期复发率较高，导致中位生存期为 16 个月，因此结果较差[1]。对于进行性或复发性疾病的挽救性治疗选择很少。 20-脱氧考福霉素已被证明对体内和体外 g/d T 细胞淋巴瘤具有特异性活性 [4,5]。据报道，阿仑单抗与挽救疗法一样有效[6]。据报道，同种异体移植后疾病生存期延长[7]，但尚不清楚这是否代表清髓性条件作用或特定的移植物抗 HSTCL 效应。以下病例通过中期随访证明了明确的移植物抗 HSTCL 效应，表明这种疾病容易受到免疫介导的细胞毒性的影响。一名 39 岁的白人男性因克罗恩病长期接受免疫抑制治疗，于 2006 年 1 月就诊，出现发烧、肝脾肿大、全血细胞减少和葡萄球菌败血症。肝脏和骨髓活检显示血窦中有明显的非典型淋巴浸润，免疫表型（CD2+、CD3+、CD47、CD57 和 CD87）和 T 细胞受体 g 链基因重排与 HSTCL 一致。正电子发射断层扫描（PET）证实脾脏受累。一个周期的 hyperCVAD [8] 并发严重假单胞菌脓毒症产生了部分反应，随后疾病迅速进展。使用异环磷酰胺、卡铂和依托泊苷进行一个周期的挽救性化疗仅取得短暂反应。 2006 年 6 月，在使用依托泊苷 (60 mg/kg) 和全身照射 (1320 cGy) 进行调理后，他接受了 HLA 匹配兄弟的外周干细胞同种异体移植。移植时，外周血涂片中观察到循环淋巴瘤细胞，血清乳酸脱氢酶（LDH）升高至 2839 IU/l（参考范围 210 – 420 IU/l）。他出现了 IV 级粘膜炎、需要有创通气支持的严重呼吸窘迫以及急性少尿性肾功能衰竭。在 G-CSF 支持下，第 16 天发生粒细胞植入。第 31 天的重新分期骨髓活检显示大约 10 – 15% 的持续性疾病受累（图 1），并且他出现了嗜睡恶化、全血细胞减少、进行性脾肿大以及 LDH 迅速增加至 5977 IU/l。他的由环孢素和泼尼松龙组成的免疫抑制方案在第 35 天迅速断奶并停止。第 40 天出现皮肤移植物抗宿主病 (GVHD)。GVHD 的发作暂时与 LDH 的逐渐下降相关（图 2）。第 59 天的计算机断层扫描显示脾肿大已消退。 Day-59 骨髓
Hepatosplenic gamma/delta T-cell lymphoma (HSTCL) is a rare clinicopathologic entity with distinctive characteristics including young male predominance, splenomegaly, thrombocytopenia, and bone marrow infiltration [1]. HSTCL has been recognised as a complication of long-term immunosuppressive therapy in solid organ transplantation and for inflammatory bowel disease [2,3]. The outcome is poor due to a complete remission (CR) rate less than 50% and a high rate of early relapse resulting in a median survival of 16 months [1]. Salvage therapeutic options for progressive or relapsed disease are few. 20-deoxycoformycin has been shown to have specific activity against g/d T-cell lymphoma both in vivo and in vitro [4,5]. Alemtuzumab has been reported as effective as salvage therapy [6]. Prolonged disease survival has been reported following allogeneic transplantation [7], but it is not clear whether this represents the effect of myeloablative conditioning or a specific graftversus-HSTCL effect. The following case demonstrates an unequivocal graft-versus-HSTCL effect with medium-term follow-up, suggesting that this disease is susceptible to immunologically mediated cytotoxicity. A 39-year-old Caucasian man on long-term immunosuppression for Crohn’s disease presented in January 2006 with fever, hepatosplenomegaly, pancytopenia, and Staphylococcal sepsis. Liver and bone marrow biopsies revealed prominent atypical lymphoid infiltrate in sinusoids with an immunophenotype (CD2þ, CD3þ, CD47, CD57, and CD87) and T-cell receptor g chain gene rearrangement consistent with HSTCL. Positron emission tomography (PET) confirmed splenic involvement. One cycle of hyperCVAD [8] complicated by severe Pseudomonas sepsis produced a partial response with subsequent rapidly progressive disease. Salvage chemotherapy with one cycle of ifosfamide, carboplatin, and etoposide achieved only a transient response. In June 2006, he underwent a peripheral stem cell allograft from his HLA-matched brother, after conditioning with etoposide (60 mg/kg) and total body irradiation (1320 cGy). At the time of transplant, circulating lymphoma cells were observed in the peripheral blood film with an elevated serum lactate dehydrogenase (LDH) of 2839 IU/l (reference range 210 – 420 IU/l). He developed grade IV mucositis, severe respiratory distress requiring invasive ventilatory support, and acute oliguric renal failure. Granulocyte engraftment occurred on Day 16 with G-CSF support. A restaging bone marrow biopsy on Day 31 revealed approximately 10 – 15% persistent disease involvement (Figure 1), and he developed worsening lethargy, pancytopenia, progressive splenomegaly, and a rapidly increasing LDH to 5977 IU/l. His immunosuppressive regimen consisting of cyclosporin and prednisolone was rapidly weaned and discontinued by Day 35. Cutaneous graft-versus-host disease (GVHD) appeared on Day 40. The onset of GVHD was temporally associated with a progressive fall in LDH (Figure 2). A computerized tomography scan on Day 59 demonstrated resolution of splenomegaly. A Day-59 bone marrow
影响因子：
20.3
作者：
Yang, YG;Qi, J;Sykes, M
通讯作者：
Sykes, M