Cesaro S, Pillon M, Visintin G, Putti M C, Gazzola M V, D'Amore E, Scarzello G, Zanesco L, Messina C, Rosolen A
Clinic of Pediatric Hematology Oncology, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy.
Eur J Haematol. 2005 Jul;75(1):22-6. doi: 10.1111/j.1600-0609.2005.00422.x.
The use of allogeneic stem cell transplantation in NHL patients is not yet clearly defined, especially in children and adolescents, but this option offers the advantages of a tumor-free graft and the possible induction of a graft-vs.-tumor effect.
We report the results of four consecutive pediatric patients affected by anaplastic large cell lymphoma (ALCL) and treated with allogeneic stem cell transplantation from an unrelated donor. The conditioning regimen was based on total body irradiation given in association with etoposide in three patients, and with thiotepa and cyclophoshamide in one patient. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporin, a short course of methotrexate and rabbit antithymocyte globulin.
All patients had rapid engraftment within 3-4 wk for neutrophils and platelets, and achieved a stable full donor chimerism that has been maintained to the last follow-up visit. One patient later developed a restrictive pneumonopathy. This patient had been heavily pretreated during the course of the disease having suffered four relapses and had received a cumulative dose of bleomycin of 160 mg/m(2). After a follow-up of 11-42 months, all patients are alive in complete hematological and molecular remission; and three of them without any chronic GVHD.
The increasing number of volunteer bone marrow donors and the reduced toxicity of unrelated stem cell transplantation, especially in children, make this therapeutic option worth more extensive investigation in the treatment of high-risk failure ALCL, although more data is needed to evaluate the long-term benefits. In this regard, the presence of factors predictive of worst outcome such as an early relapse (within 12 months from diagnosis), a refractory or relapsing ALCL and the persistent detection on blood or bone marrow of nucleophosmin-anaplastic lymphoma kinase protein (NPM-ALK) transcript may help select the patients eligible to allogeneic related or unrelated stem cell transplantation.
异基因干细胞移植在非霍奇金淋巴瘤(NHL)患者中的应用尚未明确界定,尤其是在儿童和青少年中,但该方法具有移植无肿瘤以及可能诱导移植物抗肿瘤效应的优势。
我们报告了连续4例患间变性大细胞淋巴瘤(ALCL)并接受来自无关供者异基因干细胞移植治疗的儿科患者的结果。预处理方案中,3例患者采用全身照射联合依托泊苷,1例患者采用塞替派和环磷酰胺。移植物抗宿主病(GVHD)预防措施包括环孢素、短疗程甲氨蝶呤和兔抗胸腺细胞球蛋白。
所有患者的中性粒细胞和血小板在3 - 4周内迅速植入,并实现了稳定的完全供者嵌合状态,且一直维持到最后一次随访。1例患者后来出现了限制性肺病。该患者在病程中接受了大量预处理,经历了4次复发,累计接受博来霉素剂量为160mg/m²。经过11 - 42个月的随访,所有患者均存活,处于完全血液学和分子缓解状态;其中3例无任何慢性GVHD。
志愿骨髓供者数量的增加以及无关干细胞移植毒性的降低,尤其是在儿童中,使得这种治疗选择在高危难治性ALCL的治疗中值得进行更广泛的研究,尽管需要更多数据来评估其长期益处。在这方面,存在预测不良预后的因素,如早期复发(诊断后12个月内)、难治性或复发性ALCL以及在血液或骨髓中持续检测到核磷蛋白-间变性淋巴瘤激酶蛋白(NPM-ALK)转录本,可能有助于选择适合接受异基因相关或无关干细胞移植的患者。