Allogeneic and Syngeneic Hematopoietic Cell Transplants in Patients with AL-Amyloidosis: A Report from the European Group for Blood and Marrow Transplantation (EBMT).
Allogeneic and Syngeneic Hematopoietic Cell Transplants in Patients with AL-Amyloidosis: A Report from the European Group for Blood and Marrow Transplantation (EBMT).
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AL-淀粉样变性患者的同种异体和同基因造血细胞移植：来自欧洲血液和骨髓移植小组 (EBMT) 的报告。
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
G. Gahrton
中科院分区：
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作者：
S. Schoenland;M. Baccarani;Andrew Campbell;E. Carreras;C. Cordonnier;L. Grommisch;V. Leblond;T. Littlewood;L. Verdonck;L. Wood;P. Zachée;A. Zander;H. Goldschmidt;D. Niederwieser;G. Gahrton
AL 淀粉样变性是由浆细胞恶液质引起的，其中克隆免疫球蛋白轻链沉积在组织中，导致器官衰竭和死亡。高剂量马法兰治疗和自体 PBSC 挽救使大约 40% 的可评估患者的血液学缓解，并改善器官疾病和生活质量。对于一部分患者，同种异体造血细胞移植（HCT）可能有用。对于 AL 淀粉样变性患者进行此手术的经验很少。我们报告在 EBMT 数据库中注册的患者 (pts)。 11 名患有 AL 淀粉样变性 (n=10) 或患有多发性骨髓瘤加 AL 淀粉样变性 (n=1) 的患者（中位年龄 45 岁，范围 30-63；3 名女性）在 1987 年至 2002 年期间接受了同种异体 (n=8) 或同基因 (n=3) HCT，其中 7 人在 2000 年之前。同种异体移植的捐赠者是匹配的相关兄弟姐妹。主要器官表现为肾、心、肝。同种异体 HCT 的适应症为年轻、自体 HCT 后复发 (n=2) 以及进行性或难治性疾病。 4 名患者采用消融性预处理方案，另外 4 名患者采用降低强度预处理 (RIC)。三名患者接受了 T 细胞耗竭作为移植物抗宿主病 (GvHD) 预防。 7/8 名患者的移植效果可评估，2 名患者拒绝移植物，5 名患者具有持久的移植物。五分之一的可评估患者出现急性 GvHD（IV 级），三分之一的可评估患者出现慢性 GvHD（局限性疾病）。 5 名患者 (62.5%) 在 HCT 后平均 51 天（范围 25 – 83）天死亡，均在 +100 天之前。这 5 名患者中有 4 名的死因已知：1 名患者死于脑曲霉病（+54 天），3 名患者死于淀粉样变性。 HCT 后，三名患者仍存活（中位观察时间 27 个月，范围 12-79）。存活患者中 HCT 后的最佳血液学反应为 1 名患者免疫固定阴性 CR（患有 cGvHD）、1 名患者 PR 和第三名患者 SD。接受同基因 HCT 的 3 名患者中，一名在手术后约 60 个月仍存活，另外 2 名患者仍存活。分别于TRM+7和+18天去世。总之，观察到非常高的日+100死亡率。主要问题是 HCT 后早期因淀粉样变性导致的心力衰竭。一半的患者分别在 RIC 和烧蚀调节中幸存下来。我们的结论是，为了降低死亡率，有必要严格限制患者选择，因为自体 HCT 的高剂量化疗已证明这一点。 RIC 未来是否在该患者群体中发挥更重要的作用仍有待确定。
AL amyloidosis is caused by a plasma cell dyscrasia in which clonal immunoglobulin light chains deposited in tissues leads to organ failure and death. Treatment with high dose melphalan and autologous PBSC rescue produces hematologic remissions in approximately 40% of evaluable patients and improvements in organ disease and quality of life. For a subgroup of patients, an allogeneic hematopoietic cell transplantation (HCT) may be useful. There is little experience with this procedure in patients with AL amyloidosis. We report the patients (pts) who were registered within the EBMT database. Eleven pts (median age 45 years, range 30–63; 3 female) with AL amyloidosis (n=10) or with multiple myeloma plus AL amyloidosis (n=1) underwent allogeneic (n=8) or syngeneic ( n=3) HCT during 1987–2002, 7 of them before 2000. Donors of allogeneic transplants were matched related siblings. Main organ manifestations were kidney, heart and liver. Indications for allogeneic HCT were young age, relapse after autologous HCT (n=2) and progressive or refractory disease. Conditioning regimen was ablative in 4 pts and reduced-intensity conditioning (RIC) was used in the other 4 pts. Three pts had T cell depletion as graft-versus-host-disease (GvHD) prophylaxis. Engraftment was evaluable in 7/8 pts, 2 pts rejected their grafts and 5 pts had durable engraftment. One out of 5 evaluable pts developed acute GvHD (grade IV), and 1 of 3 evaluable pts developed chronic GvHD (limited disease). Five pts (62,5%) died at a median of 51 (range 25 – 83) days after HCT, all before day +100. From 4 of these 5 pts causes of death are known: 1 pt died of a cerebral aspergillosis (day +54) and 3 pts died of amyloidosis. Three pts remain alive (median observation 27 months, range 12–79) after HCT. Best hematological responses after HCT in surviving pts were immunofixation-negative CR in 1 pt (with cGvHD), PR in 1 pt and SD in the third pt. One of the 3 pts with syngeneic HCT is alive about 60 months after the procedure, the other 2 pts. died of TRM day +7 and +18, respectively. In summary, a very high day +100 mortality was observed. Main problem was cardiac failure due to amyloidosis in the very early phase after HCT. Half of the pts survived RIC and ablative conditioning, respectively. We conclude that a very restrictive patient selection is necessary to decrease mortality as it has been shown for high-dose chemotherapy with autologous HCT. Whether RIC plays an more important role for this patient group in the future remains to be defined.