Kröger Nicolaus, Schwerdtfeger Rainer, Kiehl Michael, Sayer Herbert Gottfried, Renges Helmut, Zabelina Tatjana, Fehse Boris, Tögel Florian, Wittkowsky Georg, Kuse Rolf, Zander Axel Rolf
Bone Marrow Transplantation, University Hospital Hamburg, Hamburg, Germany.
Blood. 2002 Aug 1;100(3):755-60. doi: 10.1182/blood-2002-01-0131.
We evaluated toxicity, engraftment, chimerism, graft-versus-host disease (GVHD), and response to a dose-reduced allograft after cytoreductive autografting in 17 patients with advanced stage II/III multiple myeloma (MM). After autografting with melphalan (200 mg/m2) the patients received after a median interval of 119 days (range 60-210) a dose-reduced regimen consisting of fludarabine (180 mg/m2), melphalan (100 mg/m2), and antithymocyte globulin (3 x 10 mg/kg) followed by allografting from related (n = 7), mismatched related (n = 2), or unrelated (n = 8) donors to induce a graft-versus-myeloma effect. After dose-reduced allografting all patients became neutropenic (< 0.2 x 10(9)/L) for at least 8 days. All patients engrafted with a median time for leukocyte (> 1 x 10(9)/L) and platelet (> 20 x 10(9)/L) counts of 16 (range, 11-24) and 23 days (range, 12-43), respectively. Complete donor chimerism was detected after a median of 30 days (range, 19-38). Acute GVHD stage II occurred in 4 patients (25%) and grade III GVHD in 2 patients (13%). Chronic GVHD developed in 40% of the patients, but only 1 patient experienced extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of alveolar hemorrhage and pneumonia, resulting in a day 100 mortality rate of 11%. The rate of complete remission with negative immunofixation increased from 18% after autografting to 73% after allografting. After a median follow-up of 17 months after autologous and 13 months after allogeneic transplantation 13 patients are alive and 12 of them free of relapse or progression. The tandem auto-allotransplant protocol is highly active and provides rapid engraftment with complete donor chimerism and tolerable toxicity.
我们评估了17例晚期II/III期多发性骨髓瘤（MM）患者在进行减瘤自体移植后接受剂量降低的同种异体移植时的毒性、植入、嵌合状态、移植物抗宿主病（GVHD）以及对其的反应。患者接受美法仑（200mg/m²）自体移植后，中位间隔119天（范围60 - 210天），接受由氟达拉滨（180mg/m²）、美法仑（100mg/m²）和抗胸腺细胞球蛋白（3×10mg/kg）组成的剂量降低方案，随后接受来自相关供体（n = 7）、不匹配相关供体（n = 2）或无关供体（n = 8）的同种异体移植，以诱导移植物抗骨髓瘤效应。剂量降低的同种异体移植后，所有患者均出现至少8天的中性粒细胞减少（<0.2×10⁹/L）。所有患者白细胞（>1×10⁹/L）和血小板（>20×10⁹/L）计数的中位植入时间分别为16天（范围11 - 24天）和23天（范围12 - 43天）。中位30天（范围19 - 38天）后检测到完全供体嵌合状态。4例患者（25%）发生II期急性GVHD，2例患者（13%）发生III级GVHD。40%的患者发生慢性GVHD，但只有1例患者经历广泛的慢性GVHD，需要进一步的免疫抑制治疗。2例患者死于肺泡出血和肺炎，导致100天死亡率为11%。免疫固定阴性的完全缓解率从自体移植后的18%提高到同种异体移植后的73%。自体移植后中位随访17个月，同种异体移植后中位随访13个月，13例患者存活，其中12例无复发或进展。串联自体 - 同种异体移植方案活性高，能快速植入，实现完全供体嵌合，且毒性可耐受。
