Anderson K C, Barut B A, Ritz J, Freedman A S, Takvorian T, Rabinowe S N, Soiffer R, Heflin L, Coral F, Dear K
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Blood. 1991 Feb 15;77(4):712-20.
Eleven patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and six had received prior radiotherapy. At the time of ABMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells. Eight patients had residual monoclonal marrow plasma cells and 10 patients had paraprotein. Following high-dose melphalan and total body irradiation (TBI) there were seven complete responses, three partial responses, and one toxic death. Granulocytes greater than 500/mm3 were noted at a median of 21 (range 12 to 46) days posttransplant (PT) and untransfused platelets greater than 20,000/mm3 were noted at a median of 23 (12 to 53) days PT in 10 of the 11 patients. Natural killer cells and cytotoxic/suppressor T cells predominated early PT, with return of B cells at 3 months PT and normalization of T4:T8 ratio at 1 year PT. Less than 5% polyclonal marrow plasma cells were noted in all patients after transplant. Three of the seven complete responders have had return of paraprotein, two with myeloma, and have subsequently responded to alpha 2 interferon therapy. Eight patients are alive at 18.9 (8.9 to 43.1) months PT and four remain disease-free at 12.3, 17.5, 18.9, and 29 months PT. This preliminary study confirms that high-dose melphalan and TBI can achieve high response rates without unexpected toxicity in patients who have sensitive disease, and that MoAb-based purging techniques do not inhibit engraftment. Although the follow-up is short- and long-term outcome to be determined, relapses post-ABMT in these heavily pretreated patients suggest that ABMT or alternative treatment strategies should be evaluated earlier in the disease course.
11例浆细胞异常增生患者接受了大剂量放化疗及抗B细胞单克隆抗体（MoAb）治疗的自体骨髓移植（ABMT）。大多数患者诊断时处于Durie-Salmon分期晚期骨髓瘤，均接受过化疗预处理，6例曾接受过放疗。在进行ABMT时，所有患者表现良好，卡氏评分80%或更高，骨髓肿瘤细胞少于10%。8例患者有残留的单克隆骨髓浆细胞，10例患者有副蛋白。在接受大剂量美法仑和全身照射（TBI）后，有7例完全缓解，3例部分缓解，1例因毒性死亡。移植后（PT）中位数21天（范围12至46天）时，11例患者中有10例粒细胞大于500/mm³，中位数23天（12至53天）时未输血血小板大于20,000/mm³。移植早期自然杀伤细胞和细胞毒性/抑制性T细胞占主导，移植后3个月B细胞恢复，移植后1年T4:T8比值正常化。移植后所有患者多克隆骨髓浆细胞均少于5%。7例完全缓解者中有3例副蛋白复发，2例为骨髓瘤，随后对α2干扰素治疗有反应。8例患者在移植后18.9个月（8.9至43.1个月）存活，4例在移植后12.3、17.5、18.9和29个月无疾病。这项初步研究证实，大剂量美法仑和TBI可使敏感疾病患者获得高缓解率且无意外毒性，基于MoAb的净化技术不抑制植入。尽管随访时间短，长期结果有待确定，但这些经过大量预处理患者的ABMT后复发表明，应在疾病进程中更早地评估ABMT或替代治疗策略。
