Munshi N C, Barlogie B
Dana Farber Cancer Institute and Boston VA Healthcare Center, Harvard Medical School, Boston, MA 02115, USA.
Semin Oncol. 2003 Apr;30(2):282-5. doi: 10.1053/sonc.2003.50080.
Despite effectiveness of standard chemotherapy regimens, complete responses are infrequent in Waldenstrom's macroglobulinemia (WM) and there are no cures. Since WM shares certain biological and clinical features with myeloma, including responsiveness to alkylating agents, evaluation of high-dose therapy (HDT) with transplant, which is effective in myeloma, is an obvious next step in an effort to achieve high response rates and improve survival. Due to the indolent nature of the disease and older patients with comorbidities, such evaluations have been infrequent in the past. We have evaluated the safety and efficacy of high-dose melphalan with peripheral blood stem cell (PBSC) support in eight patients between the ages of 45 and 69 years with WM. Adequate numbers of stem cells were collected in six patients; however, two patients with more extensive prior fludarabine therapy failed to collect adequate cells and required a second attempt at stem cell collection. Seven patients were treated with melphalan 200 mg/m(2), including two patients who received tandem transplants; one patient received melphalan 140 mg/m(2) with total body irradiation (TBI). There was no treatment-related mortality and toxicities were manageable. Recovery of bone marrow after transplant was prompt except in one patient with extensive prior use of fludarabine. All the eight patients achieved at least partial response (PR), including one complete response (CR). Five patients are alive and with out relapse (77+ to 6+ months post-transplant). Other investigators have reported similar experience suggesting safety and efficacy of HDT in WM. However, therapy with purine analogues leads to stem cell damage with decreased ability to collect adequate numbers of stem cells. This suggests that the PBSCs should preferably be procured prior to extensive use of purine analogues. Future strategies in WM will include a plan to evaluate the role of HDT along with biological agents, role of purging using rituximab, post-HDT maintenance strategies (including immunotherapy), and evaluation of nonmyeloablative regimens containing fludarabine to achieve higher response rates and improve survival.
尽管标准化疗方案有一定疗效，但在华氏巨球蛋白血症（WM）中完全缓解并不常见，且无法治愈。由于WM与骨髓瘤具有某些生物学和临床特征，包括对烷化剂有反应，因此评估对骨髓瘤有效的高剂量治疗（HDT）联合移植是实现高缓解率和改善生存的下一步明显举措。由于该疾病进展缓慢且患者多为老年合并症患者，过去此类评估并不常见。我们评估了大剂量美法仑联合外周血干细胞（PBSC）支持对8例年龄在45至69岁的WM患者的安全性和疗效。6例患者收集到了足够数量的干细胞；然而，2例先前接受过更广泛氟达拉滨治疗的患者未能收集到足够的细胞，需要再次尝试收集干细胞。7例患者接受了200 mg/m²的美法仑治疗，其中2例患者接受了串联移植；1例患者接受了140 mg/m²的美法仑联合全身照射（TBI）。没有与治疗相关的死亡，毒性反应可控。除1例先前广泛使用氟达拉滨的患者外，移植后骨髓恢复迅速。所有8例患者均至少达到部分缓解（PR），其中1例完全缓解（CR）。5例患者存活且未复发（移植后77 +至6 +个月）。其他研究者也报告了类似的经验，提示HDT在WM中具有安全性和疗效。然而，嘌呤类似物治疗会导致干细胞损伤，收集足够数量干细胞的能力下降。这表明最好在广泛使用嘌呤类似物之前采集PBSC。WM未来的策略将包括评估HDT与生物制剂联合的作用、使用利妥昔单抗清除的作用、HDT后维持策略（包括免疫治疗），以及评估含氟达拉滨的非清髓方案以实现更高的缓解率和改善生存。
