Phillips G L, Meisenberg B R, Reece D E, Adams V R, Badros A Z, Brunner J L, Fenton R G, Filicko J, Grosso D L, Hale G A, Howard D S, Johnson V P, Kniska A, Marshall K W, Mookerjee B, Nath R, Rapoport A P, Sarkodee-Adoo C, Takebe N, Vesole D H, Wagner J L, Flomenberg N
Blood and Marrow Transplant Program, University of Kentucky, Lexington, KY, USA.
Bone Marrow Transplant. 2004 Apr;33(8):781-7. doi: 10.1038/sj.bmt.1704424.
High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m(2) plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial. Median age was 51 years (range 24-62 years); NHL histology was varied, but was aggressive (including transformed from indolent) in 19 patients, indolent in two patients and mantle cell in one. All 26 patients had been extensively treated; 11 were refractory to the immediate prior therapy on protocol entry and two had undergone prior AHSCT. All were deemed ineligible for other, 'first-line' AHSCT regimens. Of these 26 patients, 22 survived to initial tumor evaluation on D +100. At this time, 13 were in complete remission, including four patients who were in second CR before HDMEL+AF+AHSCT. Responses occurred at all HDMEL doses. Currently, seven patients are alive, including five without progression, with a median follow-up in these latter patients of D +1163 (range D +824 to D +1630); one of these patients had a nonmyeloablative allograft as consolidation on D +106. Conversely, 14 patients relapsed or progressed, including five who had previously achieved CR with the AHSCT procedure. Two patients, both with HL, remain alive after progression; one is in CR following salvage radiotherapy. Six patients died due to nonrelapse causes, including two NHL patients who died while in CR. We conclude that HDMEL+AF+AHSCT has significant single-agent activity in relapsed or refractory NHL and HL. This experience may be used as a starting point for subsequent dose escalation of HDMEL (probably with AF) in established combination regimens.
使用美法仑的大剂量化疗（HDMEL）是许多自体造血干细胞移植（AHSCT）前预处理方案的重要组成部分。与骨髓瘤的情况不同，在急性白血病中程度稍轻，关于将HDMEL预处理作为单一药物用于淋巴瘤（包括霍奇金淋巴瘤（HL），尤其是非霍奇金淋巴瘤（NHL））且剂量需进行AHSCT的已发表经验非常有限。因此，我们报告了在一项I-II期试验中，用220 - 300 mg/m²的HDMEL加氨磷汀（AF）进行细胞保护及AHSCT治疗26例淋巴瘤患者（22例NHL和4例HL）的结果。中位年龄为51岁（范围24 - 62岁）；NHL的组织学类型多样，但19例为侵袭性（包括由惰性转化而来），2例为惰性，1例为套细胞淋巴瘤。所有26例患者均接受过广泛治疗；11例在进入方案时对之前的直接治疗耐药，2例曾接受过AHSCT。所有患者均被认为不符合其他“一线”AHSCT方案的条件。这26例患者中，22例存活至D +100时的初始肿瘤评估。此时，13例完全缓解，包括4例在HDMEL + AF + AHSCT前处于第二次完全缓解的患者。所有HDMEL剂量均出现缓解。目前，7例患者存活，包括5例无疾病进展者，这5例患者的中位随访时间为D +1163（范围D +824至D +1630）；其中1例患者在D +106时接受了非清髓性同种异体移植作为巩固治疗。相反，14例患者复发或进展，包括5例之前通过AHSCT程序达到完全缓解的患者。2例HL患者在疾病进展后仍存活；1例在挽救性放疗后处于完全缓解。6例患者因非复发原因死亡，包括2例NHL患者在完全缓解时死亡。我们得出结论，HDMEL + AF + AHSCT在复发或难治性NHL和HL中具有显著的单药活性。这一经验可作为后续在既定联合方案中提高HDMEL（可能联合AF）剂量的起点。
