Dose Adjusted IV Busulfan/Cyclophosphamide (BU/CY) and Autologous (AU) Stem Cell Transplantation (SCT) for Recurrent Lymphoma.
Dose Adjusted IV Busulfan/Cyclophosphamide (BU/CY) and Autologous (AU) Stem Cell Transplantation (SCT) for Recurrent Lymphoma.
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剂量调整静脉注射白消安/环磷酰胺 (BU/CY) 和自体 (AU) 干细胞移植 (SCT) 治疗复发性淋巴瘤。
DOI：
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
D. Scadden
中科院分区：
文献类型：
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作者：
T. Spitzer;Benjamin F. Cox;P. Sepe;S. Mcafee;B. Dey;K. Ballan;D. Scadden
对淋巴瘤进行AuSCT的最佳预备治疗尚不清楚。高剂量Bu/CY通常是一种耐受性良好的方案，是治疗血液恶性肿瘤（HM）的同种异体SCT和治疗髓系恶性肿瘤的自体SCT的有效方案。然而，对淋巴细胞恶性肿瘤的研究较少。由于药代动力学更可预测，并且易于给药，静脉注射的丁硫芬已在很大程度上取代了口服丁硫芬。从2001年到2004年，我们治疗了46例复发性、化疗敏感性淋巴瘤或初始完全缓解未通过Bu/CY方案和AuSCT实现的淋巴瘤患者。4例为艾滋病相关NHL （ARL）。在SCT之前，患者接受了中位数的两种放化疗方案。诊断为惰性NHL (n = 12)，侵袭性NHL （n = 28）和霍奇金病（n = 6）。每6小时给药0.8 mg/kg（以实际体重或理想体重（IBW）为准，以较小者为准），共16次（IBW为20%），第3天和第2天给药。第0天进行AuSCT。对于cd34 +祖细胞少于2 × 106/ kg的患者，给予额外的自体骨髓输注（n = 2）。患者年龄中位数（范围）为56岁（24-78岁）。4例患者移植时年龄为70岁。ANC = 0.5和血小板= 20k的中位（范围）时间分别为10（8-12）天和12（8-64）天。方案相关毒性（根据Bearman毒性量表）包括II- iii级粘膜毒性（n = 7），肝脏VOD （n = 1）和II级胃肠道毒性（n = 7）。有记录的感染发生在16例（35%）患者中。2名患者（4.4%）在第100天前死于非复发原因（进行性肺毒性（n = 1），黑色素瘤复发（n = 1））。晚期（=第100天）非复发死亡率（NRM）出现2例(呼吸衰竭，（n = 1）；肝脏VOD （n = 1）。总体NRM为8.7%（4/46例）。ARL患者和70岁以上的患者均未发生NRM。40例NHL患者中有14例复发/进展。6名HD患者中有3名有复发/进展。惰性NHL患者32个月时的精算无进展生存率（PFS）和总生存率（OS）分别为67%和100%，侵袭性NHL患者25个月时的精算无进展生存率（PFS）和总生存率（OS）分别为44%和79%。对于50岁的患者，高剂量IV Bu/CY作为AuSCT的制剂，将IV busulfan剂量降低至14mg /kg具有良好的耐受性，并且与有利的PFS和OS概率相关。该方案在70岁以上的患者中也具有良好的耐受性，在该亚组中没有危及生命或致命的毒性。
The optimal preparative therapy for AuSCT for lymphoma is unknown. High dose Bu/CY is a generally well tolerated, and an effective regimen for allogeneic SCT for hematologic malignancy (HM), and autologous SCT for myeloid malignancies. It has, however, been less well studied for lymphoid malignancies. IV busulfan has largely replaced oral busulfan because of more predictable pharmacokinetics, and ease of administration. We have treated 46 patients (pts) with recurrent, chemosensitive lymphoma or lymphoma in which an initial complete remission was not achieved with the Bu/CY regimen and AuSCT from 2001 – 2004. 4 pts had AIDS related NHL (ARL). Patients had received a median of two chemoradiotherapeutic regimens prior to SCT. Diagnoses were indolent NHL (n = 12), aggressive NHL (n = 28) and Hodgkin’s disease (n = 6). IV busulfan was given at a dose of 0.8 mg/kg (based on actual or ideal body weight (IBW) whichever was less) every six hours for 16 doses (for patients 20% IBW) was given on days −3 and −2. AuSCT was performed on day 0. Additional autologous bone marrow was infused in pts who had less than 2 x 106/ kg CD 34+ progenitor cells (n = 2). Median (range) patient age was 56 (24–78) years. Four pts were = 70 years old at the time of transplant. Median (range) times to ANC = 0.5 and platelets = 20k were 10 (8–12) and 12 (8–64) days, respectively. Regimen related toxicities (according to the Bearman toxicity scale) included grade II-III mucosal toxicity (n = 7), hepatic VOD (n = 1), and grade II GI toxicity (n = 7). Documented infection occurred in 16 (35%) pts. Two pts (4.4%) died before day 100 from non-relapse causes (progressive pulmonary toxicity (n = 1), recurrence of melanoma (n = 1). Late (= day 100) non-relapse mortality (NRM) occurred in two pts (respiratory failure, (n = 1); hepatic VOD (n = 1). Overall NRM was 8.7% (4/46 patients). No NRM occurred in pts with ARL or pts > 70 yrs. Fourteen of 40 pts with NHL have had relapse/progression. Three of six pts with HD have had relapse/progression. Actuarial progression free survival (PFS) and overall survival (OS) probabilities are 67% and 100% at 32 mos for pts with indolent NHL and 44% and 79% at 25 mos for pts with aggressive NHL, respectively. High dose IV Bu/CY as preparation for AuSCT, with dose reduction of IV busulfan to 14 mg/kg for patients = 50 years is well tolerated and is associated with favorable PFS and OS probabilities. The regimen has also been well tolerated in pts over the age of 70 with no life threatening or fatal toxicities in this subgroup.