Wadhwa Punit D, Fu Pingfu, Koc Omer N, Cooper Brenda W, Fox Robert M, Creger Richard J, Bajor David L, Bedi Teja, Laughlin Mary J, Payne Jennifer, Gerson Stanton L, Lazarus Hillard M
Department of Medicine, Comprehensive Cancer Center of the University Hospitals of Cleveland/Case Western Reserve University, Cleveland, Ohio 44106, USA.
Biol Blood Marrow Transplant. 2005 Jan;11(1):13-22. doi: 10.1016/j.bbmt.2004.09.003.
Over a 10-year period (January 1993 to October 2002), 101 relapsed or refractory non-Hodgkin lymphoma patients were treated at our center with high-dose chemotherapy and autologous transplantation. The median patient age was 54 years (range, 25-70 years). Thirty-two patients had indolent (low-grade), 42 had aggressive (intermediate-grade), and 27 had very aggressive (high-grade) non-Hodgkin lymphoma. Thirty-six patients had primary refractory disease, 20 had a chemoresistant relapse, 35 patients had a chemosensitive relapse, and 10 patients were "initial high risk" patients. The median number of prior chemotherapy regimens was 2 (range, 1-5). The preparative regimen (BEP) was bischloroethylnitrosourea (BCNU) 600 mg/m 2 , etoposide 2400 mg/m 2 , and Platinol (cisplatin) 200 mg/m 2 given intravenously over 5 days. Within 3 weeks before transplantation, 70 patients received involved-field radiotherapy (IFR) 20 Gy to sites of currently active (>2 cm) or prior bulky (>5 cm) disease. Most patients (n = 93) received mobilized peripheral blood stem cells (median CD34 + cell dose, 6.7 x 10 6 /kg). Median neutrophil (>500/microL) and platelet (>20 000/microL, untransfused) recoveries were 11 days (range, 7-19 days) and 14 days (range, 7-36 days), respectively. At a median follow-up of 41 months (range, 4 to 118 months) for survivors, Kaplan-Meier 5-year probabilities of overall survival (OS) and disease-free survival (DFS) were 58.6% and 51.1%, respectively. Four patients (4%) died within 30 days of stem cell infusion (1 pulmonary embolism, 2 septicemias with multiorgan failure, and 1 progressive lymphoma). Two patients (2%) developed interstitial pneumonitis most likely secondary to high-dose BCNU. Three cases (3%) of secondary acute myelogenous leukemia occurred. On multivariate analysis, age (<60 or > or =60 years), histologic grade (low versus intermediate or high), the use of IFR, and chemotherapy response at baseline did not affect OS or DFS. Of 70 patients given IFR, 27 relapsed: 10 (37%) within and 17 (63%) outside the radiation field. The use of IFR did not affect either OS or DFS, probably because IFR was offered to patients with bulky or chemoresistant disease. BEP with or without IFR is a highly effective and well-tolerated regimen in the relapsed/refractory lymphoma setting. It has low morbidity and transplant-related mortality and a low incidence (3%) of posttransplantation malignancy.
在10年期间（1993年1月至2002年10月），我院中心对101例复发或难治性非霍奇金淋巴瘤患者进行了大剂量化疗及自体移植治疗。患者年龄中位数为54岁（范围25 - 70岁）。32例患者为惰性（低级别）非霍奇金淋巴瘤，42例为侵袭性（中级），27例为高度侵袭性（高级别）非霍奇金淋巴瘤。36例患者为原发性难治性疾病，20例为化疗耐药复发，35例为化疗敏感复发，10例为“初始高危”患者。既往化疗方案的中位数为2个（范围1 - 5个）。预处理方案（BEP）为双氯乙基亚硝脲（BCNU）600 mg/m²、依托泊苷2400 mg/m²和顺铂200 mg/m²，静脉滴注5天。在移植前3周内，70例患者对当前活动（>2 cm）或既往大包块（>5 cm）病变部位接受了20 Gy的累及野放疗（IFR）。大多数患者（n = 93）接受了动员外周血干细胞（CD34⁺细胞剂量中位数为6.7×10⁶/kg）。中性粒细胞（>500/μL）和血小板（>20 000/μL，未输血）恢复的中位数分别为11天（范围7 - 19天）和14天（范围7 - 36天）。存活者的中位随访时间为41个月（范围4至118个月），采用Kaplan - Meier法计算的5年总生存率（OS）和无病生存率（DFS）分别为58.6%和51.1%。4例患者（4%）在干细胞输注后30天内死亡（1例肺栓塞，2例败血症伴多器官功能衰竭，1例进行性淋巴瘤）。2例患者（2%）发生间质性肺炎，最可能继发于大剂量BCNU。发生了3例（3%）继发性急性髓系白血病。多因素分析显示，年龄（<60岁或≥60岁）、组织学分级（低级别与中级或高级别）、IFR的使用以及基线时的化疗反应均不影响OS或DFS。在接受IFR的70例患者中，27例复发：10例（37%）在放疗野内复发，17例（63%）在放疗野外复发。IFR的使用对OS或DFS均无影响，可能是因为IFR应用于有大包块或化疗耐药疾病的患者。含或不含IFR的BEP方案在复发/难治性淋巴瘤治疗中是一种高效且耐受性良好的方案。其发病率低，移植相关死亡率低，移植后恶性肿瘤发生率也低（3%）。
