烷化剂为主的预处理方案在造血干细胞移植中近期和远期毒性

背景:造血干细胞移植成功的主要障碍是移植后的各种并发症,早期并发症主要与预处理有关。找出合理的剂量和新的高效低毒的预处理方案是提高造血干细胞移植成功率的关键。目的:了解以烷化剂为主的联合化疗作预处理,进行造血干细胞移植治疗恶性血液病的相关毒性和移植效果。设计:观察对比实验。地点:徐州医学院附属医院血液科。对象:选择1997-07/2006-02在徐州医学院附属医院住院的45例白血病及淋巴瘤患者,男31例,女14例,年龄7～52岁,中位年龄31岁。移植时病程5～17个月,平均8个月。方法:对45例白血病及淋巴瘤缓解期患者进行骨髓及外周血干细胞移植,预处理方案为以烷化剂为主的联合化疗,髓外毒性分级采用Bearman等制订的标准,预处理相关毒性分5个级别,即由无毒性(0级)至致死性毒性(Ⅳ级)。统计分析完全缓解率、完全缓解时间、复发率和无病生存期。主要观察指标:各脏器预处理相关毒性发生情况。结果:①5例无任何毒性发生,最大毒性为Ⅲ级者占13%(6/45)。各脏器预处理相关毒性大多数为Ⅰ～Ⅱ级,严重的预处理相关毒性Ⅲ级不多见。在Ⅰ～Ⅱ级预处理相关毒性中口腔黏膜溃疡和胃肠道毒性发生率较高,分别为73%(33/45)和51%(23/45),经治疗后短期内恢复;心脏毒性发生率低,均为Ⅰ级,多为心动过速和ST-T改变;肝脏预处理相关毒性,除2例肝静脉闭塞病外,多表现为转氨酶增高,4例出血性膀胱炎,其中1例为迟发性出血性膀胱炎。肾、肺和中枢神经系统预处理相关毒性少见。②移植后43例患者造血功能获得重建,植入失败死亡2例(4%)。中位随访时间37(8～102)个月,复发10例及移植相关并发症死亡5例,28例仍长期无病生存(62.2%)。100d内移植相关死亡原因主要为急性移植物抗宿主病,巨细胞病毒性间质性肺炎,侵袭性感染,多脏器功能衰竭和早期复发。结论:烷化剂为主的预处理方案进行造血干细胞移植治疗白血病和淋巴瘤相关毒性轻,患者耐受好。

Short-term and long-term toxicity of alkylating-agent-based conditioning regimens in hematopoietic stem cell transplantation

BACKGROUND: The principal deterrent to the success for hematopoietic stem cell transplantation (HSCT) is the complications after transplantation. The complications are associates with the conditioning regimens in the early stage. The highly-effective preparative regimens of proper dose and low-toxicity are the key to the successful HSCT.OBJECTIVE: To evaluate the curative effects and regimen related toxicity (RRT) of high-dose alkylating-agent-based chemotherapy as conditioning regimens for HSCT in the patients with hematological malignancies.DESIGN: Controlled study with observation.SETTING: Department of Hematology, Affiliated Hospital of Xuzhou Medical College.PARTICIPANTS: A total of 45 patients with leukemia and lymphoma hospitalized at Affiliated Hospital of Xuzhou Medical College from July 1997 to February 2006 were enrolled, including 31 males and 14 females. The median age was 31 years (from 7 to 52 years). The median course was 8 months (from 5 to 17 months) until transplantation.METHODS: Totally 45 patients with leukemia and lymphoma approached or got complete remission were treated by bone marrow transplantation and peripheral blood stem cell transplantation with preparative regimens of high-dose alkylating-agent-based chemotherapy. RRT was graded according to Bearman proposal, from grade 0 (no toxicity) to grade Ⅳ (fatal toxicity). The period of hematopoietic reconstitution, the rates of complete remission and relapse and disease-free survival were statistically observed in transplant recipients.MAIN OUTCOME MEASURES: Occurrence of RRT as conditioning regimens.RESULTS: ①Five patients did not show any toxicity. The greatest toxicity of grade Ⅲ was uncommon (13%, 6/45). Most of the cases with RRT were in grade Ⅰ - Ⅱ and severe oases in grade Ⅲ were rare. In grade Ⅰ - Ⅱ, stomatocace and gastrointestinal toxicity were common respectively of 73% (33/45) and 51% (23/45) which were recovered in short time after treatment; Heart toxicity was rare and only in grade Ⅰ, most of which were tachyoardia and changes of ST-T shape. The increase of transaminase was common in the clinical manifestations of liver RRT except two cases of HVOD.There were four oases of HC, in which one was delayed. RRT on kidney, lungs and CNS was uncommon. ②Totally 43 patients engrafted gained hematopoietic reconstitution, 2 patients died of implant failure (4%). Within the median follow-up period of 37 (8-102) months, 10 patients relapsed, 5 patients died of transplantation-related complications and 28 patients were alive in a disease-free situation (62.2%). The cause of death within 100 days after transplantation was ordinal as acute graft-versus-host disease (GVHD), cytomegalovirus (CMV) interstitial pneumonia, disseminated infections,multiple organ failure and early relapses.CONCLUSION: Alkylating-agent-based conditioning regimens may be well tolerated with low toxicities for HSCT in leukemia and lymphoma.