CAJ | 학술논문

目的探讨单倍体造血干细胞移植联合后置大剂量环磷酰胺治疗儿童恶性血液病的临床疗效.方法回顾性分析2009年6月至2012年11月期间接受单倍体造血干细胞移植25例患儿的资料,患者中位年龄为9.0岁(1.2～13.0岁),男女比例为13∶12.其中原发疾病分别为急性淋巴细胞白血病13例,急性粒细胞白血病7例,非霍奇金淋巴瘤2例,慢性粒细胞白血病2例,幼年慢性粒-单核细胞白血病1例.供者均为1级血缘亲属,供、受者HLA配型2个位点不合6例,＞2个位点不合19例.移植前预处理主要为环磷酰胺+氟达拉滨+白消安,部分患者加用达利珠单抗、阿糖胞苷、依托泊苷或司莫司汀及接受全身照射等.移植物抗宿主病(GVHD)的预防采用大剂量环磷酰胺(40或50 mg·kg-1·d-1,用3～4 d)+他克莫司+吗替麦考酚酯.结果中位随访时间为25个月.25例28 d内供者细胞嵌合率均大于95％,60d后1例骨髓衰竭.粒细胞植活中位时间为22.5 d(17～46d),血小板植活中位时间为20.5 d(12～67 d).Ⅰ～Ⅱ度急性GVHD、Ⅲ～Ⅳ度急性GVHD和慢性GVHD分别发生7例(28％)、1例(4％)和3例(12％),另3例(12％)因复发给予供者淋巴细胞或外周血造血干细胞输注后发生Ⅲ～Ⅳ度急性GVHD.移植后3年总体存活率、无事件存活率、非复发死亡率及复发率分别为28％、28％、40％和32％.结论单倍体造血干细胞移植联合后置大剂量环磷酰胺治疗儿童恶性血液病能有效地预防GVHD,早期植入效果较好,但复发及移植后继发全血细胞减少的发生率高,治疗方案有待进一步改善.
목적 탐토단배체조혈간세포이식연합후치대제량배린선알치료인동악성혈액병적림상료효.방법 회고성분석2009년6월지2012년11월기간접수단배체조혈간세포이식25례환인적자료,환자중위년령위9.0세(1.2～13.0세),남녀비례위13∶12.기중원발질병분별위급성림파세포백혈병13례,급성립세포백혈병7례,비곽기금림파류2례,만성립세포백혈병2례,유년만성립-단핵세포백혈병1례.공자균위1급혈연친속,공、수자HLA배형2개위점불합6례,＞2개위점불합19례.이식전예처리주요위배린선알+불체랍빈+백소안,부분환자가용체리주단항、아당포감、의탁박감혹사막사정급접수전신조사등.이식물항숙주병(GVHD)적예방채용대제량배린선알(40혹50 mg·kg-1·d-1,용3～4 d)+타극막사+마체맥고분지.결과 중위수방시간위25개월.25례28 d내공자세포감합솔균대우95％,60d후1례골수쇠갈.립세포식활중위시간위22.5 d(17～46d),혈소판식활중위시간위20.5 d(12～67 d).Ⅰ～Ⅱ도급성GVHD、Ⅲ～Ⅳ도급성GVHD화만성GVHD분별발생7례(28％)、1례(4％)화3례(12％),령3례(12％)인복발급여공자림파세포혹외주혈조혈간세포수주후발생Ⅲ～Ⅳ도급성GVHD.이식후3년총체존활솔、무사건존활솔、비복발사망솔급복발솔분별위28％、28％、40％화32％.결론 단배체조혈간세포이식연합후치대제량배린선알치료인동악성혈액병능유효지예방GVHD,조기식입효과교호,단복발급이식후계발전혈세포감소적발생솔고,치료방안유대진일보개선.
Objective To evaluated the efficacy of human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (HSCT) using high-dose post-transplant (HP)cyclophosphamide (Cy) as prophylaxis of graft versus host diseases (GVHD).Method Twenty-five children with high risk acute lymphoblastic leukemias (n =13),acute myeloid leukemia (n =7),chronic myeloid leukemia (n =2),lymphoma (n =2) or childhood juvenile myelomonocytic leukemia(n =1) received HSCT from ≥2 HLA mismatched relative donors from June 2009 to November 2012.All patients received conditioning regimen which was consisted of fludarabine,busulfan,Cy,thiotepa,with or without total-body irradiation and HP Cy (40 or 50 mg/kg i.v.on day 3 and day 4 after transplantation).Result The median follow-up time was 25 months.Donor chimerism was ≥95％ on day 28 in all patients.The median time to neutrophils ≥0.5 × 109/L and platelets ≥20×109/L was 22.5 and 20.5 days,respectively.The cumulative incidence of grade Ⅰ-Ⅱ acute GVHD (aGVHD),grade Ⅲ-Ⅳ aGVHD,and chronic GVHD was 28％,4％ and 12％,respectively.Three patients developed garde Ⅲ-Ⅳ aGVHD after donor lymphocyte infusion for relapse.The cumulative incidence of relapse and non relapse mortality were 32％ and 40％,respectively.The cumulative overall survival and event-free survival at 3 years were 28％ and 28％,respectively.Conclusion HLA-haploidentical HSCT with HP Cy for children with malignant hematological disorders is a viable option when lack of HLA matched sibling and unrelated donors.The rate of severe GVHD is acceptable.But posttransplant cytopenia and relapse still are major hinder,and the protocol should be modified.