Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Second allogeneic hematopoietic stem cell transplantation in children to overcome graft failure or relapse after initial transplant

조혈모세포이식 후 생착 실패나 재발한 소아환자에서 2차 이식의 의의

  • Kim, Dong-Yeon (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Kim, Do Kyun (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Kim, Soo Young (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Kim, Seok Joo (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Han, Dong Gyun (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Baek, Hee Jo (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Kook, Hoon (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center) ;
  • Hwang, Tai-Ju (Department of Pediatrics, Chonnam National University Medical School Chonnam National University Hwasun Hospital, Blood & Marrow Transplantation Center)
  • 김동연 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 김도균 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 김수영 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 김석주 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 한동균 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 백희조 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 국훈 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터) ;
  • 황태주 (전남대학교 의과대학 소아과학교실, 화순전남대학교병원 소아과, 조혈모세포이식센터)
  • Received : 2006.08.16
  • Accepted : 2006.09.13
  • Published : 2006.12.15
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Abstract

Purpose : Failure of hematopoietic stem cell transplantation(HSCT) may be encountered in practice because of either relapse of the malignancy or dysfunction of the graft. Second HSCT may be the only option for some patients whose initial HSCT failed. Methods : From May, 1991 to December, 2004, 115 HSCTs were performed at the Pediatric Blood & Marrow Transplantation Center, Chonnam National University. This study was a retrospective analysis of the medical records of 15 patients who received the second HSCT after initial graft. Results : Among eight patients with nonmalignant diseases, two patients underwent the second HSCT because of primary graft failure and five because of late graft rejection. The remaining Fanconi anemia patient was re-transplanted due to development of AML. Two patients died and one experienced primary graft failure, but is still alive. The Kaplan-Meier 5-year overall survival rate was 75 percent and the disease free survival rate was 62.5 percent in nonmalignant diseases. All malignant patients underwent second transplants because of relapses. Four died of relapse and one of treatment-related complications. The Kaplan-Meier 2-year overall and event free survival rate was 28.6 percent each in malignant diseases. Conclusion : Second HSCT for graft dysfunction of nonmalignant disease seems to be feasible and should be considered as a standard practice. The relapse of malignant diseases remains a big obstacle even after the second HSCT, although a small portion of patients might be salvaged. Further investigation of novel therapeutic strategies, as well an the understanding of the biology should be explored.

목 적 : 조혈모세포이식은 혈액암뿐만 아니라, 유전 질환, 면역질환에서 완치의 방법으로 널리 사용되고 있다. 그러나 생착 실패나 재발로 인해 조혈모세포이식이 실패하는 경우가 종종 있고, 이때는 장기 생존이 거의 불가능한 것으로 알려져 있으며, 치료방법도 정립되지 않았다. 이에 본 저자들은 1차 이식이 실패한 경우 치료법으로써 2차 이식의 의의에 대해 알아보고자 하였다. 방 법 : 1991년 5월부터 2004년 12월까지 전남대학교병원 소아과에서 조혈모세포이식을 시행한 115례 중에서 생착 실패나 재발로 2차 이식을 시행한 비혈액암 8례(재생불량성빈혈 7례, 부신백질이영양증 1례)와 혈액암 7례(급성골수성백혈병 3례, 급성림프구성백혈병 2례, 만성골수성백혈병 1례, 골수이형성증후군 1례), 총 15례의 의무기록지를 바탕으로 치료 방법, 합병증, 치료성과 등에 대해 분석 하였다. 결 과 : 비혈액암의 경우 2례는 일차성 생착 실패, 5례는 후기 이식편 거부, 1례는 Fanconi 빈혈로 1차 이식 후 급성골수성백혈병으로 전환되어 2차 이식을 시행하였다. 1차 이식 후 이식편기능 부전까지 기간은 중앙값 130.5일(범위, 59-279일)이었고, 1차와 2차 이식 사이의 간격은 중앙값 348일(범위, 86-1,875일)이었다. 전처치는 7례에서 cyclophosphamide를 기본으로 하였고, fludarabine을 3례에서, 방사선 조사를 2례에서 사용하였다. 이식원은 6례에서 조직형 일치 형제간 말초조혈모세포를, 1례에서 조직형 일치 형제간 골수를, 1례에서 제대혈을 사용하였고, 제대혈을 사용한 1례를 제외한 7례는 2차 이식의 공여자가 1차 이식 시와 동일하였다. 급성 이식대숙주병은 1례에서 Grade IV로 발생하였다. 총 8례 중 2례가 사망하였고, 1례는 생착 실패하였으나 생존하여, 5년 Kaplan-Meier(K-M)전체생존율은 75.0%, 무병생존율은 62.5%이었다. 혈액암의 경우 모두 재발로 인해 2차 이식을 시행하였다. 1차 이식 후 재발까지 기간은 중앙값 174일(범위, 90-1,474일)이었고, 1차 이식과 2차 이식 사이의 간격은 중앙값 319일(범위, 178-1,715일)이었다. 전처치는 5례에서 fludarabine, busulfan, antithymocyte globulin 병합요법을, 1례는 busulfan, ara-C, idarubicine 병합요법을, 나머지 1례는 melphalan, busulfan 병합요법을 사용하였다. 이식원은 5례는 1차 이식과 동일한 공여자의 말초조혈모세포였고, 나머지 2례는 제대혈을 사용하였다. grade II 이상의 급성 이식대숙주병은 2례에서 발생하였다. 사망한 5례 중 4례는 재발로, 나머지 1례는 이식관련 합병증으로 사망하였다. 2년 K-M 전체생존율과 무병생존율은 각각 28.6%이었다. 결 론 : 조혈모세포이식을 시행하고 이식편 거부나 재발이 된 경우 2차 이식은 일부 환자에서 장기 생존을 가능하게 하는 방법이 될 수 있다. 비혈액암 질환, 특히 재생불량성빈혈에서 생착 실패를 보이는 경우 2차 이식을 시행하는 것을 추천할 수 있지만, 적절한 전처치와 이식원에 관한 연구가 더 필요하겠고, 혈액암 질환에서 재발한 경우에는 소수에서만 장기 생존이 가능하므로 더욱 효과적인 항백혈병 치료가 필요할 것으로 사료되었다.

Keywords

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