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김동욱,한훈,김정아,김희제,민창기,엄현석,최정현,이종욱,한치화,홍영선,최일봉,신완식,민우성,김학기,김춘추,김원일,김동집 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1
목적: 비혈연간 골수이식은 혈연내에 적절한 골수공여자가 없는 만성골수성백혈병, 고위험군의 급성별혁병, 면역억제치료에 실패한 재생불량성빈혈 및 각종 난치성 조혈모세포질환의 완치를 위한 표준적인 치료방법으로 정착되고 있다. 혈연간 표준적인 동종 이식에 비하여 비혈연간 이식시에는 생착부전, 이식편대숙주반응과 감염이 더 빈번하게 발생하며, 국내에서는 아직까지 체계적인 임상연구결과가 보고된 바 없었다. 이에 본 센터에서는 1995년 10월 이후로 약 20개월간 26예의 비혈연간 골수이식을 시행하였으며 3개월 이상의 추적관찰이 가능하여 이식초기 합병증의 관찰 및 분석이 가능하였던 20예의 환자를 대상으로 이식성적 및 문제점을 보고함으로써 새롭게 확대되고 있는 이 분야의 임상연구 및 진료의 활성화를 꾀하고자 한다. 방법: 각종 혈액 종양질환으로 비혈연간 이식을 시행한 총 26예의 환자중 3개월이상의 추적관찰이 가능하였던 20예를 대상으로 후향적으로 임상경과를 분석한 후 생존 분석을 시행하였고, 환자의 연령, 성별, 질병의 상태, 조식 적합 항원의 일치정도, 이식편대 숙주 반응의 유무와 생존기간과의 상관관계를 살펴보았다. 또한 표준위험군과 고위험군으로 나누어 생존율을 비교하였고 이식과 관계된 생착 부전, 이식편대숙주반응, 감염의 발생과 양상 그리고 그 합병증을 관찰하였다. 결과: 1. 환자와 공여자간에 HLA 불일치가 20예 중 4예에서 있었으며, 생착여부의 확인이 가능했던 17예 중 16예에서 생착이 확인되어 94.1%의 생착율을 보였다. 2. 급성이식편대숙주반응은 62.5%(10/16예)에서 발생하였으며 111도 이상의 급성의 이식편대숙주 반응은 25%(4/16예)에서 발생하였다. 만성이식편대숙주반응은 40%(2/5예)의 환자에서 발생하였으며 이들 모두 국소형으로 중증의 진행형 만성이식편대숙주반응이 관찰된 환자는 없었다. 3. 호흡기 합병증은 10예(50%)에서 발생하였으며 감염성 폐렴을 포함한 호흡기 합병증이 가장 흔한 일차적인 사망 원인이었다. 호흡기 합병증이 발생했던 10예중 6예가 감염에 의한 폐렴이 의심되었고 나머지 4예는 특발성 간질성 폐렴이었다. 4. 8.5개월의 중앙추적기간 중 35%의 생존율을 관찰할 수 있었고, 생존기간은0.5개월에서 15개월 (중앙치:4개월)이었다. 한편 고위험군은 25%(3/12예), 표준위험군은 50%(4/8)의 생존율을 관찰할 수 있었다. 5. 가장 흔한 사망 원인은 감염성 폐렴을 포함한 호흡기 합병증(6예)이었고, 이외의 사망 원인으로는 급성 이식편대숙주반응과 다장기부전이 각각 2예, 생착 부전, 간정맥 폐쇄, 그리고 재발이 각각 1예였다. Unrelated bone marrow transplantation(UBMT) has been increasingly recognized as the standard treatment for cure of chronic myelogenous leukemia, high risk acute leukemia, aplastic failed on immunotherapy, and the variety of refractory hematologic diseases in patients lacking a related donor. However, as compared to HLA identical sibing transplantation, UBMT carries higher incidence of graft failure, graft versus host disease(GVHD), and infection. In our center, 26 patients underwent UMBT between October 1995 and June 1997. The minimum follow-up of 3 months was possible in 20 patients, for whom early complications and clinical outcomes were assessed. The median age of the 20 patients was 24 years. 8 patients had standard risk disease and 12 patients had high risk disease. All patients received various preparative regimens including total body irradiation according to disease and disease status. 19 patients received CsA + short course MTX for GVHD prophylaxis. One patient received marrow that was depleted of T cells ex vivo using avidinbiotin column. The class I loci were typed by serological methods and HLA-A, HLA-B and HLA-DRB1. 3 additional pairs were one minor mismatched at the HLA-B locus. Another one patients was one major mismatched at the DRBI alleles. 17 patients were evaluable for engraftment. Successful enfraftment was confirmed in 16 patients(94.1%). Only one patient who was performed one major DRBI mismatched transplants experienced graft rejection. 16 patients were evaluable for acute GVHD. The overall incidence of acute GVHD developed in 4 patients(25%). Five patients were evaluable for the development of Ⅳ acute GVHD developed in 4 patients (25%). Five patients were evaluanle for the development of chronic GVHD. 2 patients(40%) developed limited chronic GVHD. Respiratory complications including pulmonary infection developed in 10 patients(50%) and these complications were the most common primary cause of death. Of these 10patients, 6 had pneumonia due to fungus(4 patients), pacterial (1 patient), and CMV infection (1 patient) and 4(20%) had idiopathic interstitial pneumonitis and/or adult respiratory distress syndrome. The duration of median follow- up was 8.5 months and 7 of 20 patients(35%) are alive at the time of this analysis with survival duration of 0.5 to 15 months(median survival duration: 4 months). The overall survival was 25% (3/12 patients) in high risk group and 50%(4/8 patients) in standard group. From these results, we can predict that the incidence and severity of GVHD in Korea are lesser than multiracial countries and the long-term survival of patients with standard risk disease can approach that of HLA matched sibling transplants. For the past two years, the performance of UBMT has been rapidly increasing and it will be possible to analyze much larger number of patients soon in Korea. In the future the problems of graft failure, GVHD, and infection due to long lasting immunocompromised status will need to be overcome by continued medical research. In addition, the volunteer donor pool will have to be expanded by the promotion of the national awareness of its need.
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김정아,정현식,김원석,윤성수,이홍기,박찬형,박성규,김동욱,이종욱,한치화,민우성,김춘추,김동집 대한조혈모세포이식학회 1996 대한조혈모세포이식학회지 Vol.1 No.1
Background: In most solid tumors, the CD34 antigen has not been detected, so positive selection of CD34+ cells may reduce tumor cell contamination and the CD34+ cells are capable of reconstituting hematopoiesis. We tried CD34+ cell transplantation in two patients. Method: CD34+ cells from chemotherapy + G-CSF mobilized PBPCs or bone marrow were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). Case 1. One course of chemotherapy using cyclophosphamide(200㎎/㎡) and etoposide (4.2g/㎡), combined with G-CSF(5㎍/㎏) S.C. was used in a relapsed lymphoma patient. This patient responded to the induction chemotherapy. CD34+ cells from harvested bone marrow were selected by the CellPro immunoadsorption column. The total number of mononuclear cells loaded onto the CellPro was 2.4×10^(8)/㎏, with 1.1% CD34+ cells. After column separation, the total number of positively selected cells was 5.16×10^(6)/㎏. The number of CFU-GM was 76.8×10⁴/㎏. This patient was treated with melphalan (140㎎/㎡) and TBI (1200cGy) and the positively selected CD34+ cells were infused. The time to neutrophil recovery greater than 0.5×10^(9)/L was 19 days and the time to platelet recovery greater than 50×10^(9)/L was 21 days. Case 2. Two courses of mobilizing chemotherapy were given 4 weeks apart using taxol(210㎎/m2) and adriamycin(60㎎/m2), combined with G-CSF(5㎍/㎏) S.C. in a breast cancer patients with 7 axillary node metastasis. CD34+ cells from each single leukapheresis product were selected by the CellPro immunoadsorption column. In the first collection, the total number of nucleated cells was 4.4×10^(8)/kg, with 0.42% CD34+ cells. In the second collection, the total number of nucleated cell was 2.8× 10^(8)/㎏ with 0.43% CD34+ cells. After colum separation, the total numbers of collected cells were 4.0×106/kg and 4.8×10^(6)/kg, the total number of CD34+ cells were 1.2×10^(6)/㎏ and 0.82×10^(6)/㎏. Colonogenic assays of positively selected CD34+ cells gave rise to myeloid erythroid, and multilineage colonies, with a median of 190 CFU-GM, 190 BFU-E, and 164 CFU-GEMM per 1×10³ adsorbed cells, respectively. High-dose chemotherapy with cumulative doses of 40mg/㎡ mitoxantrone, 750mg/㎡ thioptepa, and 1000mg/㎡ carboplatin was administered. Positively selected CD34+ cells were rapidly infused 24 hours after the end of high-dose chemotherapy. The time to neutrophil recovery greater than 0.5×10^(9)/L was 16 days and the time to platelet recovery greater than 50×10^(9)/L was 20 days.
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동종 골수이식 후 만성 이식편대숙주반응 환자에서 발생한 폐렴구균에 의한 수막뇌염 1예
신완식,김병욱,유진홍,김동집,김춘추,박종원,이종욱,김동욱,강문원,김양리 대한감염학회 1993 감염 Vol.25 No.3
Graft-versus-host disease (GVHD) is a frequent complication after bone marrow transplantation. Infectious complications are common in GVHD patients due to defect in cell-mediated immunity. A rare case of S. pneumoniae meningoencephalitis occured in a patient with extensive form of chronic GVHD after allogeneic bone marrow transplantation. He was immediately treated with full dosage of ceftriaxone and ampicillin. He suffered from various complications such as sepsis, acute renal failure, atelectasis, and seizure. Despite of aggressive treatment, he died probably due to renal shutdown and massive subacute cerebral infarction of left cerebral hemisphere. This report showed two unusual and rare features. First, the infection site was CNS rather than respiratory system. Second, the causative organism was S. pneumoniae, which is rare cause of CNS infection in immunocompromised patients.
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Kim, Dong Wook,Min, Woo Sung,Kim, Hee Je,Han, Chi Wha,Cho, Seok Goo,Jeong, Ik Joo,Kim, Dong Jip,Kim, Chun Choo CATHOLIC MEDICAL CENTER 1996 Bulletin of the Clinical Research Institute Vol.21 No.1
CD34+ cells, present at low frequency among leukocytes from peripheral blood(PB), human umbilical cord blood(HUC) can be rapidly and efficiently enriched by magnetic cell separation using itiimunomagnetic beads(Dynabeads^R M-450 CD34) for immunophenotyping, characterization in colony-forming cell(CFU) assays. To determine whether CD34+ cells found in the PB-chemotherapy plus cytokine stimulated stem cell mobilization- and in the normal HUC are equivalent to their marrow counterpart, we evaluated their in vitro growth characteristics by colony assays. This study is to investigate the possibility of clinical applications with stimulated PB- and normal HUC-CD34+ cells as multipotent stem cells for BMT by magnetic cell separation using immunomagnetic beads. We had the clonogenic assays and assessed the CFU-GM, CFU-GEMM colony growth in Methocult H4230, H4432 between CD34^+ isolation group and none isolation group in 6 stimulated PB by leukapheresis after chemotherapy plus rhG-CSF, 6 normal HUC, and 8 normal BM cases using Dynal CD34^+ cell selection system. The results were as follows; 1. CD34^+ cells were detected in normal BM, stimulated PB, and normal HUC at incidences of 1.12%, 0.36%, and 0.58% of total mononuclear cells, respectively. 2. The average CD34^+ cells for total mononuclear cells(5×10^7/mL) in BM, PB, and HUC were 5.6 × 10^5mL, 1.8 × 10^5/mL, 2.9 × 10^5/mL in order. 3. The colony counts after 2 week culture revealed more in CD34^+ isolation group using CD34^+ progenitor cell selection system. And the purified CD34^+ cells of each & every specimen express 130 fold, 160 fold, and 170 fold more CFU-GM colony growth than those of CD34^+ none isolation groups. The growth of CFU-GEMM revealed as 180 fold, 200 fold, and 160 fold more in CD34^+ isolation groups. These results suggest that purification of large numbers of CD34^+ cells from stimulated PB, normal HUC by MACS is not only relevant for the characterization of migrating stem cells especially in case of chemotherapy plus cytokine PB mobilization but also opens new possibilities for stem cell transplantation and genetic manipulation of the hematopoietic system. We conclude that 0034^ enrichment procedure from the use of immunomagnetic beads labelling with monoclonal antibodies(MoAbs) in stimulated PB and HUC can facilitate the more safe and the more easier autologous and allogenic BMT particularly from unrelated donors to patients with malignant solid tumors and with various kinds of hematopoietic disorders.
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