Repetitive Allogeneic PBSC Boostings to Reverse BM Aplasia caused by DLI for the Relapsed CML after Allogeneic BMT

남동기 ( Dong Ki Nam ),정철권 ( Cheol Gweon Jeong ),조도연 ( Do Yeun Cho ),박준성 ( Joon Seong Park ),임호영 ( Ho Yeong Lim ),최진혁 ( Jin Hyuk Choi ),김현수 ( Hyun Soo Kim ),김효철 ( Hugh Chul Kim ),성주명 ( Chu Myong Seong ) 대한내과학회 1999 대한내과학회 추계학술대회 Vol.57 No.-

고위험군 및 전이성 유방암 환자에서 말초혈액 자가 조혈모세포 이식술을 동반한 고용량 항암치료

박준성,정철권,고광현,조도연,김현수,최진혁,남동기,임호영,김효철 대한조혈모세포이식학회 1999 대한조혈모세포이식학회지 Vol.4 No.2

연구배경: 제4기 유방암 환자의 2년 생존율이 15-20%정도로 알려지고 있으며, 최근 20년간 사망률을 줄이기 위한 노력들이 시도되었으나 전이성 유방암 환자나 액와 림프절 10개 이상의 전이를 보이는 고위험군이 경우 근치적 수술 및 수술후의 고식적 항암 화학요법으로 장기 생존율을 놓이지 못하는 실정이다. 이에 저자 등은 최근 10년간 고용량 항암 화학요법에 대한 주목할만한 연구들이 진행되고 있는바, 고 위험군 및 초치료 후 전이성 유방암으로 재발된 환자에게 말초 및 혈액 자가 조혈모세포 이식술을 동반한 고용량 항암 화학요법에 따른 전체 생존율(Oerall survival rate: OS) 과 병기 유지 생존율 (Progression Free survival rate: PFS)을 경험하여그 경향을 보고하는 바이다. 방법: 1995년 5월부터 1998년 11월까지 고 위험군 및 초치료 후 전이성 유방암으로 재발되어 아주대학교병원에서 고용량 항암화학요법 및 말초혈액 자가조혈모세포 이식술을 시행받은 27명의 여자환자를 대상으로 고 위험군(high risk for relapse), 단순 재발군(sensitive relapse), 불응성 재발군(refractory relapse)으로 나누어 치료효과를 비교하였다. 결과: 액와 림프절 10개 이상의 전이를 보인 고위험군이 6명, 재발한 후 고식적 항암 화학 요법에 반응을 보인 단순 재발군이 11명, 반응을 보이지 않은 불응성 재발군이 11명이였고, 불응성 재발군 중 3명은 고용량 항암 화학요법 이후에도 병소가 남아있어서 한 차례 더 고용량 항암 화학 요법을 시행받았다. 중앙추적기간은 16개월(1-36개월), 중앙연령은 44세(30-58세)이었고, 말초혈액 조혈모세포 이식을 위하여 G-CSF 투여후 추출된 단핵세포 (MNC) 수는 평균 3.70×10^(8)/kg, CD34^(+) 세포는 평균 8.18×10^(8)/kg이었다. 골수 생착(말초혈액 절대 호중구 수치 >500/㎕)은 모든 환자에서 이루어졌으며, 골수 이식 후 평균 11.1일(중앙값 9일)에 이루어졌다. 치료관련 사망률(Treatment Related Mortality)은 5예로 그 중 1예는 정맥 폐쇄 질환(Ven-Occlusive Disorder), 4예는 패혈증(sepsis)으로 사망하였다. 대상포진 6예에서 발생하였고, 미만성 폐포 손상(Diffuse Alveolar Damage)이 3예 발생하였다. 전체 28명 환자의 전체 생존율(OS)은 56.5%, 고 위험군은 100%, 단순 재발군은 58.8%, 불응성 재발군은 36.4%이었으며, 고위험군의 무병 생존율(DFS)은 55.5%, 평균값(mean DFS duration)은 26개월이었고, 단순 재발군의 병기 유지 생존율(PFS)은 25.2%, 중앙값(median PFS duration)은 20개월이었으며 , 불응성 재발군의 병기 유지 생존율25%, 중앙값은 8개월이다. 결론: 이상의 결과를 고려해 볼 때, 고 위험군과 단순재발군의 경우는 비교적 높은 전체생존율을 보이는 반면, 불응성 재발군의 경우, 고용량 항암화학요법으로 병의 진행을 8개월 정도밖에는 막지 못함을 알수 있었다. 대상포진은 수두바이러스 면역 글로블린으로써 성공적으로 예방할수 있었다. 고용량 항암 화학 요법이 진행성 유방에서 어느 정도 효과적인가를 객관적으로 확인하기 위해서는 보다 많은 증례 수 및 추적기간의 누적, 추적검사의 정확성이 필요하고, 적응증의 선별에 의한 비교연구가 시행되어야 하겠고, 아마도 그에 따라서 통계학적으로 의미 있는 결과를 도출할 수 있을 것으로 기대된다. It is widely accepted that node-positive breast cancer patients should receive adjuvant chemotherapy of hormonal therapy following definitive surgery. While significant change have been made in the care of breast cancer patients over the last 20 years, particularly with regard to surgical management and adjuvant therapy, long term prognosis remains poor for patients with 10 or more involved axillary nodes (high risk for relapse group) and is dismal for patients with stage Ⅳ disease following conventional dose chemotherapy. We investigated the outcomes of 28 patients with breast cancer undergoing chemo-mobilization of peripheral blood stem cells (PBSC) and high dose chemotherapy (HDCT) with PBSC transplantation. 28 patients with a median age of 44 years (range 30-58 years) were entered to out study, three of them received HDCT twice because of residual disease after first HDCT. We divided, the patients into three groups consisting of (1) six patients with 10 or more node positive as a high risk group, (2) 11 relapsed patients who responded to conventional chemotherapy as a sensitive relapsed group, (3) 11 relapsed patients who did not respond to conventional chemotherapy as a refractory relapsed group. Mean follow-up duration was 16.5 months (range 1-36 months), Pre-mobilization chemotherapy included FEC regimen (5-FU 600 mg/m² , Epirubicin 60 mg/m² , Cyclophosphamide 600 mg/m²×3 or 6 cycles) in 15 patients, Paclitaxel with Carboplatin regimen (Taxol 160 mg/m², Carboplatin 300 mg/m²× 3 cycles) in 4 patients, anthracycline containing regimen in eight patients. We collected autologous stem cells from CSF primed peripheral blood after conventional chemotherapy. Mean mononuclear cell (MNC) count was 3.4±1.1×10^(8)/kg, CD34^(+) was 7.6±5.0×10^(6)/kg, CFU-GM was 1.8±2.1×10^(5)/kg. All of the patients engrafted at mean date of 11.1 days after transplantation (median 9 days). As the high dose chemotherapy, 22 patients received CBP regimen (Cyclophosphamide 6g/m², BCNU 400mg/m² Cisplatin 165 mg/m²), three patients ICE regimen (Ifosphamide 8g/m², Carboplatin 1.2 g/m², Etoposide 600 mg/m²), six patients ML regimen (Mitoxantrone 75 mg/m², Melphalan 180 mg/m²) Treatment-related mortality (TRM) was developed in five patients (one due to VOD, four due to sepsis). Diffuse alveolar damage was developed in three patients, and Herpes Zoster infection was developed in six patients. Overall survival (OS) rate of all patients was 56.5%(high risk group 100%, sensitive relapsed group 58.9%, refractory relapsed group 36.4%). Disease free survival (DFS) rate of high risk group was 55.5% with 26 months of mean DFS duration. Progression free survival (PFS) rate of sensitive relapsed group was 25.2% with 20 months of median PFS duration. PFS rate of refractory relapsed group was 25% with 8 months of median PFS duration.

다양한 고염투석액을 이용한 혈액투석시 혈액량의 변화 및 부작용 발생의 관찰

김홍수,김상돈,김도헌,김헌종,고광현,김승정,마경애,김명성,정철권,이한민,지석배,신규태 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.3

Chronic hemodialysis patients frequently experience hemodialysis(HD)-related side effects caused by excessive ultrafiltration and abrupt change of osmolality. Sodium ramping in HD is known to reduce ultrafiltration-related side effects, but it frequently induces symptoms related to sodium overload. We wanted to know the relationship between blood volume changes and the side effects related to ultrafiltration during hemodialysis and whether we can individualize various sodium ramping methods according to the effect of change in blood volume( BV) and side effects of sodium ramping. We studied 9 hypotension-prone patients during HD. The duration of the study lasted for 5 weeks, each week using different sodium ramping protocols: protocol 1; dialysate [Na+] of 140mEq/L, protocol 2; dialysate [Na?] same as the predialysis serum [Na+], protocol 3; dialysate [Na+] was 20mEq/L greater than that of the patient's serum for 1hr, 10mEq/L greater than patient's serum [Na+] for 2hr and then the same as patient's serum] for the last 1hr, protocol 4; at the beginning of dialysis, dialysate sodium was ramped to 20mEq/L above the patient's serum sodium and then on a straight linear fashion lowered to the predialysis serum [Na+] at the end of dialysis, protocol 5; sodium was constantly ramped to 10 mEq/L above serum [Na+]. We measured the BV with Crit-Line IIR(In-Line Diagnostics, Corp., Riverdale, USA), the blood pressure during each HD and interdialytic weight gain. We documented subjective symptoms which occurred during the 5 treatment protocols by patient's questionnaire after each HD. The results were as follows. 1) The mean age of the patients(M:F=3:6) was 54.1years and 6 patients were diabetics. 2) There was no significant difference in the BV among the 5 protocols in both whole study population and individual. Neither was there a statistically significant difference in the BV with respect to hypotension during HD. 3) There were no episodes of hypotension(P value $lt;0.001) with protocols 3, 4, 5 compared to protocs 1 and 2. 4) Three patients during protocols 4 and 5 experienced more thirst after HD than during protocol 1 and one patient during protocol 4, 5 had more interdialytic weight gain than the protocol 1. As a whole, patients while on protocol 4 & 5 experienced more thirst than protocol 1 but patients during protocol 3 experienced the same degree of thirst as protocol 1. In summary, sodium ramping reduced HD-related side effects but this benefit could not be explained on the basis of blood volume change measured by the Crit-Line IIR. Protocol 3 may be more appropiate sodium ramping method in 4 of the 9 patients. These data suggest that protocol 3 may be used before protocol 4, 5 when we apply sodium ramping to the patients who frequently have hypotension during HD.