Improved Outcome of Central Nervous System Germ Cell Tumors: Implications for the Role of Risk-adapted Intensive Chemotherapy

Yoo, Keon Hee,Lee, Soo Hyun,Lee, Jeehun,Sung, Ki Woong,Jung, Hye Lim,Koo, Hong Hoe,Lim, Do Hoon,Kim, Jong Hyun,Shin, Hyung Jin The Korean Academy of Medical Sciences 2010 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.25 No.3

<P>To determine the impact of treatment protocols on the outcome of central nervous system germ cell tumors (CNS-GCTs), we reviewed the medical records of 53 patients who received front-line chemotherapy from September 1997 to September 2006. Pure germinoma, normal alpha-fetoprotein level and beta-human chorionic gonadotropin level <50 mIU/mL were regarded as low-risk features and the others as high-risk. Patients from different time periods were divided into 3 groups according to the chemotherapy protocols. Group 1 (n=19) received 4 cycles of chemotherapy comprising cisplatin, etoposide and bleomycin. Group 2 (n=16) and group 3 (n=18) received 4 cycles of chemotherapy with cisplatin, etoposide, cyclophosphamide and vincristine in the former and with carboplatin, etoposide, cyclophosphamide and bleomycin in the latter. In group 2 and group 3, high-risk patients received double doses of cisplatin, carboplatin and cyclophosphamide. Radiotherapy was given after chemotherapy according to the clinical requirements. The event-free survivals of groups 1, 2, and 3 were 67.0%, 93.8%, and 100%, respectively (group 1 vs. 2, <I>P</I>=0.06; group 2 vs. 3, <I>P</I>=0.29; group 1 vs. 3, <I>P</I>=0.02). Our data suggest that risk-adapted intensive chemotherapy may improve the outcome of patients with malignant CNS-GCTs.</P>

Current status of pediatric umbilical cord blood transplantation in Korea: A multicenter retrospective analysis of 236 cases

Yoo, Keon Hee,Lee, Soo Hyun,Sung, Ki Woong,Koo, Hong Hoe,Chung, Nak Gyun,Cho, Bin,Kim, Hack Ki,Kang, Hyoung Jin,Shin, Hee Young,Ahn, Hyo Seop,Baek, Hee Jo,Han, Dong Kyun,Kook, Hoon,Hwang, Tai Ju,Kim, Wiley Subscription Services, Inc., A Wiley Company 2011 American journal of hematology Vol.86 No.1

<P><B>Abstract</B></P><P>We report the outcome of 236 pediatric umbilical cord blood transplantations (UCBT) performed in Korea. Given that the sources of the grafts were mostly unrelated donors (<I>n</I> = 226; 95.8%), only the results of unrelated UCBT were included for all statistics. The most frequent primary disease was acute leukemia (<I>n</I> = 167). In total, 91.7% of recipients were seropositive for cytomegalovirus (CMV). The median doses of nucleated cells and CD34+ cells were 4.84 × 10<SUP>7</SUP>/kg and 2.00 × 10<SUP>5</SUP>/kg, respectively. The median times to neutrophil (>0.5 × 10<SUP>9</SUP>/L) and platelet recovery (>20 × 10<SUP>9</SUP>/L) were 18 and 45 days, respectively. Grade 2–4 acute graft‐versus‐host‐disease (GVHD) and chronic GVHD developed in 41.1 and 36.1% of cases, respectively. Forty‐five patients developed CMV disease. The 5‐year overall and event‐free survival were 47.5 and 36.9%, respectively. Multivariate analysis revealed that adverse factors for survival of the whole cohort were total body irradiation‐based conditioning (<I>P</I> = 0.007), salvage transplant (<I>P</I> = 0.001), failure to achieve early complete chimerism (<I>P</I> < 0.0005), and CMV disease (<I>P</I> = 0.001). The outcomes of the single‐ and double‐unit UCBT (<I>n</I> = 64) were similar, while double‐unit recipients were heavier (<I>P</I> < 0.0005) and older (<I>P</I> < 0.0005). We conclude that double‐unit UCBT is a reasonable option for older or heavier children and that the thorough surveillance of CMV infection and the development of an effective CMV therapeutic strategy may be especially important for Korean children, whose CMV seroprevalence exceeds 90%. Am. J. Hematol., 2011. © 2010 Wiley‐Liss, Inc.</P>

조혈모세포이식을 위한 최적의 제대혈 선택 지침

유건희 ( Keon Hee Yoo ) 대한내과학회 2014 대한내과학회지 Vol.86 No.1

Umbilical cord blood (CB) has been an alternative hematopoietic stem cell source especially for patients without an appropriate marrow or mobilized peripheral blood donor. Although many studies have shown similar overall survival rates after CB transplantation compared with other donor sources, higher rate of non-relapse mortality is a major obstacle for a successful CB transplantation. Thus, selecting a best appropriate unit is very important to improve the outcome of CB transplantation. Adequate cell dose and better HLA matching (antigen-level for -A, -B, and allele-level for -DRB1) have been considered most important criteria of donor choice for CB transplantation. In recent, other criteria including non-inherited maternal antigens, HLA-C matching, allele-level matching at 8 loci (-A, -B, -C, -DRB1), and anti-HLA antibodies are also suggested as factors that might affect the outcome of CB transplantation. This review will highlight current issues regarding criteria of donor choice for CB transplantation. Finally, I will introduce the algorithm and detailed guideline for CB selection recently developed in Korea, which may help physicians to choose best unit available. (Korean J Med 2014;86:14-19)

Risk Stratification of Childhood Medulloblastoma Using Integrated Diagnosis: Discrepancies with Clinical Risk Stratification

Cho Hee Won,Lee Hyunwoo,Ju Hee Young,Yoo Keon Hee,Koo Hong Hoe,Lim Do Hoon,Sung Ki Woong,Shin Hyung Jin,Suh Yeon-Lim,Lee Ji Won 대한의학회 2022 Journal of Korean medical science Vol.37 No.7

Background: Recent genomic studies identified four discrete molecular subgroups of medulloblastoma (MB), and the risk stratification of childhood MB in the context of subgroups was refined in 2015. In this study, we investigated the effect of molecular subgroups on the risk stratification of childhood MB. Methods: The nCounter® system and a customized cancer panel were used for molecular subgrouping and risk stratification in archived tissues. Results: A total of 44 patients were included in this study. In clinical risk stratification, based on the presence of residual tumor/metastasis and histological findings, 24 and 20 patients were classified into the average-risk and high-risk groups, respectively. Molecular subgroups were successfully defined in 37 patients using limited gene expression analysis, and DNA panel sequencing additionally classified the molecular subgroups in three patients. Collectively, 40 patients were classified into molecular subgroups as follows: WNT (n = 7), SHH (n = 4), Group 3 (n = 8), and Group 4 (n = 21). Excluding the four patients whose molecular subgroups could not be determined, among the 17 average-risk group patients in clinical risk stratification, one patient in the SHH group with the TP53 variant was reclassified as very-high-risk using the new risk classification system. In addition, 5 of 23 patients who were initially classified as high-risk group in clinical risk stratification were reclassified into the low- or standard-risk groups in the new risk classification system. Conclusion: The new risk stratification incorporating integrated diagnosis showed some discrepancies with clinical risk stratification. Risk stratification based on precise molecular subgrouping is needed for the tailored treatment of MB patients.

Current Status and Physicians’ Perspectives of Childhood Cancer Survivorship in Korea: A Nationwide Survey of Pediatric Hematologists/Oncologists

Lee Ji Won,Yeo Yohwan,Ju Hee Young,Cho Hee Won,Yoo Keon Hee,Sung Ki Woong,Koo Hong Hoe,Jeong Su-Min,Shin Dong Wook,Baek Hee Jo,Kook Hoon,Chung Nack-Gyun,Cho Bin,Kim Young Ae,Park Hyeon Jin,Song Yun-Mi 대한의학회 2023 Journal of Korean medical science Vol.38 No.29

Background: Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians’ perspectives. Methods: A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken. Results: Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/ oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate. Conclusion: The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.

The First Case of Acute Myeloid Leukemia With Underlying Fanconi Anemia due to FANCF Variants in Korea

Suh Eunsang,Shin Sunghwan,Ju Hee Young,Yoo Keon Hee,Kim Hyun-Young,Cho Duck,Kim Sun-Hee,Kim Hee-Jin 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.2

A Case of Hereditary Spherocytosis Initially Manifested as an Aplastic Crisis Caused by Parvovirus B19 Infection

Hyungsuk Jin,Ji Won Lee,Hee Young Ju,Hee Won Cho,Ju Kyung Hyun,Ki Woong Sung,Hong Hoe Koo,Hee-Jin Kim,Keon Hee Yoo 대한소아혈액종양학회 2020 Clinical Pediatric Hematology-Oncology Vol.27 No.2

Hereditary spherocytosis (HS) is the most common inherited red cell membrane disorder. Its main laboratory finding is anemia with reticulocytosis. However, in the case of an aplastic crisis, there may be no reticulocytosis, making the diagnosis of HS difficult. We present the case of a 4-year-old boy who initially presented with persistent fever and sore throat. His 8-year old brother also had anemia of unknown etiology, and his father had a history of splenectomy in his 20s. Physical examination revealed anemic conjunctivae and hepatosplenomegaly, and laboratory findings showed anemia with decreased reticulocyte count and elevated ferritin and lactate dehydrogenase levels. A peripheral blood smear showed microcytic hypochromic anemia with severe poikilocytosis (spherocytes, acanthocytes, schistocytes), and bone marrow examination revealed decreased erythroid cells and increased hemophagocytosis. Increased osmotic fragility was observed, and parvovirus B19 was detected using polymerase chain reaction. Hence, we established the diagnosis of hereditary spherocytosis manifested as an aplastic crisis caused by parvovirus B19 infection.

A Case with Multiple Fungal Coinfections in a Patient who Presented with Pancoast Syndrome

( Hyungsuk Jin ),( Dongsub Kim ),( Joon-sik Choi ),( Hee Jae Huh ),( Nam Yong Lee ),( Joungho Han ),( Hee Won Cho ),( Youngeun Ma ),( Tae Yeon Jeon ),( So-young Yoo ),( Keon Hee Yoo ),( Hong Hoe Koo ) 대한소아감염학회 2021 Pediatric Infection and Vaccine Vol.28 No.1

소아암 환자에서 발생하는 침습성 진균 감염은 사망과 후유증에 이르는 중대한 감염이다. 18세 남자 환자가 호중구감소 기간 동안 입원하여 치료받던 중 우측 견관절과 우측 팔에 감각이상과 신경쇠약을 호소하였고, 우측폐상엽의 폐렴이 진단되었다. 기관지의 조직학적 소견과 폐 수술검체에서 시행한 polymerase chain reaction (PCR)로 털곰팡이증을 확진하였으며, 흉수액의 PCR로 페니실리움 디쿰벤스 감염, 갈락토마난 항원법으로 아스페르길루스증을 추정하였다. 환자는 백혈병이 치료되지 못하고 Staphylococcus epidermidis 패혈증이 합병되어 사망하였다. 본 증례에서는 판코스트 증후군의 증상을 보인 환자에서 진단된 다발성 폐진균증을 보고 하는 바이다. Invasive fungal infection (IFI) is a serious threat to pediatric patients with cancer given high morbidity and mortality. We present an 18-year-old male with precursor T-cell lymphoblastic leukemia who developed Pancoast syndrome, presented with paresthesia and numbness in the right shoulder and arm during a neutropenic fever period. He was diagnosed with pneumonia in the right upper lung field. He was later found to have an invasive pulmonary fungal infection caused by multiple fungi species, including Rhizomucor, confirmed by histology and polymerase chain reaction (PCR) (proven infection), Penicillium decumbens diagnosed by PCR, and Aspergillus suspected from galactomannan assay (probable infection). Unfortunately, the patient's condition further worsened owing to the aggravation of leukemia, chemotherapy-induced neutropenia, and bacterial coinfection, leading to multiorgan failure and death. Here, we report a case of IFI caused by multiple fungal species that presented as Pancoast syndrome.

The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis

Yoon, Hoi Soo,Im, Ho Joon,Moon, Hyung Nam,Lee, Jae Hee,Kim, Hee-Jin,Yoo, Keon Hee,Sung, Ki Woong,Koo, Hong Hoe,Kang, Hyung Jin,Shin, Hee Young,Ahn, Hyo Seop,Cho, Bin,Kim, Hack Ki,Lyu, Chuhl Joo,Lee, M Blackwell Publishing Ltd 2010 Pediatric transplantation Vol.14 No.6

<P>Yoon HS, Im HJ, Moon HN, Lee JH, Kim H-J, Yoo KH, Sung KW, Koo HH, Kang HJ, Shin HY, Ahn HS, Cho B, Kim HK, Lyu CJ, Lee MJ, Kook H, Hwang TJ, Seo JJ. The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis.Pediatr Transplantation 2010: 14:735–740. © 2010 John Wiley & Sons A/S.</P><P>Abstract: </P><P>Chemoimmunotherapy-based treatments have improved the survival of patients with HLH, but outcomes of the patients are still unsatisfactory. We report here the outcome of Korean children with HLH who underwent HSCT, which was analyzed from the data of a nation-wide HLH registry. Retrospective nation-wide data recruitment for the pediatric HLH patients diagnosed between 1996 and 2008 was carried out by the Histiocytosis Working Party of the Korean Society of Hematology. Nineteen patients who received HSCT among the total of 148 enrolled children with HLH were analyzed for the transplant-related variables and events. The probability of five-yr survival after HSCT was 73.3% with a median follow-up of 57. Two months compared to 54.3% for the patients who were treated with chemoimmunotherapy only (p<I> </I>=<I> </I>0.05). The reasons for HSCT were active disease after eight wk of initial treatment (n = 9), relapsed disease (n = 5), and FHL (n = 5). Fourteen patients are currently alive without disease after HSCT, four patients died of treatment-related events (infection in two and graft failure in two) at early post-transplant period, and one patient died of relapse at one yr post transplantation. The survival of patients who were transplanted because of active disease after eight wk of initial treatment was worse compared to those patients who had inactive state at that time (60.6% vs. 100%, respectively, p<I> </I>=<I> </I>0.06). Of the four patients who received transplants using cord blood, three died of graft failure (n = 2) and relapse (n = 1). The five-yr probability of survival after HSCT according to the donor type was 85.7% for the MRDs (n = 6), 87.5% for the MUDs (n = 8), and 40% for the MMUDs (n = 5) (p<I> </I>=<I> </I>0.03). Other variables such as age, CNS involvement at the time of diagnosis, the etiology of HLH (familial or secondary), and the conditioning regimens had no influence on the five-yr OS of the HLH patients who underwent HSCT. HSCT improved the survival of the patients who had familial, relapsed, or severe and persistent SHLH in the Korean nation-wide HLH registry. Although numbers were small, these results are similar to other reports in the literature. The disease state after initial treatment, the stem cell source of the transplant, and the donor type were the important prognostic factors that affected the OS of the HLH patients who underwent HSCT.</P>

유전성 대사질환에서의 동종조혈모세포이식 : 단일 기관에서의 경험 A single center experience

유건희,김흥렬,이지은,이호영,천정미,성기웅,구홍회,이문향,진동규,김종원,김대원,김형록 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

배경: 유전성 대사질환의 치료로서 효소 요법 및 유전자 치료가 제한적인 현실에서 동종 조혈모세포이식이 현재로선 가장 중요한 치료가 될 수 있다. 본 연구에서는 단일 기관에서 유전성 대사질환에 대해 동종 조혈모세포이식을 시행한 경험을 보고하고자 하였다. 방법: 삼성서울병원 유전성 대사질환 조혈모세포이식팀에서는 1999년 12월부터 2001년 3월까지 총 6례의 유전성 대사질환을 대상으로 동종 조혈모세포이식을 시행하였다. 대상 질환은 Hunter 증후군 3례, galactosialidosis 1례, 이염성 백질이영양증 1례, 부신백질이영양증 1례였으며 성별 분포는 남아가 5명, 여아가 1명이었으며 연령 분포는 2년 9개월에서 15년 9개월이었다. 5례는 HLA 일치 혈연간 골수이식이었으며 1례는 HLA 불일치 T 림프구 제거 말초혈액 조혈모세포이식이었다. 전처치는 모두 BuCy를 사용하였으며 이식편대숙주반응의 예방에는 cyclosporine을 사용하였다. 이식된 세포는 유핵세포가 4.81×10^(8)(2.40~7.01×10^(8))/kg이었으며 CD34+ 세포는 3.65×10^(6)(0.88~10.72×10^(6))/kg이었다. 결과: 이식 후 조혈기능의 회복은 모두 조기에 달성되었으며(ANC>500: 정중 9.5일, 범위 9~14일; PLT>50K: 정중 32일, 범위 23~34일) 이식과 관련된 합병증은 Gr I의 aGVHD 3례, 국한성의 cGVHD 1례, 경증의 간정맥 폐쇄성 질환이 1례이었다. 모든 환자에서 직간접적으로 이식 후 효소의 생산이 증가함이 확인되었으며 임상적인 호전을 보인 경우가 4례, 질병 진행이 중단된 경우가 1례, 질병이 진행된 경우가 1례이었다. 질병 진행이 중단되었던 1례는 면역억제제 투여 중 수두 감염에 의한 폐출혈로 사망하였다. 결론: 유전성 대사질환에서 동종 조혈모세포이식이 가장 중요한 치료법으로 사용될 수 있고 중추신경계 증상이 나타나기 전, 가능한 조기에 조혈모세포이식을 시행하는 것이 바람직할 것이며 적극적인 지지 요법이 필요하다. 향후 더 많은 임상 경험이 필요하리라 사료된다. Background: Allogeneic hematopoietic stem cell transplantation (HSCT) may be the most important treatment modality to cure a number of genetic metabolic disorders because of the limitation of enzyme replacement or gene therapy. In this study, we report our single center experience about HSCT in several genetic metabolic disorders. Methods: We performed 6 cases of HSCT for genetic metabolic disorders from December 1999 to March 2001. Patients' diagnoses were Hunter syndrome (3), galactosialidosis (1), metachromatic leukodystrophy (1), and adrenoleukodystrophy (1). Stem cell sources were bone marrow from HLA matched sibling donors in 5 patients and mother's peripheral blood stem cells in one patient who did not have HLA matched donors. Busulfan and cyclophosphamide for conditioning, and cyclosporine for the prevention of graft versus host disease were used in all patients. Transplanted total nucleated cell counts were median 4.81×10^(8)(2.40~7.01×10^(8))/kg , and CD34+ cells 3.65×10^(6)(0.88~10.72×10^(6))/kg. Results: All patients achieved early hematologic recovery (median 9.5 days, range 9~14 days for ANC>500/μL; median 32 days, range 23~34 days for PLT>50,000/μL). Transplant-related complications were 3 cases of grade 1 acute GVHD, a case of limited chronic GVHD, and a case of mild hepatic veno-occlusive disease. Enzyme levels were normalized in 4 patients evaluated and there were indirect evidences of enzyme production in the other 2 patients after HSCT. Four of the 6 patients showed symptomatic improvement, 1 patient (galactosialidosis) experienced disease stabilization without progression before he eventually died due to pulmonary hemorrhage, and the other 1 patient deteriorated progressively even after HSCT. Conclusions: Allogeneic HSCT can be done as the only curative treatment in a number of genetic metabolic disorders. It seems desirable to perform HSCT as early as possible before the onset of central nervous system symptoms. More experience and long term follow up is needed to evaluate the efficacy and to monitor the long term transplant-related complications.