필라델피아 염색체 양성 급성골수성백혈병에서 Imatinib Mesylate로 분자학적 관해를 유도한 후 성공적인 자가 말초혈액 조혈모세포이식이 시행되었던 1예

김여경,이제중,이병환,변정래,조덕,이일권,정익주,양동욱,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1

저자들은 필라델피아 염색체 양성 급성골수성백혈병 환자에서 복합항암화학요법으로 혈액학적 완전관해를 유도하고, imatinib mesylate를 이용하여 분자학적 관해를 유도한 후, 성공적으로 자가 말초혈액조혈모세포이식을 시행하였던 1예를 경험하였기에 이를 보고하는 바이다. Philadelphia chromosome (Ph¹)-positive acute myeloid leukemia (AML) is very rare disease, comprising 3~4% of the AML, and is a clinically distinct entity with poor clinical outcome with conventional chemotherapy. We report a case of Ph¹-positive AML who underwent successful autologous peripheral blood stem cell transplantation after achieving a molecular remission with imatinib mesylate.

진행성 비호지킨 림프종 환자에서 ICE 구제 요법에 의한 조혈모세포 가동화 후 자가 말초혈액 조혈모세포이식

이제중,이병환,김여경,변정래,이일권,박무림,정익주,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1

연구배경: 비호지킨 림프종에서 자가 말초혈액 조혈모세포이식술이 폭넓게 이용됨으로 인해서, 높은 치료효과뿐만 아니라 조혈모세포의 가동화 효율이 높은 구제 요법이 요구되었다. 방법: 본 연구에서는 진행성 비호지킨 림프종에서 ICE 요법을 이용하여 조혈모세포를 가동화시킨 후 자가 말초혈액 조혈모세포이식이 시행하였던 환자를 후향적으로 분석하였다. 결과: 대상 환자의 중앙 연령은 38세(범위, 16~61)였으며, ICE 요법은 환자당 4주기(범위, 1~6주기)가 투여되었고, 투여 간격은 중앙값이 24일(범위, 16~36일)이었다. 고위험도 관해군을 제외한 13예의 환자 중 완전반응은 7예(53.8%), 부분반응은 4예(30.8%), 진행성질환은 2예(15.4%)를 보였다. 치료에 따른 3~4등급의 혈액학적 독성은 중성구감소증이 13예(81.3%), 혈소판감소증이 7예(42.8%)에서 관찰되었다. 조혈모세포 채집은 ICE 요법 후 중앙값이 12일(범위, 6~20일)에 시행되었고, 각 ICE 요법당 채집한 단핵구치는 중앙값이 5.75× 10^(8)/체중, CD34^(+) 세포는 중앙값이 1.25× 10^(6)/체중, CFU-GM치는 중앙값이 1.19× 10^(5)/체중이었다. 조혈모세포이식은 11예에서 시행되었고, 중앙 추적기간 401일에 평가한 2년 전체생존율은 70.1±14.7%, 1년 및 2년 무사건생존율은 각각 60.7±15.4%와 32.3±17.1%를 보였다. 결론: ICE 요법은 재발성/불응성 비호지킨 림프종 환자에서 높은 치료 반응률과 만족할 만한 조혈모세포 가동화를 보여 주었지만, 치료에 대한 순응도가 낮아서 투여 간격이 연장되는 문제점을 안고 있어서, 우리나라 환자의 실정에 적합한 구제요법에 대한 연구가 필요할 것으로 생각된다. Background: Due to the extensive application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT), a salvage chemotherapeutic regimen with high response rate as well as effective capacity of PBSC mobilization is needed in non-Hodgkin's lymphoma (NHL). Methods: We analyzed the applicability of ICE (ifosphamide, carboplatin, and etoposide) regimen in NHL patients who underewent autologous PBSCT. Results: The median age was 38 years (range, 16~61 years), the patients received median 4 cycles (range, 1~6 cycles) of ICE regimen, and the median interval between each chemotherapeutic cycle was 24 days (range, 16~36 days). There were 7 (53.8%) complete responses, 4 (30.8%) partial responses, and 2 (15.4%) progressive diseases after ICE regimen. Toxicity included grade 3/4 neutropenia and throm bocytopenia in 13 (81.3%) and 7 (42.8%) patients, respectively. PBSC collection began on median day 12 (range, 6~20 days) after ICE therapy. The median number of mononuclear cells, CD34+ cells, and CFU-GM was 5.75× 10^(8)/kg, 1.25× 10^(6)/kg, and 1.19× 10^(5)/kg, respectively. With a median follow- up of 401 days, the patients who underwent autologous PBSCT had overall survival with 70.1±14.7% at 2 year and event free survival with 60.7±15.4% and 32.3±17.1% at 1 year and 2 years, respectively. Conclusion: ICE chemotherapy is an effective cytoreduction and mobilization regimen in patients with NHL, but profound myelosuppression with delayed recovery might pose difficulties in applying for Korean patients. Further evaluation for appropriate salvage regimens in Korean patients should be needed.

동종 골수이식을 시행받은 환자에서 폐색성 세기관지염에 의하여 발생한 자발성 기종격동과 피하 기종

이병환,이제중,이연경,안재숙,김여경,황호인,박무림,조상희,정익주,김형준 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2

저자들은 만성골수성백혈병으로 동종 골수이식과 이식편 부전으로 인하여 추가적인 말초혈액 조혈모세포이식을 시행 받은 환자에서 만성 이식편대숙주질환과 그 폐 합병증인 폐색성 세기관지염에 동반된 자발성 기종격동과 피하 기종이 병발한 1예를 경험하였기에 이를 보고하는 바이다. Obstructive lung disorders following after allogeneic bone marrow transplantation (BMT) in association with graft- versus-host disease (GVHD) contribute significant morbidity and mortality. We report a case of a 28-year-old man who developed spontaneous pneumomediatinum and subcutaneous emphysema complicating bronchiolitis obliterans after allogeneic BMT. He received an allogeneic BMT for chronic phase of chronic myeloid leukemia. Five months after BMT, he was boostered by allogeneic peripheral blood stem cells from the same donor due to graft failure. One month after the boostering, chronic GVHD developed and were treated with cyclosporine and steroid. The patients developed spontaneous pneumomediatinum and subcutaneous emphysema secondary to severe bronchiolitis obliterans 4 months after boostering donor cells. The air-leak syndromes were recovered by conservative management, including high-flow oxygen.

KIT D816 mutation associates with adverse outcomes in core binding factor acute myeloid leukemia, especially in the subgroup with RUNX1/RUNX1T1 rearrangement.

Kim, Hee-Jin,Ahn, Hee Kyung,Jung, Chul Won,Moon, Joon Ho,Park, Chang-Hun,Lee, Ki-O,Kim, Sun-Hee,Kim, Yeo-Kyeoung,Kim, Hyeoung-Joon,Sohn, Sang Kyun,Kim, Sung Hyun,Lee, Won Sik,Kim, Kyoung Ha,Mun, Yeung Springer International 2013 Annals of hematology Vol.92 No.2

<P>Core binding factor (CBF)-positive acute myeloid leukemia (AML) presents a favorable prognosis, except for patients with KIT mutation, especially D816 mutation. The current retrospective study attempted to validate a prognostic role of KIT mutation in 121 Korean patients with CBF AML. The study patients consisted of 121 patients with CBF AML (82 patients with RUNX1/RUNX1T1 [67.8?%] and 39 patients with CBFB/MYH11 [32.2?%]) recruited from eight institutions in Korea. All patients received idarubicin plus cytarabine or behenoyl cytosine arabinoside 3?+?7 induction chemotherapy. The KIT gene mutation status was determined by direct sequencing analyses. A KIT mutation was detected in 32 cases (26.4?%) in our series of patients. The KIT mutation was most frequent in exon 17 (n?=?18, 14.9?%; n?=?16 with D816 mutation), followed by exon 8 (n?=?10, 8.3?%). The presence of KIT D816 mutation was associated with adverse outcomes for the event-free survival (p?=?0.03) and for the overall survival (p?=?0.02). The unfavorable impact of D816 mutation was more prominent when the analysis was confined to the RUNX1/RUNX1T1 subtype. The KIT mutation was detected in 26.4?% of Korean patients with CBF AML. The KIT D816 mutation demonstrated an unfavorable prognostic implication, particularly in the RUNX1/RUNX1T1 subtype.</P>

A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia

Kim, Dong Hwan (Dennis),Lee, Seung-Tae,Won, Hong-Hee,Kim, Seonwoo,Kim, Min-Ji,Kim, Hee-Jin,Kim, Sun-Hee,Kim, Jong-Won,Kim, Hyeoung-Joon,Kim, Yeo-Kyeoung,Sohn, Sang Kyun,Moon, Joon Ho,Jung, Chul Won,Li American Society of Hematology 2011 Blood Vol.117 No.25

<B>Abstract</B><P>In the current study, we identified 2 genetic markers for susceptibility to chronic myeloid leukemia (CML) using a genome-wide analysis. A total of 2744 subjects (671 cases and 2073 controls) were included, with 202 Korean CML patients and 497 control subjects enrolled as a discovery set. Significant findings in the discovery set were validated in a second Korean set of 237 patients and 1000 control subjects and in an additional Canadian cohort of European descent, including 232 patients and 576 control subjects. Analysis revealed significant associations of 2 candidate loci, 6q25.1 and 17p11.1, with CML susceptibility, with the lowest combined P values of 2.4 × 10−6 and 1.3 × 10−12, respectively. Candidate genes in those regions include RMND1, AKAP12, ZBTB2, and WSB1. The locus 6q25.1 was validated in both Korean and European cohorts, whereas 17p11.1 was validated only in the Korean cohort. These findings suggest that genetic variants of 6q25.1 and 17p11.1 may predispose one to the development of CML.</P>

Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma

Kim, Hee Nam,Kim, Yeo-Kyeoung,Lee, Il-Kwon,Lee, Je-Jung,Yang, Deok-Hwan,Park, Kyeong-Soo,Choi, Jin-Su,Park, Moo Rim,Jo, Deog Yeon,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2007 American journal of hematology Vol.82 No.9

<P>Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate-dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population-based case-control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population-based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C > T and 1298 A > C, methionine synthase (MS) 2756 A > G, methionine synthase reductase (MTRR) 66A > G, thymidylate synthase (TS) 28-bp repeat (2R→3R) and 6-bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5-fold lower risk of MM (OR = 0.66, 95%CI; 0.43–0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R and 6-bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R, and 6-bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc.</P>

Association between folate-metabolizing pathway polymorphism and non-Hodgkin lymphoma

Kim, Hee Nam,Lee, Il-Kwon,Kim, Yeo-Kyeoung,Tran, Huong Thi Thanh,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min–,Ho,Park, Kyeong-Soo,Shin, Myung-Geun,Choi, Jin-Su,Kim, Hyeoung-Joon Blackwell Publishing Ltd 2008 British journal of haematology Vol.140 No.3

<P>Summary</P><P>Polymorphisms in the genes coding folate-metabolizing enzymes affect the risk of some forms of cancer. We investigated the association between these polymorphisms and non-Hodgkin lymphoma (NHL) risk in a population-based study (583 cases and 1700 controls). The <I>MTHFR</I> 677TT and CT genotypes were associated with reduced risk for NHL [odds ratios (OR) = 0·79; 95% confidence intervals (CI) = 0·65–0·98 for 677CT and 0·61; 0·45–0·82 for 677TT] and diffuse large B-cell lymphoma (DLBCL) (OR = 0·68; 0·51–0·88 for 677CT; OR = 0·56; 0·38–0·83 for 677TT). The <I>MTHFR</I> 1298CC genotype was associated with increased risk for NHL (OR = 1·71; 1·07–2·75) and T-cell lymphoma (OR = 3·05; 1·53-6·11). The <I>MTRR</I> 66GG genotype was associated with increased risk for DLBCL (OR = 1·56; 1·03-2·38) and the <I>TYMS</I> 2R2R genotype was associated with increased risk for T-cell lymphoma (OR = 2·83; 1·33–6·01). Using subjects with 3RG3RG as a reference group, <I>TYMS</I> 2R2R was associated with increased risk for T-cell lymphoma (OR = 2·46; 1·04–5·79). Interestingly, we observed a reduced association between the <I>TYMS</I> 2R3RG genotype and DLBCL (OR = 0·61; 0·38–0·99). These results suggest that <I>MTHFR</I>, <I>MTRR</I> and <I>TYMS</I> polymorphisms may play a significant role in the risk for NHL.</P>

Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy

Kim, TaeHyung,Tyndel, Marc S.,Kim, Hyeoung Joon,Ahn, Jae-Sook,Choi, Seung Hyun,Park, Hee Jeong,Kim, Yeo-kyeoung,Kim, Soo Young,Lipton, Jeffrey H.,Zhang, Zhaolei,Kim, Dennis (Dong Hwan) American Society of Hematology 2017 Blood Vol. No.

<P>Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; 37 patients carried mutations. Sixteen of these had evidence of mutations originating from preleukemic clones. Using unsupervised hierarchical clustering, we identified 5 distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy. This study demonstrates that patterns of mutation acquisition, persistence, and clearance vary but have a number of interesting correlations with clinical outcomes. Mutation burden often persisted despite successful TKI response (pattern 1), providing indirect evidence that these mutations also originated from preleukemic mutations, whereas patients exhibiting mutation clearance (pattern 3) showed mixed clinical outcomes. Unsurprisingly, patients acquiring new mutations during treatment failed TKI therapy (pattern 2). These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms. In summary, clinical implications of mutation profiles and dynamics in CML should be interpreted with caution.</P>

Association with TP53 codon 72 polymorphism and the risk of non-Hodgkin lymphoma

Kim, Hee Nam,Yu, Li,Kim, Nan Young,Lee, Il-Kwon,Kim, Yeo-Kyeoung,Yang, Deok-Hwan,Lee, Je-Jung,Shin, Min–,Ho,Park, Kyeong-Soo,Choi, Jin-Su,Kim, Hyeoung-Joon Wiley Subscription Services, Inc., A Wiley Company 2010 American journal of hematology Vol.85 No.10

Efficacy and safety of eltrombopag in adult refractory immune thrombocytopenia

Yeo-Kyeoung Kim,Seung-Sin Lee,Sung-Hoon Jeong,Jae-Sook Ahn,Deok-Hwan Yang,이제중,김형준 대한혈액학회 2015 Blood Research Vol.50 No.1

BackgroundEltrombopag is a thrombopoietin receptor agonist with excellent treatment outcomes inimmune thrombocytopenia (ITP). Here, we analyzed the dose of eltrombopag requiredto achieve and maintain safe platelet counts in Korean ITP patients. MethodsAdult refractory ITP patients (<30,000 platelets/μL) were enrolled. Eltrombopag doseswere increased to achieve a target platelet count (≥50,000 cells/μL). After achieving thetarget platelet count, the dose of concomitant ITP medications and eltrombopag was reducedto identify the lowest effective dose required to maintain the platelet count. ResultsAmong 18 patients, 66.7% achieved complete response, 5.6% achieved platelet countsbetween 50,000 and 100,000 cells/μL, and 27.8% failed to achieve the target plateletcount. The median ITP duration was significantly shorter in patients who achieved thetarget platelet count. The initial dose required to achieve the target platelet count was25 mg/d. The adjusted maintenance doses were 25 mg twice per week or 25 mg/d. Afterdiscontinuation, 83.3% relapsed, and the median relapse-free survival was 15 days. Tworelapsed and 1 failed patient switched to romiplostim. The response to romiplostim wassimilar to eltrombopag. During eltrombopag treatment, 38.9% showed hepatobiliary laboratoryanomalies. Among 9 follow-up bone marrow examinations, 1 revealed fibrosisafter 1 year of treatment. ConclusionEltrombopag was well tolerated with excellent treatment outcomes in refractory adultITP patients. Low-dose eltrombopag effectively maintained the target platelet count. However, some patients required longer or higher-dose treatment to maintain the targetplatelet count, especially in heavily pretreated or longer ITP cases.