• Clinical and Experimental Pediatrics
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• v.56 no.8
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• pp.343-350
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• 2013

Purpose: Despite the established role of imatinib (IM) in chronic myelogenous leukemia (CML) in adults, there are few reports on its efficacy in children. In this study, we compared the outcomes of children with CML before and after the advent of IM-based treatment. Methods: The study cohort consisted of 52 patients treated for CML at the Department of Pediatrics, The Catholic University of Korea from January 1995 to October 2010. Patients were divided and analyzed according to the preImatinib group (pre-IMG) and imatinib group (IMG). Results: Median age at diagnosis for the overall cohort (pre-IMG, n=27; IMG, n=25) was 9 years, with a median follow-up duration of survivors of 84 months. Except for 5 patients in the IMG, all were diagnosed in chronic phase (CP). The overall survival (OS) of patients diagnosed in CP was 45.7% and 89.7% for pre-IMG and IMG, respectively (P=0.025). The OS of hematopoietic stem cell transplantation (HSCT) recipients in the 2 groups was similar, but the OS of patients diagnosed in CP who did not receive HSCT was superior in IMG (91.7% vs. 16.7%, P=0.014). Of the 12 patients in IMG who remained on IM without HSCT, 2 showed disease progression, compared to 11 of 12 in pre-IMG. No difference was observed in the progression free survival (PFS) of matched donor HSCT recipients and IM-based treatment recipients. Conclusion: Similar PFS of patients treated with IM and those who received matched donor HSCT underscore the potential of IM as effective first-line treatment in childhood CML.

• Journal of Oral Medicine and Pain
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• v.37 no.3
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• pp.147-154
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• 2012

Hematopoietic stem-cell transplantation (HSCT) is a treatment for immune deficiency, autoimmune diseases, and hematopoietic malignancies. The main complication of allogenic HSCT is graft-versus-host disease (GVHD). Oral mucosal biopsy is needed for a definitive diagnosis and treatment planning of GVHD, but this procedure causes bleeding and bacteremia in a poor general condition. We evaluated the efficacy of laser-assisted biopsy as a minimally invasive treatment. Three cases were described in this article. All patients' medical records, clinical photographs, and histopathologic findings were reviewed. All patients felt comfortable and no severe complications occurred. The quality of the obtained biopsy material was adequate for a definitive diagnosis of GVHD. Laser-assisted, minimally invasive biopsy of the oral mucosa does not cause bleeding, and it reduces the chances of infection, bacteremia, and postoperative scarring compared to the usual histopathologic biopsy procedure. It would thus be advantageous to use this procedure to biopsy GVHD patients.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.57-59
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• 2016

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days -8 to -5), and the target area under the curve was $75,000{\mu}g{\cdot}hr/L$. Fludarabine ($40mg/m^2$) was administered once daily for 6 consecutive days from days -8 to -3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days -4 to -2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.287-294
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• 2003

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

• Journal of the korean academy of Pediatric Dentistry
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• v.50 no.4
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• pp.421-433
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• 2023

This study was to examine the developmental dental abnormalities in childhood cancer survivors. Risk factors were assessed for 125 children with radiographic data through a retrospective analysis of medical records and panoramic images. 68.0% of childhood cancer survivors exhibited at least one dental abnormality. The types of abnormalities varied depending on the age at cancer diagnosis and treatment intensity, ranging from microdontia (43.2%), to abnormal root development (39.2%) and tooth agenesis (33.6%). Logistic regression analysis demonstrated that a young age at diagnosis (under 3 years), the use of heavy metal agents, a history of hematopoietic stem cell transplantation (HSCT), and combination treatment of chemotherapy, radiation therapy, and HSCT were associated with a significantly higher risk for overall dental abnormalities. The increased risk ratios were 6.00, 3.06, 3.22, and 7.87, respectively (p < 0.05). The results of this study will predict dental abnormality in permanent dentition according to the diagnosis age and treatment method of childhood cancer.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.305-310
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• 2011

조혈모세포이식술(또는 HSCT)을 받은 환자에게는 이식관련 부작용의 예방 또는 치료를 위해 면역억제 약물이 투여되는데, 그 중 하나인 cyclosporine은 therapeutic index가 작고 다양한 요인에 의해 혈중농도가 변화되므로 사용시에는 세심한 관찰과 조절이 필요하다. 특히 HSCT 환자에서 발생하는 호중구 감소성 발열(또는 NPF)의 치료목적으로 투여하는 항생제에 의하여 cyclosporine의 혈중농도가 변화될 수 있고, 또 임상적 경과에 따라 항생제 처방이 중도에 변경되는 경우도 빈번하지만, 실제로 항생제 처방의 중간변경에 의한 cyclosporine의 혈중농도 변화양상을 연구한 결과는 많지 않다. 이에, 과거 2년 동안 한 상급종합병원에서 HSCT후 cyclosporine을 투여 받았던 환자 중에서 통상적인 NPF 치료용 항생제인 ciprofloxacin을 투여하다가 치료성과를 높이기 위하여 cefepime으로 대체 투여했던 환자들의 의무기록을 후향적으로 분석하였다. 1차 선택약인 ciprofloxacin에서 항생제를 변경했을 때 cyclosporine의 혈중농도가 유의성 있게 증가했는데, 이는 ciprofloxacin 보다 cefepime이 간에서 cyclosporine을 분해시키는 효소생성을 억제시켰기 때문일 것으로 예측되며, HSCT 환자에서 NPF 치료용 항생제를 ciprofloxacin에서 cefepime으로 변경 시에는 병용중인 cyclosporine 유지용량을 약 13% 감량하는 것이 cyclosporine의 효과는 유지하면서 부작용의 발생위험을 감소시키는 데 유용한 방안이 될 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.178-185
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• 2005

Purpose : The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia(JMML) treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods : Eleven JMML patients aged 8-39 months underwent allo-HSCT. The sources of grafts were unrelated donors(n=7), HLA-matched siblings(n=3) and an HLA 1-antigen mismatched familial donor. All patients had received chemotherapy ${\pm}13$-cis-retinoic acid(CRA) before transplant, and CRA was used, posttransplant, in six patients. Results : Only three patients were in complete remission(CR) at the time of transplantation. Initial chimeric status revealed complete donor chimerism(CC) in five patients, mixed chimerism(MC) in five and autologous recovery(AR) in one. One patient with MC having persistent splenomegaly eventually turned to CC and CR after rapid tapering of cyclosporine, combined with daily use of CRA. An AR case relapsed shortly after transplant but was rescued with second, unrelated cord blood transplantation. Ultimately, six patients are alive, event-free, with a median follow-up of 15.5 months posttransplant. All three deaths occurred in patients who failed to achieve CC, leading to disease progression. Conclusion : We suggest that graft-versus-leukemia effect play an important role and CRA a possible role in posttransplant leukemic involution in JMML. In patients whose leukemic burden is still high with MC after transplant, early tapering of immunosuppressants and introduction of CRA might provide a chance of a cure for some patients.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.29-36
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• 2014

Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic diseases caused by deficiency of lysosomal enzymes. MPSs are clinically heterogeneous and characterized by progressive deterioration in visceral, skeletal and neurological functions. The aim of this article is to review the treatment of MPSs, the unmet needs of current treatments and vision for the future including recent clinical trials. Until recently, supportive care was the only option available for the management of MPSs. Hematopoietic stem cell transplantation (HSCT), another potentially curative treatment, is not routinely advocated in clinical practice due to its high risk profile and lack of evidence for efficacy. From the early 2000s, enzyme replacement therapy (ERT) was approved and available for the treatment of MPS I, II and VI. ERT is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment. However, no benefit was found in the neurological symptoms because the enzymes do not readily cross the blood-brain barrier (BBB). In recent years, intrathecal (IT) ERT, substrate reduction therapy (SRT) and gene therapy have been rapidly gaining greater recognition as potential therapeutic avenues. Although still under investigation, IT ERT, SRT and gene therapy are promising MPS treatments that may prevent the neurodegeneration not improved by ERT.

• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.9-16
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• 2010

Purpose: 본 연구는 한국인 성인 조혈모세포이식환자를 대상으로 경구용 사이클로스포린의 집단약동학 분석을 통하여 사이클로스포린의 약동학적 파라미터에 영향을 미치는 요인 분석을 실시하고자 하였다. Methods: 2000년 12월부터 2006년 8월까지 서울대학교병원에서 동종조혈모세포이식을 받고 면역억제제로 사이클로스포린을 복용한 성인 백혈병환자를 대상으로 후향적으로 자료를 수집하였다. 사이클로스포린의 약동학에 영향을 미치는 인자로는 연령, 성별, 이식 후 날짜, 신기능, 공여자와의 관계, 질병의 종류, 혈중 빌리루빈 농도, 사이클로스포린의 대사를 유도하는 프레드니솔론의 투여량, 헤마토크리트, 사이클로스포린의 대사를 저해하는 약물의 병용여부 등을 검토하였다. 분석은 NONMEM$^{(R)}$ VI 프로그램을 이용하였으며, 변수를 추가하지 않은 기본 모형을 만든 후에 단계적인 요인의 추가와 제거를 통해 최종모형을 제작하였다. Results: 최종 상관 모형은 다음과 같다; CL/F (L/h) = $85.6{\times}e^{(0.646\;{\times}\;HCT/28.9\;+\;0.0464\;{\times}\;Gender)}$. 사이클로스포린의 겉보기 클리어런스는 환자의 성별이 남자일 때 또는 헤마토크릿이 감소할수록 증가하였다. 그 외 파라미터는 다음과 같이 계산되었다; $K_{\alpha}=0.0787\;(h^{-1})$; Q=57.1(L/kg/h); $V_{d-central\;compartment}$=1,100 (L); $V_{d-peripheral\;compartment}$ = 213,000(L). 개체간 편차는 40% 미만이었으며, 개체내 편차를 포함하는 잔차는 24.02%였다. Conclusions: 사이클로스포린의 약동학적 특징과 그 클리어런스에 영향을 끼칠 수 있는 임상적 요인을 이해하는 것은 환자 개개인의 용량과 용법의 결정 및 이상반응 발생의 예방에 유용할 수 있다. 한국인 조혈모세포이식환자에서 사이클로스포린의 약동학에 영향을 미치는 최종 파라미터를 구한 본 연구의 결과는 조혈모세포이식을 받은 한국인 성인환자에서 사이클로스포린의 모니터링 및 용량조절에 유용할 것으로 전망된다.

• Tuberculosis and Respiratory Diseases
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• v.72 no.3
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• pp.284-292
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• 2012

Background: The aim of this study was to investigate therapeutic outcomes and assess factors associated with therapeutic outcomes in hematologic patients with invasive pulmonary aspergillosis (IPA). Methods: We analyzed all consecutive cases of IPA in adults with hematologic diseases from January 2008 to January 2009 at a Catholic Hematopoietic Stem Cell Transplantation (HSCT) Center in Seoul, Korea. Results: A total of 54 patients were identified. Underlying diseases were acute myelogenous leukemia (n=25), acute lymphoblastic leukemia (n=10), myelodysplastic syndrome (n=7), chronic myelogenous leukemia (n=3), multiple myeloma (n=3), severe aplastic anemia (n=2) and other hematologic diseases (n=4). Twenty six patients (48.2%) were assessed as having a favorable response, of which 16 patients (29.6%) showed complete response. Overall 12-week mortality and IPA attributable mortality were 38.9% (n=21) and 33.3% (n=18), respectively. In multivariate analysis, uncontrolled underlying disease (odds ratio [OR], 7.31; 95% confidence interval [CI], 1.49~35.94; p=0.014) was associated with an unfavorable response, and for 12-week mortality, uncontrolled underlying disease (OR, 11.79; 95% CI, 1.49~93.46; p=0.020) and hypoalbuminemia (OR, 9.89; 95% CI, 1.42~68.99; p=0.021) were significantly poor prognostic factors. Conclusion: IPA still remains as a poor therapeutic outcome, especially in patients with refractory hematologic diseases.