Gemtuzumab Ozogamicin (MylotargⓇ) as a Single Consolidation Therapy in Relapsed Pediatric Acute Myeloid Leukemia Patient: a Patient Who Refused Transfusion and Stem Cell Transplantation for Religious Belief

Despite improvement of long-term survival rate in pediatric acute myeloid leukemia (AML) during the last two decades, relapse/refractory disease remains a major obstacle to further improvement of prognosis. Moreover, there are only few therapeutic options which stimulate investigations for targeted, less toxic therapy. Gemtuzumab ozogamicin (GO, MylotargⓇ) is an anti-CD33 monoclonal antibody and there are ongoing studies evaluating safety and efficacy of this drug in relapsed/refractory AML patients. Still, the response rate is only 30% and the response does not last more than a year. We present a case of pediatric central nervous system relapsed AML who was treated with GO as a single consolidation therapy without stem cell transplantation because of religious belief and maintained CR status for more than 3 years.ope

Late Effect of Pediatric Cancer Therapy on Thyroid Function

Purpose: According to advances in childhood cancer therapy, survival outcomes are markedly improved during the past few decades. On the other hand, late effects of childhood cancer survivors are nowadays having been issued owing to its importance of early detection and proper management. It is now known from references abroad that thyroid disorders have frequently occurred in long-term survivors since endocrine organs are sensitive to both cytotoxic drugs and radiation. However, research in Korea has not been published yet. The aim of this study was to investigate the late effect of cancer therapy on thyroid disorders in childhood cancer survivors. Methods: Medical records of 129 childhood cancer survivors who visited long term follow up clinic between 2005 and 2008 were retrospectively reviewed. Clinical characteristics including individual cancer therapy were reviewed. We analyzed the relationship between thyroid function status with variable clinical factors and types of cancer therapy. Results: The incidence of thyroid dysfunction was 30.2% (39/129) in long-term survivors with cancer therapy. Thyroid dysfunction were more frequently in patients treated with radiotherapy (P=0.021) and stem cell transplantation (P=0.001). We also found a significant association between underlying disease and thyroid dysfunction (P＜0.001). Conclusion: These findings emphasize the need for long-term follow-up of thyroid function in childhood cancer survivors after radiotherapy or/and stem cell transplantation in order to offer proper treatment.ope

Role of Cyclosporine A in Pediatric Patients with Refractory Chronic Idiopathic Thrombocytopenic Purpura

Purpose: Since the treatment of chronic idiopathic thrombocytopenic purpura (ITP) remains unsatisfactory in patients refractory to standard therapy, alternative therapies such as splenectomy, danazol, rituximab and cyclosporine A (CsA) are being considered as recently. The efficacy and safety of CsA has already been proved to adult patients with chronic ITP, however, there was no previous study in pediatric patients. The purpose of this study was to evaluate the efficacy and side effect of CsA in pediatric chronic ITP patients. Methods: We reviewed medical records of nine steroid refractory chronic ITP patients diagnosed as chronic ITP who were treated with CsA during 2007 and 2009 retrospectively. Results: All nine patients received standard treatment of intravenous immunoglobulin G and steroid before receiving CsA. Average time duration to start CsA from diagnosis was 52 months. Three children (33%) showed more than partial response maintaining platelet count over 50×109/L, the other six patients did not show any effect. There were no remarkable toxicities other than mild chest discomfort and headache in two patients. Conclusion: CsA therapy is considered as a safe and effective treatment option in adult chronic ITP patients recently, however, there is nearly no study in pediatric patients only with few case reports. In this study only small portion of patients showed response to CsA. Since it was a small sized study with short term follow up, long term follow up with larger patient number is required to make conclusionope

A Case of Cystic Partially Differentiated Nephroblastoma

Cystic partially differentiated nephroblastoma is a rare renal mass in children. Since its clinical characteristics and radiologic findings are very similar to those of cystic Wilms tumor and cystic nephroma, the discrimination between these disease categories are known to be difficult and only possible by histology. A 9-month-old female presented with 2 months history of abdominal distension. Renal ultrasonography showed a mass with multiple cystic components in the upper to lower poles of the right kidney and computer tomography showed a well-marginated low attenuation multilocular cystic mass. Right nephrectomy was performed and cystic partially differentiated nephroblastoma was diagnosed by pathologic findings. There have been only few reports in the literature with only one case report in Korea. Here we report a case of cystic partially differentiated nephroblastoma with some review of the literaturesope

Two cases of Wernicke's encephalopathy in young age patients receiving allogeneic hematopoietic stem cell transplantation

Wernicke's encephalopathy is an acute neurolopsychiatric syndrome caused by thiamine deficiency, and classically presents with the triad of opthalmopathy, ataxia and altered mentality. Both prolonged total parenteral nutrition and reduced oral intake can induce Wernicke's encephalopathy during hematopoietic stem cell transplantation (HSCT). Although early treatment is important for recovery from Wernicke's encephalopathy, the vague symptoms and characteristics hinder early diagnosis. Furthermore, Wernicke's encephalopathy is not infrequent and can develop at any age during HSCT. Herein, we present two young patients developing Wernicke's encephalopathy during HSCT.ope

Increasing and Worsening Late Effects in Childhood Cancer Survivors during Follow-up

Recent advances in childhood cancer treatment have increased survival rates to 80%. Two out of three survivors experience late effects (LEs). From a group of 241 survivors previously described, 193 were followed at the long-term follow-up clinic (LTFC) of Severance Hospital in Korea; the presence of LEs was confirmed by oncologists. We reported the change in LEs during 3 yr of follow-up. The median follow-up from diagnosis was 10.4 yr (5.1-26.2 yr). Among 193 survivors, the percentage of patients with at least one LE increased from 63.2% at the initial visit to 75.1% at the most recent visit (P = 0.011). The proportion of patients having multiple LEs and grade 2 or higher LEs increased from the initial visit (P = 0.001 respectively). Forty-eight non-responders to the LTFC were older and had less frequent and severe LEs than responders at initial visit (all P < 0.05). In multivariate analysis, younger age at diagnosis, older age at initial visit, a diagnosis of a brain tumor or lymphoma, and use of radiotherapy were significant risk factors for LEs (all P < 0.05). Adverse changes in LEs were seen among the survivors, regardless of most clinical risk factors. They need to receive comprehensive, long-term follow up.ope

Aberrant DNA Methylation of CDH1, p16 and DAPK in Childhood Acute Lymphoblastic Leukemia

Background: Hypermethylation of tumor suppressor gene has been reported in various types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. Methods: To evaluate the methylation status at initial diagnosis and morphologic complete remission (CR) period in childhood acute lymphoblastic leukemia (ALL), we analyzed the methylation status of three key genes (CDH1, p16 and DAPK) in 43 childhood ALL patients and 7 healthy bone marrow (BM) donors. Results: CDH1 was methylated in 26 (60.4%) patients, p16 in two (4.6%) patients and DAPK in six (13.9%) patients at the time of diagnosis. Twenty nine (67.4%) patients had methylation of at least one gene. None of the healthy BM donors showed methylation of the above genes. Age was the only factor which showed significant association with the presence of DNA methylation (P=0.03). None of the other clinicopathological factors showed association with initial methylation status. At the time of morphologic CR, all patients who had aberrant DNA methylation at the time of diagnosis had no detectable residual methylation. Conclusion: Since hypermethylation was found in around two thirds of pretreatment ALL patients and none in healthy BM donor, we suggest hypermethylation of some important genes is a biologic marker of childhood ALL. We recommend that further studies with a large number of patients should be conducted.ope

Comparison of Dose between Radiotherapy Alone and Concurrent Radio-chemotherapy in Treatment of Intracranial Germinoma

Purpose: Intracranial germinoma is the most frequent intracranial germ cell tumor. Radiotherapy has so far been considered as the standard treatment. Radiotherapy could unfavorably affect the quality of life, so there have been many trials to reduce the radiation dose. We report significant reduction of radiation dose on tumor field when it was combined with chemotherapy. Methods: From January 1997 to January 2007, 31 patients were enrolled in this study. 12 patients received radiotherapy alone, 19 patients received radio-chemotherapy. We compared craniospinal irradiation (CSI) dose, total irradiation dose on tumor bed and incidence of CSI between two groups. Results: There were 21 male and 10 female patients, with a mean age of 19.3 years. Solitary tumors were found in 26 cases (83.9%), multiple tumors in 5 cases (16.1%). All patients were survived. The average CSI dose in radiotherapy alone group was 18.88±6.18 Gy and that of radio-chemotherapy group was 13.25±9.54 Gy. CSI dose in radiotherapy alone group was higher than that of radio-chemotherapy group (P=0.002). The average total radiation dose in radiotherapy alone group was 38.98±2.71 Gy and that of radio-chemotherapy group was 33.87±5.55 Gy. The total irradiation dose in radiotherapy alone group was also higher than that of radio-chemotherapy group (P=0.001). The incidence of CSI was higher in radiotherapy alone group (P＜0.05). Conclusion: We discovered that there was a significant reduction of radiation dose in radio- chemotherapy group. It suggested that we could reduce the radiation dose in treatment of intracranial germinoma when we combine chemotherapy with radiation therapy, which could reduce the side effects of radiation.ope

Comparison of Dose between Radiotherapy Alone and Concurrent Radio-chemotherapy in Treatment of Intracranial Germinoma

Purpose: Intracranial germinoma is the most frequent intracranial germ cell tumor. Radiotherapy has so far been considered as the standard treatment. Radiotherapy could unfavorably affect the quality of life, so there have been many trials to reduce the radiation dose. We report significant reduction of radiation dose on tumor field when it was combined with chemotherapy. Methods: From January 1997 to January 2007, 31 patients were enrolled in this study. 12 patients received radiotherapy alone, 19 patients received radio-chemotherapy. We compared craniospinal irradiation (CSI) dose, total irradiation dose on tumor bed and incidence of CSI between two groups. Results: There were 21 male and 10 female patients, with a mean age of 19.3 years. Solitary tumors were found in 26 cases (83.9%), multiple tumors in 5 cases (16.1%). All patients were survived. The average CSI dose in radiotherapy alone group was 18.88±6.18 Gy and that of radio-chemotherapy group was 13.25±9.54 Gy. CSI dose in radiotherapy alone group was higher than that of radio-chemotherapy group (P=0.002). The average total radiation dose in radiotherapy alone group was 38.98±2.71 Gy and that of radio-chemotherapy group was 33.87±5.55 Gy. The total irradiation dose in radiotherapy alone group was also higher than that of radio-chemotherapy group (P=0.001). The incidence of CSI was higher in radiotherapy alone group (P＜0.05). Conclusion: We discovered that there was a significant reduction of radiation dose in radio- chemotherapy group. It suggested that we could reduce the radiation dose in treatment of intracranial germinoma when we combine chemotherapy with radiation therapy, which could reduce the side effects of radiation.ope

진행된 소아 고형 종양에서 조혈모세포 구제를 동반한 sequential high-dose chemotherapy 의 시행 가능성

Dept. of Medicine/석사[한글] 배경: 파종성 혹은 재발성 소아 고형 종양은 고식적인 항암치료로는 그 예후가 매우 불량하여 다양한 방법의 고용량 항암 치료 방법이 시도되어 왔으나, 독성을 최소화하면서 충분히 강력한 발전적인 고용량 항암 치료 방법의 개발이 필요한 실정이다.목적: 본 연구에서는 2회의 reduced conditioning high-dose chemotherapy (HDCT) 후 최종 고용량 항암치료를 시행하는 총 3회의 sequential HDCT 의 시행 가능성과 치료 반응에 대하여 알아보고자 하였다.방법: Sequential HDCT를 시행 받은 9명의 환자들의 특성, 진단 후 진행된 초기 치료와 고용량 항암 치료의 치료 과정에 대해 후향적으로 조사하였으며, 주입된 조혈모세포의 양과 조혈기능 회복 기간 및 독성 효과와 합병증에 대해 분석하였다. 또한 치료 종료 후의 치료 반응과 생존에 대하여 분석하였다.결과: 9명중 7명에서 부분 반응 및 완전 반응을 보여 78%의 반응율을 보였다. 1명에서 이식 관련 사망이 발생하였으며 1명이 치료 중 병의 진행으로 인해 최종 HDCT 를 시행하지 않았다. 이외의 독성 합병증들은 보조적인 치료로 모두 회복되었다.결론: 2회의 reduced conditioning HDCT를 포함한 총 3회의 sequential HDCT 는 진행된 소아 고형 종양 환자에서 적용 가능할 것으로 생각되며, 완전 반응에 도달하고 이를 유지하는데 효과를 기대할 수 있으리라 사료되나, 더 많은 수의 환자에서의 시도와 장기 추적 관찰의 결과가 필요하다. [영문]Background: Even though high-dose chemotherapy (HDCT) supported by autologous hematopoietic stem cell (HSC) infusion may improve the survival outcome in advanced pediatric solid tumors, most patients have had only brief response ending with early recurrence of primary tumor, which results in further need for maximum tolerated dose regimen with minimal toxicity.Purpose: To evaluate the feasibility and early tumor response of 3 cycles of sequential HDCT which is consisted of two consequent cycles of reduced conditioning HDCT followed by final HDCT with autologous HSC infusion.Patients and Methods: Medical records of 9 patients with advanced pediatric solid tumor diagnosed between June 2005 and December 2006 who underwent 3 cycles of sequential HDCT followed by HSC infusion were reviewed in retrospective manner.Results: Each median CD 34 positive HSC dose infused after 3 cycles of sequential HDCT were 3.4 x 106/kg, 3.2 x 106/kg and 4.4 x 106/kg. Each median time to an absolute neutrophil count > 0.5 x 109/L were 12, 13 and 12 days. Major toxic reactions after 3 cycles of HDCT included fever, microbiologically documented infection, stomatitis and vomiting. 7 out of 9 patients showed response (six complete responses and one partial response) to the therapy, 1 patient with no response showed progression of disease. 1 patient died of transplantation related mortality after 2nd cycle of reduced conditioning HDCT.Conclusion: 3 cycles of sequential HDCT including 2 times of reduced conditioning HDCT supported by autologous HSC infusion seems to be feasible and effective in treating advanced childhood solid tumors, approaching and maintaining complete response status. Further studies with larger patient group and long term follow-up analysis are required.ope