Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Development of Kompetitive Allele Specific PCR markers for identification of persimmon varieties using genotyping-by-sequencing

BACKGROUND: Persimmon (Diospyros kaki Thunb.) is the most widely cultivated species of the genus Diospyros. In this study, genetic diversity and variations in persimmon genotypes were investigated using single nucleotide polymorphism (SNP) markers identified by genotyping-by-sequencing (GBS) analysis. RESULTS: Ninety-five persimmon accessions grown in the Pear Research Institute, National Institute Horticultural and Herbal Science, were sequenced using the Illumina Hiseq2500 platform and polymorphic SNPs were detected to develop molecular markers. These reliable SNPs were analyzed using the Kompetitive Allele Specific PCR (KASP) assay to discriminate among persimmon genotypes. GBS generated a total of 447,495,724 trimmed reads, of which 89.7% were raw reads. After demultiplexing and sequence quality trimming, 108,876,644 clean reads were mapped to the reference transcriptome. An average of 1,146,070 genotype reads were mapped. Filtering of raw SNPs in each sample led to selection of a total of 1,725,401 high-quality SNPs. The number of homozygous and heterozygous SNPs ranged from 1,933 to 6,834 and from 846 to 5,927, respectively. CONCLUSIONS: Of the 49 SNPs selected for development of an identification system for persimmons, 15 SNPs were used in the KASP assay to analyze 32 persimmon accessions. These KASP markers discriminated among all accessions.

Palliative Transcatheter Arterial Chemoembolization for Relieving Metastatic Bone Pain due to Hepatocellular Carcinoma: A Case Report

Bone metastasis is the third most common extrahepatic metastasis from hepatocellular carcinoma (HCC), following lung and lymph node metastasis. Although transcatheter arterial chemoembolization (TACE) is widely used for the treatment for unresectable HCC in the liver, its effects on bone metastasis from HCC have not been well described in past literature. We report a case of a patient with a metastatic bone lesion from an HCC treated with TACE. After the procedure, the patient's pain and narcotic requirement significantly decreased without major complications.

Effects of Self-breast Pumping in Primiparous Women after Cesarean Delivery

PURPOSE: This study was done to identify the effects of self-breast pumping on breastfeeding rates and, the degree of breast milk fullness among primiparous women giving birth by cesarean section. METHODS: The study design was a non-synchronized posttest control group experiment with repeated measures. The participants were 60 women, 31 in the experimental group who used a manual pump 5 times a day after exclusive breastfeeding and 29 in the control group who breastfed exclusively with no other interventions. RESULTS: While self-breast pumping did not improve breastfeeding rates or the degree of breast milk fullness at any of the time points studied, breastfeeding rates continued to remain high till 12 weeks postpartum in both groups. Conclusion: Although some modifications in research methods will be required to identify the effects of breast pumping and exclusive breastfeeding, both these approaches can be used as interventions to improve breastfeeding rates and breast milk quantity.

Evaluation of Stability Following Two-Jaw Surgery

Analysis of Keratocystic Odontogenic Tumor

Multicentric retrospective clinical study on the clinical application of mini implant system

INTRODUCTION: Mini-implant system is applicable to areas of narrow space and area requiring temporary loading support. The purpose of this study was to evaluate the clinical outcome of a mini-implant system as well as the application of mini-implant system in the dental clinical field. MATERIALS AND METHODS: The patients who had been operated from Jan 2007 to Dec 2007 in the four dental facility including Seoul National University Bundang Hospital were enrolled. To evaluate the factors associated with the clinical outcome, the patients were classified according to gender, age, area of surgery, type of implant, diameter and length of the implant, and the purpose of the mini-implant system application. RESULTS: From 147 implants, only three implants failed, one of them was for temporary loading. There were no serious surgical or prosthetic complications in this study. CONCLUSION: An analysis of the preliminary data revealed a satisfactory clinical outcome. However, more long-term evaluation of narrow ridge type as well as the patient's satisfaction on the use of a provisional type mini-implant system is needed.

Ototoxicity in children receiving cisplatin chemotherapy / 소아과

PURPOSE: Cisplatin is highly effective for the treatment of solid tumors in children. However, the clinical use of cisplatin is limited by its ototoxicity. The aim of this study was to evaluate the ototoxicity in children treated with cisplatin. Method: We performed a single institution retrospective analysis of pediatric oncology patients who received cisplatin therapy between January 2001 and January 2008. Thirty-seven patients with sufficient medical and audiologic data were included in this study. RESULTS: The median age at the time of diagnosis was 10.7 (range 3.8-16.7) years. There were 16 males and 21 females. The underlying diseases were osteosarcoma (15 cases), medulloblastoma (14 cases), germ cell tumors (7 cases), and hepatoblastoma (1 case). The median individual dose was 100 mg/m2/cycle (56-200). The median cumulative dose was 480 mg/m2 (200-1,490). Sixteen patients (43%) received cranial radiotherapy. Of the 37 patients, 17 developed hearing loss, leading to an overall incidence of 46%. Logistic regression showed that age at treatment (P=0.04) and cumulative dose of cisplatin (P=0.005) were the significant risk factors in predicting hearing loss in children treated with cisplatin. In all the patients who had hearing loss, there was neither improvement nor aggravation during the follow-up (3-68 months). CONCLUSION: The cumulative dose of cisplatin (>500 mg/m2) and younger age at treatment (<12 years) were 2 most important risk factors for ototoxicity in patients treated with cisplatin. Serial audiometric evaluations are needed in the patients with risk factors during and after cisplatin treatment.

Endocrine dysfunction after bone marrow transplantation during childhood and adolescence / 소아과

PURPOSE: Several complications can occur in patients who received bone marrow transplantation (BMT) during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. METHODS: One hundred patients (61 males, 39 females) were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD), growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. RESULTS: Height standard deviation score (SDS) at BMT, after 1 year of BMT, and at the last visit were 0.08+/-1.04, -0.09+/-1.02, and -0.27+/-1.18, respectively (P=0.001). Height SDS significantly decreased in patients who received total body irradiation (TBI) (P=0.017). One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9%) of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P=0.025). Of the 32 patients (17 males, 15 females) who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females) had increased luteinizing hormone (LH) or follicle-stimulating hormone (FSH). Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P=0.001). CONCLUSION: The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients developed grade II-IV acute graft-versus-host disease (GVHD) and 8 developed extensive chronic GVHD. With median follow-up of 39.1 months, event free survival and overall survival were 60.4% and 67.5%, respectively, at 5 yr. Events included relapse in 10 and treatment-related mortality (TRM) in 10. The causes of TRM included sepsis in 4, GVHD in 4 (1 acute GVHD and 3 chronic GVHD), veno-occlusive disease in 1 and fulminant hepatitis in 1. Patients transplanted with CB had event free survival of 57.1%, comparable to 63.2% for those transplanted with other than CB. In conclusion, HCT with unrelated donors is effective treatment modality for children with acute leukemia. In children with acute leukemia candidate for HCT but lack suitable sibling donor, unrelated HCT may be a possible treatment option at the adequate time of their disease.

Risk Factors of Bloodstream Infection Associated Mortality in Pediatric Patients with Hemato-oncologic Disease / 대한혈액학회지

BACKGROUND: Bloodstream infection is one of the important causes of mortality, and morbidity in pediatric patients with hemato-oncologic disease. The purpose of this study was to identify the risk factors related to mortality in patients who suffered from a bloodstream infection. METHODS: We retrospectively reviewed and analyzed the medical records of 133 pediatric patients with hemato-oncologic diseases who had episodes of bloodstream infection documented at Asan Medical Center from June 2002 through May 2005. RESULTS: A total of 288 pathogens were isolated, and there were 17 episodes of polymicrobial infections. Among the episodes of bloodstream infection, 93.4% were caused by bacteria of which 60.1% were gram-positive bacteria, and 33.3% were gram-negative bacteria. Fungal infections accounted for 6.6% of the infections. The main pathogens included Staphylococcus epidermidis (31.3%), Pseudomonas aeruginosa (8.3%), and Klebsiella pneumoniae (7.3%). Gram-positive organisms were isolated more frequently than gram-negative organisms, and non-albicans Candida species were documented more frequently than C. albicans in our study. Infection related mortality was 8.3% (11 of 133 patients). The pulmonary infiltration on chest X-ray (CXR) (P=0.001), and a low absolute neutrophil count (< or = 500/micorL) (P=0.017) at the time of blood culture were significantly associated with mortality. Gram-negative bacterial infection (especially with Stenotrophomonas maltophilia) and fungal infection often progressed to the septic shock or death. CONCLUSION: This study revealed that the presence of pulmonary infiltration on a CXR, neutropenia (< or = 500/microL), and gram-negative bacterial infection might be important risk factors of mortality in pediatric patients with hemato-oncologic diseases necessitating more aggressive and vigilant supportive care.

Relationship between In Vitro Chemosensitivity assessed with MTT Assay and Clinical Outcomes in 103 Patients with Acute Leukemia / 대한진단검사의학회지

BACKGROUND: Cellular drug resistance is supposed to play a major role in chemotherapy failure or relapse. The purpose of this study was to analyze the relationship between in vitro chemosensitivity test results using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clinical response on chemotherapy, and to find the possibility of optimizing the treatment protocol for individual patients according to their actual drug resistance. METHODS: For MTT assay, we obtained bone marrow aspirates from 103 patients with acute leukemia at the time of initial diagnosis or relapse. The following drugs were tested: cytarabine, vincristine, methotrexate, daunorubicin, dexamethasone, L-asparaginase, and mitoxantrone. To evaluate clinical responses after induction chemotherapy, we followed up on their bone marrow study. RESULTS: In our study, in vitro chemosensitivity test with the MTT assay significantly predicted whether patients with AML remained continuous complete remission or went into relapse. It also predicted whether or not child patients with ALL would acquire complete remission after induction chemotherapy. CONCLUSIONS: Although it does not provide the insight into the mechanisms that cause drug resistance, the MTT assay may be a useful tool in individually optimizing the chemotherapy of patients with acute leukemia.

Current Status of Hematopoietic Stem Cell Transplantation in Korean Children / 대한혈액학회지

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is one of the most important armamentarium against various hematologic malignancies or some solid tumors. We investigated the number of patients who might need transplants and compared with that of actual transplants to conceptualize current status and circumstances of HSCTs in Korean children. METHODS: Questionnaires were sent to Korean Society of Hematopoietic Stem Cell Transplantation (KSHSCT) members who were taking care of children with malignancies or hematologic diseases. Almost all of the newly diagnosed patients between Jan, 1st and Dec, 31st, 2003 were enrolled in the study. RESULTS: Seven hundred forty eight children (male to female ratio = 1.4:1) were enrolled. The median age was 6.1 years old (8 days~28.8 years old). Malignant diseases consisted of 695 cases (92.9%), and among them almost half were hematologic malignancies. The participating members speculated that HSCTs should be indicated in 285 children (38.1%) which included 209 allogeneic, and 76 autologous transplants. In reality, however, allogeneic HSCTs were performed only in 140 children (67.0%) with the median interval of 5.9 month, and autologous transplants in 44 children (57.9%) with 8.3 month. In autologous setting, all the patients received peripheral blood stem cells (PBSCs), whereas bone marrow (61%), cord blood (34%), and PBSC (5%) were used in allogeneic HSCTs. Donor types were as follows: unrelated donor (37%), cord blood (34%), sibling donor (25%), and family (4%). The reasons for not performing HSCTs were unfavorable disease status or death, no availability of suitable donor, economical situation, and refusal by parental preferences. Under the strict insurance regulations, many transplants were not covered by insurance. More autologous transplants were performed without insurance coverage than allogeneic HSCTs (P=0.013). Those cases were advanced cases and HLA mismatch transplants for allogeneic setting, and relatively rare diseases still awaiting favorable results of transplants for autologous setting. CONCLUSION: HSCTs are essential part of treatment strategies for children with various diseases. Unfortunately, however, a third of patients who were in need of transplants did not receive HSCTs due to various reasons. It is necessary to expand unrelated donor pool or cord blood banks for the cases lacking HLA-identical sibling donors. Also medical insurances should cover HSCTs for rare diseases as well as for less favorable but novel situations where there are no suitable alternatives.

Treatment Outcome and Prognostic Factors for Children with Advanced Non-Hodgkin's Lymphoma at a Single Institution / 대한혈액학회지

BACKGROUND: Non-Hodgkin's lymphoma (NHL) accounts for over 80% of pediatric malignant lymphoma in Korea; the event free survival (EFS) of advanced stage NHL has been reported to be 60 to 70%. We accessed the outcome of advanced stage pediatric NHL at a single institution. METHODS: Pediatric patients who were diagnosed as stage 3 or 4 with NHL from May 1991 to June 2004 at Asan Medical Center were analyzed for outcomes according to histopathology, gender, age at present, involvement of bone marrow or central nervous system (CNS), and serum level of lactate dehydrogenase (LDH). RESULTS: Sixty-three patients were enrolled in this study. The head and neck were the most common primary site. The five-year EFS and overall survival (OS) were 68% and 78%, respectively. Five-year EFS for lymphoblastic, Burkitt, anaplastic large cell and diffuse large B cell lymphoma were 62%, 86%, 74% and 63%, respectively. Five-year EFS and OS for patients with LDH 500IU/L were 64% and 72% (P=0.04). There was no significant difference in EFS or OS with regard to other factors. Sixteen out of the 63 patients relapsed, and the five-year OS for those who relapsed was 44%. CONCLUSION: The outcome of patients with advanced stage NHL treated at our institution was comparable with previous reports. High serum level of LDH at diagnosis proved to be a poor prognostic factor. New effective treatment regimens are needed to improve the outcome of pediatric patients with relapsed NHL.

Prognostic Significance of Multidrug Resistance Gene 1 (MDR1), Multidrug Resistance-related Protein (MRP) and Lung Resistance Protein (LRP) mRNA Expression in Acute Leukemia

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

Prophylactic Low-dose Heparin or Prostaglandin E1 may Prevent Severe Veno-occlusive Disease of the Liver after Allogeneic Hematopoietic Stem Cell Transplantation in Korean Children

Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive disease (VOD) development are rare in children that have undergone allogeneic hematopoietic stem cell transplantation (HSCT). This study examined risk factors for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1 (lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic HSCT. Eighty five children underwent HSCT between June 1997 and September 2004. Patients were diagnosed and classified as having mild, moderate or severe VOD according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed VOD. VOD occurred more frequently in patients receiving busulfan-based conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other (0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non-malignant disease compared to those with malignant disease (p<0.05). Survival at day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%, p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis developed severe VOD. Given severe VOD is associated with a high mortality rate, this study indicates that prophylactic heparin or lipo-PGE1 may decrease mortality in children undergoing HSCT.

Dementia Knowledge and Related Factors in Middle-aged Adults / 성인간호학회지

PURPOSE: The purpose of this study was to identify the level of knowledge about dementia and to find the related factors in middle-aged adults. METHOD: The research design was a descriptive study by using a constructive self-report questionnaire with 34 items. Data were collected from 397 middle-aged adults using structured questionnaire. Data analysis was done by SPSS/WIN Programs using frequency, range from minimum to maximum, percentage, mean, SD, chi-square-test, t-test, ANOVA, and Duncan's Multiple Range test. RESULTS: The rate of correct answer of middle-aged adults was 68.7%, showing the mid-level of knowledge about dementia. There were significant differences according to age, education, marital status, job, income, information and information sources for dementia in middle-aged adults. CONCLUSION: These results indicate that Korean middle-aged adults need more education and counseling on dementia. Further studies are needed to overcome regionalism in sampling of this study and to develop standard measuring tools for the level of knowledge about dementia.

Hematopoietic Stem Cell Transplantation for Children with Malignant Lymphoma in Korea: Multicenter Retrospective Study / 대한소아혈액종양학회지

PURPOSE: Children with Malignant lymphoma who is in the advanced stage at diagnosis or relapses during treatment have a poor prognosis. Recently, hematopoietic stem cell transplantation (HSCT) for advanced stage or refractory/relapsed lymphoma performed frequently. However, the role for HSCT for children with malignant lymphoma is still controversial. In this study, we reviewed children with malignant lymphoma who received HSCT and analyzed the results. METHODS: Questionnaires were made and sent to a group of teaching hospitals, with a return of 37 questionnaires from 11 hospitals. 33 patients with Non-Hodgkin lymphoma (NHL) and 4 patients with Hodgkin disease (HD) who received HSCT from 1997 to 2004 in Korea were enrolled in this study. Disease state at diagnosis, relapses during treatment, disease state at HSCT, and survival record were analyzed. All Data were reviewed with the questionnaires from the 11 teaching hospitals. RESULTS: Four patients with HD received HSCT at the 2nd complete remission after relapse. Survival rate for HD was 100% and their follow up duration ranged from 0.2 to 6.2 years (median 2.4 years). The 2-year survival rate for NHL was 68.1+/-9.0% and their follow up duration ranged from 0.1 to 7.6 years (median 1.5 years). The 2-year survival rate in patients with advanced stage at diagnosis and in relapsed/refractory patients were 83.6+/-1.1% and 55.9+/-12.9%, respectively (P=0.12). The mortality asssociated with HSCT was only 1 case, and most of the transplantation related complications did not resulted in death. CONCLUSION: Our results suggest that high dose chemotherapy followed by HSCT in children with malignant lymphoma is a safe procedure, which at the same time improves the results of standard treatment.

Treatment Outcome of Childhood B-cell Lymphoma and L3 Acute Lymphoblastic Leukemia from a Single Institution / 대한소아혈액종양학회지

PURPOSE: High survival rate can be obtained in B-cell lymphoma (Burkitt's lymphoma, diffuse large B-cell lymphoma) and L3 acute lymphoblastic leukemia (ALL) with multiagent chemotherapy. Objectives of this study were to evaluate the treatment outcomes of B-cell lymphoma and L3 ALL diagnosed at the Department of Pediatrics, Asan Medical Center. METHODS: The medical records of 32 children who were diagnosed with Burkitt's lymphoma, diffuse large B-cell lymphoma and L3 ALL from March 1992 to July 2004 at Asan Medical Center were reviewed retrospectively. The 5 year event free survival (EFS) according to the diagnosis, age, risk group and lactic dehydrogenase (LDH) level were analyzed. RESULTS: There were 23 boys and 9 girls. Age ranged from 9 months to 14.4 years old with a median of 7.1 years. Fourteen patients had L3 ALL, 11 had Burkitt's lymphoma and 7 had diffuse large B-cell lymphoma. Five patients (15.6%) had CNS involvement and 5 with B-cell lymphoma (27.8%, 5/18) had BM involvement. All patients who received appropriate chemotherapy achieved a complete remission (CR), but 18.8% (6/32) relapsed. Among 6 relapsed patients, 5 achieved CR after reinduction chemotherapy. One who had no response to secondary chemotherapy and 2 with isolated CNS relapse died due to disease progression. The most common treatment-related toxicity was myelosuppression (87.5%) followed by neutropenic fever (81.3%). Median follow up is 25 months (3 months to 74 months). Four patients who achieved CR after proper induction therapy (4/32, 12.5%) died, 3 due to relapse and 1 due to toxicity-related complication (neutropenia and sepsis). The 5 year EFS for all patients was 77.5+/-7.5% and the 5 year overall survival was 84.6+/-7.3%. The 5 year EFS of B-cell lymphoma compared with that of L3, ALL was 94.4+/-5.4% versus 55.1+/-13.9% (P=0.012) and 5 year overall survival of relapsed patients was 50.0+/-13.9%. CNS disease at diagnosis, age, LDH had no significant influence on EFS. CONCLUSION: High survival rate of childhood B-cell lymphomas and L3 ALL was obtained with recent intensive multiagent chemotherapy and about 50% of relapsed patients were salvaged with reinduction. High incidence of the treatment-related toxicity such as myelosuppression, neutropenic fever and TLS was observed, but the treatment-related mortality was very low with recent supportive therapies. Survival rate was improved with prompt and appropriate management for the treatment-related toxicity of the intensive chemotherapy.

Prognostic Significance of WT1 Gene Expression in Patients with Acute Leukemia / 대한진단검사의학회지

BACKGROUND: The Wilms' tumor gene (WT1) is located on chromosome 11p13. Several authors have shown that the expression of WT1 gene is associated with prognosis of acute leukemia. It was the aim of this study to investigate the relationship between WT1 positivity and the response to treatment in terms of rate of complete remissions (CR), and survival and to evaluate the prognostic value of WT1 expression in patients with acute leukemia. METHODS: We examined the presence of WT1 specific mRNA in bone marrow samples of 71 patients with acute leukemia at diagnosis (AML 39, ALL 32) by nested RT-PCR. The integrity and the amount of RNA were analyzed by amplification of the -actin gene as an internal control. The relative ratio of WT1 gene expression/ -actin was calculated and classified as not amplified (0), weakly amplified (1+), moderately amplified (2+), or strongly amplified (3+). RESULTS: Thirty-four (47.9%) of the patients with acute leukemia at diagnosis were WT1 PCR positive. Among the WT1 positive patients, 10 patients (14.1%) showed 1+, 20 patients (28.2%) 2+, and 4 patients (5.6%) 3+. The patients with WT1 mRNA expression were younger than those without it in AML. There was a tendency of a higher CR rates in WT1 negative patients than in WT1 positive ones (AML 61.9% vs. 50%, ALL 75.0% vs. 68.8%). The probability of 5 year survival was 62.2% for WT1 negative group and 44.1% for WT1 positive group in all patients. The median survival days accord-ing to levels of WT1 expression was 709 days for negative group, 310 days for 1+ or 2+ groups and 294 days for 3+ group. CONCLUSIONS: The present data suggest a clinical relevance of WT1 expression for the achieve-ment of CR and long term survival in acute leukemia. Analysis of WT1 expression with bone mar-row aspirates at the diagnosis of acute leukemia may be useful to predict prognosis.