Prediction of nonresponsiveness to medium-dose intravenous immunoglobulin (1 g/kg) treatment: an effective and safe schedule of acute treatment for Kawasaki disease / 소아과

PURPOSE: Medium-dose (1 g/kg) intravenous immunoglobulin (IVIG) is effective in the majority of patients with Kawasaki disease (KD) but some patients who do not respond to medium-dose IVIG are at high risk for the development of coronary artery lesions (CALs). The purpose of this study was to identify the clinical predictors associated with unresponsiveness to medium-dose IVIG and the development of CALs. METHODS: A retrospective study was performed in 91 children with KD who were treated with medium-dose IVIG at our institution from January 2004 to December 2013. We classified the patients into responders (group 1; n=68) and nonresponders (group 2; n=23). We compared demographic, laboratory, and echocardiographic data between the 2 groups. RESULTS: Multivariate logistic regression analysis identified 6 variables as predictors for resistance to medium-dose IVIG. We generated a predictive scoring system assigning 1 point each for percentage of neutrophils ≥65%, C-reactive protein≥100 mg/L, aspartate aminotransferase≥100 IU/L, and alanine aminotransferase≥100 IU/L, as well as 2 points for less than 5 days of illness, and serum sodium level≤136 mmol/L. Using a cutoff point of ≥4 with this scoring system, we could predict nonresponsiveness to medium-dose IVIG with 74% sensitivity and 71% specificity. CONCLUSION: If a patient has a low-risk score in this system, medium-dose IVIG can be recommended as the initial treatment. Through this process, we can minimize the adverse effects of high-dose IVIG and incidence of CALs.

Usefulness of anterior uveitis as an additional tool for diagnosing incomplete Kawasaki disease / 소아과

PURPOSE: There are no specific tests for diagnosing Kawasaki disease (KD). Additional diagnostic criteria are needed to prevent the delayed diagnosis of incomplete Kawasaki disease (IKD). This study compared the frequency of coronary artery lesions (CALs) in IKD patients with and without anterior uveitis (AU) and elucidated whether the finding of AU supported the diagnosis of IKD. METHODS: This study enrolled patients diagnosed with IKD at The Catholic University of Korea, Uijeongbu St. Mary's Hospital from January 2010 to December 2014. The patients were divided into 2 groups: group 1 included patients with IKD having AU; and group 2 included patients with IKD without AU. We analyzed the demographic and clinical data (age, gender, duration of fever, and the number of diagnostic criteria), laboratory results, and echocardiographic findings. RESULTS: Of 111 patients with IKD, 41 had uveitis (36.98%, group 1) and 70 did not (63.02%, group 2). Patients in group 1 had received a diagnosis and treatment earlier, and had fewer CALs (3 of 41, 1.7%) than those in group 2 (20 of 70, 28.5%) (P=0.008). All 3 patients with CALs in group 1 had coronary dilatation, while patients with CALs in group 2 had CALs ranging from coronary dilatation to giant aneurysm. CONCLUSION: The diagnosis of IKD is challenging but can be supported by the presence of features such as AU. Group 1 had a lower risk of coronary artery disease than group 2. Therefore, the presence of AU is helpful in the early diagnosis and treatment of IKD and can be used as an additional diagnostic tool.

Normal Left Ventricular Torsion Mechanics in Healthy Children: Age Related Changes of Torsion Parameters Are Closely Related to Changes in Heart Rate

BACKGROUND AND OBJECTIVES: This study was aimed at assessing left ventricular torsion (LVtor) mechanics using speckle tracking echocardiography (STE), establishing normal reference values of principal LVtor parameters, and analyzing the age-related changes in normal children. SUBJECTS AND METHODS: Eighty children (aged 3 months to 15 years) with normal cardiac function and rhythm were recruited. LVtor parameters including rotations, twist and untwist, torsion, and their rate indices were measured using STE. Age and heart rate related changes of the parameters were analyzed. RESULTS: Speckle tracking echocardiography analyses for LVtor parameters had excellent reliability in 64 of 80 subjects (80%) (intraclass correlation coefficients; 0.93-0.97). Early systolic twist (EST) motions (-8.4--0.1degrees) were observed in all subjects during an early 20+/-7% of systolic time intervals. The peak systolic twist and torsion were 17.0+/-6.5degrees and 2.9+/-1.3degrees/cm, respectively. The peak twist velocity was recorded at 51+/-13% of systolic time and the peak untwist velocity at 13.8+/-11.5% of diastolic time intervals. Multivariate analysis showed that heart rate change was an independent predictor of changes in torsion parameters; significantly decreasing LV length-normalized apical and basal rotation, torsion, and twist and untwist rate with increasing age. Isovolumetric recoil rate was independent of change in age and heart rate. CONCLUSION: Left ventricle showed unique torsion mechanics in children with EST, torsion, and untwists. Heart rate was an independent predictor of the change in torsion parameters with aging.

Baseline heart rate variability in children and adolescents with vasovagal syncope / 소아과

PURPOSE: This study aimed to evaluate the autonomic imbalance in syncope by comparing the baseline heart rate variability (HRV) between healthy children and those with vasovagal syncope. METHODS: To characterize the autonomic profile in children experiencing vasovagal syncope, we evaluated the HRV of 23 patients aged 7-18 years and 20 healthy children. These children were divided into preadolescent (<12 years) and adolescent groups. The following time-domain indices were calculated: root mean square of the successive differences (RMSSD); standard deviation of all average R-R intervals (SDNN); and frequency domain indices including high frequency (HF), low frequency (LF), normalized high frequency, normalized low frequency, and low frequency to high frequency ratio (LF/HF). RESULTS: HRV values were significantly different between healthy children and those with syncope. Student t test indicated significantly higher SNDD values (60.46 ms vs. 37.42 ms, P=0.003) and RMSSD (57.90 ms vs. 26.92 ms, P=0.000) in the patient group than in the control group. In the patient group, RMSSD (80.41 ms vs. 45.89 ms, P=0.015) and normalized HF (61.18 ms vs. 43.19 ms, P=0.022) were significantly higher in adolescents, whereas normalized LF (38.81 ms vs. 56.76 ms, P=0.022) and LF/HF ratio (0.76 vs. 1.89, P=0.041) were significantly lower in adolescents. In contrast, the control group did not have significant differences in HRV values between adolescents and preadolescents. CONCLUSION: The results of this study indicated that children with syncope had a decreased sympathetic tone and increased vagal tone compared to healthy children. Additionally, more severe autonomic imbalances possibly occur in adolescents than in preadolescents.

Articulation Patterns of Children who Developed Articulation Disorders Associated with Ankyloglossia / 대한소아신경학회지

PURPOSE: We investigated articulation patterns in children with ankyloglossia who developed articulation disorders in order to determine the relationship between ankyloglossia and articulation disorders, and to clinically detect children who have articulation disorders associated with ankyloglossia. METHODS: The participants of this study were 23 children with articulation disorders that accompanied ankyloglossia and 55 controls with functional articulation disorders independent of anatomical problems, who were admitted to our hospital from January 1, 2002 to December 31, 2012. All children underwent speech-language pathologic evaluation using the Picture Consonant Articulation Test (PCAT; Young-Tae Kim, 1994). We retrospectively compared collected data between the subject and control groups using Fisher's exact test and odds ratio tests with a 95% confidential interval for categorical variables and the independent Mann-Whitney U-test for continuous variables. RESULTS: The number of patients with articulation errors in the velar nasal was lower significantly only in the subject group (P=0.038). The total numbers of articulation errors in the bilabial plosive, velar plosive and velar nasal also were lower (P=0.007, P<0.001, and P=0.034, respectively). There were no differences in the numbers of patients with articulation errors according to phonological changes between the two groups. However, the total numbers of fronting and frication were lower in the subject group (both P<0.001), but the total numbers of plosivation and tensing were higher (P=0.002 and P=0.008, respectively). CONCLUSION: This study showed that the relationship between an articulation disorder and ankyloglossia is doubtful, although some results suggest that ankyloglossia may cause articulation errors only in certain individuals. Therefore, clinicians should be careful when determining the relationship between ankyloglossia and articulation disorders and use caution when making a treatment decision.

Recent incidence of congenital heart disease in neonatal care unit of secondary medical center: a single center study / 소아과

PURPOSE: With feasibility in the diagnoses of congenital heart disease (CHD) in the antenatal period, we suspect changes have occurred in its incidence. No data have been reported about the current incidence of simple forms of CHD in Korea. We have attempted to assess the recent incidence and characteristics of CHD in the neonatal care unit of a secondary referral medical center. METHODS: Medical records of 497 neonatal care unit patients who underwent echocardiography in the past 5 years were reviewed. Pre-term infants with patent ductus arteriosus and other transient, minimal lesions were excluded from this study. RESULTS: Although the number of inpatients remained stable, the incidence of simple forms of CHD showed a gradual decrease over the 5-year study period; a markedly low incidence of complex forms was seen as well. CHD was observed in 3.7% full-term and 6.8% pre-term infants. CHD was observed in 152 infants weighing >2,500 g (3.5% of corresponding birth weight infants); 65 weighing 1,000 to 2,500 g (9.3%); and 6 weighing <1,000 g (8.0%). The incidence of CHD was higher in the pre-term group and the low birth weight group than in each corresponding subgroup (P<0.001); however, the incidence of complex CHD in full-term neonates was high. The number of patients with extracardiac structural anomalies has also shown a gradual decrease every year for the past 5 years. CONCLUSION: Findings from our study suggest that the recent incidence and disease pattern of CHD might have changed for both complex and simple forms of CHD in Korea.

Haddad Syndrome with 27 Polyalanine Repeats in PHOX2B Gene in a Korean Infant / 대한주산의학회잡지

Haddad syndrome is an extremely rare disorder which combines congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease. Several reports have demonstrated that CCHS was related to mutation of the PHOX2B gene. We report here a newborn male infant with apnea and bowel obstruction. He has been diagnosed with combined congenital central hypoventilation syndrome and Hirschsprung's disease, and had 27 polyalanine repeats in the PHOX2B gene. Two cases of Haddad syndrome with identified PHOX2B gene mutation have been recently reported in Korea. Both of them had extended alleles containing 26 polyalanine repeats. It is known that increased number of polyalanine repeat mutations is associated with a more severe clinical phenotype. The baby reported here had 27 alanine repeats (i.e. one more than the previously reported cases in Korea) and ganglion cells could be found only in the distal 70 cm of his small bowel.

The Genotype and Clinical Phenotype of Korean Patients with Familial Hypokalemic Periodic Paralysis

Familial hypokalemic periodic paralysis (HOPP) is a rare autosomal-dominant disease characterized by reversible attacks of muscle weakness occurring with episodic hypokalemia. Mutations in the skeletal muscle calcium (CACNA1S) and sodium channel (SCN4A) genes have been reported to be responsible for familial HOPP. Fifty-one HOPP patients from 20 Korean families were studied to determine the relative frequency of the known mutations and to specify the clinical features associated with the identified mutations. DNA analysis identified known mutations in 12 families: 9 (75%) were linked to the CACNA1S gene and 3 (25%) to the SCN4A gene. The Arg528His mutation in the CACNA1S gene was found to be predominant in these 12 families. Additionally, we have detected one novel silent exonic mutation (1950C>T) in the SCN4A gene. As for a SCN4A Arg669His mutation, incomplete penetrance in a woman was observed. Characteristic clinical features were observed both in patients with and without mutations. This study presents comprehensive data on the genotype and phenotype of Korean families with HOPP.

Final Height of Children after Stem Cell Transplantation

BACKGROUND: Growth impairment is a common complication after hematopoietic stem cell transplantation (SCT). The aim of this study was to evaluate the final adult height of patients who underwent SCT in childhood and to identify the factors that influence long-term growth in these patients. METHODS: A retrospective review of 15 children who underwent SCT before puberty at Chonnam National University Hospital and reached final adult height was undertaken. To assess the severity of height reduction and to monitor the height changes longitudinally, height measurements of each patient both at the time of SCT and the final height were expressed as the height standard deviation score (SDS). RESULTS: Seven children were males and eight were females with a median age of 12.8+/-2.4 years (range, 6.3~14.7) at SCT. The median follow-up period was 7.1+/-2.0 years (range, 4.5~11.1) and their final height was achieved at 18.1+/-1.5 years (range, 17.0~21.8). Final height SDS values were within normal for the healthy population in all except two who had short stature (below -2.0 SDS). No patient achieved height values greater than +2.0 SDS. The final height SDS value (-0.5+/-1.2) was not decreased from the height SDS value at SCT (-0.8+/-0.8). The younger age group at SCT (6.1~10.0 years, n=5) showed significantly lower final height SDS and greater Delta SDS than the older age group (10.1~15.0 years, n=10) (-1.5+/- 0.6 vs. -0.1+/-1.1, P.05) and the final height SDS (P<.05). The gender, type of disease, donor type or the presence of chronic graft-versus-host disease did not influence height. CONCLUSION: Growth impairment may be encountered in children after SCT. A younger age at transplant and irradiation were found to be factors associated with reduced final height. However, most patients (13/15) reached a final adult height within normal limits for the general healthy population.

Metabolic Syndrome in Children

The prevalence of obesity and overweight among children and adolescents has increased during the past decade. Obesity during the children and adolescents constitutes the major components of metabolic syndrome (MS) and is considered as a significant independent predictor of cardiovascular risk. The MS is a grouping of clinical characteristics including insulin resistance, abdominal obesity, impaired glucose tolerance. elevated blood pressure, elevated triglycerides, and reduced high-density lipoprotein cholesterol (HDL-cholesterol). Other common manifestations include systemic inflammation and a prothrombotic state. Studies suggest that a substantial percentage of overweight children and adolescents may be affiliated the metabolic syndrome because many have 1 or more of the following: an elevated triglyceride level, a low HDL-cholesterol level, and high blood pressure. Many overweight children also have elevated insulin levels. So, clinicians should assess overweight children for manifestations of the MS. The metabolic and cardiovascular consequences of the MS are well demonstrated and have a major impact on the development of atherosclerosis and lifetime cardiovascular risk. Despite the degree to which the MS has been established, it is not without controversy in point of several definitions, physiologic accuracy, and its value as risk factor of atherosclerotic cardiovascular disease. This review will summarize recent data about the metabolic syndrome in the pediatric age group.

Epstein-Barr Virus Antibodies in Kawasaki Disease

The prevalent ages at onset for Kawasaki Disease (KD) and Epstein-Barr virus (EBV) infection are known to be similar in Korea and Japan. We evaluated the correlation between EBV infection and KD. The antibodies to EBV such as anti-viral capsid antigen (VCA) IgG and IgM, anti-diffuse and restricted early antigen IgG (anti-EADR IgG), and the anti-EBV determined nuclear antigen IgG (anti-EBNA IgG) were examined in 29KD patients at five separate times sequentially during a period of one year, and also in 14 other children with a past history of KD. The results of each group were compared with those of age-matched controls. The positive rates of anti-VCA IgG and IgM at presentation in the KD patients were 41.4% (12/29) and 0% (0/29), respectively. Only one patient was found to be anti-VCA IgM-positive within two months. There were no cases of anti-VCA IgG except one, anti-EADR IgG and anti-EBNA IgG positive to negative seroconversion during the year. The children with a past history of KD showed higher anti-EBNA IgG-positive rates than the controls (p=0.04). There was no difference in the seropositive rates of the antibodies to EBV, cytomegalovirus, herpes simplex virus and herpes zoster virus. In conclusion, children with KD were noted to have normal immune responses to EBV infection. Children with a past history of KD seemed to be infected with EBV at a later age than children with no history of KD.

The Clinical Characteristics and Coronary Complication of Infantile Kawasaki Disease

PURPOSE: We evaluated Kawasaki disease(KD) in children in order to evaluate the clinical characteristics and coronary complication of infantile Kawasaki disease. METHODS: A total of 226 medical records of children with KD admitted to The Catholic University of Korea, St. Mary's Hospital, from 1994 to 2003 were retrospectively analyzed. RESULTS: The incidence of lymphadenopathy was statistically lower in infantile Kawasaki disease than in Kawasaki disease of children older than one year. The incidence of atypical Kawasaki disease in infant(32%) was greater than that of total patients(24%), but there was no statistically significant difference in two groups. The incidence of coronary complication in atypical Kawasaki disease in children younger than one year was 50%(6/12), which was greater than that of coronary complication in typical KD of children older than one year. CONCLUSION: Diagnostic difficulties in infantile Kawasaki disease are due to high incidence of atypical characteristics of Kawasaki disease. Yet, early treatment with IVGV and aspirin is necessary because of its high incidence of coronary complication.

Comparison of Intervals to Peak Values of Laboratory Findings in Patients with Coronary Complication to Those without Complication in Kawasaki Disease

PURPOSE: Intravenous immune globulin(IVIG) as a treatment for the Kawasaki disease (KD) has reduced the coronary complications. But, some patients suffer from coronary complication despite early IVIG infusion, and it is difficult to discriminate the susceptible patients in the acute phase. It is also challenging to decide additional therapy in cases showing fever after IVIG therapy. We investigated the relationship between intervals from the onset of fever to the day of peak laboratory values and coronary complications. METHODS: We reviewed the charts of KD patients with coronary aneurysm(group A, n=13) and without aneurysm(group B, n=35). All patients got IVIG therapy early in the acute phase and additional therapy in cases fever recurred. We counted the days from onset of fever to the peak level of acute phase reactants and analyzed the differences between two groups with t-test. RESULTS: In the comparison of two groups, the mean intervals from the onset of fever to peak CRP level was 9.23+/-4.71 days in group A, 6.63+/-2.47 days in group B. The mean intervals to peak ESR was 13.31+/-7.06 days in group A, 8.37+/-3.01 days in group B. The mean intervals to highest platelets counts was 14.62+/-4.96 days in group A, 11.14+/-3.59 days in group B. All of these results showed statistically significant differences. CONCLUSION: Our results show that the KD patients with coronary aneurysm have longer intervals between the onset of fever to day of peak acute reactants in spite of the aggressive treatment than those without aneurysm. So, in cases of KD with relapsing fever in spite of IVIG and the acute reactants are in the course of increment, additional immune modulation therapy and short term follow ups with echocardiography would be needed.

A Case of Hypertrophic Cardiomyopathy Associated with Wolff-Parkinson-White Syndrome

Hypertrophic cardiomyopathy(HCM) is defined as a thickened wall of heart muscles and non-dilated left ventricle, but is not accompanied underlying cardiac or systemic diseases that induce ventricular hypertrophy. HCM is responsible to exercise limitation for all ages and also is known as the most common cause of heart-related sudden death during childhood and adolescents. Epidemiological studies showed that prevalence in young adults is 0.2% and HCM is caused by a mutations in genes that code the proteins of cardiac muscles. HCM with Wolff-Parkinson-White Syndrome is extremely rare and associated with a high risk of tachyarrhythmia and sudden death. We report an infantile HCM with WPW syndrome who died suddenly.

Two Cases of Cerebral Salt Wasting Syndrome Developing after Cranial Vault Remodeling in Craniosynostosis Children

Hyponatremia has been recognized as an important postoperative metabolic complication after central nervous system (CNS) operations in children. If not appropriately treated, the postoperative hyponatremia can cause several types of CNS and circulatory disorders such as cerebral edema, increased intracranial pressure. The postoperative hyponatremia after CNS surgery has been considered as one of the underlying causes of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In some cases, however, the cerebral salt wasting (CSW) syndrome has been detected. CSW syndrome is far less well-known than SIADH and also different from SIADH in diagnosis and treatment. It causes an increase in urine output and urine sodium after a trauma of CNS and dehydration symptoms. The appropriate treatment of CSW syndrome is opposite the usual treatment of hyponatremia caused by SIADH. The latter is treated with fluid restriction because of the increased level of free water and its dilutional effect causing hyponatremia, whereas the former is treated with fluid and sodium resuscitation because of the unusual loss of high urinary sodium. Early diagnosis and treatment of CSW syndrome after CNS surgery are, therefore, essential. We made a diagnosis of CSW syndrome in two craniosynostosis children manifesting postoperative hyponatremia and supplied them an appropriate amount of water and sodium via intravenous route. The hyponatremia or natricuresis of the children improved and neurologic and circulatory sequelae could be prevented.

Outcome of Treatment in Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

PURPOSE: The prognosis of Philadelphia chromosome-positive acute lymphoblastic leukemiaacute lymphoblastic leukemia with Philadelphia chromosome (Ph ALL) is generally poor and reports from large studies are scarce. We evaluated the clinical characteristics and the efficacy of allogeneic bone marrow transplantation (Allo-BMT) and chemotherapy for children with this type of leukemia. METHODS: Fifteen children diagnosed with Ph ALL among 278 childhood acute lymphoblastic leukemia patients in our St. Mary's hospital from February 1997 to July 2002 were retrospectively reviewed. RESULTS: Of 278 eligible cases, 15 (5.4%) had a Philadelphia chromosome. There were 12 males and 3 females with a median age 9 years (range, 4~13). Initial white blood cell counts ranged from 6.3~446.0 109/L (median, 87.2 109/L). Immunophenotyping studies indicated B-lymphoid phenotype in 13, myeloid/B-lymphoid biphenotype in 2. Of 15 Ph ALL children, 12 patients entered remission after first induction therapy and remained other 3 cases finally had delayed remission. Among evaluable 14 patients, seven received Allo-BMT from HLA-identical sibling or unrelated donor and three of these patients died following recurrence and severe graft versus host disease. Only three patients are alive recently and of them two patients have durable disease free survival more than 24 months. All seven patients who treated with only chemotherapy only died of disease recurrence. CONCLUSION: Unlike the usual type of ALL, Ph ALL is associated with extremely poor prognosis and short remission duration. Therefore, Allo-BMT in first remission was the only treatment modality to cure children with Ph ALL in this study. However, even with Allo-BMT, the relapse rate is quite high. Thus, further study is needed to identify the risk factors affecting treatment outcome and to develop new treatment strategy to overcome this factors.

The Clinical Manifestations of Hemophagocytic Lymphohistiocytosis / 대한소아혈액종양학회지

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is an important differential diagnosis in infants and children who present with prolonged fever, hepatosplenomegaly, marked hypertriglyceridemia and cytopenia. HLH is currently curable with immunomodulatory therapy, chemotherapy and stem cell transplantation. We evaluated the clinical characteristics and treatment outcomes in patients with HLH. METHODS: We reviewed retrospectively the medical records of 22 children with HLH from January 1996 to June 2003 at Catholic University St. Mary's Hospital. RESULTS: Among the 22 patients, 11 patients were male and the others were female. The median age of onset was 5.5 (0.6~14.4) years including 6 cases presenting before 2 years of age. Family history of suspicious HLH was observed in 3 patients and Epstein Barr virus (EBV) was demonstrated in 10 patients. The most frequent manifestation was fever and the median duration of fever at diagnosis was 18 (6~46) days. Common laboratory findings were neutropenia, anemia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia and abnormal liver function tests. Bone marrow examinations showed significant hemophagocytic lymphohistiocytosis in all of these patients. No treatment was needed in 3 patients and 6 patients were treated with high dose immunoglobulin and antiviral agents, 9 cases with chemotherapy and 4 patients were transplanted with sibling bone marrow or unrelated cord blood. The causes of death were refusal to treatment in 1 patient, disease progression in 6 and pulmonary hemorrhage in 1. CONCLUSION: If the disease is familial or relapsing, progressive or persistent even without family history, hematopoietic stem cell transplantation from the best available donor is strongly recommended. In less severe secondary HLH cases, either no treatment or a short duration of therapy might suffice, but future studies are necessary to define these subsets, possibly with additional genetic markers.

A Case of Cystinosis

Cystinosis, an autosomal recessively inherited lysosomal storage disease, results from impaired transport of the amino acid cystine out of cellular lysosomes. The consequent accumulation and crystallization of cystine destroys tissues, causing growth retardation, Fanconi syndrome, renal failure, eye problems, and endocrinopathies. The gene for cystinosis, CTNS, was mapped to chromosome 17p13. The diagnosis of cystinosis was made by measuring the leukocyte cystine content. The presence of typical corneal crystals on slit-lamp examination is also diagnostic. Since treatment with cysteamine has proved extremely effective, early diagnosis and treatment are critical aspects. We experienced a typical case of cystinosis in a 12-year-old boy with growth retardation.

Complete Remission by Imatinib Mesylate (Glivec) in a Child Relapsing with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph (+) ALL) after Unrelated Donor Stem Cell Transplantation / 대한소아혈액종양학회지

The prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL) who relapsed after allogeneic stem cell transplantation (allo-SCT) is poor. Imatinib mesylate (Glivec (R) ) is an inhibitor of the ABL tyrosine kinase with potent antileukemic activity in advanced Ph ALL. The clinical effects of imatinib on Ph ALL recurring after allo-SCT have not been established. We describe the clinical activity of imatinib in a 7 year-old boy with Ph ALL relapsing after unrelated donor stem cell transplantation. Imatinib as a single agent resulted in rapid elimination of leukemic cells with ensuing prolonged neutropenia and thrombocytopenia. Subsequent hematological recovery by donor-derived cells was associated with grade 3 graft-versus-host disease (GvHD), which responded to cyclosporine A and steroid. Imatinib successfully induced hematologic, cytogenetic and molecular remission of Ph ALL, and restored complete donor chimerism, along with controllable GvHD.

The Effects of Multiple Transfusion on the Outcomes of Bone Marrow Transplantation from HLA-matched Sibling Donor in Patients with Severe Aplastic Anemia / 대한소아혈액종양학회지

PURPOSE: We investigated the effects of pretransplant-transfusion on engraftment, graft versus host disease (GVHD) and graft rejection after bone marrow transplantation (BMT) in children with severe aplastic anemia who had HLA-identical sibling donor. METHODS: We reviewed retrospectively the medical records of 47 children with severe aplastic anemia who received grafts from HLA-matched sibling donor using same conditioning regimen (procarbazine, antithymocyte globulin, and cyclophosphamide) from September 1986 to May 2001. GVHD prophylaxis consisted of cyclosporine and short-term methotrexate. Patients receiving multiple transfusion more than 40 transfused units in total before BMT were defined as high-risk group (HRG) and those with less than 40 transfused units were as standard-risk group (SRG). RESULTS: Among 47 patients, 30 patients were classified into SRG and remaining 17 were into HRG. The median time from diagnosis to transplant was 4 (range, 1~14) months in SRG and 36 (range, 3~360) months in HRG. Primary engraftment was achieved in all patients. Acute GVHD (> or =grade II) in HRG (13.3%) was comparable with in SRG (5.9%) (P=0.221), meanwhile corresponding fugures for chronic GVHD was 1 (3.3%) and 2 (11.8%). All of these patients have experienced complete resolution of GVHD and are no longer receiving immunosuppressive therapy. Booster stem cell infusion was needed for poor graft function (n=3) in SRG and also for poor graft function (n=1) or progressive rejection (n=3) in HRG. Five-year disease free survival rate was 100% in SRG and 94.1 6% in HRG (P=0.18). CONCLUSION: These findings suggest that multiple transfusion may be not a risk factor for rejection or poor outcome. Progressive rejection was observed only in patients with multiple transfusion but did not affect the survival.