Pichia ohmeri is an yeast-like fungus used in the food industry for fermentation. This organism has been implicated in human disease only in a few case reports. We describe herewith two cases of Pichia ohmeri fungemia in immunocompromised pediatric patients with central venous catheters. A 7-year-old patient with Burkitt's lymphoma undergoing chemotherapy and a newborn with low birth weight developed fungemia during hospitalizations. Both patients were receiving parenteral nutrition through central venous catheters. Both patients succumbed despite empiric treatment with amphotericin B in Case 1. A brief review of the literature ensues with the case reports.
Amphotericin B ; Burkitt Lymphoma ; Central Venous Catheters ; Child ; Drug Therapy ; Fermentation ; Food Industry ; Fungemia* ; Fungi ; Hospitalization ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Parenteral Nutrition ; Pichia*

Self-healing reticulohistiocytosis is a perinatal disease characterized by rapidly developing and involuting benign histiocytic infiltration of the skin and other organ. We had recently experienced a case of a self-healing reticulohistiocytosis in 99-day-old infant who presented with multiple erythematous nodular lesions on face and trunk and pancytopenia. Our case differed from those previously reported in that extracutaneous involvement was found. The patient had pancytopenia, hypertriglyceridemia, hypofibrinogenemia hyperferritinemia and hepatosplenomegaly as well as skin lesions. Bone marrow showed a marked lymphocytosis with many histiocytes. We described a detailed clinical features of this case and reviewed the literatures.
Bone Marrow ; Histiocytes ; Humans ; Hypertriglyceridemia ; Infant ; Lymphocytosis ; Pancytopenia ; Skin

A 4-day-old patient with Down syndrome (DS) visited out patient department (OPD) because of jaundice and VSD. Peripheral blood smear showed 21% of myeloblast. After 4 weeks of observation, WBC count was 55,100/mm3 (blast 90%). BM aspirate showed AML (M7) and treatment was started with low dose Ara-C (20 mg/m2 for 21 days). After remission, maintenance therapy was done with low dose Ara-C (16 mg/m2 for 21 days), 6-TG (40 mg/m2 for 21 days) and low dose IL-2 (0.5 106U/m2 for 21 days) alternatively for 2 years. The patient remained in complete remission and VSD was corrected at 9 months of age. This case shows that remission can be achieved with low dose Ara-C and it can be maintained thereafter with low dose Ara-C, 6-TG and IL-2. Low dose IL-2 has the advantage of selectively activating immune cells with high affinity receptors, low treatment related morbidity, good compliance which can be injected at OPD. As the patients with DS have defect in IL-2 secretion, IL-2 may have an beneficial effects on treating AML in DS.
Compliance ; Cytarabine ; Down Syndrome* ; Drug Therapy* ; Granulocyte Precursor Cells ; Humans ; Interleukin-2* ; Jaundice ; Leukemia, Myeloid, Acute*

Acute lymphoblastic leukemia (ALL), in general, can be diagnosed by detecting blasts in peripheral blood or bone marrow. Some of the cases of ALL do not show typical leukemic features, and only manifest as refractory anemia, thrombocytopenia, myelofibrosis and lymphocytic infiltration into bone marrow. Several months after presentation, they may reveal typical leukemic features and are diagnosed as ALL. This kind of leukemia is called ALL with aleukemic prodrome. Although the incidence of ALL with aleukemic prodrome is 1.5~2.2% of childhood ALL cases, it is rarely reported in Korea. We experienced a 6 month-old female infant who presented with refactory anemia and thrombocytopenia, and two serial of bone marrow examination revealed only myelofibrosis. She subsequently developed ALL 3 months later. We report this case with a brief review of related literatures.
Anemia ; Anemia, Refractory ; Bone Marrow ; Bone Marrow Examination ; Female ; Humans ; Incidence ; Infant ; Korea ; Leukemia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Primary Myelofibrosis ; Thrombocytopenia

PURPOSE: If primitive hematopoietic cells expanded ex vivo can be used in stem cell transplantation, duration for hematologic recovery will be shortened. In this study, CD34 cells were cultured with various hematopoietic growth factors which are known to stimulate proliferation of primitive hematopoietic cells. METHODS: CD34 cells isolated from cord blood were cultured and expanded ex vivo with IL-3, stem cell factor (SCF), flt-3 ligand (FL), thrombopoietin (TPO), granulocyte-colony stimulating factor (G-CSF). To find optimal combination of growth factors, CD34 cells were cultured for 9 days with various combinations of growth factors. To find optimal duration of culture, CD34 cells were cultured for 5, 7, 9, 12 days. To evaluate expansion of primitive hematopoietic cells, the number of CD34 cells, colony forming cells and long-term culture-initiating cells (LTC-IC) were counted by flow cytometry, colony forming cell assay and limiting dilution assay respectively. RESULTS: Primitive hematopoietic cells were successfully expanded from CD34 cells of cord blood. Maximal expansion of LTC-IC and CFU- GEMM were 2.58 and 2.37 fold respectively after 9 days of culture, and were obtained with the combination of IL-3 SCF FL TPO. When CD34 cells were cultured for 5, 7, 9, 12 days with the combination of IL-3 SCF FL TPO, expansion of LTC-IC was maximal (2.95 fold) after 9 days culture. After reaching maximal expansion of LTC-IC, the number of nucleated cells increased, but that of primitive hematopoietic cells decreased. CONCLUSION: Primitive hematopoietic cells can be successfully expanded ex vivo by using hematopoietic growth factors. Duration for hematologic recovery after stem cell transplantation will be shortened by using primitive hematopoietic cells expanded ex vivo.
Fetal Blood ; Flow Cytometry ; Intercellular Signaling Peptides and Proteins* ; Interleukin-3 ; Stem Cell Factor ; Stem Cell Transplantation ; Thrombopoietin ; Transplantation

PURPOSE: Umbilical cord blood is increasingly being used in the setting of allogeneic marrow transplantation. However, while neutrophil engraftment is comparable to that of marrow transplants, delayed platelet engraftment is often a concern for cord blood transplant recipients. This delay may be due to relative weakness of the megakaryocyte lineage in cord blood. We evaluated the potential of ex vivo expansion and clonality from different stem cell sources. METHODS: The CD34 cells from bone marrow (BM), umbilical cord blood (CB), and mobilized peripheral blood (PB) were cultured for burst-forming unit of erythrocyte (BFU-E), colony-forming unit of granulocyte and monocyte (CFU- GM) and colony-forming unit of megakaryocyte (CFU-MK) at day 0, day 4, day 7, and day 14 under the combination of growth factors, with cell counts. Cytokines included recombinant human megakaryocyte growth and development factors (100 ng/mL), interleukin-3 (10 ng/mL), stem cell factor (100 ng/mL), and flt-3 ligand (50 ng/mL). RESULTS: CB-derived CD34 cells had significantly higher total cell proliferation than either BM or PB at day 7 (1.6 to 18.2 fold) and day 14 (1.2 to 17.2 fold). The colony count of BFU-E was in general more plentiful in CB than in BM and PB at day 4, day 7 and day 14, among which the difference was the most distinct at day 7 culture. Also, CB CD34 cells produced more CFU-Mk colonies than did BM or PB at day 4 and day 7. There were no differences in colonies count of BFU-E and CFU-Mk between BM and PB. CONCLUSION: Ex vivo expansion of CB cells may be most promising in producing total cellular expansion, CFU-Mk and BFU-E compared with BM and PB, especially at day 7, because the former was the most productive hematopoietic source on a per volume basis.
Blood Platelets ; Bone Marrow* ; Cell Count ; Cell Proliferation ; Culture Media, Serum-Free* ; Cytokines ; Erythrocytes ; Erythroid Precursor Cells ; Fetal Blood* ; Granulocytes ; Hematopoietic Stem Cells ; Humans ; Intercellular Signaling Peptides and Proteins ; Interleukin-3 ; Megakaryocytes ; Monocytes ; Neutrophils ; Stem Cell Factor ; Stem Cells ; Thrombopoietin ; Transplantation ; Umbilical Cord*

PURPOSE: In children, at least two or more stem cell mobilization processes are needed in autologous peripheral blood stem cell transplantation to prevent delayed engraftment. And to decrease the risk of tumor cell contaminations, the use of CD34 positive cell selcetion is in increasing tendency. The first leukapheresis product is stored overnight and undergoes CD34 positive selection process mixed with the next day leukapheresis product to save the costs. We intended to find out the optimal overnight storage condition that might minimize the loss of stem cell components. METHODS: RBC (red blood cell)- depleted human umbilical cord bloods (UCB) were used as the source of stem cells because of their easy availability. UCB were processed by isolating the mononuclear cell (MNC) layer using Ficoll-Paque to make the nature similar to leukapheresis products. Fifteen individual UCB were analyzed by several parameters (MNC count and viability, live CD34 positive cell fraction, clonogenic potential) at fresh conditions and under four different overnight storage conditions (room temperatiure (RT), room temperature with autoplasma (AP), 4degrees C, 4degrees C with autoplasma). Analysis of variance, Kruskal-Wallis test, and Wilcoxon signed rank test were used for statistical analyses. RESULTS: Though MNC counts were statistically not different between each conditions (P=0.07), the best recovery (mean 86.9%) was observed at 4degrees C with AP but without statistical significance. MNC viability decreased at RT with or without AP (P<0.05). On the other hand, no difference in MNC viability was noted at 4degrees C with or without AP (P> 0.05). Live CD34 positive cell fractions were significantly decreased under all four different storage conditions compared with fresh ones. However, the samples stored at 4degrees C showed less prominent decreases in live CD34 positive cell fractions than those of RT conditions irrespective of the presence of AP (P=0.0001). CONCLUSION: It seems that 4degrees C condition is superior to RT when short term storage of stem cell products is mandatory. The addition of AP seemed to be advantageous but without statistical significance. The overnight storage of stem cell products at 4degrees C seems to be mandatory because it offers relatively high recovery and less loss of stem cell components. Although the effect of AP was statistically not significant, the role of AP should be studied further because there was a tendency of higher recovery of stem cells in the presence of AP.
Cell Survival* ; Child ; Fetal Blood* ; Hand ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukapheresis ; Peripheral Blood Stem Cell Transplantation ; Stem Cells

PURPOSE: Langerhans cell histiocytosis (LCH) has a wide spectrum of clinical features. Especially, disseminated disease has been associated with a chronic course, high rate of morbidity and possible mortality. The purpose of our study was to investigate the clinical features, subsequent disease course, survival and late sequelae in multisystem LCH (ms-LCH). METHODS: Fourteen cases diagnosed to histologically proven ms-LCH at Pusan National University Hospital between January 1991 and December 1997 were enrolled in this study. All patients received combination chemotherpy. The medical records were retrospectively reviewed for organ involvement at diagosis, disease course, and late sequelae. RESULTS: 1) The peak incidence was between 6 months and 2 years and sex distribution revealed female predominance with the ratio of 1.8:1. 2) Mean number of involved organs was 4.4 and the most frequently involved organ was liver (85.7%) followed by bone, middle ear, skin and spleen. 3) The mean duration of follow up was 41.6 27.5 months. And the overall estimated survival rate at 5 years was 75.9%, with an estimated disease free survival rate of only 40.8% at 5 years. 4) Three patients died and the causes of death were respiratory failure due to pneumonia, gastrointestinal bleeding due to hepatic failure and septicemia. 5) Late sequelae were seen in 42.8% among 14 patients. The most common sequelae were skeletal defects in 21.4% and diabetes insipidus in 21.4%. 6) Among the late sequelae, 3 patients had vertebra plana. Conservative treatment was done and long term follow up of 28.7 7.0 months demonstrated partial healing of the vertebra plana in two cases and no improvement in one. 7) The diabetes insipidus developed in 3 cases, at diagnosis, at 14 months and 20 months after diagnosis respectively. None of the cases received radiation therapy. All of them responded to anti-diuretic CONCLUSION: These data show that, despite the favorable survival, about half of ms-LCH patients had further dissemination of disease or late sequelae. Further treatment needs to be designed to prevent disease progression and late sequelae. hormone replacement therapy.
Busan ; Cause of Death ; Diabetes Insipidus ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Ear, Middle ; Female ; Follow-Up Studies ; Hemorrhage ; Histiocytosis, Langerhans-Cell* ; Hormone Replacement Therapy ; Humans ; Incidence ; Liver ; Liver Failure ; Medical Records ; Mortality ; Pneumonia ; Respiratory Insufficiency ; Retrospective Studies ; Sepsis ; Sex Distribution ; Skin ; Spine ; Spleen ; Survival Rate

PURPOSE: As increased level of prostaglandin has been identified in the bony lesions of Langerhans cell histiocytosis (LCH), we speculated that indomethacin, a potent prostaglandin inhibitor, may be effective for patients with LCH. METHODS: Retrospective review of 8 children with LCH (male 7, female 1) treated with indomethacin at Seoul National University Children's Hospital from September 1999 to February 2001 was done. The dose of indomethacin ranged from 1.8 to 2.8 mg/kg/day in two divided doses. RESULTS: Four patients with single bony lesion had a complete response to treatment. Among them one patient was treated with indomethacin after fourth relapse. Two patients with multiple bony lesions seemed to have partial response to treatment with indomethacin initially but showed disease progression later. Two patients with extraosseous lesion did not respond, but skull lesions were resolved after treatment. No serious toxicities of indomethacin treatment were observed. CONCLUSION: Indomethacin seems to be a very convenient and useful therapy for LCH involving single bony lesion. The mechanism how the LCH imporves in response to indomethacin has to be elucidated. Whether it has a specific role in slowing disease progression or we are seeing merely a spontaneous remission has to be studied in large scale.
Child ; Disease Progression ; Female ; Histiocytosis, Langerhans-Cell* ; Humans ; Indomethacin* ; Prostaglandin Antagonists ; Recurrence ; Remission, Spontaneous ; Retrospective Studies ; Seoul ; Skull

PURPOSE: Children with cancer are immunosuppressed as a result of the underlying malignancies and their treatment. The aim of this study was to investigate immunophenotypic recovery of lymphocyte populations following completion of treatment in children with hematologic malignancies. METHODS: Thirty eight patients were followed up to the Department of Pediatrics, Chonnam National University Hospital from Jan. 1995 to Nov. 1999. Using flow cytometry with fluorescein-conjugated monoclonal antibodies of lymphocytes, T-, B-, and Natural killer (NK) cells and CD4/CD8 ratio were enumerated in 38 patients {acute lymphoblastic leukemia (ALL), 19; acute myeloid leukemia (AML), 14; non-Hodgkin's lymphoma (NHL), 5} from 3 months after completion of therapy and every 3 months thereafter over 2 years. The recovery rates of each parameters were compared according to diseases, age and gender. RESULTS: Absolute lymphocyte count was achieved in 50.0% (19/38) and 73.7% (28/38) of patients at 3 and 12 months after completion of therapy, respectively. Absolute B cell counts as well as the proportion of patients with normal B cell counts were low in NHL than in AML (298+/-250/microliter vs 594+/-356/microliter; P=0.037) at 12 months. T cell recovery tended to be faster in ALL, followed by AML and NHL. NK cell recovery was comparable among 3 disease subgroups. CD4/CD8 ratio was significantly lower in NHL (0.14+/-0.16) than ALL (0.79+/-0.33; P=0.018) at 3 months. CD4/CD8 ratio of NHL (0.41+/-0.14) was lower than ALL (0.79+/-0.29; P=0.033) at 6 months. Differences of CD4/CD8 ratio among the three disease groups were not statistically significant after 9 months. CD4/CD8 ratio was inverted in 22 of 38 (57.9%) patients even after 24 months of therapy. At 12 months higher proportion of male (47.4%, 9/19) achieved a normal CD4/CD8 ratio than that of female (15.8%, 3/19; P=0.036). Age did not make any differences in the recovery. CONCLUSION: Children with hematologic malignancies have persistent abnormalities of lymphocyte subpopulations often after 2 years following completion of chemotherapy. These results suggest that immunologic assessment are required and that preventive measures for infections might be required for more than 2 years after chemotherapy in some patients. Duration of follow-up observation should be differed according to underlying malignancies and their treatment intensity.
Antibodies, Monoclonal ; Cell Count ; Child* ; Drug Therapy* ; Female ; Flow Cytometry ; Follow-Up Studies ; Hematologic Neoplasms* ; Humans ; Jeollanam-do ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; Lymphocyte Count ; Lymphocyte Subsets* ; Lymphocytes* ; Lymphoma, Non-Hodgkin ; Male ; Pediatrics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma