Serial Changes of Cytokines in Children with Cerebral Palsy Who Received Intravenous Granulocyte-colony Stimulating Factor Followed by Autologous Mobilized Peripheral Blood Mononuclear Cells

BACKGROUND: This study was performed to assess serial cytokine changes and their clinical impact in children with cerebral palsy (CP) who received granulocyte-colony stimulating factor (G-CSF) followed by infusion of autologous mobilized peripheral blood mononuclear cells (mPBMCs). METHODS: Peripheral blood (PB) samples were collected from 16 CP children at enrollment, and 1 month and 7 months after G-CSF infusion as well as at the end of the study. Cytokine levels were measured by enzyme-linked immunosorbent assays with plasma samples. RESULTS: There were no significant differences in cytokine levels between the mPBMC and placebo groups over 6 months. However, when clinical responders and non-responders were compared, interleukin (IL)-6 (P = 0.050) as well as G-CSF (P = 0.010) were higher in the responders than the non-responders at 1 month, while brain-derived neurotrophic factor (BDNF) (P = 0.030) and insulin-like growth factor (IGF)-1 (P = 0.001) were lower. In addition, BDNF was higher at baseline in the responders than the non-responders (P = 0.030). CONCLUSION: The changes of G-CSF itself, as well as G-CSF-induced cytokines such as IL-6, may be associated with the clinical improvement of neurologic functions. The G-CSF-induced changes of IL-6, BDNF and IGF-1, and BDNF levels before treatment, could be used as prognostic factors in G-CSF trials in CP children.

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows.METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters.RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both).CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Effect of Intravenous Infusion of G-CSF-Mobilized Peripheral Blood Mononuclear Cells on Upper Extremity Function in Cerebral Palsy Children

OBJECTIVE: To investigate the effect of intravenous infusion of peripheral blood mononuclear cells (mPBMC) mobilized by granulocyte-colony stimulating factor (G-CSF) on upper extremity function in children with cerebral palsy (CP). METHODS: Fifty-seven children with CP were enrolled. Ten patients were excluded due to follow-up loss. In total, 47 patients (30 males and 17 females) were analyzed. All patients' parents provided signed consent before the start of the study. After administration of G-CSF for 5 days, mPBMC was collected and cryopreserved. Patients were randomized into two groups 1 month later. Twenty-two patients were administered mPBMC and 25 patients received normal saline as placebo. Six months later, the two groups were switched, and administered mPBMC and placebo, respectively. Quality of Upper Extremity Skills Test (QUEST) and the Manual Ability Classification System (MACS) were used to evaluate upper motor function. RESULTS: All subdomain and total scores of QUEST were significantly improved after mPBMC and placebo infusion, without significant differences between mPBMC and placebo groups. A month after G-CSF, all subdomain and total scores of QUEST were improved. The level of MACS remained unchanged in both mPBMC and placebo groups. CONCLUSION: In this study, intravenously infused mPBMC showed no significant effect on upper extremity function in children with CP, as compared to placebo. The effect of mPBMC was likely masked by the effect of G-CSF, which was used in both groups and/or G-CSF itself might have other neurotrophic potentials in children with CP.

Differences in Mobilization Efficiency between Small Children and Adults with Healthy Marrows / 임상소아혈액종양

BACKGROUND: We compared the yields of mobilized PBSCs from single day of normal volume leukapheresis (NVL) in children and adults, and factors affecting the yields, to understand differences in mobilization efficiency between adults and small children with healthy marrows. METHODS: This study involved 18 adult volunteer donors and 47 small children weighing less than 20 kg who participated in a clinical trial of cell therapy in children with cerebral palsy. Donor factors analyzed to identify predictors of the yield of apheresis included age, gender, weight and complete blood cell count (CBC) with differential counts as well as equipment parameters. RESULTS: The yields of total nucleated cells (TNCs) and CD34⁺cells in the apheresis products of the children were significantly lower than in those from healthy adults. However, the efficiency of recovery of PBSCs (total CD34⁺ cell counts/TNCs) was significantly higher in small children (0.48±0.30%) than in adults (0.10±0.05%) (P < 0.05). Multivariable analysis of adult donor factors showed that the processed volume and flow rate of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both), but not of CD34⁺cells. However, in multivariable analysis of child donor factors, body weight and circulating WBC count on the day of apheresis were significantly associated with the yield of TNCs (P < 0.05, for both) and of CD34⁺cells (P < 0.05, for both). CONCLUSION: The predictors of PBSC yields from a single day of NVL in adults and small children are different. Also mobilization is more effective in small children than in adults.

Clinical Applicability of Newly Developed Image-based Cell Counter for Counting CD34+ Cells: Comparison with Flow Cytometric Analysis / 임상소아혈액종양

BACKGROUND: Flow cytometric analysis is the standard method for enumerating CD34+ stem cells in hematopoietic stem cell transplantation. However, it has some limitations such as expensive instrumentation, high reagent costs, and discrepancies between technicians and laboratories. We compared counts of total nucleated cells (TNCs) and CD34+ cells counts obtained from a flow cytometer with a newly-developed image-based microscopic cell counter (ADAM II) to evaluate the possibility of clinical application of the ADAM II.METHODS: We used 18 samples of circulating peripheral blood (PB) and waste tube fractions of peripheral blood stem cells (PBSCs) harvested by apheresis after G-CSF mobilization from adult volunteer donors. We assessed the reproducibility and linearity of the new procedure and compared the numbers of TNCs and viable CD34+ cells determined with the ADAM II and two different flow cytometers (FACSCalibur, FACSCanto II).RESULTS: Numbers of viable CD34+ cells determined with the ADAM II were accurate over the expected range; the intra-assay coefficient of variation was ≤19.8%. Linearity was also satisfactory (R²=0.99). TNC counts obtained with the ADAM II were highly correlated with those obtained with the FACSCalibur (R²>0.9841, P<0.0001) and FACSCanto II (R²>0.9620, P<0.0001), as were the numbers of viable CD34+ cells obtained with the ADAM II and the FACSCalibur and FACSCanto II (R²>0.9911, P<0.0001 and R²>0.9791, P<0.0001), respectively.CONCLUSION: The newly developed image-based microscopic cell counter (ADAM II) appears to be suitable for enumerating TNCs and viable CD34+ cells.

Pre-engraftment syndrome: clinical significance and pathophysiology

No abstract available.

The development of patient-tailored asthma prediction model for the alarm system

PURPOSE: The increased incidence of asthma due to rising allergic diseases requires the prevention of worsening asthma. It is necessary to develop a patient-tailored asthma prediction model. METHODS: We developed causative factors for the asthma forecast system: infant and young children (0–2 years), preschool children (3–6 years), school children and adolescents (7–18 years), adults (19–64 years), old aged adult (>64 years). We used the Emergency Department code data which charged the short-acting bronchodilator (Salbutamol sulfate) from Health Insurance Review and Assessment Service for the development of asthma prediction models. Three kinds of statistical models (multiple regression models, logistic regression models, and decision tree models) were applied to 40 study groups (4 seasons, 2 sex, and 5 age groups) separately. RESULTS: The 3 kinds of models were compared based on model assessment measures. Estimated logistic regression models or decision tree models were recommended as binary forecast models. To improve the predictability, a threshold was used to generate binary forecasts. CONCLUSION: We suggest the binary forecast models as a patient-tailored asthma prediction system for this category. It may be needed the extended study duration and long-term data analysis for asthmatic patients for the further improvement of asthma prediction models.

Clinical Applicability of Newly Developed Image-based Cell Counter for Counting CD34+ Cells: Comparison with Flow Cytometric Analysis / 임상소아혈액종양

BACKGROUND: Flow cytometric analysis is the standard method for enumerating CD34+ stem cells in hematopoietic stem cell transplantation. However, it has some limitations such as expensive instrumentation, high reagent costs, and discrepancies between technicians and laboratories. We compared counts of total nucleated cells (TNCs) and CD34+ cells counts obtained from a flow cytometer with a newly-developed image-based microscopic cell counter (ADAM II) to evaluate the possibility of clinical application of the ADAM II. METHODS: We used 18 samples of circulating peripheral blood (PB) and waste tube fractions of peripheral blood stem cells (PBSCs) harvested by apheresis after G-CSF mobilization from adult volunteer donors. We assessed the reproducibility and linearity of the new procedure and compared the numbers of TNCs and viable CD34+ cells determined with the ADAM II and two different flow cytometers (FACSCalibur, FACSCanto II). RESULTS: Numbers of viable CD34+ cells determined with the ADAM II were accurate over the expected range; the intra-assay coefficient of variation was ≤19.8%. Linearity was also satisfactory (R²=0.99). TNC counts obtained with the ADAM II were highly correlated with those obtained with the FACSCalibur (R²>0.9841, P0.9620, P0.9911, P0.9791, P<0.0001), respectively. CONCLUSION: The newly developed image-based microscopic cell counter (ADAM II) appears to be suitable for enumerating TNCs and viable CD34+ cells.

Evaluation of Immune Response after Vaccinations Post-chemotherapy in Childhood Cancer Survivors / 임상소아혈액종양

BACKGROUND: Survivors of childhood cancers are recommended to receive revaccinations after chemotherapy, although the universally recommended vaccination schedule for such children has not been established. We evaluated immune response following post-chemotherapy vaccinations in childhood cancer survivors.METHODS: The study included 59 patients who survived at least 5 years after completion of chemotherapy without evidence of recurrence. The patients received hepatitis-B virus (HBV) and measles, mumps, and rubella (MMR) vaccines 1 year after finishing chemotherapy according to our institutional protocol. Immune response to HBV and MMR vaccines was measured and seropositivity and factors hindering immune response to HBV and MMR vaccines were analyzed.RESULTS: The seropositivity for HBV was 88%; with a higher rate in patients with non-hematologic malignancies (100%, 18/18) than those with hematologic malignancies (78.3%, 18/23) (P=0.05) and reciprocally associated with the duration of chemotherapy (P=0.0043). The seropositivity for MMR viruses was 61%, 37% and 83% respectively, showing significantly lower response to mumps and was not different between hematologic malignancy group and non-hematologic malignancy group. Unlike HBV, the duration of chemotherapy did not affect seropositivity for MMR viruses. Ten children who failed to be immune to any of the MMR viruses received booster vaccination which resulted in seropositivity of 60% (3/5), 56% (4/9), 100% (2/2) respectively.CONCLUSION: Longer duration of chemotherapy and underlying hematologic malignancies were adversely associated with achieving immune response to HBV vaccine, but not to MMR vaccine. Our results also underline the need for booster vaccinations in non-responders to vaccinations post-chemotherapy.

A Hypervascular Inflammatory Myofibroblastic Tumor in the Mediastinum Resected Completely Following Embolization of the Feeding Vessels / 임상소아혈액종양

Inflammatory myofibroblastic tumors (IMTs) are rare tumors of intermediate malignant potential that can occur anywhere in the body. We describe an interesting case of a hypervascular IMT in the mediastinum that could be resected completely following embolization of the feeding vessels. A 17-month-old girl with complaints of cough and fever for 3 months was referred to our hospital. Computed tomography (CT) scan showed a large mass in the right hemithorax that shifted the mediastinum to the left. Primary excision was considered but not performed because there was very active capsule wall bleeding due to the hypervascular tumor. After embolization of the feeding vessels, successful complete resection was carried out. Approximately 6 weeks after the operation, follow-up CT scan showed no evidence of recurrent disease. Preoperative embolization is a good option for performing complete resection of hypervascular IMTs that could reduce the recurrence rate.

Evaluation of Immune Response after Vaccinations Post-chemotherapy in Childhood Cancer Survivors / 임상소아혈액종양

BACKGROUND: Survivors of childhood cancers are recommended to receive revaccinations after chemotherapy, although the universally recommended vaccination schedule for such children has not been established. We evaluated immune response following post-chemotherapy vaccinations in childhood cancer survivors. METHODS: The study included 59 patients who survived at least 5 years after completion of chemotherapy without evidence of recurrence. The patients received hepatitis-B virus (HBV) and measles, mumps, and rubella (MMR) vaccines 1 year after finishing chemotherapy according to our institutional protocol. Immune response to HBV and MMR vaccines was measured and seropositivity and factors hindering immune response to HBV and MMR vaccines were analyzed. RESULTS: The seropositivity for HBV was 88%; with a higher rate in patients with non-hematologic malignancies (100%, 18/18) than those with hematologic malignancies (78.3%, 18/23) (P=0.05) and reciprocally associated with the duration of chemotherapy (P=0.0043). The seropositivity for MMR viruses was 61%, 37% and 83% respectively, showing significantly lower response to mumps and was not different between hematologic malignancy group and non-hematologic malignancy group. Unlike HBV, the duration of chemotherapy did not affect seropositivity for MMR viruses. Ten children who failed to be immune to any of the MMR viruses received booster vaccination which resulted in seropositivity of 60% (3/5), 56% (4/9), 100% (2/2) respectively. CONCLUSION: Longer duration of chemotherapy and underlying hematologic malignancies were adversely associated with achieving immune response to HBV vaccine, but not to MMR vaccine. Our results also underline the need for booster vaccinations in non-responders to vaccinations post-chemotherapy.

A Hypervascular Inflammatory Myofibroblastic Tumor in the Mediastinum Resected Completely Following Embolization of the Feeding Vessels / 임상소아혈액종양

Inflammatory myofibroblastic tumors (IMTs) are rare tumors of intermediate malignant potential that can occur anywhere in the body. We describe an interesting case of a hypervascular IMT in the mediastinum that could be resected completely following embolization of the feeding vessels. A 17-month-old girl with complaints of cough and fever for 3 months was referred to our hospital. Computed tomography (CT) scan showed a large mass in the right hemithorax that shifted the mediastinum to the left. Primary excision was considered but not performed because there was very active capsule wall bleeding due to the hypervascular tumor. After embolization of the feeding vessels, successful complete resection was carried out. Approximately 6 weeks after the operation, follow-up CT scan showed no evidence of recurrent disease. Preoperative embolization is a good option for performing complete resection of hypervascular IMTs that could reduce the recurrence rate.