Pre-engraftment Syndrome in Allogeneic Hematopoietic Stem Cell Transplantation / 대한소아혈액종양학회지

PURPOSE: Characteristic clinical findings of fever, skin rash with or without the evidence of fluid retention, mimicking engraftment syndrome (ES), have been observed during the pre-engraftment period in patients with hematopoietic stem cell transplantation (HSCT). We described these findings as pre-engraftment syndrome (pES) and analyzed the incidence and risk factors of pES in the pediatric patients who received HSCT with various stem cell sources. METHODS: Among 53 patients who received HSCT at Dong-A University Medical Center from Sep. 1997 to Mar. 2004, 37 patients with allogeneic HSCT were analyzed retrospectively to characterize the clinical syndrome. RESULTS: In 3 (21.4%) out of 14 patients with cord blood stem cell transplantation, non-infectious fever, skin rash and tachypnea developed on 4~15 days prior to neutrophil engraftment. Two of them spontaneously recovered just with fluid restriction and oxygen inhalation, however, one patient died of complicated pulmonary hemorrhage in spite of aggressive supportive therapy and steroid treatment. In 4 (17.4%) out of 23 patients with allogeneic bone marrow transplantation (BMT), non-infectious fever and skin rash developed on 4~5 days prior to neutrophil engraftment. All of them recovered with steroid treatment only. We could not find any risk factors for this syndrome, however, the speed of neutrophil engraftment was significantly faster in the patients with pES. CONCLUSION: We established a distinctive clinical syndrome during pre-engraftment period, which is very similar but different in occurrence timing from ES. The pES may be associated with enhanced engraftment, but has no impact on the other clinical outcomes.

Early Inflammatory Syndrome following Cord Blood Stem Cell Transplantation / 대한혈액학회지

PURPOSE: We experienced the early toxicities in preengraftment period following cord blood stem cell transplantation (CBSCT), mimicking engraftment syndrome, characterized by fever, skin rash and fluid retention. We report these toxicities here, first in Korea, as an early inflammatory syndrome (EIS). METHODS: We retrospectively reviewed the clinical data of 13 patients who received CBSCT with conventional conditioning chemotherapy for hematologic malignancies and immunodeficiency at Dong-A University Medical Center from 1998 to 2003. We defined the criteria for EIS as follows: noninfectious fever, skin rashes mimicking acute graft versus host disease and the evidence of fluid retention. These clinical signs should be appeared before neutrophil engraftment. RESULTS: We experienced 3 cases of EIS in patients received the conventional dosage of conditioning chemotherapy for CBSCT, which developed on post-transplant day 7~10 and persisted for 2~7 days. Two out of 3 patients were recovered from EIS spontaneously or by supportive treatment, except 1 patient who expired due to complicated pulmonary hemorrhage. CONCLUSION: The definition of EIS is yet obscure, thus more close observations for clinical course of CBSCT and pathophysiological research would be required.

A Case of Acute Necrotizing Encephalopathy with a Thalamic Hemorrhage

Acute necrotizing encephalopathy predominantly affects young children and infants living in Japan and Taiwan, and is characterised by acute encephalopathy with seizures and decreased level of consciousness. The Hallmark of the disease is diffuse and symmetrical CNS lesions of both thalami, brainstem tegmentum, cerebral periventricular white matter and cerebellar medula. The clinical, radiological and pathological features of this disease, a disease entity established recently, is proposed by Masashi Mizuguchi et al in 1995. The aetiology is unknown but infectious or parainfectious process seems likely. The diagnosis can be made without difficulty on the basis of the combination of a typical clinical figures and characteristic radiologic findings. There is no specific therapy or prevention. The prognosis was poor in the 1980s but has improved recently. We experienced a case of 6-month-old female infant with acute necrotizing encephalopathy and a thalamic hemorrhage. We report this case with a review of the related literatures.

Homing-Associated Cell Adhesion Molecules and Cell Cycle Status on the Nucleated Cells in the Bone Marrow, Mobilized Peripheral Blood and Cord Blood

Homing-associated cell adhesion molecules (H-CAM) on the CD34+ cells play an important role for the engraftment process following hematopoietic stem cell transplantation (HSCT). However, it seems that not only CD34+ cells but also other nucleated cells (NCs) with H-CAM could be implicated in the engraftment process and the proliferation of hematopoietic stem cells. We investigated the differences of HCAM and cell cycle status on the NCs in cord blood (CB), bone marrow (BM), and mobilized peripheral blood (PB). The proportions of CXCR4+ cells within the NC populations were greater in CB than in PB or BM (p=0.0493), although the proportions of CXCR4+, CD44+, and CD49d+ cells within the CB CD34+ cell populations were same within BM or PB. A lower proportion of CD34+CD49d+ cells within the CD34+ cell populations was more noted in CB than in PB or BM (p=0.0085). There were no differences in cell cycle status between CB and BM or PB. Our results suggest that the migrating potential of CB would be enhanced with increased CXCR4 expression on the NCs, but the adhesion potential of CB CD34+ cells would be less than that of PB and BM. These findings may help explain why the lower cell dose is required and engraftment is delayed in cord blood stem cell transplantation.

Studies of the Change of Antibody Titers after Vaccination of Haemophilus Influenzae PRP-T Conjugate Vaccine

PURPOSE: This study was carried out to survey the serum anti-PRP titers after the completion of a primary series with 3 doses of the PRP-T conjugate vaccine(ACT-HIBTM), to evaluate the necessity of booster vaccination. METHODS: One hundred twenty healthy infants who went for consultations at Moon Hwa hospital between December 1999 to May 2001 were vaccinated at two, four and six months after birth. The serum antibody levels were measured at 7-8 months and 19-20 months of age by the "Farr" type of radioimmunological method at Aventis Pasteur International in France. RESULTS: The geometric mean of Anti-PRP titers were 24.6 microgram/mL at 7-8 months and then fell to 2.10 microgram/mL at 19-20 months. Minimum Anti-PRP titer was 0.75 microgram/mL at 7-8 months, and 0.1 microgram/mL at 19-20 months. Maximum Anti- PRP titer was 99.2 microgram/mL at 7-8 months, and 9.1 microgram/mL at 19-20 months. Subjects of Anti-PRP titers more than 0.15 microgram/mL were 100% at 7-8 months, and 97.0% at 19-20 months, and subjects of Anti-PRP titers more than 1.0 microgram/mL were 98.3% at 7-8 months, and 61.6% at 19-20 months. CONCLUSION: The Anti-PRP titers at 7-8 months were very high but rapidly decreased at 19-20 months of age, so the necessity of booster vaccination could be considered in Korean children.

Outcomes of Hematopoietic Stem Cell Transplantation with Different Stem Cell Sources in Children with Malignant and Non-malignant Hematologic Diseases / 대한소아혈액종양학회지

PURPOSE: We compared the clinical outcomes of allogeneic bone marrow transplantation (BM), peripheral blood stem cell transplantation (PB) and cord blood stem cell transplantation (CB) in children with malignant and non-malignant diseases. METHODS: We retrospectively analysed the engraftment speed, episodes of infection, acute graft versus host disease (GVHD), and survival rate in 27 children who underwent hematopoietic stem cell transplantation (HSCT) at Dong-A Cancer Center from August 1998 to July 2001. RESULTS: HSCT were done with BM in 16 patients, CB in 6 and PB in 5. The neutrophil and platelet engraftment were achieved at 13.27+/-4.10, 24.58+/-9.41 days in BM, 12.00+/-1.09, 15.88+/-4.42 days in PB, and 39.00+/-15.68, 76.50+/-37.01 days in CB (P=0.001, P=0.001). There were 17 episodes of bacteremia and 10 episodes of viral infections without any significant differences between stem cell sources. There were 8 cases (7 in BM, 1 in CB) of acute GVHD, 4 cases (2 in BM, 2 in CB) of graft failure and 3 cases of relapse (1 in BM, 2 in CB) after HSCT. The duration of median follow-up was 14.34+/-8.32 months in BM, 11.43+/-10.03 months in PB, and 16.56+/-13.76 months in CB. The overall and event free survival rate were 81.5% and 63.0%, respectively. CONCLUSION: There were no significant differences in episodes of infection between the types of HSCT. Although there were HLA mismatched donors for CB, the incidence of acute GVHD was lower, and graft failure or relapse rate was higher than BM.

The Risk Factors of Septic Shock in Childhood Cancer Patients with Neutropenic Fever / 대한소아혈액종양학회지

PURPOSE: We evaluated the easily-assessable risk and prognostic factors of septic shock in children with neutropenic fever (NF) which developed after anticancer chemotherapy. METHODS: We retrospectively reviewed the medical records and laboratory data of 97 children who received anticancer chemotherapy at Dong-A University Hospital and had NF between March, 1993 and February, 2001. RESULTS: There were 223 episodes of NF in 97 children, of which 71 episodes (31.8%) of bacteremia and 18 episodes (8.1%) of septic shock developed. The incidence of septic shock was associated with fever duration (> 5 days, odds ratio=7.367, P=0.0159), tachycardia (odds ratio=11.857, P=0.0001), and serum bicarbonate level (<24 mEq/L, odds ratio=6.235, P=0.0378), whereas not with the underlying disease, age, sex, causative organisms, absolute neutrophil count, absolute monocyte count, absolute phagocyte count, the presence of central venous catheter, the accompanied focal infection, and the use of hematopoietic growth factor. Septic shock developed 3.2 (1~11) days after NF. The prognosis of septic shock patients was not associated with the therapeutic timing, antibiotics, fever duration, tachycardia, or serum bicarbonate level. CONCLUSION: We suggest that the fever duration, tachycardia, and serum bicarbonate level could be important risk factors of septic shock in children with NF. Although We could not reveal the prognostic factors in children with septic shock, further studies will be required.