Tai Ju Hwang

The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis

Yoon HS, Im HJ, Moon HN, Lee JH, Kim H‐J, Yoo KH, Sung KW, Koo HH, Kang HJ, Shin HY, Ahn HS, Cho B, Kim HK, Lyu CJ, Lee MJ, Kook H, Hwang TJ, Seo JJ. The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis.
Pediatr Transplantation 2010: 14:735–740.

Current status of pediatric umbilical cord blood transplantation in Korea: A multicenter retrospective analysis of 236 cases

We report the outcome of 236 pediatric umbilical cord blood transplantations (UCBT) performed in Korea. Given that the sources of the grafts were mostly unrelated donors (n = 226; 95.8%), only the results of unrelated UCBT were included for all statistics. The most frequent primary disease was acute leukemia (n = 167). In total, 91.7% of recipients were seropositive for cytomegalovirus (CMV). The median doses of nucleated cells and CD34+ cells were 4.84 × 107/kg and 2.00 × 105/kg, respectively. The median times to neutrophil (>0.5 × 109/L) and platelet recovery (>20 × 109/L) were 18 and 45 days, respectively. Grade 2–4 acute graft‐versus‐host‐disease (GVHD) and chronic GVHD developed in 41.1 and 36.1% of cases, respectively. Forty‐five patients developed CMV disease. The 5‐year overall and event‐free survival were 47.5 and 36.9%, respectively. Multivariate analysis revealed that adverse factors for survival of the whole cohort were total body irradiation‐based conditioning (P = 0.007), salvage transplant (P = 0.001), failure to achieve early complete chimerism (P < 0.0005), and CMV disease (P = 0.001). The outcomes of the single‐ and double‐unit UCBT (n = 64) were similar, while double‐unit recipients were heavier (P < 0.0005) and older (P < 0.0005). We conclude that double‐unit UCBT is a reasonable option for older or heavier children and that the thorough surveillance of CMV infection and the development of an effective CMV therapeutic strategy may be especially important for Korean children, whose CMV seroprevalence exceeds 90%. Am. J. Hematol., 2011.

Recombinant urate oxidase (Rasburicase) for the treatment of hyperuricemia in pediatric patients with hematologic malignancies: Results of a compassionate prospective multicenter study in Korea†

Hyperuricemia accompanying tumor lysis syndrome is a serious complication in neoplasia with rapid proliferation and destruction. To confirm the efficacy of recombinant urate oxidase (rasburicase) and its safety profile, a phase IV compassionate use prospective study was performed in Korean pediatric patients with hematologic malignancies.

Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Predictor of Engraftment and Acute Graft-versus-Host Disease

Pre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 10(7)/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity.

Epidemiology and clinical long-term outcome of childhood aplastic anemia in Korea for 15 years: retrospective study of the Korean Society of Pediatric Hematology Oncology (KSPHO).

Purpose Aplastic anemia (AA) is a rare hematologic disease characterized by pancytopenia and hypocellular marrow. The Korean Society of Pediatric Hematology Oncology investigated retrospectively the incidence, survival, and transfusion independency according to treatment strategies in AA. Methods All the questionnaires were sent to members for medical records. We collected and analyzed 702 available data. Results The male and female ratio was 1.2, and the median age at diagnosis was 9.3 years. The annual incidence of Korean children with AA was 5.16 per million per year. Constitutional anemia was diagnosed in 44 children. In acquired AA, causes were identified in 39 children. Severe AA (SAA) at initial diagnosis was more common than nonsevere AA. The overall survival was 47.8% with supportive care, 68.1% with immunosuppressive therapy (IST), and 81.8% with hematopoietic stem cell transplantation. In IST, response rate was 65.7%, and relapse rate after response was 54.4% within a median of 23.0 months. The factors with overall survival were severity of disease in supportive care, severity and response in IST, donor type, graft failure, and posttransplant events in hematopoietic stem cell transplantation. Conclusions Long-term outcome in AA was dependent on treatment strategies. These Korean results may help research and prospective international clinical trials for childhood AA.

Perivascular epithelioid cell tumor (PEComa) of the ascending colon: the implication of IFN-α2b treatment

A 7-year-old boy presented with hematochezia and abdominal pain. A 3.7-cm-sized mass was identified in the ascending colon by abdominal computed tomography and colonoscopy. The patient underwent surgical resection. Pathological examination revealed a low-grade perivascular epithelioid cell tumor (PEComa). PEComa in the colon is very rare. Only a few cases have been reported so far. An effective treatment method for this rare tumor has not been established yet. The patient received adjuvant interferon-α immunotherapy for 1 year. He has been tumor-free for 26 months since the initial diagnosis. This report is the first documented case of the use of interferon-α for pediatric PEComa of the colon.

Selective embolization of the internal iliac arteries for the treatment of intractable hemorrhage in children with malignancies

Purpose Acute internal hemorrhage is an occasionally life-threatening complication in pediatric cancer patients. Many therapeutic approaches have been used to control bleeding with various degrees of success. In this study, we evaluated the efficacy of selective internal iliac artery embolization for controlling acute intractable bleeding in children with malignancies. Methods We retrospectively evaluated the cases of 6 children with various malignancies (acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, T-cell prolymphocytic leukemia, Langerhans cell histiocytosis, and rhabdomyosarcoma), who had undergone selective arterial embolization (SAE) of the internal iliac artery at the Chonnam National University Hwasun Hospital between January 2004 and December 2009. SAE was performed by an interventional radiologist using Gelfoam® and/or Tornado® coils. Results The patients were 5 boys and 1 girl with median age of 6.9 years (range, 0.7-14.8 years) at the time of SAE. SAE was performed once in 4 patients and twice in 2, and the procedure was unilateral in 2 and bilateral in 4. The causes of hemorrhage were as follows: hemorrhagic cystitis (HC) in 3 patients, procedure-related internal iliac artery injuries in 2 patients, and tumor rupture in 1 patient. Initial attempt at conservative management was unsuccessful. Of the 6 patients, 5 (83.3%) showed improvement after SAE without complications. Conclusion SAE may be a safe and effective procedure for controlling acute intractable hemorrhage in pediatric malignancy patients. This procedure may obviate the need for surgery, which carries an attendant risk of morbidity and mortality in cancer patients with critical conditions.

Unicentric Castleman disease relapsed after rituximab-CHOP chemotherapy or radiation therapy in an adolescent.

Castleman disease (CD), an atypical lymphoproliferative disorder of unknown etiology, is rare. Unicentric CD can be cured after resection of the involved lymph nodes. However, rarely, patients with the unicentric-plasma cell variant may require additional therapy after resection for persistent systemic symptoms. The clinical course of such patients has not been well characterized. We report the case with relapsed unicentric-plasma cell variant CD who was eventually treated with complete surgical resection. This patient had no response to combination chemotherapy with rituximab after incomplete resection and no response to radiation after relapse.

Efficacy of tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma: the Korean Society of Pediatric Hematology-Oncology experience over 6 years (2000-2005).

The efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) was investigated in patients with high-risk neuroblastoma. Patients over 1 yr of age who were newly diagnosed with stage 4 neuroblastoma from January 2000 to December 2005 were enrolled in The Korean Society of Pediatric Hematology-Oncology registry. All patients who were assigned to receive HDCT/ASCR at diagnosis were retrospectively analyzed to investigate the efficacy of single or tandem HDCT/ASCR. Seventy and 71 patients were assigned to receive single or tandem HDCT/ASCR at diagnosis. Fifty-seven and 59 patients in the single or tandem HDCT group underwent single or tandem HDCT/ASCR as scheduled. Twenty-four and 38 patients in the single or tandem HDCT group remained event free with a median follow-up of 56 (24-88) months. When the survival rate was analyzed according to intent-to-treat at diagnosis, the probability of the 5-yr event-free survival±95% confidence intervals was higher in the tandem HDCT group than in the single HDCT group (51.2±12.4% vs. 31.3±11.5%, P=0.030). The results of the present study demonstrate that the tandem HDCT/ASCR strategy is significantly better than the single HDCT/ASCR strategy for improved survival in the treatment of high-risk neuroblastoma patients.

Idarubicin Plus Behenoyl Cytarabine and 6-thioguanine Compares Favorably with Idarubicin Plus Cytarabine-based Regimen for Children with Previously Untreated Acute Myeloid Leukemia: 10-Year Retrospective, Multicenter Study in Korea

We investigated the outcome of idarubicin plus N4-behenoyl-1-β-D-arabinofuranosyl cytosine (BHAC)-based chemotherapy (BHAC group, n=149) compared to idarubicin plus cytarabine-based chemotherapy (cytarabine group, n=191) for childhood acute myeloid leukemia (AML). Between January 1996 and December 2005, 340 children with AML from 5 university hospitals in Korea received the BHAC-based or cytarabine-based chemotherapy, with or without hematopoietic stem cell transplantation. After induction therapy, 264 (77.6%) of 340 children achieved a complete remission (CR) and 43 (12%) achieved a partial remission (PR). The CR rate in the BHAC group was higher than in the cytarabine group (85.2% vs. 71.7%, P=0.004). However, the overall response rate (CR+PR) was not different between the two groups (93.3% vs. 87.9%, P=0.139). The 5-yr estimates of overall survival (OS) of children in the two groups were similar (54.9% for the BHAC group vs. 52.4% for the cytarabine group, P=0.281). Although the results were analyzed according to the treatment type and cytogenetic risk, the OS showed no significant difference between the BHAC group and the cytarabine group. In the present study, the clinical outcomes of the BHAC-based chemotherapy, consisting of BHAC, idarubicin, and 6-TG, are comparable to that of the cytarabine-based chemotherapy for childhood AML.