Jun Eun Park

Successful Engraftment with Fludarabine, Cyclophosphamide, and Thymoglobulin Conditioning Regimen in Unrelated Transplantation for Severe Aplastic Anemia: A Phase II Prospective Multicenter Study

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective for preventing graft-versus-host disease (GVHD) and the rejection of organ transplants. After the promising results of our preliminary study, we conducted a phase II prospective multicenter clinical trial using a fludarabine (Flu), cyclophosphamide (Cy), and thymoglobulin conditioning regimen to allow good engraftment in patients who underwent unrelated transplantation for SAA. Twenty-eight patients underwent bone marrow (N = 15) or mobilized peripheral blood (N = 13) transplantation from HLA-matched unrelated donors with Cy (50 mg/kg once daily intravenously (i.v.) on days -9, -8, -7, and -6), Flu (30 mg/m² once daily i.v. on days -5, -4, -3, and -2), and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2, and -1). Donor-type hematologic recovery was achieved in all patients. The estimated survival rate (SR) was 67.9%, and all the events were treatment-related mortality (TRM), which included thrombotic microangiopathy (N = 2), pneumonia (N = 1), myocardiac infarction (N = 1), posttransplantation lymphoprolifarative disease (N = 3), and chronic GVHD-associated complications (N = 2). The SR of patients who received bone marrow (60.0%) was not different from that of patients who received mobilized peripheral blood (76.9%) (P = .351), but the SR of patients who received more than 15 units of red blood cells before transplantation (45.5%) was significantly lower than that of the other patients (82.4%) (P = .048). The Flu, Cy, and thymoglobulin conditioning regimen achieved promising results for successful engraftment, but the TRM was high. This study was registered at www.clinicaltrials.gov (NCT00737685), and now we are performing a new multicenter study (NCT00882323) to decrease the TRM by reducing the dose of Cy.

Clinical features and treatment outcomes of Langerhans cell histiocytosis: a nationwide survey from Korea histiocytosis working party.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO−), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO+). The 5-year overall survival (OS) rates in the SS, MS-RO−, and MS-RO+ groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ⩽2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO+ patients and reduce reactivation in younger patients with MS involvement.

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.

Pediatric primary cutaneous marginal zone B-cell lymphoma treated with intralesional rituximab

Auteur(s) : Minxa0Young Park1, Hyunxa0Joo Jung2, Junxa0Eun Park2, Youxa0Chan Kim1 1Department ofxa0Dermatology 2Department ofxa0Pediatrics, Ajou University School ofxa0Medicine, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, South Korea Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an indolent lymphoma which is extremely rare in children. Recently, intralesional therapy with anti-CD20 monoclonal antibodies (rituximab) has shown favorable results for the treatment [...]

Comparison of multiplex reverse transcription polymerase chain reaction and conventional cytogenetics as a diagnostic strategy for acute leukemia

To clarify the usefulness of multiplex reverse transcription polymerase chain reaction (mRT‐PCR) in diagnosing acute leukemia, mRT‐PCR detecting 28 different translocations was performed on bone marrow aspirates of 156 patients with acute leukemia, and the results were compared with conventional chromosomal karyotypes. About 113 of 156 patients had acute myeloid leukemia (AML), and 36 had acute lymphoid leukemia (ALL) with patients’ ages ranging from 1 to 84 (median: 34.5). Concordance rate between karyotyping and mRT‐PCR was 50% (51% in AML and 44% in ALL). Karyotype revealed chromosomal abnormalities in 70 patients (45%) while mRT‐PCR showed some aberrations in 59 patients (38%). mRT‐PCR detected t(1;19), t(4;11), t(9;11), t(10;11), t(11;19), t(12;21), and TAL1d, which were not detected by G‐banding. In addition, 10 patients with t(15;17), one patient with t(8;21), and four patients with t(9;22) detected by mRT‐PCR revealed normal karyotypes. However, mRT‐PCR did not detect numerical abnormalities, deletions, and translocations other than the 28 translocations included in the assay as expected. In conclusion, although it cannot be a substitute of the conventional chromosome analysis, mRT‐PCR could be a complementary diagnostic strategy of acute leukemia.

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.

Acute myeloid leukemia with t(16;21)(q24;q22) and eosinophilia: case report and review of the literature

The t(16;21)(q24;q22), a rare chromosomal translocation involving chromosome 21 in de novo and therapy-related acute myeloid leukemia (AML), produces a RUNX1-CBFA2T3 fusion gene (previously AML1-MTG16) fusion gene. The translocation has been reported in 20 patients with AML, with eosinophilia present in 3 cases. Here we report a pediatric case of t(16;21)(q24;q22) in de novo AML with eosinophilia and suggest that eosinophilia is a hematologic characteristic of at least a subpopulation of AML with t(16;21)(q24;q22). A 4-year-old Korean girl was admitted with complaints of pale appearance and dizziness, and was diagnosed with acute myelomonocytic leukemia. On admission, laboratory evaluation revealed hemoglobin at 3.3 g/dL, platelets at 9.0 x 10(9)/L, and white blood cells at 9.1 x 10(9)/L with 10% eosinophils and 1% blasts. The bone marrow aspirate contained 31% blasts and 11% eosinophils. Flow cytometric analysis revealed the expression of CD13, CD14, CD19, CD33, CD34, and HLA-DR by the leukemic blasts. The karyotype was 47,XX, + 8,t(16;21)(q24;q22)[18]/46,XX[2]. Interphase fluorescence in situ hybridization analysis with a dual-color, dual-fusion translocation LSI AML1/ETO probe set for RUNX1 and RUNX1T1 produced three signals for each probe in 90% of interphases, but no fusion signals. We confirmed the presence of RUNX1-CBFA2T3 fusion transcripts with reverse transcriptase-polymerase chain reaction, using primers AML1ex5f1 and MTG16r2.

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.

Reduced-intensity allogeneic stem cell transplantation for children with neuroblastoma who failed tandem autologous stem cell transplantation.

To date, no effective curative option is available for children with neuroblastoma (NB) who failed tandem high‐dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). The present study evaluated the feasibility and efficacy of reduced‐intensity allogeneic stem cell transplantation (RI alloSCT) in six children with NB who failed tandem HDCT/autoSCT.

Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates ±95% confidence intervals (CI) were 33.3±12.2% and 26.7% ±11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates ±95% CI was 40.0±15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.