Hyung Nam Moon

Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia.

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to β-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1%, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.

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.

Cytomegalovirus infection in children who underwent hematopoietic stem cell transplantation at a single center: A retrospective study of the risk factors

Abstract:  CMV infection is one of the major causes of morbidity and mortality after HSCT. The aim of this single center retrospective study was to analyze risk factors for CMV infection in pediatric patients who underwent HSCT. We retrospectively reviewed the medical records of 117 pediatric patients who underwent allogeneic HSCT at Asan Medical Center between December 2000 and January 2007. After HSCT, CMV antigenemia was detected by identifying CMV pp65 early antigen in white blood cells. The incidence of CMV antigenemia was 24% (28/117) at a median of 38 days (range: 19–123 days) after HSCT. In multivariate analysis, CMV antigenemia occurred significantly more often in CMV seropositive recipients, patients who received grafts from alternative donors, T‐cell depleted grafts, patients on ATG‐containing conditioning regimens, or patients who received steroid for acute GVHD (p < 0.05). CMV antigenemia tend to develop earlier in patients who received ATG‐containing conditioning regimens (p = 0.09). A second episode of CMV antigenemia was observed in three out of 28 patients (11%). The incidence of CMV disease was 5.9% (7/117) at a median of 97 days (range: 34–120 days). Manifestation of CMV disease included retinitis in two, pneumonitis in two, hepatitis in one, hepatitis with colitis in one, and gastritis in one. Six of the 12 patients (50%) with HG antigenemia (CMV pp65 antigen positivity ≥40 cells) developed clinical CMV disease, a rate that was significantly higher than seen in patients with LG antigenemia (6.25%; p < 0.01). We recommend that patients with these risk factors should carefully undergo regular evaluations for CMV infection. We also suggest that earlier and more aggressive preemptive treatment and serial follow‐up of CMV disease is necessary in patients with HG‐antigenemia.

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.

Prophylactic Low-dose Heparin or Prostaglandin E1 may Prevent Severe Veno-occlusive Disease of the Liver after Allogeneic Hematopoietic Stem Cell Transplantation in Korean Children

Studies investigating the effect of prophylactic drugs on hepatic veno-occlusive disease (VOD) development are rare in children that have undergone allogeneic hematopoietic stem cell transplantation (HSCT). This study examined risk factors for VOD, the effect of prophylactic low-dose heparin or lipo-prostaglandin E1 (lipo-PGE1) and the survival rate at day +100 in children undergoing allogeneic HSCT. Eighty five children underwent HSCT between June 1997 and September 2004. Patients were diagnosed and classified as having mild, moderate or severe VOD according to Seattle clinical criteria. Among 85 patients, 25 (29%) developed VOD. VOD occurred more frequently in patients receiving busulfan-based conditioning (24/65, 37%) than in those receiving TBI-based (1/10, 10%) or other (0/10, 0%) regimens (p<0.05). The incidence of VOD was lower in patients with non-malignant disease compared to those with malignant disease (p<0.05). Survival at day +100 for non-VOD patients was better than that for VOD patients (92% vs. 76%, p<0.05). No patients receiving prophylactic heparin or lipo-PGE1 were found to develop severe VOD, whereas 5 of 35 patients not receiving such prophylaxis developed severe VOD. Given severe VOD is associated with a high mortality rate, this study indicates that prophylactic heparin or lipo-PGE1 may decrease mortality in children undergoing HSCT.

Successful Treatment of Retroperitoneal Infantile Hemangioendothelioma With Kasabach-Merritt Syndrome Using Steroid, α-Interferon, and Vincristine

Infantile hemangioendothelioma (IHE) is a rare benign vascular tumor with potentially life-threatening complications. Various therapeutic options have been recommended according to the site, extent, and behavior of the IHE. Because of the slow and unpredictable response to treatment with using a single drug in critically ill patients, there is a tendency to administer drugs in combination to treat this disease. Here, we report on a 1-month-old female infant who had a retroperitoneal IHE with Kasabach-Merritt syndrome and she was successfully treated with a combination of steroid, interferon-alpha, and vincristine.

Unrelated hematopoietic stem cell transplantation for children with acute leukemia: experience at a single institution.

We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients developed grade II-IV acute graft-versus-host disease (GVHD) and 8 developed extensive chronic GVHD. With median follow-up of 39.1 months, event free survival and overall survival were 60.4% and 67.5%, respectively, at 5 yr. Events included relapse in 10 and treatment-related mortality (TRM) in 10. The causes of TRM included sepsis in 4, GVHD in 4 (1 acute GVHD and 3 chronic GVHD), veno-occlusive disease in 1 and fulminant hepatitis in 1. Patients transplanted with CB had event free survival of 57.1%, comparable to 63.2% for those transplanted with other than CB. In conclusion, HCT with unrelated donors is effective treatment modality for children with acute leukemia. In children with acute leukemia candidate for HCT but lack suitable sibling donor, unrelated HCT may be a possible treatment option at the adequate time of their disease.

Idiopathic Thrombocytopenic Purpura: Better Therapeutic Responses of Patients with B- or T-Cell Clonality than Patients without Clonality

Results of recent studies of the pathogenesis of idiopathic thrombocytopenic purpura (ITP) have suggested activated helper T-cells drive B-lymphocytes to produce antibodies. Twenty-eight children and 85 adults with ITP entered this study. We performed polymerase chain reaction (PCR) using framework III variable region (VH FRIII)- and joining region (JH)-specific primers to analyze immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell clonality. We used multiplex PCR to analyze T-cell receptor (TCR) γ-chain gene rearrangement (TCRγ GR) for T-cell clonality. We diagnosed 10 cases as acute ITP and 97 cases as chronic ITP. The IgH GR result was positive in 77.8% of the acute-form cases and in 58.8% of the chronic-form cases. The TCRγ GR result was positive in 11.1% of the acute cases and in 10.6% of the chronic cases. There was no dif-ference in frequency of clonality between the acute and chronic forms. After treatment the platelet count normalized in 81.8% (36/44) of the chronic ITP cases with B-cell clonality and in 88.9% (8/9) of the chronic ITP cases with T-cell clonality, compared with a normalized platelet count in 46.2% (12/26) of the chronic ITP cases without clonality. The patients with T- or B-cell clonality appeared to have better therapeutic responses than patients without clonality. In conclusion,T- and B-cell clonality may play a positive role in determining therapeutic response.