Meerim Park

Clinical features of infantile hepatic hemangioendothelioma

Purpose Infantile hepatic hemangioendothelioma (IHHE) is the most common type of hepatic vascular tumor in infancy. We conducted this study to review our clinical experience of patients with IHHE and to suggest management strategies. Methods We retrospectively analyzed the medical records of 23 IHHE patients (10 males, 13 females) treated at the Asan Medical Center between 1996 and 2009. Results Median age at diagnosis was 38 days (range, 1 to 381 days). Seven patients (30%) were diagnosed with IHHE based on sonographically detected fetal liver masses, 5 (22%) were diagnosed incidentally in the absence of symptoms, 5 (22%) had congestive heart failure, 3 (13%) had skin hemangiomas, 2 (9%) had abnormal liver function tests, and 1 (4%) had hepatomegaly. All diagnoses were based on imaging results, and were confirmed in three patients by histopathology analysis. Six patients were observed without receiving any treatment, whereas 12 received corticosteroids and/or interferon-alpha. One patient with congestive heart failure and a resectable unilobar tumor underwent surgical resection. Three patients with congestive heart failure and unresectable tumors were managed by hepatic artery embolization with/without medical treatment. At a median follow-up of 29 months (range, 1 to 156 months), 21 (91%) patients showed complete tumor disappearance or >50% decrease in tumor size. One patient died due to tumor-related causes. Conclusion IHHE generally has a benign clinical course with low morbidity and mortality rates. Clinical course and treatment outcome did not differ significantly between medically treated and non-treated groups. Surgically unresectable patients with significant symptoms may be treated medically or with hepatic artery embolization.

Lineage Switch at Relapse of Childhood Acute Leukemia: A Report of Four Cases

Lineage switch in acute leukemia is an uncommon event at relapse, and therefore rarely reported in the literature. Here, we have described the clinical laboratory features of four cases in which the cell lineage switched from acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML). One patient was initially diagnosed with B-ALL, switched to T-ALL at the first relapse, and eventually, AML at the second relapse. A lineage switch represented either relapse of the original clone with heterogeneity at the morphologic level or emergence of a new leukemic clone. Further sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanisms of leukemic recurrence, with possible implications for treatment selection.

Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children.

Background Central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been well characterized in the pediatric population. Methods We retrospectively analyzed data of 202 consecutive children who underwent allogeneic HSCT (60 from matched related donors, 9 from mismatched related donors, and 133 from unrelated donors) at Asan Medical Center between 1998 and 2009. Results Twenty-seven children (13.5%) developed CNS complications within 6 months after HSCT. Calcineurin inhibitor (CNI)-associated neurotoxicity was the most common CNS complication (n=16), followed by CNS infection (n=2), cerebrovascular events (n=2), thrombotic microangiopathy-associated events (n=2), metabolic encephalopathy (n=2), irradiation/chemotherapy injury (n=1), and encephalopathy/myelopathy of unknown causes (n=2). Univariate analysis showed that a transplant from an alternative donor and the occurrence of acute graft-versus-host disease (GVHD) (>grade 2) were associated with a significantly increased risk of CNS complications. In the multivariate analysis, acute GVHD >grade 2 was identified as an independent risk factor for early CNS complications. The 5-year overall survival rate was significantly lower in patients with CNS complications (52.1% vs. 64.9%, P=0.014), whereas CNI-associated neurotoxicity did not affect the survival outcome. Conclusion CNS complications are frequent among children undergoing HSCT, contributing to early death after transplant. More attention should be paid to the development of CNS complications for recipients of alternative donor transplants and patients with severe acute GVHD who are at increased risk for CNS complications.

The impact of HLA matching on unrelated donor hematopoietic stem cell transplantation in Korean children

Background The impact of HLA matching on outcomes of unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) varies in different racial or ethnic groups. Since little is known about the impact of such matching on URD HSCT in Korean children, we analyzed this issue. Methods We analyzed the outcomes of 142 patients who underwent URD HSCT at 4 Korean medical centers. All patient donor pairs were fully typed for HLA-A, -B, -C, and -DR alleles. Results At a median follow-up of 22 months, 3-year survival rates for patients with 8, 7, and ≤6 matched alleles were 88.4%, 70.7%, and 53.6%, respectively. A single mismatch (Mm) at HLA-B or -C was associated with lower survival compared with that associated with 8 matched alleles. No significant differences were observed between single-allele and single-antigen Mms with respect to survival rate or acute graft-versus-host disease (aGVHD) incidence rates. HLA disparity had a greater impact on the survival of patients with high-risk malignancy than of those with low-risk malignancy. Among pairs with a single Mm, only locus A showed a significant association and higher risk of grade III-IV aGVHD compared to those in patients with 8 matched alleles. Conclusion Disparity in HLA class I, regardless of antigen or allele Mm, adversely affected both survival and grade III-IV aGVHD development. An increased number of HLA Mms was associated with a higher risk of post-transplantation complications. Further investigations using larger cohorts are required to confirm the effects of HLA mismatching on URD HSCT patient outcomes.

Prognostic significance of minimal residual disease detected by a simplified flow cytometric assay during remission induction chemotherapy in children with acute lymphoblastic leukemia

Purpose Our study attempted to determine the prognostic significance of minimal residual disease (MRD) detected by a simplified flow cytometric assay during induction chemotherapy in children with B-cell acute lymphoblastic leukemia (B-ALL). Methods A total of 98 patients were newly diagnosed with precursor B-ALL from June 2004 to December 2008 at the Asan Medical Center (Seoul, Korea). Of those, 37 were eligible for flow cytometric MRD study analysis on day 14 of their induction treatment. The flow cytometric MRD assay was based on the expression intensity of CD19/CD10/CD34 or aberrant expression of myeloid antigens by bone marrow nucleated cells. Results Thirty-five patients (94.6%) had CD19-positive leukemic cells that also expressed CD10 and/or CD34, and 18 (48.6%) had leukemic cells with aberrant expression of myeloid antigens. Seven patients with ≥1% leukemic cells on day 14 had a significantly lower relapse-free survival (RFS) compared to the 30 patients with lower levels (42.9% [18.7%] vs. 92.0% [5.4%], P=0.004). Stratification into 3 MRD groups (≥1%, 0.1-1%, and <0.1%) also showed a statistically significant difference in RFS (42.9% [18.7%] vs. 86.9% [8.7%] vs. 100%, P=0.013). However, the MRD status had no significant influence on overall survival. Multivariate analysis demonstrated that the MRD level on day 14 was an independent prognostic factor with borderline significance. Conclusion An MRD assay using simplified flow cytometry during induction chemotherapy may help to identify patients with B-ALL who have an excellent outcome and patients who are at higher risk for relapse.

Role of p16 in the pathogenesis of Langerhans cell histiocytosis.

Background It has been hypothesized that genetic alteration at the cellular level may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of Langerhans cells (LCs). Methods We examined whether p16 protein expression can be used to predict the outcome of Langerhans cell histiocytosis (LCH). Archival paraffin blocks from children diagnosed with LCH and followed at the Asan Medical Center and Chungnam National University Hospital between March 1998 and February 2008 were studied. Results Slides were stained with p16 antibody and evaluated semi-quantitatively using the following scale: negative, no staining; ±, weakly positive; 1+, staining similar to lymphocytes surrounding the LCs; 2+, stronger staining than lymphocytes; 3+, much stronger staining than lymphocytes. Negative and ± groups were assigned to a lower expression group (LEG) and the 1+, 2+, and 3+ groups were assigned to a higher expression group (HEG). The median age of the 51 patients (24 girls, 27 boys) was 49 (range, 0.6-178) months, and LCH was diagnosed based on CD1a positivity. p16 protein was expressed to varying degrees in all but one specimen. There was a greater tendency toward multisystem disease, risk organ involvement, and relapse in the HEG than in the LEG. Conclusion The p16 protein may have a significant effect on cellular mechanisms controlling the proliferation and apoptosis of LCs, and thus may influence the clinical outcome and prognosis of LCH.

Clinical features of late onset non‐infectious pulmonary complications following pediatric allogeneic hematopoietic stem cell transplantation

Park M, Koh KN, Kim BE, Im HJ, Seo JJ. Clinical features of late onset non‐infectious pulmonary complications following pediatric allogeneic hematopoietic stem cell transplantation. 
Clin Transplant 2011: 25: E168–E176.