Yourha Kim

Clinical impact of thrombotic microangiopathy on the outcome of patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

The impact of thrombotic microangiopathy (TMA) on outcome was studied in 148 patients with acute graft-versus-host disease (GVHD) (⩾grade II). The Blood and Marrow Transplant Clinical Trials Networks definition for TMA was used to diagnose definite TMA. Probable TMA was diagnosed when none of the features of nephropathy and neurologic abnormalities associated with definite TMA were present. Overall, TMA developed in 43 (29%) patients; 16 definite and 27 probable. The occurrence of TMA, the maximum grade of acute GVHD and initial treatment failure were associated with shorter overall and GVHD-specific survival. The development of probable as well as definite TMA affected the survival of patients with acute GVHD adversely. These results show the clinical impact of TMA on patients with acute GVHD, and suggest that the proposed definitions and grading of TMA may need to be modified.

Screening of sepsis using leukocyte cell population data from the Coulter automatic blood cell analyzer DxH800

Introduction:  We determined the utility of leukocyte cell population data (CPD) for the screening of sepsis and fungemia.

A case of therapy-related acute myeloid leukemia associated with inv(16), with subsequent development of t(9;22).

A case of therapy-related acute myeloid leukemia associated with inv(16), with subsequent development of t(9;22)

Impact of NRAS Mutations on the Diagnosis of Follicular Neoplasm of the Thyroid

Background. Most patients with a preoperative diagnosis of thyroid follicular neoplasm (FN) undergo diagnostic surgery to determine whether the nodule is benign or malignant. Point mutations at NRAS codon 61 are the most common mutations observed in FN. However, the clinical significance of NRAS mutation remains unclear. Methods. From 2012 to 2013, 123 consecutive patients undergoing thyroidectomy for FN were evaluated prospectively. Molecular analyses for NRAS codon 61 were performed with pyrosequencing. Results. The overall malignancy rate in FN was 48.8% (60/123). Of 123 FNs, 33 (26.8%) were positive for the NRAS mutation. The sensitivity, specificity, positive predictive value, and negative predictive value of a NRAS mutation-positive FN specimen to predict malignancy were 37%, 83%, 67%, and 58%, respectively. Patients with a NRAS-positive FN had a higher malignancy rate in additional thyroid nodules beyond the FN than patients with a NRAS-negative FN. The overall malignancy rate of patients with a NRAS-positive FN was significantly higher than that of patients with a NRAS-negative FN (79% versus 52%; P = 0.008). Conclusions. Determining NRAS mutation status in FN helps to improve the accuracy of thyroid cancer diagnosis and to predict cancer risk in accompanying thyroid nodules.

A novel HLA‐Cw*0436 allele identified by haplotype‐specific extraction and sequence‐based typing

A novel HLA-Cw*04 variant allele, Cw*0436, was identified in three members of a Korean family. This allele shows only one nucleotide difference from Cw*0411 in exon 2 at nucleotide position 268 (codon 90 GCC-->GAC), resulting in an amino acid change from Alanine (A) to Aspartic acid (D).

Transient trisomy 8 abnormality in Philadelphia‐negative cells during imatinib mesylate treatment of chronic myelogenous leukemia

We investigated chronic myelogenous leukemia (CML) patients who developed trisomy 8 abnormalities in Philadelphia‐negative (Ph−) cells during imatinib mesylate treatment to evaluate the clinical outcome and laboratory features. Of the 470 CML patients, 1.5% (n = 7) developed trisomy 8 chromosomal abnormalities in Ph− cells. The median interval of the first trisomy 8 observation was 12 months. Our follow‐up cytogenetic evaluations revealed that six of the patients demonstrated a complete or partial cytogenetic response and that all of the six patients revealed no dysplastic changes following a bone marrow examination. Moreover, the percentage of trisomy 8 in metaphase karyotyping has decreased in five of the seven subjects. In conclusion, these results suggest that the emergence of trisomy 8 in Ph− cells is transient and not related to therapy‐related myelodysplasia or acute leukemia.

Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL

We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.

Antiviral Prophylaxis Versus Preemptive Therapy to Prevent Cytomegalovirus Infection and Related Death in Liver Transplantation: A Retrospective Study With Propensity Score Matching

BACKGROUND Cytomegalovirus (CMV), the most significant viral infection in liver transplant recipients, is addressed by 2 methods: Preemptive therapy (PT) or universal prophylaxis (UP). METHODS We analyzed medical records including at least 1 year follow-up of patients who underwent liver transplantation from 2006 to 2009 in 3 tertiary hospitals. PT was used in 2 hospitals (PT group), whereas UP with valganciclovir for 3 months was adopted in the other hospital (UP group). The 2 groups were matched using propensity scoring by perioperative variables. We performed a 1:1 comparison of the efficacy of UP and PT. RESULTS We analyzed 634 liver transplant patients, including 562 matched subjects. Baseline characteristics and underlying liver status were comparable. CMV immunoglobulin G of recipients was positive in 98.9% of the PT group and 99.3% of the UP group. CMV viremia episodes that required administration of an antiviral agent occurred in 26 (9.3%) PT and 37 (13.2%) UP subjects (P = .18). CMV-related mortalities were similar (0.7% vs 1.8%; P = .45), but all-cause mortality was higher in the PT group (18.5% vs 13.2%; P = .08). CONCLUSION The efficacy of PT was similar to UP to prevent CMV disease and related mortality among a group at moderate risk for CMV infection.

TERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary Thyroid Carcinoma

The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare thyroid neoplasm characterized by unique morphologic findings and association with familial adenomatous polyposis. The biologic behavior of this variant has been reported to behave similarly to classic PTC. We report a rare sporadic case of CMV-PTC occurring in a 45-year-old female with multiple lymph nodes and bone metastases, which were detected after total thyroidectomy and radioactive iodine remnant ablation. Molecular analyses of primary thyroid and metastatic tumor tissues revealed a telomerase reverse transcriptase (TERT) promoter mutation, but absence of BRAF, KRAS, NRAS, HRAS, and PIK3CA mutations. Over a 4-year follow-up period, structurally identifiable bone metastases were persistent, but serial post-operative serum thyroglobulin levels remained undetectable in the absence of thyroglobulin antibody. The literature was reviewed. This is the first case of aggressive CMV-PTC showing TERT promoter mutation. TERT promoter mutations may help in predicting aggressive clinical behavior in CMV-PTC. Postoperative serum thyroglobulin measurement may have no impact on clinical decision-making in this type of tumor.

Prognostic implication of histological features associated with EHD2 expression in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is a heterogeneous tumor with various histological and molecular subtypes. EHD2 is involved in endocytosis and endosomal recycling. This study aimed to investigate the prognostic significance of EHD2 expression in PTC and develop a new model for predicting persistent/recurrent disease after thyroidectomy. Pathologic slides of 512 consecutive patients with PTC ≥ 1 cm were retrospectively reviewed. BRAF mutation analysis and immunohistochemistry for EHD2 were performed. Clinical significance of EHD2 mRNA expression was analyzed in 388 PTC patients using The Cancer Genome Atlas dataset. The presence of dyscohesive cells and psammoma bodies were found have significant association with persistent/recurrent disease (p = 0.049 and p = 0.038, respectively). The best discrimination of disease-free survival was found by dividing patients into three prognostic groups based on the following two risk factors according to the size category: psammoma bodies ≥ 4 and dyscohesive cells (≥ 1% and ≥ 20% in PTCs of < 2.0 cm and ≥ 2.0 cm, respectively). In PTCs of ≥ 2.0 cm, patients with the two risk factors had a hazard ratio of 13.303 (p = 0.005) compared to those without risk factors. High expression level of EHD2 was associated with BRAF V600E (p < 0.001), presence of dyscohesive cells (p = 0.010), and absence of psammoma bodies (p = 0.001). Increased EHD2 mRNA expression level was associated with extrathyroidal extension (p < 0.001), pT3-4 (p < 0.001), lymph node metastasis (p < 0.001), higher risk of recurrence (p < 0.001), and BRAF V600E (p < 0.001). Our prognostic model is useful for predicting persistent/recurrent disease after surgery of PTC. EHD2 mRNA expression could be a novel prognostic marker for PTC patients.