The First Korean Family with Hemoglobin-M Milwaukee-2 Leading to Hereditary Methemoglobinemia.

Hemoglobin M (HbM) is a group of abnormal hemoglobin variants that form methemoglobin, which leads to cyanosis and hemolytic anemia. HbM-Milwaukee-2 is a rare variant caused by the point mutation CAC>TAC on codon 93 of the hemoglobin subunit beta (HBB) gene, resulting in the replacement of histidine by tyrosine. We here report the first Korean family with HbM-Milwaukee-2, whose diagnosis was confirmed by gene sequencing. A high index of suspicion for this rare Hb variant is necessary in a patient presenting with cyanosis since childhood, along with methemoglobinemia and a family history of cyanosis.

Better Failure-Free Survival and Graft-versus-Host Disease-Free/Failure Free Survival with Fludarabine-Based Conditioning in Stem Cell Transplantation for Aplastic Anemia in Children.

BACKGROUND: This study aimed to assess the outcome of stem cell transplantation (SCT), including overall survival (OS), failure-free survival (FFS) and graft-versus-host disease (GvHD)-free/failure-free survival (GFFS), and to analyze prognostic factors in children with aplastic anemia (AA). METHODS: From 1991 to 2018, 43 allogeneic SCT recipients were enrolled in the study to investigate the demographic characteristics, survival outcomes and prognostic factors. RESULTS: With the median follow-up of 7.1 years, the estimated 10-year OS, FFS, GFFS were 86.0%, 60.5%, and 51.2%, respectively. Matched related donors (MRD, n = 28) showed better 10-year OS than unrelated donors (n = 15) (96.4% vs. 66.7%; P = 0.006). Engraftment failure was seen in 13 patients (30.2%). Donor-type aplasia was seen in 13.8% (4/29) after fludarabine (Flu)-based conditioning (Flu-group), while in 42.6% (6/14) after cyclophosphamide (Cy)-based regimen (Cy-group) (P = 0.035). Six patients died. The 10-year OS in Cy-group was 92.9% (n = 14, all MRD), while that of Flu-group was 82.1% (n = 29; P = 0.367). But Flu-group tended to have better FFS and GFFS than Cy-group, although Flu-group had less MRDs (41.4% vs. 100%; P = 0.019), and higher proportion of previous immunosuppressive treatment (IST; 62% vs. 21.4%, P = 0.012). In MRD transplants, OS was similar between Flu-group (100%, n = 14) and Cy-group (92.9%, n = 14), while FFS (100.0% vs. 42.9%; P = 0.001) and GFFS (85.7% vs. 35.7%; P = 0.006) were significantly better in Flu-group. Stem cell sources, irradiation in the conditioning, and method of GvHD prophylaxis did not significantly influence the outcome. CONCLUSION: This study reviewed SCT outcomes for pediatric AA with changes of transplant strategies over the last 25 years. The FFS and GFFS were higher in Flu-group than in Cy-group, especially in matched related transplantation. Graft failure including donor-type aplasia remains troublesome even with Flu-based conditioning. Further refinement of transplant strategies to ensure better quality-of-life should be pursued.

Clinical utility of spot urine protein-to-creatinine ratio modified by estimated daily creatinine excretion in children.

BACKGROUND: The spot urine protein-to-creatinine ratio (UPCR) is widely used to predict 24-h urine protein (24-h UP) excretion. In patients with low daily urine creatinine excretion (UCr), however, the UPCR may overestimate 24-h UP. The aim of this study was to predict 24-h UP using UPCR adjusted by estimated 24-h UCr in children. METHODS: This study included 442 children whose 24-h UP and spot UPCR were measured concomitantly. Estimated 24-h UCr was calculated using three previously existing equations. We estimated the 24-h UP excretion from UPCR by multiplying the estimated UCr. The results were compared with the measured 24-h UP. RESULTS: There was a strong correlation between UPCR and 24-h UP (r = 0.801, P < 0.001), and the correlation improved after multiplying the UPCR by the measured UCr (r = 0.847, P < 0.001). Using the estimated UCr rather than the measured UCr, there was high accuracy and strong correlation between the estimated UPCR weighted by the Cockcroft-Gault equation and 24-h UP. Improvement was also observed in the subgroup (proteinuria vs. non-proteinuria) analysis, particularly in the proteinuria group. CONCLUSIONS: The spot UPCR multiplied by the estimated UCr improved the accuracy of prediction of the 24-h UP in children.