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Mercaptopurine intolerance is an adverse effect of mercaptopurine administration in pediatric acute lymphoblastic leukemia. Recently, NUDT15 variants were identified as a major determinant of mercaptopurine intolerance. Two NUDT15 variants, c.36_37insGGAGTC and c.415C > T, are located on exons 1 and 3, respectively. Patients with heterozygous c.36_37insGGAGTC and c.415C > T can be either compound heterozygous with two variants on different alleles or heterozygous with both variants on the same allele. Because patients with biallelic NUDT15 variants are extremely sensitive to mercaptopurine, clinical identification of NUDT15 diplotype would be advantageous. A cohort of 37 patients with c.36_37insGGAGTC and c.415C > T NUDT15 variants were selected for haplotyping by targeted sequencing. NUDT15 complementary DNA was amplified and sequenced by 300-bp paired-end sequencing on Illumina MiSeq. Of the 37 patients carrying NUDT15 variants, 35 had heterozygous NUDT15*1/*2 variants and two had compound heterozygous NUDT15*3/*6 and NUDT15*2/*7 variants. These two patients with compound heterozygous variants could only tolerate low doses of mercaptopurine, similar to patients with homozygous NUDT15 variants. Targeted sequencing of NUDT15 cDNA can be used to determine NUDT15 diplotype and identify patients with compound heterozygous NUDT15 variants.

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

Sir, Fanconi anemia (FA) is rarely associated with vitamin B12 deficiency. We first report a patient of FA with vitamin B12 deficiency, who developed retinal pigment epithelial changes in two different sites of the retina, including bilateral maculopathy and significant pigmentary changes nasal to the optic disc.