Long-term Erythrocytapheresis Is Associated With Reduced Liver Iron Concentration in Sickle Cell Disease.

BACKGROUND: Erythrocytapheresis procedures are increasingly used in sickle cell disease. Serum ferritin and noninvasive magnetic resonance imaging measurements of liver iron concentration (LIC) are frequently used to monitor iron overload secondary to hypertransfusion. There is a paucity of data describing the impact of long-term erythrocytapheresis (LTE) on LIC. MATERIALS AND METHODS: We measured magnetic resonance imaging liver and cardiac iron on LTE subjects and stratified them into 2 groups: higher LIC (>3 mg/g) and lower LIC (<3 mg/g). χ(2) and t test were used to test for differences between the 2 groups. Logistic regression and generalized linear mixed-effects models were used to test what impacted LIC. RESULTS: None of 29 sickle cell disease subjects maintained on LTE had high cardiac iron concentration. LIC was associated with serum ferritin (r=0.697, P<0.001) but was not associated with the total number of LTE procedures (r=-0.088, P=0.656) or total number of simple transfusions (r=0.316, P=0.108). The total number of LTE procedures was not associated with serum ferritin (r=0.040, P=0.838), the total number of simple transfusions (r=-0.258, P=0.184), or LIC group (r=-0.111, P=0.566). CONCLUSION: There was no significant correlation between duration of LTE maintenance and LIC.

Late effects in cancer survivors: "the shared care model".

Advances continue to be made in the field of pediatric oncology ever since treatment for childhood cancer began in 1948. Since then, there has been exponential progress in the care for children with cancer as reflected in the current survival rates, which approach 90%. With such incredible survival rates, the number of childhood cancer survivors has increased significantly, with present estimates being above 300,000 in the United States alone. This success has, however, not been without cost. Long-term studies of cancer survivors have brought to light specific adverse effects of therapy, which often present years after treatment is finished, termed "late effects." Over the years, it has become apparent that monitoring for and treating these late effects of treatment is essential for the continuing health of young cancer survivors. It is now well recognized that childhood cancer survivors require long-term follow-up care given by an integrated team of qualified and invested specialty-care providers in collaboration with their primary caregivers. These teams deliver care using a risk-based approach, following a systematic plan for lifelong screening,surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions,lifestyle behaviors, and co-morbid health conditions.

Functional single nucleotide polymorphism haplotypes in the human equilibrative nucleoside transporter 1.

The human equilibrative nucleoside transporter 1 gene (hENT1) is the primary nucleoside transporter for cytosine arabinoside (AraC), a deoxycytidine analog used for treatment of acute leukemias and lymphomas. We screened approximately 1.6 kb upstream of the transcription initiation site of hENT1 for single nucleotide polymorphisms (SNPs) that affect gene expression. We identified one SNP at position -706G>C with a frequency of 21% in whites and 5% in African-Americans. In African-Americans, we observed two SNPs at positions -1345C>G and -1050G>A with allele frequencies of 8% and 19%, respectively. TRANSFAC analysis suggested that -1345C>G and -706G>C may alter transcription factor binding sites. Four naturally occurring haplotypes (CGG, CAG, CGC and GAG) were cloned into a luciferase expression plasmid, transfected into Cos-1 cells, and reporter activity measured at 24 and 48 h. Three haplotypes, CAG, CGC and GAG, respectively, showed average expression that was approximately two-fold (P<0.05), 1.4-fold (P<0.05) and 1.1-fold (P>0.05) higher than lowest expression haplotype CGG at 48 h. When reanalysed as single SNPs, the differences in expression were significant for -1345C>G and -1050G>A genotypes, and not for -706G>C. However, the magnitude of difference was reduced, suggesting that no single SNP completely accounts for the expression differences observed at the haplotype level. By real-time quantitative reverse transcriptase-polymerase chain reaction assay, individuals with CGG/CGC haplotypes showed 1.37-fold higher median expression of hENT1 transcript than those with common CGG/CGG haplotypes. Although not statistically significant (P=0.12), this difference is in the direction predicted by the in vitro data. hENT1 promoter region haplotypes may influence gene expression and alter AraC chemosensitivity.

Successful engraftment following unrelated donor transplant in an alloimmunized patient with Kostmann syndrome.

Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial infections during infancy. Blood or marrow transplantation (BMT) is the only curative option for patients with refractory disease. This report describes the case of a 4-year-old girl with refractory SCN, who received a bone marrow transplant from a highly matched donor after becoming HLA sensitized to multiple granulocyte transfusions. She is clinically well with normal blood counts and stable mixed chimerism 3 years after BMT. She experienced no graft rejection or graft versus host disease.

Lead poisoning and asthma: an examination of comorbidity.

OBJECTIVES: To determine the comorbidity of lead poisoning and asthma in urban children, and to examine associated clinical factors. METHODS: One-hundred-one patients at an inner-city clinic with blood lead levels (BLLs) of 25 microg/dL or higher (> or =1.2 micromol/L) (BLL25 group) were randomly selected from a tracking lead database and matched on age, sex, and primary language to 101 randomly selected patients with a first BLL recorded in the database of lower than 5 microg/dL (<0.2 micromol/L) (BLL5 group) and no subsequent BLLs of 10 microg/dL or higher (> or =0.5 micromol/L). Medical records were reviewed to determine diagnosis or symptoms of asthma or wheezing at any visit, immunization status, and number of visits. Analyses for matched pairs were conducted. RESULTS: The BLL25 and BLL5 groups did not differ on age at diagnostic BLL (26.6 months vs 24.2 months), sex (54% male), or language (12% Spanish). The BLL25 and BLL5 groups had a similar number of subjects with a diagnosis of asthma (6% vs 11%; odds ratio, 0.5; 95% confidence interval, 0.2-1.6); 26% of BLL25 and 34% of BLL5 subjects had either a diagnosis or symptoms of asthma or wheezing (odds ratio, 0.7; 95% confidence interval, 0.4-1.3). Subjects with BLL25 were more likely to have delayed immunization and a first clinic visit when older than subjects with BLL5. CONCLUSIONS: There was no increased likelihood of asthma diagnosis or symptoms among young children with lead poisoning. Children with lead poisoning also had delayed medical care. These data may help guide interventions aimed at preventing or reducing the impact of lead poisoning and asthma.