Prolonged Chronic Graft-versus-Host Disease is a Risk Factor for Thyroid Failure in Long-Term Survivors After Matched Sibling Donor Stem Cell Transplantation for Hematologic Malignancies

AbstractWe studied thyroid function in 81 long-term survivors of allogeneic stem cell transplantation (allo-SCT), with a median follow-up of 84 months (range, 45 to 166 months). Median age at transplantation was 35 years (range, 6 to 66). Seventy-two of the patients received a total body irradiation (TBI)–containing conditioning regimen (n = 23, 12 Gy; n = 49, 13 Gy). Twenty-one of the patients (25.9%) had subclinical hypothyroidism, and 9 (11.1%) developed overt hypothyroidism at a median of 28 months (range, 3 to 78 months) after allo-SCT. Multivariate logistic regression analysis demonstrated that prolonged immunosuppressive therapy (IST) was significantly associated with subclinical hypothyroidism (odds ratio [OR] = 3.8) and overt hypothyroidism (OR = 2.6). Antithyroglobulin and thyroid peroxidase antibody were detected in 12 of 60 patients tested (20%). No correlation was found between the occurrence of thyroid antibodies and hypothyroidism (P = .13) or chronic graft-versus-host disease (cGVHD) (P = .55). In conclusion, thyroid dysfunction is relatively common after allo-SCT and is more likely to occur in patients receiving prolonged IST for cGVHD; however, thyroid dysfunction does not appear to be related to an antibody-mediated autoimmune process

Repair of Impaired Pulmonary Function Is Possible in Very-Long-Term Allogeneic Stem Cell Transplantation Survivors

AbstractBoth early- and late-onset noninfectious pulmonary injury are important contributors to the nonrelapse mortality seen after allogeneic stem cell transplantation (allo-SCT), particularly in subjects conditioned with high-dose total body irradiation (TBI). To characterize the kinetics of recovery from pulmonary injury in long-term survivors, we collected data on 138 subjects who survived > 3 years (median survival, 10.2 years) after predominantly TBI-based allo-SCT from their HLA-matched siblings. Baseline pulmonary function tests served as the reference for subsequent measurements at 3, 5, 10, and 15 years for each survivor. The only parameter showing a clinically and statistically significant decline post-transplant was adjusted diffusion capacity of lung for carbon monoxide (DLCO), which reached a nadir at 5 years but surprisingly normalized at the 10-year mark. Multivariable modeling identified chronic graft-versus-host disease (P < .02) and abnormal baseline-adjusted DLCO (P < .03) as the only significant factors associated with the decline in adjusted DLCO at 5 years but excluded smoking, conditioning intensity, baseline C-reactive protein level, TBI dose to the lungs, disease, and demographic variables. In conclusion, pulmonary injury as monitored by the adjusted DLCO continues to deteriorate in the first 5 years after allo-SCT but recovers at 10 years

Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy

In the first trimester the extravillous cytotrophoblast cells occlude the uterine spiral arterioles creating a low oxygen environment early in pregnancy, which is essential for pregnancy success. Paradoxically, shallow trophoblast invasion and defective vascular remodelling of the uterine spiral arteries in the first trimester may result in impaired placental perfusion and chronic placental ischemia and hypoxia later in gestation leading to adverse pregnancy outcomes. The hypoxia inducible factors (HIFs) are key mediators of the response to low oxygen. We aimed to elucidate mechanisms of regulation of HIFs and the role these may play in the control of placental differentiation, growth and function in both normal and pathological pregnancies. The Pubmed database was consulted for identification of the most relevant published articles. Search terms used were oxygen, placenta, trophoblast, pregnancy, HIF and hypoxia. The HIFs are able to function throughout all aspects of normal and abnormal placental differentiation, growth and function; during the first trimester (physiologically low oxygen), during mid-late gestation (where there is adequate supply of blood and oxygen to the placenta) and in pathological pregnancies complicated by placental hypoxia/ischemia. During normal pregnancy HIFs may respond to complex alterations in oxygen, hormones, cytokines and growth factors to regulate placental invasion, differentiation, transport and vascularization. In the ever-changing environment created during pregnancy, the HIFs appear to act as key mediators of placental development and function and thereby are likely to be important contributors to both normal and adverse pregnancy outcomes

"Blind" vaginal fetal fibronectin as a predictor of spontaneous preterm delivery

To assess the accuracy of vaginal fetal fibronectin sampling without use of a sterile speculum examination as a screening test for predicting spontaneous preterm birth. A historical cohort of patients who were followed up with serial fetal fibronectin testing between 1998 and 2001 was identified. All patients were considered to be at high risk for preterm delivery and were screened with fetal fibronectin testing without using a speculum at 2- to 3-week intervals from 22 weeks to 32 weeks of gestation. Charts were reviewed for fetal fibronectin results and pregnancy outcome data. Groups were compared using chi(2) analysis or Fisher exact test with significance defined as P < .05. A total of 1,396 fetal fibronectin tests from 416 pregnancies were performed via the "blind" sampling technique. Overall, 24.9% of pregnancies delivered spontaneously before 37 weeks; 9.1% delivered spontaneously before 34 weeks. For delivery before 34 weeks of gestation, the test had a sensitivity of 44.7%, a specificity of 88.4%, a positive predictive value of 27.9%, and a negative predictive value of 94.1%. For delivery within 14 and 21 days of a single fetal fibronectin assessment, the test had a sensitivity of 52% and 45.5%, a specificity of 94.5% and 94.9%, a positive predictive value of 14.6% and 22.5%, and a negative predictive value of 99.1% and 98.2%, respectively. "Blind" vaginal fetal fibronectin sampling has high negative predictive values and specificities in predicting spontaneous preterm birth. II-2