Pretransplantation 18F-Fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non-hodgkin lymphoma undergoing reduced-intensity conditioning follone by allogeneic stem cell transplantation

Background: The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (HG-NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced-intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date. Methods: PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG-NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n = 41) or alternative donors (n = 39). Results: At the time of the last follow-up, 48 patients were alive (60%), and 32 had died. The 3-year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET-negative patients (25% vs 56%; P =.007), but there was no significant difference between the patients with or without chronic graft-versus-host disease (P =.400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3-year overall survival (76% vs 33%; P =.001) and 3-year progression-free survival (73% vs 31%; P =.001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling). Conclusions: The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting

Preponderance of the oncogenic V599E and V599K mutations in B-raf kinase domain is enhanced in melanoma cutaneous/subcutaneous metastases

BACKGROUND: Downstream of Ras, the serine/threonine kinase B-raf has been reported to be mutated, among other carcinomas, in a substantial subset of primary melanomas with a preponderance of mutations within the kinase domain including the activating V599E and V599K transitions. METHODS: We here investigated a representative series of 60 resection specimens of cutaneous and subcutaneous melanoma metastases for the presence of mutations within the activation segment (exon 15) of the B-raf kinase domain by polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) gel electrophoresis. RESULTS: Sequencing of cloned PCR-SSCP amplicons resulted in 24 (40%) samples harbouring somatic mutations which is not exceeding the mutation frequency in recently investigated primary melanomas. The activating mutation T1796A was present in 24/60 (40%) resection specimens, followed in frequency by the oncogenic g1795A mutation in 8/60 (13%) cases. As to the B-raf protein sequence, the acidic amino acid transitions V599E and V599K were predicted in 19/60 (32%) and 6/60 (10%) cases, resepectively, but were not associated with enhanced risk for subsequent metastasis in patients' follow up. In comparison to the primary melanomas that we recently investigated, the spectrum of predicted B-raf protein mutations narrowed significantly in the cutaneous/subcutaneous metastases. Unexpectedly, V599 and V599E mutations were absent in cutaneous/subcutaneous metastases derived from acrolentiginous melanomas as preceding primary tumours. CONCLUSION: During transition from primary melanomas towards cutaneous/subcutaneous metastases, the spectrum of predicted B-raf mutations narrows significantly. Focusing on the V599E and V599K, these oncogenic mutations are likely to affect melanocyte-specific pathways controlling proliferation and differentiation

Serum leptin and lipid variations after a long-distance ski-alpinism race

J Endocrinol Invest 22, Suppl. to n 4\ub0, 159P, 199

Serum IGF-I, IGFBP-3, and IGFBP-2 levels during acute and Chronic high altitude exposure

J Endocrinol Invest 21, Suppl. to n\ub0 7: 155, 199

Lack of effects of circulating thyroid hormone levels on serum leptin concentrations.

Leptin is the protein product of the ob gene, secreted by adipocytes. It has been suggested that it may play an important role in regulating appetite and energy expenditure. The aim of this study was to evaluate a possible interaction of thyroid hormones with the leptin system. We studied 114 adult patients (65 females and 49 males): 36 were affected with primary hypothyroidism (PH), 38 with central hypothyroidism (CH) and 40 with thyrotoxicosis (TT). Patients with CH were studied both before and after 6 months of L-thyroxine replacement therapy. Body mass index (BMI; kg/m2), thyroid function and fasting serum leptin were assessed in all patients. Since BMI has been proved to be the major influencing variable of circulating leptin levels, data were expressed as standard deviation score (SDS) calculated from 393 male and 561 female controls matched for age and BMI. No difference in SDS was recorded between males and females whatever the levels of circulating thyroid hormones. In males, no significant difference was recorded among the SDSs of PH (-0.36 +/- 1.2), TT (-0.35 +/- 1.2) and CH (0.01 +/- 1.4) patients. Females with PH had an SDSs significantly lower than TT females (-0.77 +/- 1.0 vs -0.06 +/- 1.2; P < 0.02), while no significant differences between CH (-0.34 +/- 0.7) and TT females or between CH and PH females were observed. SDS in CH patients after 6 months of L-thyroxine therapy significantly varied only in females (0.25 +/- 1.4). In conclusion, circulating thyroid hormones do not appear to play any relevant role in leptin synthesis and secretion. However, as females with either overt hypo- or hyper-thyroidism or central hypothyroidism after L-thyroxine therapy show differences in their SDSs, a subtle interaction between sex steroids and thyroid status in modulating leptin secretion, at least in women, may occur

Leptin reduction after endurance races differing in duration and energy expenditure

Serum leptin concentrations are reduced in the presence of a negative energy balance. It has been demonstrated, however, that strenuous and prolonged exercise, which induces a marked negative energy balance, is not always followed by a reduction in serum leptin levels. We therefore analysed serum leptin concentrations before and after three endurance races, which differed in duration and energy expenditure (EE), with the aim of clarifying the relationship between the level of EE and the reduction in leptin levels. Forty-five males participated in one of three competitive endurance races, a half-marathon run [21.097 km, estimated EE 1,400 kcal (5,852 kJ)], a ski-alpinism race [about 45 km, estimated EE 5,000 kcal (20,900 kJ)], and an ultramarathon race [100 km, estimated EE 7,000 kcal (29,269 kJ)]. Blood samples for analysis of serum leptin, and plasma free fatty acids (FFA) were collected before and after the races. Pre-race leptin values were significantly correlated with both body mass index and body fat mass (r=0.672 and r=0.699, respectively; P<0.0001). After exercise, serum leptin levels decreased significantly in the ultramarathon [from 4.15 (0.63) \ub5g/l to 1.01 (0.15) \ub5g/l; P<0.001] and in the ski-alpinism race [from 1.10 (0.28) \ub5g/l to 0.62 (0.15) \ub5g/l; P<0.01], but not in the half-marathon [from 1.38 (0.40) \ub5g/l to 1.20 (0.36) \ub5g/l]. Plasma FFA were found to have significantly increased in all three of the races, showing a negative correlation with the percent reduction in leptin (r=0.369, P<0.02). Our data indicate that only a prolonged endurance exercise involving a high EE can induce a marked reduction in circulating serum leptin levels

Different dosage schedules of short term GH therapy: effects on serum leptin levels in accord of GH deficient adults

Poster presentation (P3 - 336