Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 beta-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated beta-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients.

Background: β-Thalassemia is a prevalent genetic disease in Mediterranean countries. The most common treatments for this disease are blood transfusion plus iron chelation (BTIC) therapy and bone marrow transplantation (BMT). Patients using these procedures experience different health-related quality of life (HRQoL). The purpose of the present study was to measure HRQoL in these patients using 2 different multiattribute quality of life (QoL) scales. Methods: In this cross-sectional study, data were gathered using 3 instruments: a socio-demographic questionnaire, EQ-5D, and SF-36. A total of 196 patients with β-thalassemia were randomly selected from 2 hospitals in Shiraz (Southern Iran). Data were analyzed using logistic regression and multiple regression models to identify factors that affect the patients' HRQoL. Results: The average EQ-5D index and EQ visual analog scale (VAS) scores were 0.86 (95% CI: 0.83-0.89) and 71.85 (95% CI: 69.13-74.58), respectively. Patients with BMT reported significantly higher EQ VAS scores (83.27 vs 68.55, respectively). The results showed that patients who lived in rural area and patients with BMT reported higher EQ VAS scores (rural; β = 10.25, P = .006 and BMT; β = 11.88, P = .000). As well, SF-36 between 2 groups of patients were statistically significant in physical component scale (PCS). Conclusion: Patients in the BMT group experienced higher HRQoL in both physical and mental aspects compared to those in the BTIC group. More studies are needed to assess the relative cost-effectiveness of these methods in developing countries.

Several clinical trials have shown the superiority of high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) over conventional dose therapy for patients with multiple myeloma. There is limited experience with non-cryopreserved autologous hematopoietic stem cell transplantation. Between January 2004 and February 2010, we treated 38 patients with myeloma (mean age = 50.6) with a preparative regimen of Melphalan 140-200 mg/m(2) and non-cryopreserved ASCT. All the apheresis products were kept in a conventional blood bank refrigerator at 4°C for 2 d before infusion. The median time to platelet count of >20 × 10(9) /L was 13 d (range 10-31). Also, the median time to absolute neutrophil count >0.5 × 10(9) /L was 11 d (range 9-21). All the 38 patients were engrafted and there was not graft failure in this study group. Twenty-nine of 38 (76.3%) patients are alive and without disease activity after a median follow-up of 31 months (range 6-77). Responses (complete and partial response) were seen in all the 38 patients. The median progression-free survival was 27 months with 95% confidence interval 23.52-30.48, whereas the median overall survival was 30 months. One hundred days transplant-related mortality was 0%. HDT and autologous transplantation without cryopreservation is an effective and safe method which simplifies the procedure and is feasible and cost saving in our patients.

A novel strategy was developed for the synthesis of N(7)-purine acyclic nucleosides 9 and 14. The key step involved the reaction between [2-(p-methoxyphenyloxy)ethoxy]methyl chloride and N(9)-tritylated nucleobases 6 or 11 followed by concomitant self-detritylation. N(7)-Guanine acyclic nucleoside 9 exhibited antiviral activity, but was phosphorylated by both HSV and Vero cell thymidine kinases. Thus, it showed more potent cellular toxicity than acyclovir (2). N(7)-Adenine acyclic nucleoside 14 was found to be an excellent antiviral agent as well as a good inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows for a greater expression of antiviral activity of antiviral agents, such as N(9)-adenine acyclic nucleoside 1 and ara-A (3). Compound 14 was phosphorylated neither by herpes simplex virus (HSV) thymidine kinase nor by Vero cell thymidine kinase, yet it enhanced the rate constant for the monophosphorylation of acyclovir (2) by HSV thymidine kinase. Consequently, the combination of acyclovir (2) and 14 exhibited greater antiviral activity than acyclovir alone. 7-[2-(Phosphonomethoxy)ethyl]adenine (20) was also synthesized. The key step involved the reaction of 9-(2-cyanoethyl)adenine (15) with methyl iodoacetate in the presence of lithium 2,2,6,6-tetramethylpiperidine in THF. Unlike 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA, 4), the N(7)-isomer 20 was not phosphorylated effectively by 5-phosphoribosyl 1-pyrophosphate synthetase (PRPP synthetase). Thus, it did not exhibit pronounced antiviral activity. Dinucleotide 5'-monophosphate 24 and its butenolide ester 25 were also synthesized. Compound 24 showed substrate activity toward PRPP synthetase and exhibited notable activity against DNA viruses. The antiviral activity of the ester derivative 25 was found to be higher than that of the parent molecule 24. Dinucleotide 5'-monophosphate 24 is susceptible to degradation by snake venom and spleen phosphodiesterases. However, its respective butenolide ester derivative 25 was completely resistant to snake venom and spleen enzymes. Butenolide ester derivatives 28 and 29 were also synthesized and exhibited notable anti-DNA virus and anti-retrovirus activity in vitro. Compounds 2, 4, 9, 14, 20, 24, 25, and 28 were also evaluated for their inhibitory effect on HSV-1-induced mortality in NMRI mice. N(7)-adenine acyclic nucleoside 14 [LD(50) (intraperitoneal, ip) 950 mg/kg], nucleotide-containing butenolide 25 [LD(50) (ip) 675 mg/kg], and butenolide 28 [LD(50) (ip) 710 mg/kg] were found to be potent anti-HSV-1 agents in vivo. In addition, butenolide 28 efficiently decreased tumor formation induced by Moloney murine sarcoma virus (MSV) in NMRI mice while significantly increasing the survival time of MSV-infected mice.

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The expression of several myeloid and non-lineage associated surface antigens in 70 patients with acute myeloblastic leukemia was investigated in relation to patient and disease characteristics, response to therapy, and prognosis. A leukocyte integrin, CD11b, was the only antigen that showed a significant association with complete remission (CR) duration and survival (P < .025). The mean survival for CD11b+ patients was longer than for CD11b- patients (578 +/- 76 versus 397 +/- 7 days, respectively). CR duration was 897 +/- 84 for CD11b+ patients and 366 +/- 71 for CD11b- patients. Multivariate analysis confirmed the predictive value of CD11b expression for longer survival (relative risk, 3.2; P = .02) and CR duration (relative risk, 3.2; P = .03). CR rate was also significantly higher in CD11b+ patients (77.3%) than in CD11b- patients (46.1%) (P = .01). Survival and remission duration were not influenced by expression of other surface markers including CD13, CD14, CD33, CD34, CD71, CD38, and HLA-DR or by other variables including French-American-British subtype, age, and leukocyte count. Extramedullary disease (EXD) was associated with the presence of both CD13 and CD14 expression (P < .04) but occurred less frequently in CD13+ cases. CD13 expression occurred more frequently in female patients (P = .03). CD38 expression was associated with lower platelet count and an increase in the number of blasts (P < .02).

Determinative associations may exist between costimulatory molecule gene polymorphisms with a variety of post hematopoietic stem cell transplantation (HSCT) viral related clinical outcomes especially acute graft versus host disease (aGVHD). Therefore in this study the associations between costimulatory molecule gene polymorphisms including: cytotoxic T-lymphocyte antigen-4 (CTLA4), programmed cell death-1 (PD-1), inducible T cell costimulator (ICOS), and cluster differentiation 28 (CD28) with active cytomegalovirus (CMV) infection were evaluated in HSCT patients. The 72 allogeneic HSCT patients with and without aGVHD were enrolled in this cross sectional study between years: 2004-2011. The single nucleotide polymorphisms in loci of the costimulatory molecules including: CTLA4 gene (-318 C/T, 1722 T/C, 1661 A/G, +49 A/G), PD-1 gene (PD-1.3 A/G, PD-1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (+17 C/T) were analyzed in studied HSCT patients by PCR-RFLP methods. The active CMV infection was evaluated in fresh EDTA-treated blood samples of each allogeneic HSCT patients by CMV antigenemia kit according to manufacturer's instruction. Active CMV infection was found in 11 of 72 (15.27 %) of allogeneic HSCT patients. The T allele and TT genotype of the CD28 +17 C/T were significantly higher frequency in active CMV infected allogeneic HSCT patients experienced aGVHD. The G allele and GG genotype of the CTLA4 -1661 A/G were significantly higher frequent in active CMV infected allogeneic HSCT patients experienced low grade of aGVHD. Finally, finding of significant associations between CD28 +17 C/T and CTLA4 -1661 A/G genotypes with CMV active infection in allogeneic HSCT patients experienced aGVHD emphasize on the importance of the genetic pattern of costimulatory genes in outcomes of active CMV infection in HSCT patients needs completed studies.

Conclusions: These data demonstrate the safety and feasibility of BEAM-like regimen as a new and modified regimen; longer follow-up is required to evaluate fully efficacy and long-term safety of our method.