Adherence to practice guidelines for the management of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation: An observational study in a referral center in Iran.

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. METHODS: This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. RESULTS: Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. CONCLUSION: Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.

Post-Marketing Surveillance of a generic Oxaliplatin (AlvoxalⓇ) in Iranian Patients with Cancer.

BACKGROUND: CRC is the second and third most common cancer in women and men, respectively. The national comprehensive cancer network guidelines recommend oxaliplatin-based chemotherapy as a preferred regimen for patients with advanced or metastatic colon cancer. Oxaliplatin is also used in the off-label treatment of gastric cancer. FDA uses post-marketing study commitments to gather additional information about a product's safety, efficacy, or optimal use. It is necessary to perform safety monitoring after marketing authorization is received; such monitoring can be done by means of characterizing the safety of drugs in patients being treated in real-world clinical practice settings. OBJECTIVES: This Phase IV study aimed to evaluate the safety profile of a brand-name formulation of the generic drug oxaliplatin (AlvoxalⓇ, NanoAlvand, Tehran, Iran) in Iranian patients diagnosed with either colorectal or other, different types of cancer. METHODS: Patients with colorectal cancer, gastric cancer, or other malignancies receiving oxaliplatin as a part of their treatment were included in this open-label, multicenter, observational Phase IV study. This study aimed to assess the safety profile of oxaliplatin in patients diagnosed with different cancers. FINDINGS: A total of 483 patients from 16 cities in Iran were enrolled. The most common malignancy was colorectal cancer (55.49%), followed by gastric cancer (28.16%). Based on the results, 405 patients experienced at least 1 adverse event. Most of these adverse events were grade 1 or 2, and the most commonly reported adverse event was anemia (60.66%). During the study, 26 serious adverse events occurred in 15 (3.11%) patients, which were perhaps related to oxaliplatin. There were no remarkable differences in the incidences of adverse events in the system organ classes of blood and lymphatic system disorders, gastrointestinal disorders, or nervous system disorders among patients with different malignancies (ie, colorectal cancer, gastric cancer, and other malignancies) or between genders. The results of this open-label, multicenter, observational, postmarketing surveillance study demonstrated no unexpected safety findings from the use of this oxaliplatin product (AlvoxalⓇ) in Iranian patients diagnosed with different types of cancer. CONCLUSIONS: This Phase IV study provides data on the safety profile of a number of chemotherapy regimens containing an oxaliplatin product given to Iranian patients diagnosed with different types of cancer.

EPA and DHA have selective toxicity for PBMCs from multiple myeloma patients in a partly caspase-dependent manner.

Poly-unsaturated fatty acids (PUFAs) have been shown to have cytotoxic effects in both solid and non-solid tumors. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among the most studied PUFAs. The aim of the present study was to evaluate the cytotoxic effects of these two fatty acids (FAs) in the peripheral blood mononuclear cells (PBMCs) obtained from untreated patients (new cases) with confirmed symptomatic multiple myeloma (MM). Our results showed that EPA at the concentration of 100 µM and DHA at 50 and 100 µM induce potent apoptotic effects in the PBMCs of MM patients (P < 0.05) as evidenced by Annexin V and propidium iodide (PI) staining, while they have little or no effects on the PBMCs isolated from healthy donors (P > 0.05). The observed effects were concentration- and time-dependent and 72 h treatment with DHA at a concentration of 100 µM had the strongest effect (P < 0.01). CD138 + cells isolated from MM patients showed great sensitivity to EPA/DHA. EPA- and DHA-induced apoptosis was significantly inhibited by the pan-caspase inhibitor (Z-VAD-FMK), indicating that cell death was at least partly dependent on caspase activation. The results of the present study showed that EPA and DHA have selective toxicities for malignant human plasma cells from MM patients, but not for mononuclear cells of healthy donors. These results warrant further studies with larger study populations to investigate the usefulness of PUFAs as a promising adjunctive therapy in the treatment of MM.

Autologous Platelet-Released Growth Factor and Sexual Dysfunction Amendment: A Pilot Clinical Trial of Successful Improvement Sexual Dysfunction after Pelvic Irradiation

Sexual dysfunction (SDF) is a common sequel to cancer treatment which affects the quality of life in women treated with pelvic radiotherapy. The aim of this study was to evaluate the safety, symptom resolution and objective improvement the injection of autologous platelet released growth factor (APRGF) for treatment of SDF in cited patients. This prospective pilot study enrolled 10 cancer-free patients with SDF who underwent pelvic radiotherapy at least 5 years ago, randomly. Each patient was received 1-2 cc APRGF within four weeks and all patients were re-evaluated at eight weeks and six months. CD34 immuno histochemistry and Masson's trichrome staining were performed on vaginal biopsy section for angiogenesis and fibrosis assay respectively. Sexual satisfaction after the injection of APRFG was clinically difference and the entire patient had sexual satisfaction. In the patient's follow-up, none of them needs to repeat the treatment. Our results declared that APRGF injection was effective and symptoms were disappeared in the entire patients. Significant objective improvements in vaginal diameter (mean before injection, 6.5 cm vs 7.1 cm after injection) (p-value = 0.001) and vaginal flexibility (mean before treatment, 0.72 cm vs 1.85 cm after injection) (P-value = 0.026) were observed. Characteristics of discharge before the injection in 60% of patients were included dry vagina and 40% had mild discharge but after injection 40% of patients had moderate and also 60% had mild and sufficient discharge (P-value= 0.190). Overally, our patients reported better sexual function and showed better vaginal function indexes, after APRFG injection.

A double-blind, randomized, controlled trial on N-acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9 and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan-Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients.