Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients.

BACKGROUND: Second line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. PATIENTS AND METHODS: Forty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. RESULTS: Thirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. CONCLUSION: Our results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

Neurotoxicity evaluation of three root canal sealers on cultured rat trigeminal ganglion neurons.

BACKGROUND: The aim of this study was to investigate the possible neurotoxic effects of 3 root canal sealers (RCSs) (AH Plus, GuttaFlow, iRoot SP) on cultured rat trigeminal ganglion (TG) neurons. MATERIAL AND METHODS: Primary cultures of TG neurons were obtained from 1 to 2-day old rats. Freshly mixed RCSs were incubated in sterile phosphate buffered saline and cells were incubated with supernatants of the RCSs for different time intervals (1-, 3-, 6- and 24-h; 1 or 1/10 diluted) and viability/cytotoxicity was tested by counting the number of live cells. Pair of dishes with cells from the same culture incubated with only culture medium was considered as negative controls. Cell images were captured and acquired at x200 magnification using a microscope equipped with a camera using special image program. The viable cells were manually counted assigned from the images for each dose and incubation duration. Data was analysed by using 1-way analysis of variance with Tukey post hoc tests. RESULTS: There was no significant change in cell viability after short duration of incubation (1- and 3-h) with the supernatant of any of RCSs, except for undiluted-AH Plus at 3-h. When AH Plus was compared with other RCSs, for diluted supernatants, there was only significant difference between iRoot SP and AH Plus at 24-h (P<0.05). Whereas undiluted-AH Plus was significantly more cytotoxic for 3-, 6- and 24-h periods as compared to respective incubation periods of undiluted other groups (P<0.05). GuttaFlow groups had similar neurotoxic effect on cells for all test periods. CONCLUSIONS: All tested RCSs exhibited a variable degree of neurotoxicity on these primary sensory neurons of orofacial tissues, depending on their chemical compositions. GuttaFlow and iRoot SP evoked a less toxic response to TG cells than AH Plus. Key words:Neurotoxicity, trigeminal ganglia, cell culture, root canal sealer, AH Plus, GuttaFlow, iRoot SP.

Association of Toll-like receptors 2, 3, and 4 genes polymorphisms with periapical pathosis risk

BACKGROUND: The aim of this study was to investigate the role of gene variations of Toll-like receptors (TLR) 2, 3, and 4 on genetic susceptibility to periapical pathosis. MATERIAL AND METHODS: One hundred patients were included in the study and divided into two groups as follows; Control Group (n=50) that have root canal treatment and no periapical lesion, Patient Group (n=50) that have root canal treatment and periapical lesion. TLR2 Arg753Gln, TLR3 (c.1377C/T) and TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped by using PCR-RFLP. Genotypical analysis of control and patient groups were investigated to disclose whether there is any association between periapical lesions and gene variations. RESULTS: There are no significant statistical differences between control and patient groups according to TLR 2 and 4 gene sequence. On the contrary, CC allele detected 74% for TLR 3 in patient group, and this difference was found to be statistically significant (p < 0.005). CONCLUSIONS: According to these results, it can be suggested that patients with Toll-like receptor 3 gene polymorphisms could be susceptible to periapical pathosis

Effect of propolis on survival of periodontal ligament cells: new storage media for avulsed teeth.

Propolis is a multifunctional material used by bees in the construction and maintenance of their hives. Propolis possesses several biologic activities such as anti-inflammatory, antibacterial, antioxidant, antifungal, antiviral, and tissue regenerative, among others. The purpose of this study was to determine the ability of propolis to serve as a temporary storage medium for the maintenance of periodontal ligament (PDL) cell viability of avulsed teeth. PDL cells were obtained from healthy third molars and cultured in Dulbecco's Modified Eagles Medium (DMEM). Cultures were subjected to 10% propolis solution, 20% propolis solution, long-shelf life light milk with lower fat content (milk), Hank's Balanced Salt Solution, tap water as the negative control, and DMEM as the positive control. Tissue culture plates were incubated with experimental media at 37 degrees C for 1, 3, 6, 12, or 24 hours. PDL cell viability was assessed by trypan blue exclusion. Statistical analysis of the data was accomplished by using one-way analysis of variance complemented by the Tukey test. The level of significance was 5% (p<0.05). The results showed that 10% propolis was a more effective storage medium than other groups. In conclusion, propolis can be recommended as a suitable transport medium for avulsed teeth.

Nonsurgical endodontic treatment of dens invaginatus in a mandibular premolar with large periradicular lesion: a case report.

This case report describes the treatment of a dens invaginatus in a mandibular premolar with large periradicular lesion. A nonsurgical endodontic treatment was performed to tooth #28. During the treatment procedure, calcium hydroxide and a triple antibiotic paste were separately used for intracanal dressing. The apical third of the canal was obturated with mineral trioxide aggregate (MTA), and the remaining canal space was obturated with gutta-percha and AH 26 root canal sealer, using a lateral condensation technique. At follow-up examination after 1 year, the tooth was asymptomatic and radiographically showed repair of the lesion. Healing was achieved without any need for further endodontic surgical intervention.

Effect of mouthrinse containing propolis on oral microorganisms and human gingival fibroblasts.

OBJECTIVES: The aim of this study was to compare the effects of four different mouthrinse containing propolis solutions and mouthrinse containing 0.2% chlorhexidine (CHX) on oral microorganisms and human gingival fibroblasts. METHODS: Four different solutions of propolis were prepared and propylene glycol and alcohol were used as solvents for each propolis sample. Mouthrinse containing propolis was prepared at four different concentrations as 10%, 5%, 2.5% and 1%. Besides, CHX was used as control group. The antibacterial effects of five solutions on oral microorganisms were tested and their cytotoxic effects on human gingival fibroblasts were evaluated by agar diffusion test. RESULTS: At this concentrations effectiveness of mouthrinse containing propolis samples on oral microorganisms were not found as effective as CHX. On the contrary, samples found less cytotoxic on human gingival fibroblasts than CHX. CONCLUSIONS: Standardized preparations of propolis can be used as a mouthrinse at appropriate concentrations. To obtain a standardized chemical composition, advanced researches are needed.

Endodontic treatment of a large cyst-like periradicular lesion using a combination of antibiotic drugs: a case report.

This case report describes the endodontic treatment of a large cyst-like periradicular lesion using a combination of antibiotic drugs. A 15-yr-old boy with a large cyst-like lesion from the apices of his teeth 29 to 31. Conservative root canal treatment was performed (tooth #30). During treatment procedure, 2.5% sodium hypochlorite solution was used for irrigation and a combination of antibiotic drugs was used for the intracanal dressing. Periapical healing was observed 3-month after initial treatment and continued at the 7-month review.

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BACKGROUND: Although bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event. METHODS: To underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow. RESULTS: The main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO). CONCLUSION: Our series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML). Outcome of discontinuation of imatinib therapy after achieving a molecular remission.

Because of the teratogenicity data in rats, it is recommended that women treated with imatinib should be aware of the potential teratogenicity of imatinib and effective contraception should be used during imatinib therapy to prevent pregnancy. We describe successful pregnancy and delivery, without any congenital anomaly, in a patient with CML under treatment of imatinib. The fetus had been exposed to imatinib for 8 weeks. The patient remained off treatment during gestation and cytogenetic relapse of CML (5 months after discontinuation of imatinib therapy) developed at seventh month of gestation.

Successful pregnancy and delivery in a patient with chronic myelogenous leukemia (CML), and management of CML with leukapheresis during pregnancy: a case report and review of the literature.

Although infrequently seen, the management of cancer during pregnancy can be difficult for patients, their families and physicians. The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 26-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in chronic phase by using only leukapheresis. She was treated with leukapheresis until her delivery at 36 weeks of gestation. The procedure was without significant adverse effects on the patient or fetus. We applied a total of 15 leukapheresis treatments throughout the pregnancy. The patient gave birth vaginally to a healthy 2800 g boy at 36 weeks of gestation. We conclude that leukapheresis may provide an alternative treatment to chemotherapy, alpha-interferon or imatinib in pregnant patients with CML, particularly with concern over their potential teratogenic and other adverse effects.

Maternal and fetal outcomes in pregnancy complicated with acute leukemia: a single institutional experience with 10 pregnancies at 16 years.

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.