Selmin Ataergin

Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 μg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 μg/kg/day is equavalent to 10 μg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G‐CSF was given at 5 μg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G‐CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 μg/kg/day is as efficious as filgrastim 10 μg/kg/day for autologous PBSC mobilization and transplantation. Am. J. Hematol., 2008.

Transient Efficacy of Double High-Dose Chemotherapy and Autologous Peripheral Stem Cell Transplantation, Immunoglobulin, Thalidomide, and Bortezomib in the Treatment of Scleromyxedema

Scleromyxedema is a rare disorder characterized by mucin deposits in the dermis and monoclonal gammopathy. No definitive treatment of this condition has been described to date. We present the case of a 38-year-old male patient with scleromyxedema who underwent double consecutive autologous peripheral stem cell transplantations and received immunoglobulin, thalidomide, and bortezomib. This resulted in considerable clinical and pathologic amelioration of the patient’s condition. However, 3 years after the second transplant, the patient relapsed and manifested the same skin lesions evident at his initial presentation.

Paraneoplastic Motor Neuron Disease Resembling Amyotrophic Lateral Sclerosis in a Patient with Renal Cell Carcinoma

Objective: To report an unusual paraneoplastic syndrome, amyotrophic lateral sclerosis, associated with renal cell carcinoma. Case Presentation and Intervention: A 59-year-old man presented with muscle weakness and fasciculations in the upper extremities. Neurological examination showed that the fasciculations arose spontaneously in the upper limbs. Electrodiagnostic studies revealed an active neurogenic disorder. The patient was diagnosed with a motor neuron disease mimicking amyotrophic lateral sclerosis. Urine analysis revealed microscopic hematuria. Abdominal computerized tomography scans showed a 9.5 × 8 cm renal mass in the lower pole of the right kidney. Curative right radical nephrectomy was performed. Pathologic examination showed a clear cell adenocarcinoma. After nephrectomy, the muscle weakness and fasciculations disappeared spontaneously within 2 months. The patient was disease-free for 58 months after right radical nephrectomy. He complained of muscle weakness and fasciculation at the last follow-up again. Physical examination revealed fasciculation in the upper limbs. Abdominal tomography showed a 22 × 20 mm solid mass in the lower pole of the left kidney. Kidney-saving surgery was performed and the diagnosis of renal cell carcinoma was confirmed pathologically. Following surgery, fasciculations completely disappeared and muscle weakness diminished within 3 months. Conclusion: This case highlights motor neuron disease as a rare paraneoplastic syndrome in association with renal cell carcinoma and resolution after removal of the tumor.

Efficacy of melatonin, mercaptoethylguanidine and 1400W in doxorubicin- and trastuzumab-induced cardiotoxicity.

Abstract:  Doxorubicin (DOX) and Trastuzumab (TRAST) are effective agents for the treatment of many neoplastic diseases. Cardiotoxicity is a major side effect of these drugs and limit their use. In this study, the possible protective effects of melatonin (MEL), mercaptoethylguanidine (MEG), or N‐(3‐(aminomethyl) benzyl) acetamidine (1400W) against the cardiotoxicity of DOX and TRAST were tested. Male Sprague‐Dawley rats received an injection of DOX (20 mg/kg) alone or in combination with TRAST (10 mg/kg) to induce cardiotoxicity; daily treatments with MEL (10 mg/kg × 2), MEG (10 mg/kg × 2), or 1400W (10 mg/kg × 2) were begun 36 hr before and continued for 72 hr after DOX and TRAST administration. Oxidant/antioxidant indices of the cardiac tissue, namely, malondialdehyde, superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px), as well as serum levels of creatine phosphokinase (CK‐MB) were measured. Additionally, the injury scores were evaluated histopathologically. Malondialdehyde levels were significantly higher, while SOD and GSH‐Px activities were significantly reduced in rats with DOX‐ or DOX+TRAST‐induced cardiotoxicity compared to normal values. All three treatment agents significantly reversed oxidative stress markers. Serum CK‐MB levels were significantly increased after treatment with DOX and DOX+TRAST; these changes were also reversed by each of the treatments and resulted in near normal levels. Both the DOX‐ and DOX+TRAST‐treated rats presented similar histopathologic injuries; in the animals treated with the protective agents, histologic protection of the cardiac tissue was apparent. These results suggested that MEL, MEG, as well as 1400W are effective in preventing DOX‐ or DOX+TRAST‐induced cardiotoxicity.

Modified outpatient dexamethazone, cytarabine and cisplatin regimen may lead to high response rates and low toxicity in lymphoma.

Objective: Our purpose was to investigate the efficacy of and establish a toxicity profile for a modified regimen of dexamethasone, cytarabine and cisplatin (DHAP) for lymphoma outpatients. Subjects and Methods: Fifty-one lymphoma patients, 26 with Hodgkin’s disease and 25 with non-Hodgkin’s lymphoma, were included. The patients’ median age was 32 years (range: 17–61). Twenty had progressive/refractory disease and 31 relapsed disease. Twenty-five were in clinical stage I/II and 26 in clinical stage III/IV before the initiation of salvage chemotherapy. DHAP consisted of dexamethasone (40 mg i.v. on days 1–4), cytarabine (2 g/m2 i.v. as 3-hour infusion on days 2 in the evening and 3 in the morning) and cisplatin (35 mg/m2 as 2-hour infusion on days 1–3) were administered every 21 days. A total of 154 cycles of modified DHAP were administered, with a median of 3 cycles per patient (range: 2–4). Results: The main toxicity was myelosuppression. WHO grade III–IV neutropenia and grade III–IV thrombocytopenia were observed in 27 (52.9%) and 21 (41%) patients, respectively. The overall response rate (85% for Hodgkin’s disease and 95% for non-Hodgkin’s lymphoma) was 88.3% (39.2% complete response and 49.1% partial response). Conclusion: The results showed that this outpatient schedule of DHAP was well tolerated and an effective salvage regimen.

The management of gastric adenocarcinoma with postoperative chemoirradiation. A non-randomized comparison of oral UFT and 5-FU.

Aims and background We assessed the therapeutic results and tolerability of postoperative chemoradiotherapy with either oral UFT or 5-fluorouracil for carcinoma of the stomach. Methods and study design Forty-six patients treated with chemoradiotherapy following total or subtotal gastrectomy for gastric carcinoma formed the cohort evaluated. The group included 39 males and 7 females whose ages ranged from 21 to 74 years (median, 53 years). In all patients, surgical therapy was the initial approach with a curative intent. The types of operations performed were total gastrectomy in 11 or subtotal gastrectomy in 35 patients. Radiotherapy began from 14 to 161 days after surgery (median, 55 days). Twenty patients received concomitant oral UFT (200 mg/m2), and 26 patients were given 5-fluorouracil (425 mg/m2, iv bolus) concurrently with irradiation consisting of one or two cycles, usually as a 3-day bolus at the start and last 3 days of irradiation therapy for radiosensitizing purposes. The patients were treated using either cobalt-60 or 6 MV photons, and irradiation doses delivered to the tumor bed and regional lymphatics ranged from 40 to 50 Gy (median, 46 Gy). Results Median follow-up for the entire group was 24 months (range, 2–67). The 2-year overall survival of the entire group of patients was 64%. The 2-year overall survival rates for 5-fluorouracil and oral UFT groups were 72% and 66%, respectively (P = 0.3). Treatment-related factors were reviewed to identify any impact on survival. Analyses included type of surgery and dissection, fraction size, the total dose of irradiation and the type of chemotherapy. A significant detrimental effect in survival in the patients treated with D2 dissection compared to the patients treated with D1 dissection was noted (P = 0.01). Overall grade II-III toxicity of oral UFT was significantly lower than 5-FU (4 patients vs 14 patients, P = 0.03). Conclusions Concomitant use of oral UFT with radiation seems to be more tolerable and an equally effective regimen in the treatment of locally advanced gastric cancer compared with 5-fluorouracil. D2 dissection was found to have detrimental effects on survival in this cohort.

Unusual Severe Complication Following Transarterial Chemoembolization for Metastatic Malignant Melanoma: Giant Intrahepatic Cyst and Fatal Hepatic Failure

We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

A Rare Presentation of Follicular Lymphoma: Cerebellar Involvement, Successfully Treated with a Combination of Radiotherapy and Chemotherapy

The central nervous system (CNS) is an important area of involvement for both high-grade, aggressive primary and secondary lymphomas. Although follicular lymphoma represents a low-grade histology, it may rarely present with CNS involvement. Here, we describe a patient diagnosed with follicular lymphoma who was presented with cerebellar involvement.

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high-dose chemotherapy in patients with Stage III breast cancer

The purpose of this study is to determine the presence of disseminated tumor cells in bone marrow or apheresis product, and also to evaluate the clinical significance of contaminated products and the efficacy of CD34+ selection and high‐dose chemotherapy in patients with Stage III breast cancer. Fifty‐five patients were enrolled in this prospective cohort study. Whereas CD34+ positive selection was not carried out in the first group (unselected group, n:31), CD34+ positive selection was performed in the second group (CD34 selected group, n:24). Tumor cells were detected with anticytokeratin monoclonal antibody in the bone marrow, apheresis product and positive fraction. Tumor cells were found in six (19.3%) patients in unselected group and four patients (16.6%) in CD34 selected group (P = 0.76). The percentages of distant metastases were found higher in unselected group (51.6% vs. 25%, P < 0.01). Although there were no differences between the two groups for disease free survival (DFS; 44% vs. 74%, P = 0.24) or overall survival (54% vs. 68%, P = 0.84), DFS was significantly lower in patients with tumor cells than in patients without tumor cells (21% vs. 62%, P = 0.02). In conclusion, the presence of tumor cells in bone marrow or apheresis product decreases DFS in patients with Stage III breast cancer who underwent high‐dose chemotherapy. CD34+ selection does not change survivals, but it may decrease the distant metastases. J. Clin. Apheresis 2009.

Successful Treatment of Osteosarcoma Arising in Osteogenesis Imperfecta with High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation Followed-by Limb Sparing Surgery

Oxaliplatin plus 5Fluorouracil (5FU) and leucovorin (LV) is the standard treatment of metastatic colorectal cancer (CRC). We describe a rare clinical case of acute renal failure probably oxaliplatin-related at one day from the end of the palliative treatment. A 36 year-old woman developed a stage I CRC. Five months later a liver lesion was detected and treated with FOLFOX4 schedule. Because of progression the patient underwent surgery and she repeated the Oxaliplatin-based therapy for more than one cycle. After many months of therapy, on the second day, the patient noticed urine discoloration. Immediate urinanalysis demonstrated haemoglobinuria. The patient’s complete blood count exhibited signs consistent with acute hemolysis, neutrophilic leucocytosis, thrombocytopenia and acute renal failure. She was treated with blood transfusion and hemodialysis and she was managed conservatively with monitored intravenous hydration and loop diuretics. The patient gradually recovered and the results of successive hematological and biochemical tests confired the improvement of her condition but a cardiologic evaluation showed a iatrogenic depressed systolic function (ejection fraction of 40%).Introduction Pharyngo-laryngeal tumors classified as T3-4, N0-3, M0, are conventionally treated by mutilating surgery (total (pharyngo)-laryngectomy). Neo-adjuvant chemotherapy with 5-FU/platinum salt can be proposed in an attempt to preserve the larynx. The level of the response to chemotherapy ranges from 36 to 54% of cases. Thus, a large number of patients receive chemotherapy that is ineffective and not free from adverse effects. Three main enzymes are involved in the metabolism of 5-FU: thymidylate synthase (TS), thymidylate phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Several studies suggest that a high level of expression of these three genes correlates with a poor clinical response to 5-FU. The main purpose of our study was to look for a correlation between the levels of expression of the genes for sensitivity to 5-FU (TS, TP, DPD) within the tumor and the clinical response observed after three courses of chemotherapy combining 5-FU/platinum salt in patients presenting with advanced cancer of the pharyngo-larynx. Methods This was a prospective genetic study that had required approval from the Ethics Committee. The main assessment criterion was based on the assessment of the clinical response by an ENT panendoscopy and a cervical CT scan, after three courses of chemotherapy. The expression of the genes was determined by quantitative RT-PCR, using total RNA extracted from tumor biopsies taken during the initial panendoscopy. Results The means calculated, in our study, for the three genes of interest (TS, TP, DPD) were lower in the responder group than those in the non-responder group. Discussion Our preliminary findings reveal trends that confirm the hypothesis that the lower the level of expression of the sensitivity genes, the better the clinical response to chemotherapy. They now form part of a larger study that is currently in progress.Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, and it is responsible for up to one million deaths annually. Although multiple risk factors for HCC have been identifi ed, and despite preventive measures, the incidence of HCC continues to rise to epidemiologic proportions in the United States. In general, tumor resection and orthotopic liver transplantation are the treatment with the best outcome; however, HCC is generally diagnosed late in its course when patients are not eligible for curative treatment options. HCC is a relatively Chemo-refractory tumor secondary to heterogeneity of the tumor and the high rate of multidrug resistant gene expression. There are no standard treatments for HCC, multiple palliative treatment modalities have been used for patients with unresectable disease. None of these modalities have shown any superiority; and the retrospective nature of these available data has confounded any reasonable conclusions. Different institutions use different treatment schema dependent on the center expertise. Sorafenib, a tyrosine kinase inhibitor, has recently demonstrated a survival advantage in metastatic HCC, and if approved by the FDA, might become the standard of care. In this article we will review the rationale behind the currently available treatment options for HCC.In 125 early breast cancer patients who underwent multiple bone marrow aspirates, there was no significant difference in terms of disease-free and overall survival after a median follow-up of 163 months between the patients with or without micrometastasis at the time of primary surgery. However, when the time-dependent evolution of the bone marrow aspirates was taken into account, some evidence for a longer disease-free and overall survival was found for the patients with negative bone marrowWe present a 20-year-old male patient with localized osteosarcoma arising in osteogenesis imperfecta who underwent high-dose chemotherapy together with autologous peripheral blood stem cell transplantation followed-by a successful extremity sparing surgery.A 74-year-old man presented with gradual wall thickening of a cystic lung lesion. Serologic tests indicated Aspergillus infection, but neither fungal organisms nor evidence of malignant disease were recovered from repeated sputum collections, a bronchoscopic lung biopsy specimen, or bronchial washings. Treatment with antifungal agents did not result in clinical improvement. Surgical resection of the lesion demonstrated both squamous cell carcinoma and aspergillosis. These distinct disorders share common radiologic manifestations that can present a diagnostic challenge, as in the present case.DCIS is a heterogeneous group of non-invasive cancers of the breast characterized by various degrees of differentiation and unpredictable propensity for transformation into invasive carcinoma. We examined the expression and prognostic value of 9 biological markers with a potential role in tumor progression in 133 patients with pure DCIS treated with breast conserving surgery alone, between 1982–2000. Histology was reviewed and immunohistochemical staining was performed. Pearson correlation coefficient was used to determine the associations between markers and histopathological features. Univariate and multivariate analysis examined associations between time to recurrence and clinicopathologic features and biological markers. Median age at diagnosis was 55 years (25–85). With a median follow up of 8.91 years, 41/133 patients recurred (21 as invasive recurrence). In this cohort 13.5% had low, 43% intermediate and 42% high nuclear grade. Comedo necrosis was found in 65% of cases. Expression of ER (62.4%), PR (55.6%), HER2/neu (31.6%), MIB1 (39.8%), p53 (22.6%), p21 (39.8%), Cyclin D1 (95.5%) calgranulin (20.5%), psoriasin (12%), was found in DCIS. HER2/neu was overexpressed in 45% that recurred as DCIS and 42.9% that recurred as invasive cancer, and only in 26.1% in cases that never recurred. On univariate analysis, HER2/neu overexpression was the only marker associated with an increased risk for any recurrence (p = 0.044). The hazard ratio for recurrence for HER2/neu positive DCIS was 1.927 (confidence interval 1.016–3.653) compared to HER2 negative DCIS. On multivariate analysis, HER2/neu overexpression remained the only independent variable significantly associated with any recurrence (p = 0.014) and with invasive recurrence (p = 0.044). This data suggest that HER2/neu testing may become an important parameter in the management of DCIS and the treatment of cases with positive HER2/neu status could be modified accordingly, similar to the current approach for HER2/neu positive invasive disease.