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.

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

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 1400 W are effective in preventing DOX- or DOX+TRAST-induced cardiotoxicity.

Factors affecting engraftment time in autologous peripheral stem cell transplantation.

BACKGROUND: Rapid hematological engraftment at autologous peripheral stem cell transplantation (APSCT) is a significant factor in reduction of early transplant-related complications and costs. For this reason, it is important to determine influences on hematological recovery. METHODS: This study was designed to evaluate factors affecting leukocyte and platelet engraftment times after high dose chemotherapy following APSCT. A total of 228 patients (131 males and 97 females) were enrolled. RESULTS: There were statistically significant differences between patients with CD34+ cell doses ≥ 2.5 x 106/kg (n=180) and < 2.5 x 106/kg (n=48), regarding leukocyte engraftment at 11 and 12 days, respectively (p<0.02), between G-CSF (n=167) and GM-CSF (n=61) posttransplant regarding median leukocyte engraftment times (p=0.005), and between with (n=75) or without (n=153) history of pretransplant radiotherapy for both leukocyte and platelet engraftment times (p<0.001). CONCLUSIONS: For leukocyte engraftment, a history of pretransplant radiotherapy, type of growth factor used and number of CD34+ cells infused, and for platelet engraftment, a history of pretransplant radiotherapy were found to be independent variables on multivariate analysis with the Cox regression method.

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/m(2) i.v. as 3-hour infusion on days 2 in the evening and 3 in the morning) and cisplatin (35 mg/m(2) 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.

Abnormal 18F-FDG Uptake Detected with Positron Emission Tomography in a Patient with Breast Cancer: A Case of Sarcoidosis and Review of the Literature.

18F-FDG PET is a useful and sensitive imaging method for a variety of malignancies, however, the specificity is low in active infections and inflammatory diseases. We describe a female patient with stage IIIA breast cancer in first complete remission with combination chemotherapy who developed nodular formations in the lung and axilla 12 years later. Imaging studies as well as FDG PET showed nodular lesions and increased metabolic activity which was interpreted as the progression of the primary disease. She was first given combination chemotherapy and hormonal therapy but was proven thereafter to have sarcoidosis by pathologic examination and was successfully treated with corticosteroid treatment.

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.

Self-reported experience of mucositis in cancer patients who underwent conditioning regimen and stem cell transplantation.

PURPOSE: This study was done to evaluate the frequency and severity of mucositis in the early period of stem cell transplantation (SCT) and the relation of conditioning regimens with mucositis. PATIENTS AND METHODS: Patients with hematologic or solid tumors who underwent conditioning regimen were asked to score mucositis severity daily from the first day to the tenth day of reinfusion. Patient-reported scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total mucositis score (TMS) was defined as the addition of daily mucositis scores for 10 days. A total of 68 SCT (58 autologous and 10 allogeneic) patients, 48 men (71%) and 20 women (29%) were included to the study. Median age of patients was 32.5 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (37%, n = 25), Hodgkin's lymphoma (12%, n = 8), and multiple myeloma (12%, n = 8). BEAM (n = 27), ICE (n = 17), melphelan 200 mg/m(2) (M200)(n = 8), and TBI+C (total body irradiation + cyclophosphamide) (n = 16) were used as conditioning regimens. RESULTS: All of the patients experienced mucositis at any grade. TMS in the sixth day was higher than TMS in the first day (p < 0.05). TMS was not related to the diagnosis or gender (p > 0.05). TMS at ICE regimen in the first 5 days after transplantation was more severe than BEAM regimen. TMS at TBI+C regimen was higher than TMS at BEAM regimen from day 4 to day 10 (p < 0.05). The mean percentages of patients who scored severe or very severe mucositis in 10 days was 7.4% in BEAM, 8.9% in ICE, 12.5% in M200, and 31.2% in TBI+C groups. CONCLUSION: Patients experience mucositis frequently following conditioning regimen and SCT. The necessity and the timing of prophylaxis for mucositis change due to the type of conditioning regimens.

New generation pharmacotherapy in elderly multiple myeloma patients.

BACKGROUND: Observational databases have demonstrated that the overall prognosis of multiple myeloma patients has markedly improved over the past decade, yet the greatest strides have been attained in younger rather than older patients. OBJECTIVE: To review recent clinical trials that include new generation agents (thalidomide, lenalidomide and bortezomib) and autologous stem cell transplantation in older multiple myeloma patients. RESULTS: Conventional regimens such as melphalan plus prednisone can be improved with the addition of thalidomide or bortezomib: more patients attain complete and near-complete remission, and progression-free survival rates are nearly doubled. In addition, autologous hematopoietic stem cell transplantation studies show that this treatment approach can be used successfully in selected older myeloma patients in whom the toxicity profile of autotransplant and resulting overall survival may be similar to that obtained in the younger patient group. CONCLUSIONS: In the advanced-age population, implementation of new therapies results in significant benefits in older as well as younger patients.

Abnormal FDG uptake on 18F-fluorodeoxyglucose positron emission tomography in patients with cancer diagnosis: case reports of tuberculous lymphadenitis.

Although 18F-FDG-PET is very sensitive for a variety of malignancies, it can lack specificity. In addition to malignant tissue, any active infectious or inflammatory process can demonstrate FDG avidity. We report 3 patients with different types of cancer who had abnormal 18F-FDG uptake on PET scan caused by tuberculous lymphadenitis. All were found to have incidental multiple lymph adenopathies with increased FDG uptake on PET scan. All three patients were proved to have tuberculosis lymphadenitis by pathologic examination and were successfully treated with anti-tuberculous therapy.

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.

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 x 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 x 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.

Long-lasting multiagent chemotherapy in adult high-risk Ewing's sarcoma of bone.

The outcome of Ewing's sarcoma depends on the anatomical site of the tumor. Studies conducted in high-risk patients are limited. We evaluated the outcome of high-risk Ewing's sarcoma patients that received long-term treatment protocol. Twenty-five patients (22 males, 3 females) with poor prognostic features were treated according to long-term Ewing's sarcoma protocol. Central-axis localization, inadequacy or unavailability of surgical resection, older than 15 years of age, are accepted as high-risk factors. The median age of patients was 23 years (range, 18-55). The tumor localization was pelvis (9), femur (1), tibia (1), fibula (1), maxilla (1), clavicle (1), vertebrae (5), metatarse (1), and ribs (5). Neoadjuvant chemotherapy was applied between weeks 0 and 6, local therapy on week 9, and adjuvant maintenance chemotherapy between weeks 11 and 41. All patients received neoadjuvant and adjuvant maintenance chemotherapy. Local therapy consisted of radiotherapy (32%), surgery alone (12%), or surgery and radiotherapy (56%). The median total treatment period was 10 months. The median follow-up was 25 months (range, 7-89). Three-year cumulative OS and DFS rates were 43% (95% CI, 28.5-57.85) and 40% (95% CI 23.63-52.19), respectively. The most common grade III/IV toxicities observed during the treatment protocol were neutropenia (16%) and gastrointestinal toxicities (16%). Our study indicated that long-term multiagent combination chemotherapy may result in better outcome in adult high-risk patients undergoing adequate surgical resection of the tumor and local radiotherapy. Further randomized studies are needed to assess the efficacy of this treatment protocol in patients with adequate surgical margins.

Acute renal toxicity of 2 conditioning regimens in patients undergoing autologous peripheral blood stem-cell transplantation. Total body irradiation-cyclophosphamide versus ifosfamide, carboplatin, etoposide.

OBJECTIVE: To compare acute renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide (TBI-Cy) and Ifosfamide, Carboplatin, and Etoposide (ICE). METHODS: Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-seven patients received ICE regimen with 12 g/m2; 1.2 g/m2; and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI (6 fractions twice daily in 3 consecutive days) and 60 mg/m2/day cyclophosphamide for 2 days. RESULTS: Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity (23.4%) in the ICE group while one patient (4.8%) in the TBI-Cy group developed nephrotoxicity (p=0.06). Five out of 11 patients developing nephrotoxicity in ICE group required hemodialysis and subsequently 4 (8.5%) of them died. In contrast, one patient (4.8%) died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm. CONCLUSION: This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation.

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.

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 microg/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 microg/kg/day is equavalent to 10 microg/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 microg/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 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.

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.

Impact of c-erb2 status on survival after high dose chemotherapy in high-risk breast cancer patients.

OBJECTIVE: To investigate the impact of c-erb2 status on survival after high-dose chemotherapy. METHODS: Between March 1997 and June 2004, a total of 54 women with breast cancer who has at least 8 metastatic lymph nodes underwent high-dose chemotherapy with hematopoietic stem cell transplantation in Gulhane Military Medical School, Ankara, Turkey. Archival specimens were analyzed by fluorescent in situ hybridization to determine the impact of c-erb2 status after peripheral blood stem cell transplantation on survival. The patients were divided into c-erb2 negative (n=20) and positive (n=11) groups. RESULTS: No statistically significant differences were detected between c-erb2 negative and positive groups regarding 5-year disease-free survival (41 and 27%, log rank p=0.11), and overall survival (60 and 45%, p=0.33). Transplant related mortality did not differ between groups. CONCLUSION: We found no differences between c-erb2 negative and positive groups regarding disease-free and overall survival. To clarify the value of the c-erb2 status in predicting outcome after high-dose chemotherapy, prospective randomized studies are needed.

Malignant peripheral primitive neuroectodermal (pPNET) of tongue.

Primitive neuroectodermal tumors (PNETs) are relatively rare tumors. Tumors that once would have been diagnosed as Ewing's sarcoma are now often designated as peripheral neuroepithelioma or synonymously PNET. This paper reports a case of PNET located orally on the tongue, which is, to our knowledge, the first case reported in medical literature. The patient was treated with postoperative radiotherapy and chemotherapy. Multiple liver metastases occurred 5 months after the initial diagnosis and following extensive chemotherapy the patient was only able to survive for a further 10 months.