Ayse Kars

Primary Breast Lymphomas: A Retrospective Analysis of Twelve Cases

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkins lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Extrahepatic Hodgkin’s Disease with Intrahepatic Cholestasis: Report of Two Cases

Liver is involved in about 5–8% of newly diagnosed Hodgkin’s disease (HD) cases. The incidence reaches up to 50–60% in postmortem studies. In the literature only a few cases of idiopathic cholestatic jaundice have been described without an apparent cause and a paraneoplastic etiology has been suggested. We report 2 cases with HD presenting with obstructive jaundice without obvious liver involvement. The first case died soon after diagnosis; the second case received chemotherapy and radiotherapy, and she is well at 26 months’ follow-up. Extrahepatic HD with intrahepatic cholestasis is an extremely rare situation without an established approach. Such cases like the present ones may help to understand the pathogenesis of the liver involvement of HD and determine the best management of these cases.

Dihydropyrimidine Dehydrogenase Enzyme Deficiency: Clinical and Genetic Assessment of Prevalence in Turkish Cancer Patients

Background: Fluorouracil has been reported to induce severe side-effects in particular subjects who have deficiency in dehydropyrimidine dehyrogenase activity, the major enzyme in the catabolism of fluorouracil. Patients and methods: In this study, we aimed to analyze the heterozygote and homozygote frequencies of dehydropyrimidine dehyrogenase gene mutation in 200 patients receiving fluorouracil based chemotherapy together with the assessment of the toxicity profile of these chemotherapy regimens. Results: According to the results of clinical toxicity assessments, grade 3–4 hematologic toxicity was noted in 12% of the patients. Grade 3 gastrointestinal toxicity was present in 5% of the subjects with no grade 4 side effects. The heterozygote (2q(1−q)) and homozygote (q2) frequencies of dehydropyrimidine dehyrogenase gene mutation were calculated as 1.5% (3/200) and 0.000055% (1/18,043) in the analyzed samples. Conclusion: In this report, for the first time we documented the frequency of dehydropyrimidine dehydrogenase gene mutation in Turkish cancer patients. The determination of enzyme activity in suspected individuals and analysis of other mutations on a population basis would be the next steps for our country.

Recurrent Asymptomatic Bradycardia Episodes after Cisplatin Infusion

TO THE EDITOR:Cisplatin has been used in the treatment of various malignancies. 1 Its major adverse effects are nephrotoxicity, ototoxicity, and neurotoxicity, while cardiac toxicity is a rare event. 2-4 We describe a case of recurrent sinus bradycardia after cisplatin infusion in a patient with relapsed Hodgkin’s disease. Case Report.In January 1997, a 35-year-old white man was diagnosed with nodular sclerosing stage IIA Hodgkin’s disease. He was treated with six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine plus involved field radiation. The patient had been in remission for 14 months and was readmitted to the hospital because of fatigue, cough, and weight loss. Physical examination and diagnostic work-up, including complete blood count, serum biochemistry, X-ray, and a bone marrow biopsy, were performed, which revealed relapsed stage IV Hodgkin’s disease. Salvage chemotherapy consisting of intravenous cytarabine–arabinoside 2000 mg/m2 over three hours (0900–1200) on day 1, intravenous cisplatin 25 mg/m 2

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkins disease (HD) or non-Hodgkins lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 – 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.

Alterations in immune parameters in foundry and pottery workers

To assess the immune competence of workers occupationally exposed to mainly silica, peripheral blood lymphocytes, serum immunoglobulins (IgG, IgA and IgM), C3 and C4 complement protein concentrations of foundry and pottery workers were evaluated and compared to healthy controls with no history of silica and other chemical exposure. The absolute number and percentage of functionally different subsets of peripheral blood mononuclear lymphocytes, i.e. T, T-suppressor and natural killer cells were unchanged. However, T-helper lymphocytes in pottery (P<0.05) and B cells in foundry (P<0.01) workers were significantly lower when compared to their controls. In addition, silica-exposed foundry workers had a significant reduction in the IgG, IgA and IgM levels. No significant differences were observed in the serum complement C3 and C4 levels of the workers. These results suggest that human chronic exposure to mainly silica and other chemicals originating from foundry and pottery settings may be detrimental to the immune system.

Modified ESHAP as Salvage Chemotherapy for Recurrent or Refractory Non-Hodgkin’s Lymphoma: Results of a Single-Center Study of 32 Patients

Background: We have evaluated the clinical efficacy and toxicity of a modified etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) chemotherapy regimen that has been used by the Hacettepe University Department of Medical Oncology (Ankara, Turkey) since 1993. Methods: Thirty-two patients (18 men and 14 women) with refractory or recurrent non-Hodgkin’s lymphoma (NHL) were treated with this protocol. The median age of the patients was 39 years (range 21–66 years). Patients were hospitalized during therapy. On the first day, 2 g/m2 cytarabine was given, followed on days 2–5 by 60 mg/m2 etoposide, 500 mg of methylprednisolone and 25 mg/m2 cisplatin. After two cycles of chemotherapy, clinical efficacy was assessed by clinical examination, chest radiography, ultrasonography and/or computed tomography. The complications were assessed on the basis of the World Health Organization criteria. Results: Nine patients (28%) had a complete response and 8 patients (25%) had a partial response. In responders, the median duration of remission was 6 months. By the end of the first year, 27% of the patients were still disease free and 66% were alive. High serum levels of lactate dehydrogenase had an adverse effect on disease-free survival, but no effect on overall survival (OS). The only unfavorable prognostic factor for OS was the presence of bulky disease. Neutropenia developed in 59% of patients, and febrile neutropenia developed in 74% of these patients, requiring hospitalization for an average of 8 days. Three patients died of neutropenia-associated sepsis despite broad-spectrum antibacterial and antifungal treatment. Thrombocytopenia was detected in 10 patients and anemia in 3 patients; among these, 7 patients with thrombocytopenia and 1 patient with anemia required transfusions. Conclusions: The modified ESHAP regimen induced remission in more than half of the patients with refractory or recurrent NHL. However, the duration of remission was brief. Moreover, significant myelotoxicity was common, and the risk of treatment-related death was 9%.

Ceruloplasmin Level in Women with Breast Disease Preliminary Results

The average ceruloplasmin levels of 29 patients with active breast cancer and 22 patients in remission were 824 +/- 61 mg/l and 630 +/- 18 mg/l respectively. The average ceruloplasmin level of 17 patients with benign breast diseases was 555 +/- 29 mg/l and of 18 healthy women in a control group 584 +/- 17 mg/l. Breast cancer patients not in remission had ceruloplasmin levels which were significantly increased when compared to the other 3 groups. The CA 15-3 levels and ceruloplasmin levels were positively correlated. We propose that ceruloplasmin may be used as a tumour marker in the follow-up of patients with breast cancer.

Granulocyte-Colony Stimulating Factor (G-CSF) Administration for Chemotherapy-Induced Neutropenia.

This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.

Maintenance therapy with alpha-interferon following first-line VAD in multiple myeloma

Abstract: The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first‐line chemotherapy and to determine the efficacy of maintenance alpha‐interferon (α‐IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n = 31), and those recruited after 1990 (n = 33) were planned to be maintained with α‐IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow‐up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD‐only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression‐free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD‐only group. VAD regimen was well tolerated and IFN‐related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.