Assessment of therapeutic apheresis procedures

Tıpta Uzmanlık TeziTerapötik aferez çeşitli hastalıklarda primer veya yardımcı tedavi olarak kullanılmaktadır. Trakya Üniversitesi Sağlık-Araştırma ve Uygulama Hastanesi Terapötik Aferez Merkezi'nde Ocak 2007 ve Ekim 2012 tarihleri arasında yapılan terapötik aferez işlemleri geriye dönük ve ileriye yönelik olarak incelenmiştir. Her bir hastanın; yaş, cinsiyet, boy, kilo, klinik endikasyon uygulama öncesi ve sonrası lökosit, biyokimyasal parametreleri kaydedildi. Her işlem için şu parametreler incelendi: cihaz ve venöz yol tipi (santral/periferal), kan miktarı ve plazma türü, işlem süresi, verilen yedek sıvının tipi, tedavi yanıtı ve yan etkiler. Ocak 2007 ve Ekim 2012 tarihleri arasında 126 hastaya 753 işlem yapıldı (64 erkek ve 62 kadın, ortalama yaş aralığı 50,5 ± 18,3 yıl). Bu işlemlerin 628'i terapötik plazma değişimi, 79'u kaskad filtrasyonu ve 46`sı sitaferez (lökositaferez ve trombositaferez) oluşturdu. Terapötik aferez uygulanan hastalıkların başında hematolojik (%42,9) ve nörolojik hastalıklar (%25,4) yer aldı. En sık üç hastalık grubu: Trombotik trombositopenik purpura, Gullian-Barre Sendromu ve Multipl Miyelom idi. American Society for Apheresis kılavuzuna göre terapötik plazma değişiminin %76,7'si, kaskad filtrasyonunun %63,2'si ve sitaferez işlemlerinin %82,6'sı kategori I-II idi. Trombotik trombositopenik purpura hastalık grubunda terapötik plazma değişimi sonrası trombosit sayısı anlamlı bir şekilde yükseldi. Lökosit sayısı lökositaferez sonrası, trombosit sayısı ise trombositaferez sonrası istatiksel olarak anlamlı bir şekilde düştü. Çalışmamızda total terapötik aferez komplikasyon oranı %9,6 olarak bulundu. Komplikasyonların %3,9'u damar yolu ve cihaz, %5,7'si ise tedavi ile ilgili idi. En sık görülen yan etki; hipokalsemik semptomlardı. Akut myeloblastik lösemi tanılı bir hasta lökositaferez işlemi sırasında öldü. Sonuç olarak verilerimizin diğer yapılan çalışmalara benzer olduğu ve çeşitli hematolojik, nörolojik, metabolik ve diğer hastalıklarda uygulanabilen güvenli bir işlem olduğu düşünüldü.AbstractTherapuetic apheresis is used in certain diseases as a primary or supplementary treatment. In this study, therapuetic apheresis procedures performed between January 2007 and October 2012 in Trakya University Therapeutic Apheresis Unit was assessed retrospectively. Age, gender, height, weight, indications of the procedure, blood count and biochemistry panel before and after the procedure were recorded. Device and the access (central/peripheral), the volume and replacement modality as well as period of time, response to treatment and adverse effects were also recorded for every patient and procedure. A total of 753 procedures were performed for 126 patients from January 2007 to October 2012 (64 male and 62 female, median age 50.5+_18.3 years). Of these 753 procedures, 628 were therapeutic plasma exchange, 79 were cascade filtration, 46 were cytoapheresis (leucocytoapheresis and thrombocytoapheresis). Indications for therapuetic apheresis were majorly hematologic and neurologic. The most frequent indications for therapuetic apheresis were thrombotic thrombocytopenic purpura, Gullian-Barre syndrome and Multiple myeloma. The categories I and II indications for therapuetic apheresis according to American Society for Apheresis were observed in 76,2% of therapeutic plasma exchange, 63,2% of cascade filtration and 82,6% of cytoapheresis procedures. In 9,6% of the procedures, complications related with access and treatment itself were observed. The most frequent adverse effect was symptoms related with hypocalcemia. Only one patient with acute myeloblastic leukemia has died during leucocytoapheresis. In conclusion, our data are similar to other studies, and various hematological, neurological, metabolic, and orher diseases were thought to be a safe procedure that can be applied

Is the prognostic nutritional index a prognostic and predictive factor in metastatic non-small cell lung cancer patients treated with first-line chemotherapy?

*Şakalar, Teoman ( Aksaray, Yazar )Purpose: We aimed to assess the prognostic and predictive significance of pretreatment Onodera’s prognostic nutritional index (OPNI) in metastatic non-small cell lung cancer patients (NSCLC) treated with first-line chemotherapy. Materials and methods: Patients with metastatic NSCLC who attended five different medical oncology clinics between December 2008 and January 2018 were retrospectively analyzed. The optimal cut-off point for OPNI was performed by a receiver operating characteristic (ROC) curve analysis. Patients were assigned to either the low OPNI group or high OPNI group. Results: A total of 333 patients were included in the study. Significant differences between the low and high OPNI groups were found regarding the rates of response to chemotherapy, sex, and hemoglobin level (p < 0.05). The patients in high OPNI group had a longer overall survival (OS) (15.3 vs. 10.6 months, p < 0.001) and progression-free survival (PFS) (6.7 vs. 5.3 months, p < 0.001) compared to the patients in low OPNI group. A multivariate analysis using Cox regression model revealed that a high OPNI score was an independent prognostic factor of OS (HR = 1.535, p = 0.002) and PFS (HR = 1.336, p = 0.014), but failed to demonstrate a statistical significance of pretreatment OPNI scores in predicting treatment response (p = 0.56). Conclusions: Pretreatment OPNI is an independent prognostic factor for OS and PFS in metastatic NSCLC patients treated with first-line chemotherapy. Thus, it may be used as easily calculated and low-cost prognostic tool in the routine clinical practice in this patient group

The efficacy of modified docetaxel-cisplatin-5-fluorouracil regimen as first-line treatment in patients with alpha-fetoprotein producing gastric carcinoma

Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC) were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001). A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001).Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%), and 82.2% (complete response - 3%, PR - 36.2%, SD - 43%) in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively). Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area

5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as a third-line chemotherapy treatment in metastatic gastric cancer, after failure of fluoropyrimidine, platinum, anthracycline, and taxane

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first- and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m² irinotecan and 400 mg/m² leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m² 5-fluorouracil IV bolus then 2600 mg/m² continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: >2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane

Effectiveness of low-dose oral etoposide treatment in patients with recurrent and platinum-resistant epithelial ovarian cancer

The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50 mg/day, days 1–14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment. The overall response rate was 19.2% and clinical benefit rate was 40.4% [PR (19.2%), SD (21.2%)]. Median overall survival (OS) and progression-free survival (PFS) was 9.95 months (95%CI, 0.2–19.7 months) and 3.2 months (95%CI 2.6–3.8 months), respectively. Grade III–IV haematologic and non-haematologic adverse events were observed in 7 (13.4%) patients. We consider that oral etoposide (50 mg/day, days 1–14, every 3 weeks) is an effective treatment with a manageable adverse effect profile in recurrent platinum-resistant EOC patients.Impact statement What is already known on this subject: Oral etoposide is an effective option for recurrent EOC patients at a dose of 50–100 mg/m2/day (1–21 days, every 28 days) regimen. However, it has a high toxicity rate. What the results of this study add: Oral etoposide at a dose of 50 mg/kg (1–14 days, every 21 days) is an effective treatment with a manageable toxicity profile in platinum- resistant ovarian cancer patients when it is used as ≤4th-line palliative setting. What the implications are of these findings for clinical practice and/or further research: We need trials evaluating the effect of low-dose oral etoposide combination with bevacizumab or other chemotherapy agents (irinotecan and gemcitabine) in platinum-resistant EOC patients