Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

CD4+CD25(high), CD8+CD28- cells and thyroid autoantibodies in breast cancer patients.

AIM OF THE STUDY: To investigate the percentage of CD4+CD25(high) cells (including Treg cells) and CD8+CD28- cells in breast cancer patients with and without high levels of autoimmune thyroid antibodies. MATERIAL AND METHODS: Thirty-five women with breast cancer (9 of them having high thyroid antibodies) and fourteen healthy subjects were enrolled in this study. Flow cytometry was used to count CD4+CD25(high) cells and CD8+CD28- suppressive cells (CD8 cell subtypes). RESULTS: In the patient group, the percentage of CD28- cells in CD8+ lymphocytes were higher [67.50% (55.1180.33) vs. 51.56% (42.5766.38); p = 0.021] and the percentage of CD28+CD45RO- cells (memory cells) in CD8+ lymphocytes were lower than in the control group. CD4+CD25(high) cell percentage in CD4+ lymphocytes was elevated in the patient group [6.44% (4.528.74) vs. 2.97% (1.724.34); p < 0.001]. When the cytometric parameters were compared between patients (with high vs. normal thyroid antibodies), the distribution of CD8+ cell subgroups was also similar. CD4+CD25(high) cells among CD4+ lymphocytes were decreased in patients with high levels of thyroid antibodies [5.19% (3.426.17) vs. 6.99% (4.829.95); p = 0.043]. CONCLUSIONS: CD4+CD25(high) cells may play a role in autoimmunity of breast cancer patients, and may be a predictive marker. Advanced studies which evaluate the possible links between regulatory cells and autoimmunity should be established in cancer patients.

CD8+CD28- cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients.

AIM: To evaluate the CD8+CD28- and CD4+CD25+ regulatory T (Treg) cells in addition to other some lymphocyte subgroups in peripheral blood of advanced stage lung cancer patients. METHODS: The study group (n = 28) comprised chemotherapy and radiotherapy naïve patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The control group (n = 22) consisted of age- and sex-matched healthy volunteers. Flow cytometry was used to count T cells, natural killer (NK) cells and CD4+CD25 Treg cells, and for CD8+ T cell subgroup analysis. Flow cytometry was performed and annexin V binding was used for apoptotic cell evaluation. RESULTS: In patient group, the percentage of CD8+CD28- cells among lymphocytes was elevated, and there was also an increase in the CD28-/CD28+ cell ratio among CD8 lymphocyte population. The distribution of CD8 cells was different in lung cancer patients when compared with the control group. The absolute count of CD4+CD25(bright) cells and the percentages of these cells among total lymphocytes were higher in the patient group. The Annexin V(+) cell percentages among CD8+CD28- and CD8+CD28+ lymphocytes were higher in the patient group than in the control group. No differences were found between the NSCLC and SCLC patients with respect to the hematological parameters and the distribution of lymphocyte subgroups. In NSCLC patients, the percentage of CD8+CD28- cells among the lymphocyte population was higher in patients with stage IV than those with stage III. CONCLUSION: These findings may reflect the possibility of tumor-induced immunosuppression and they should be complemented with further studies.

Hemicentral retinal artery occlusion in a breast cancer patient using anastrozole.

BACKGROUND: Anastrozole, an aromatase inhibitor, is commonly used in the adjuvant treatment of breast cancer. Anastrozole treatment is associated with a risk of thromboembolic events and retinal vascular side effects. Herein, we present a case of hemi-central retinal artery occlusion diagnosed in a breast cancer patient using anastrozole. CASE REPORT: A 53-year-old woman with a hypertensive and diabetic background was admitted to our hospital with breast cancer. Anastrozole treatment was started after surgery, adjuvant chemotherapy, and radiotherapy. Sudden painless loss of vision in the patient's right eye occurred within 13 months of Anastrozole treatment. A fluorescein angiogram revealed hemi-central retinal artery occlusion. CONCLUSION: To the best knowledge of the authors, this is the first report of hemi-central retinal artery occlusion in an anastrozole user.

Cerebrovascular accident after chemotherapy for testicular cancer.

Arterial thromboembolic events are not common after chemotherapy. We present a case of a cerebrovascular accident, which developed after chemotherapy in a patient with a germ cell tumor. A 34-year-old man with a testicular germ cell tumor who did not have any comorbid disease was admitted to hospital. After a radical inguinal orchiectomy, BEP (bleomycin, etoposide, and cisplatin) chemotherapy regimen was given. On the 10th day of the third cycle, aphasia and hemiplegia developed. Cerebrovascular accident was diagnosed. This event is a rare complication in a patient receiving BEP chemotherapy who did not have cardiovascular disease or thromboembolic risk factors.

Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma.

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with L-ornithine-L-aspartate, a remarkable improvement in the level of patient's sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient's condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.

Results of combination therapy with amifostine, pentoxifylline, ciprofloxacin and dexamethasone in patients with myelodysplastic syndrome and acute myeloid leukemia.

Myelodysplastic syndrome (MDS) is a clonal disease of the bone marrow characterized by abnormal hematopoiesis and cytopenias. It has been shown that abnormal cytokine production together with apoptosis are major contributors to the cytopenias associated with the disorder. As the interaction of cytokines plays a role in the pathogenesis, suppression of the cytokine production by the administration of the combination of pentoxifylline, ciprofloxacin, and dexamethasone (PCD combination) has resulted in the correction of at least some aspects of the cytopenias in the majority of patients and in complete hematologic remission in a small percentage. The aminothiol prodrug amifostine, a compound to protect tissues from cytotoxic drugs and radiotherapy has been found to stimulate proliferation of normal hematopoiesis and suppress apoptosis in patients with MDS. In this study we report the results of combination therapy of amifostine and PCD in 12 patients with MDS and acute myeloid leukemia (AML). Amifostine was given in a dose of 200 mg/m(2), as an i.v. infusion administered in 10 min, three times a week; pentoxifylline 2400 mg/day, (3 x 800 mg) p.o.; ciprofloxacin, 1 g/day p.o.; dexamethasone 4.5 mg/day p.o. We achieved 66% response rate in our patients. In some cases responses were achieved in only thrombocytopenia or anemia whereas in others responses were achieved in multiple series. As a result it was found that amifostine + PCD combination may be beneficial in reversing cytopenias in the treatment of MDS and AML and is worth further study.

Closing the manufacturing process of dendritic cell vaccines transduced with adenovirus vectors.

Anticancer immunotherapy using dendritic cell (DC) based vaccines provides an adjuvant therapeutic strategy that is not cross reactive with conventional therapeutics. However, manufacturing of DC vaccines requires stringent adherence to Good Manufacturing Practice (GMP) methods and rigorous standardization. Optimally this includes a closed system for monocyte isolation, in combination with closed culture and washing systems and an effective vector transduction strategy. In this study, we used the Gambro Elutra to enrich monocytes from non-mobilized leukapheresis products collected from healthy donors. This approach enriched monocytes from an average frequency of 13.6+3.2% (mean+SEM), to an average frequency of 79.5+4.3% following enrichment with a yield of 79 to 100%. The monocytes were then cultured in a closed system using gas permeable Vuelife fluoroethylene propylene (FEP) bags and X-vivo-15 media containing 10 ng/ml granulocyte-macrophage colony-stimulation factor (GM-CSF) and 5 ng/ml Interleukin (IL) 4. The cultures were re-fed on days two and four, with a 25% media volume and cytokines. Following culture for seven days, the cells were harvested using a Cobe-2991 and concentrated using a bench centrifuge retrofitted with blocks to allow centrifugation of 72 ml bags and supernatant removed using a plasma extractor. This approach reduced the media volume to an average of 17.4 ml and an average DC concentration of 6.3+1.0x10(7) cells/ml, a viability of 93.8+2.2%, a purity of 88.9+3.3% and a total yield of 8.5+1.4x10(8) DCs. Based on the identification of DR+ cells as DCs we had an average yield of 46+8% using a calculation based on the number of monocytes in the apheresis product and the resulting DCs differentiated from monocytes. The use of DCs as a vaccine, required transduction with an adenovirus (Adv) vector with the tumor suppressor, p53 transgene (Adv5CMV-p53) as the antigen at a DC concentration of 9x10(6) DCs/ml at an Ad5CMV-p53: DC ratio of 20,000:1, and a 2 or 3 hour co-culture, followed by a 1:10 dilution with media and an additional 16-22 hour incubation. Following incubation, the DCs were washed twice and the supernatants removed using a plasma extractor. The average viability after infection with Ad5CMV-p53 was 87.9+/-2.6% with an average of 20.3+5.4% of the DCs expressing p53. The calculated yield of DCs following Ad5CMV-p53 transduction, based on the number of monocytes in the apheresis products, averaged 12.4+3.8%. We conclude that it is possible to efficiently manufacture Adv transduced DCs using a functionally closed system.

Peripheral blood gamma-delta T cells in advanced-stage cancer patients.

Gamma-delta T (gammadelta T) cells form a subgroup which has been reported to play a role in both natural and acquired immunity. Their levels have been found to increase in some tumour tissues. The aim of this study was to investigate the ratio of gammadelta T cells to all T cells in the peripheral blood of advanced-stage cancer patients; the level of gammadelta T cells expressing the Vdelta2-T-cell receptor (TCR) chain; NKG2D receptor expression; and apoptotic (Annexin-V) gammadelta T-cell levels. Twenty patients with advanced-stage cancer and 13 healthy controls were included. No statistical differences were found between control and patient groups in terms of the gammadelta T/total T-cell ratio (P=0.53), the Vgamma2-TCR expressing gammadelta T-cell ratio (P=0.19) or the Annexin-V ratio (P=0.48). However, NKG2D expression in gammadelta T cells was significantly different between the control and patient groups (P=0.014). In summary it was shown that the levels of NKG2D receptors, which are responsible for the cytolytic effect of gammadelta T cells, were lower in cancer patients than in healthy adults. However, no significant differences were observed in the other parameters studied between groups.

Hyperbaric oxygen therapy does not potentiate doxorubicin-induced cardiotoxicity in rats.

The current use of doxorubicin is regarded as an absolute contraindication for hyperbaric oxygen (HBO2) therapy because of the increased risk of cardiotoxicity. The aim of this study was to investigate whether additional exposure to HBO2 during the course of doxorubicin treatment would further increase the cardiotoxicity of doxorubicin in rats. Female Wistar rats were treated with either HBO2 (n = 10) or doxorubicin (n = 8) or a combination of both treatments (n = 10) for 4 consecutive weeks and followed up for an additional 4 weeks. Cardiomyopathy was evaluated using two-dimensional and M-mode echocardiography at baseline, at the fourth, sixth and eighth weeks, and by histopathological investigation of the rat hearts at the eighth week. Doxorubicin treatment significantly reduced ejection fraction and fractional shortening (P < 0.001) and caused severe histopathological injury (P < 0.05) indicating development of cardiotoxicity. Although the combination of doxorubicin and HBO(2) also markedly reduced ejection fraction and fractional shortening (P < 0.001), this reduction was significantly less than that of doxorubicin treatment (P < 0.05). HBO2 therapy also attenuated doxorubicin-induced histopathological changes in rat hearts (P < 0.05). HBO2 alone did not alter echocardiographic parameters or histopathological findings (P > 0.05). In conclusion, HBO2 therapy does not potentiate doxorubicin-induced cardiotoxicity in rats. Cardioprotection conferred by HBO2 against doxorubicin warrants further investigation.

Results of paclitaxel (day 1 and 8) and carboplatin given on every three weeks in advanced (stage III-IV) non-small cell lung cancer.

BACKGROUND: Both paclitaxel (P) and carboplatin (C) have significant activity in non-small cell lung cancer (NSCLC). The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT) regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. METHODS: Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS) ECOG 0-2 were given P 112.5 mg/m2 intravenously (IV) over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. RESULTS: Median age was 58 (age range 39-77) and 41 patients (80%) were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1-6). Seven patients (14%) did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR) in 45% and stable disease (SD) in 18%. Twelve patients (24%) received local RT. Thirteen patients (25%) received 2nd line CT at progression. At a median follow-up of 7 months (range, 1-20), 25 (49%) patients died and 35 patients (69%) progressed. Median overall survival (OS) was 11 +/- 2 months (95% CI; 6 to 16), 1-year OS ratio was 44%. Median time to progression (TTP) was 6 +/- 1 months (95% CI; 4 to 8), 1-year progression free survival (PFS) ratio was 20%. We observed following grade 3 toxicities: asthenia (10%), neuropathy (4%), anorexia (4%), anemia (4%), hypersensitivity to P (2%), nausea/vomiting (2%), diarrhea (2%) and neutropenia (2%). Two patients (4%) died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%). CONCLUSIONS: P on day 1 and 8 and C every three weeks is practical and fairly well tolerated outpatient regimen. This regimen seems to be comparably active to regimens given once in every three weeks.

24-year-old female with amenorhea: bilateral primary ovarian Burkitt lymphoma.

OBJECTIVES: Burkitt's lymphoma (BL) occurs mostly in children. Isolated bilateral ovarian involvement presenting with amenorrhea is extremely rare in young adults. CASE: A 24-year-old female presented with secondary amenorrhea. Bilateral adnexal masses were identified on physical examination and abdominal computed tomography (CT). She underwent total abdominal histerectomy and bilateral salpingoophorectomy. Histopathologic evaluation yielded a diagnosis of BL of ovaries. Combined chemotherapy was administered. After complete remission an autologous bone marrow transplantation (ABMT) was performed. She died 35 days after ABMT. CONCLUSIONS: Although rare, BL should be kept in mind when isolated ovarian tumors are detected in young patients.

Breast cancer in association with thyroid disorders.

BACKGROUND: The relationship between breast cancer and thyroid diseases is controversial. Discrepant results have been reported in the literature. The incidences of autoimmune and nonautoimmune thyroid diseases were investigated in patients with breast cancer and age-matched control individuals without breast or thyroid disease. METHODS: Clinical and ultrasound evaluation of thyroid gland, determination of serum thyroid hormone and antibody levels, and fine-needle aspiration of thyroid gland were performed in 150 breast cancer patients and 100 control individuals. RESULTS: The mean values for anti-thyroid peroxidase antibodies were significantly higher in breast cancer patients than in control individuals (P = 0.030). The incidences of autoimmune and nonautoimmune thyroid diseases were higher in breast cancer patients than in control individuals (38% versus 17%, P = 0.001; 26% versus 9%, P = 0.001, respectively). CONCLUSION: Our results indicate an increased prevalence of autoimmune and nonautoimmune thyroid diseases in breast cancer patients.

Thrombotic thrombocytopenic purpura associated with ticlopidine.

Thrombotic thrombocytopenic purpura is a syndrome characterized by hemolytic anemia, thrombocytopenia, neurological symptoms, fever and renal dysfunction. Although the syndrome is usually associated with various infections, vasculitis and pregnancy, rarely can it be associated with certain neoplasms and drugs such as ticlopidine. A 63-year-old woman, who had undergone coronary angioplasty and had been started on ticlopidine, was admitted to our clinic with a history of vomiting, fatigue, hematuria and deterioration in her cognitive abilities. Thrombotic thrombocytopenic purpura was diagnosed on the basis of neurological changes, an increase in LDH, urea, creatinine, indirect bilirubin levels, anemia and peripheral smear findings. Treatment was initiated with daily plasmapheresis and complete clinical and laboratory recovery developed. The patient was discharged after 14 days.

Muscle metastasis as initial manifestation of epidermoid carcinoma of the lung.

Typical sites of squamous cell carcinoma of lung metastases include liver, brain, bones, pulmonary and adrenal glands. In advanced dissemination it can rarely involve the skeletal muscle. The patient in this case report was a 46-year-old man, with no significant medical history. He was admitted to hospital because of a large swelling on his left thigh. Investigations resulted in a diagnosis of primary squamous cell carcinoma of the lung. Biopsy of the left great adductor muscle produced similar pathology to that of the lung primary. This case report describes a skeletal muscle metastasis as the first sign of metastatic disease.

Acute myeloblastic leukemia achieving complete remission with amifostine alone.

Amifostine, a phosphorylated thiol-amine, is known as a cytoprotective agent especially for cisplatin containing chemotherapies. Apart from the cytoprotective role, Amifostine could also be used in the treatment of hematologic malignancies such as myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML), as a treatment option or for potentiating the effects of cytotoxic agents. We tried to use Amifostine in a patient with AML, which did not respond to conventional cytotoxic chemotherapy and aimed to publish the results. The patient was a 77-year-old male patient, he was diagnosed as AML by peripheral blood smear and bone marrow aspiration. Treatment commenced with low dose cytosine arabinoside (Ara-C) but the therapy should have ceased due to patient intolerance. The patient refused further therapy and he was offered to have Amifostine treatment. Amifostine was administered 200 mg/m2 three times a week, with ciprofloxacin, pentoxifyllin and dexamethasone. Dramatic response was obtained after 8 weeks of administration. Blast rate was reduced from 35 to 7% in bone marrow aspiration; pancytopenia was restored to normal levels. This remission was maintained through 8 more weeks. Amifostine treatment was restarted after he relapsed but this time he did not respond to the treatment and died of gastrointestinal bleeding on the 8th week of treatment.

A Case Report: Large Granular Cell Leukemia/Lymphoma (LGL).

We presented a 64-year-old male patient with T-large granular cell leukemia/lymphoma with an agressive clinical course. Large granular lymphocytes were noted on peripheral blood smear. The phenotyping of the cells was typical T-cell lineage [CD2 (+), CD3 (+), CD5 (+)]. Clonal rearrangement of the T-cell receptor gene (TCR) was demonstrated by DNA hybridization technique. Large granular cell leukemia/lymphoma is a distinct entity with spesific clinicobiological aspects. The clinical spectrum is wide and immunophenotyping and genotyping studies need to make a diagnosis.