How do cancer patients refuse treatment? A grounded theory study.

BACKGROUND: All cancer patients, except for a small fraction, seek treatment after becoming aware of the disease. That small fraction do not seek any treatment due to various reasons, and this phenomenon is unknown to us. Therefore, the present study aimed to discover the reasons for treatment refusal in cancer patients. METHODS: This qualitative grounded theory study was conducted on 22 participants including patients, caregivers, physicians, and nurses. Purposive theoretical sampling was employed. Data were collected through in-depth interviews. All interviews were gradually transcribed and analyzed. Data analysis was carried out through the three-step method of open, axial, and selective coding and was continued until theoretical saturation. Straussian Grounded Theory was used for data analysis. RESULTS: A total of 4 themes and 20 sub-themes were extracted in this study. The core variable extracted from the interviews was "resilience" Other related themes included encounter with cancer, fighting cancer, and coping with cancer. The findings showed that in the context of fighting cancer, patients lost their resilience through various processes and refused treatment. CONCLUSION: Cancer patients abandon the treatment in silence, oncologists and even family members being unaware of the matter. In other words, refusal of treatment is like an iceberg and the majority of the patients who have abandoned treatment are unknown to the health system. The model obtained in this study can increase the knowledge of the process that leads patients to lose their resilience against cancer and abandon treatment, which can increase the possibility of recognizing and predicting treatment refusal for oncologists.

Sildenafil for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: A Phase I/II Randomized Clinical Trial, SILDAT-TAHA6 Trial.

Background: Previous animal studies have shown a protective effect of 5-phosphodiesterase inhibitors on cancer therapeutics-related cardiac dysfunction (CTRCD) of anthracyclines. Aim: The aim of this study was to evaluate the clinical effect of sildenafil on the primary prevention of CTRCD in human. Materials and Methods: In this randomized double-blind clinical trial, the primary end point was efficacy in preventing the reduction of left ventricular ejection fraction (LVEF). The intervention group patients received sildenafil at a dose of 25 milligrams twice a day before starting the chemotherapeutic regimen, and the control group received placebo. All the patients at baseline and after the 6-month follow-up underwent 4D and speckle-tracking echocardiography and cardiac MRI, accompanied by hs-troponin I and NT-Pro-BNP measurement. Results: Sixty patients were enrolled in this study, and data from 52 patients (24 patients in the intervention group and 28 patients in the control group) were used in the final analysis. Our findings showed that in the intervention and control groups, LVEF was dropped from 61.28 ± 7.36 to 51.57 ± 7.67 (difference (D) = -9.71 ± 11.95, p=0.003) and from 57.9 ± 7.29 to 50.2 ± 7.02% (D = -7.7 ± 5.93; p=0.001), respectively (between-group difference = -2.01%, p=0.26). CTRCD was detected in 11 patients in the control group (42.8%) and 10 in the intervention group (41.6%, p=0.51). Conclusion: Consumption of sildenafil for primary prevention of anthracycline-induced cardiac toxicity seems to be unbeneficial. This trial is registered with IRCT20180506039554N1.

Autologous Natural Killer Cell-enrichment for Immune Cell Therapy: Preclinical Setting Phase, Shiraz Experience.

Natural killer (NK) cell therapy has proven to be a promising approach for the treatment of malignancies. Osaki method for ex-vivo autologous NK cell expansion has been recently introduced in Japan. To start clinical trial phase I at Shiraz University of Medical Sciences in collaboration with the Japanese group, this preclinical setting study aimed to evaluate the proliferative efficacy of the method, the activation status of expanded autologous NK cells, and the likely unwanted contamination of the final cell product. Peripheral blood mononuclear cells (PBMCs) were isolated from 5 healthy individuals' peripheral blood and transferred directly to the specified initial culture bag containing anti-CD52 and anti-CD3 and Interleukin (IL)-2. The cells were cultured for 14-17 days in an incubator, during which the cells received condition media, and underwent several passages into bigger culture bags. All the procedures were carried out in a cleanroom and associated facilities. Before and after activation PBMCs were analyzed for their phenotype and cytotoxic activity; using flow cytometry and cytokine release assay. Our results indicated that NK (CD3-CD16+/-CD56+) cells were expanded 510-fold on average (range 200-1100 fold), and the purity of NK cells per whole lymphocytes exceeded 68%. The expanded cells were highly lytic as indicated by in-vitro cytotoxic assay, with a strong expression of Natural killer group 2 member D (NKG2D) and CD16. The prepared final cell products were negative for HCV, HBV, HIV, mycoplasma, and endotoxin. In the preclinical phase, large numbers of activated and un-contaminated NK cells from healthy individuals' peripheral blood were successfully generated. The method seems to provide ample clean cell product with no contamination and has the potential to be used for NK cell therapy in future clinical trials, suitable to be infused back to the donors in phase I clinical trial.

Kaposi Sarcoma After Allogeneic Hematopoietic Stem Cell Transplant: A Rare Complication.

Kaposi sarcoma is a multicentric angioproliferative neoplasm of lymphatic endothelium-derived cells. Although this malignancy is relatively frequent after solid-organ transplant, it is extremely rare after bone marrow transplantation. Allogeneic stem cell transplantation is associated with severe prolonged immunosuppression; however, a few cases of Kaposi sarcoma after hematopoietic stem cell transplant were previously reported. Here, we report a case of Kaposi sarcoma after haploidentical allogeneic hematopoietic stem cell transplant. The patient was a known case of acute myelogenous leukemia and underwent transplant after relapse. Four months posttransplant, she presented with 3 dark blue or purplish small nodules on her face above the upper lip. Histopathologic study confirmed Kaposi sarcoma. Serum antibody against human herpes virus type 8 was positive. After discontinuation of immunosuppressive medication and cryotherapy for local control, Kaposi sarcoma skin nodules healed with residual pigmented skin lesions. The patient is currently in complete remission for Kaposi sarcoma and cured from acute myelogenous leukemia 36 months after stem cell transplant. Only 14 cases of Kaposi sarcoma after hematopoietic cell transplant have been previously reported in the literature (11 after allogeneic and 3 after autologous hematopoietic stem cell transplant). According to our knowledge from literature review, this case is the first report of Kaposi sarcoma after a haploidentical HLA match transplant.

Glucocorticoid induced diabetes and lipid profiles disorders amongst lymphoid malignancy survivors.

BACKGROUND AND AIMS: Hyperglycemia and glucose test abnormalities are problems during the treatment of patients with lymphoid malignancy, caused by corticosteroid therapy. However, its long-term complications or risk of developing diabetes are not available. METHODS: Two hundred patients with lymphoid hematologic malignancy were recruited and followed up for median of 47 months. The underlying hematologic malignancy includes Hodgkin's disease (HD), Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia(CLL), Multiple Myeloma (MM) and Acute Lymphocytic Leukemia (ALL). Fasting blood sugar, glucose tolerance test and lipid profiles were measured before each chemotherapy cycle and every 3 months after. This study was designed to evaluate patients for long-term follow up of glucose tests abnormalities. RESULTS: The mean age of the non-diabetic patients was significantly lower than that of diabetics and patients with fasting glucose disorder (p < 0.001). The prevalence of diabetes and impaired FBS and GTT was higher in NHL (9%), CLL (6.5%) and MM (1.5%), respectively. For lipid profiles, the highest levels of cholesterol and triglycerides were observed in multiple myeloma and the lowest in Hodgkin's lymphoma (P:0.004). CONCLUSIONS: The most important factor for steroid-induced diabetes is age, which was more prevalent with age increase (P < 0.001). Glucocorticoid-induced diabetes is common in multiple myeloma and then in chronic lymphocytic leukemia and non-Hodgkin's lymphoma in comparison with Hodgkin's lymphoma and acute lymphoblastic leukemia.

Economic Burden of Avoidable Hospitalizations among Patients with Cancer at Namazi Hospital in Shiraz, 2013

Introduction: Hospitalization of patients with cancer has a significant economic impact and avoidance where unnecessary has great potential for significant cost savings for patients, individual hospitals and the health system in general. Methods: Demographic, clinical and economical data were collected from medical records in our hospital retrospectively. Oncology clinicians reviewed medical records to categorize each hospitalization as "potentially avoidable" or "not avoidable." Patient demographic and clinical data were abstracted and quantitative and qualitative analyses were performed to identify patient characteristics and outcomes associated with potentially avoidable hospitalizations. Finally data on the cost of the latter were estimated. Results: Of 451 hospitalizations, medical oncologists identified 55 (12.2%) as potentially avoidable. Avoiding these and caring for the patients in alternative locations would save some $ US 641,240 yearly. Among patients with avoidable hospitalization, 70.9% were males and the median age and median length of stay was 55 years and 4.7 days. Most of them had general signs (83.6%) and a fever body temperature lower than 38.5'C (96.4%). Lung, kidney and urinary tract cancers were the most common diagnoses (10.9%). The majority of avoidable hospitalized patients had local cancer (85.5%) and poor performance status (43.6%). The most prevalent procedure for patients with avoidable hospitalization was sonography and the least frequent were laboratory tests and MRI. Most cases received no treatment. Conclusion: Avoidable hospitalizations are common in patients with cancer. Age, final results of hospitalization and length of stay were established as significant variables for patients with avoidable hospitalization.

Glomus tumor as a cause of oncogenic osteomalacia.

Many tumors that occasionally are benign in origin causes hypophosphatemic osteomalacia. Here we present a case of glomus tumor in a 59-year-old man with oncogenic osteomalacia. Diagnosis was made after observation of abnormal increase activity in octreotide scan. The magnetic resonance imaging showed a round lesion in left ankle joint. Surgical excision of tumor was curative and all symptoms and intractable hypophosphatemia improved after few weeks.

Signs, Symptoms and Complications of Non-Hodgkin's Lymphoma According to Grade and Stage in South Iran.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is a heterogeneous type of neoplasm of the lymphatic system. To have a more accurate and early diagnosis we need to know signs, symptoms and complications of lymphoma in early stages besides pathology and immunohistochemistry. MATERIALS AND METHODS: This prospective study included 110 cases of NHL that were followed since February 2012 till November 2013. Biopsies were taken from all the patients besides bone marrow study. Signs and symptoms were categorized into "B" symptoms, general, lymphadenopathy and extranodal involvement and we compared the frequencies by stage and grade. RESULTS: Of 110 cases, 88.9% had B-cell and 11.1% T-cell type with mean age 48.5±18.6 years. "B" symptoms and lymphadenopathy were more common in men. Cervical lymphadenopathy was the most common sign (44.8%). and hematologic, bone marrow, bone and neurologic lesions were the most common complications. All complications were more common in males. "B" symptoms were seen mostly in stage III, general signs and symptoms in stage IV, and lymphadenopathy in stage II. Intermediate grade was also the most common in all signs and symptoms. In this study 12 (10.9%) patients had relapse, with neurologic and bone marrow as the most common sites of tumor recurrence. CONCLUSIONS: There is a meaningful relationship between male gender for NHL and anemia that can be due in part to higher incidence of bone marrow involvement and stage IV disease in male cases. We also found a strong relationship between low grade NHL and age. On the other hand extranodal involvement is more common in female groups.

Conjunctival mass as an initial presentation of mantle cell lymphoma: a case report.

BACKGROUND: To describe a rare manifestation of mantle cell lymphoma (MCL) in conjunctiva, with clinical, hisologic, immunohistologic and genetic findings together with review of the Literature. CASE PRESENTATION: Most ocular adnexal lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). A few cases of ocular adnexal mantle cell lymphomas have been reported in the literature. We present a case of mantle cell lymphoma presenting as right conjunctival mass of at least three months duration in a 64-year-old man. Histopathologic examination showed a proliferation of monomorphous small-to-medium-sized lymphoid cells with cleaved nuclei in the subconjunctiva. By immunohistochemistry, the infiltrate was positive for CD20, CD5, BCL-2, cyclin D1, and the transcription factor SOX11. Fluorescent in situ hybridization demonstrated the presence of IGH-CCND1 fusion indicating t(11;14). CONCLUSION: A rigorous approach to initial diagnosis and staging of small cell lymphomas of the ocular adnexa is needed. The recognition of ocular MCL requires appropriate immunohistochemical staining and/or genetic confirmation to differentiate this rare form of presentation of MCL from other more frequent small cell lymphomas.

Autologous noncryopreserved hematopoietic stem cell transplant with CEAM as a modified conditioning regimen in patients with Hodgkin lymphoma: a single-center experience with a new protocol.

OBJECTIVES: A BEAM regimen including carmustine (BiCNU: bis-chloroethyl nitrosourea), etoposide, cytarabine (cytosine arabinoside), and melphalan is a widely used conditioning regimen for autologous stem cell transplant in patients with Hodgkin lymphoma. We report the results of noncryopreserved autologous stem cell transplant of 45 patients with Hodgkin lymphoma given an alternative regimen, modified BEAM-like regimen (CEAM regimen: lomustine, etoposide, cytarabine, and melphalan), in which carmustine (BiCNU IV) was substituted by oral lomustine (CCNU: 2 chloroethyl cyclohexyl nitrosourea). PATIENTS AND METHODS: Forty-five eligible patients with relapsed/refractory Hodgkin lymphoma were consecutively enrolled and underwent conditioning regimen with BEAM-like regimen protocol as follows: Lomustine 200 mg/m(2) on day -3; etoposide 1000 mg/m(2) on day -3 and -2; cytarabine 1000 mg/m(2) on days -3, -2; and Melphalan 140 mg/m(2) on day -1. RESULTS: All 45 patients showed engraftment of infused stem cell, and there was no graft failure in the study group. The median mononuclear cell dose was 3.4 × 10(8). The median time to absolute neutrophil count > 0.5 × 10(9)/L was 11 days, and the median time to platelet count > 20 × 10(9) was 14 days. Grade 2 and grade 3 mucositis was seen in 64.5% our patients. Transplant-related mortality at 100 days occurred in 1 patient (2.2%). With a median follow-up of 27 months, median disease-free survival was 20 months, mean overall survival was 27 months, and median overall survival has not yet been reached. CONCLUSIONS: These data demonstrate the safety and feasibility of BEAM-like regimen as a new and modified regimen; longer follow-up is required to evaluate fully efficacy and long-term safety of our method.

Non-cryopreserved hematopoietic stem cell transplantation in multiple myeloma, a single center experience.

Several clinical trials have shown the superiority of high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) over conventional dose therapy for patients with multiple myeloma. There is limited experience with non-cryopreserved autologous hematopoietic stem cell transplantation. Between January 2004 and February 2010, we treated 38 patients with myeloma (mean age = 50.6) with a preparative regimen of Melphalan 140-200 mg/m(2) and non-cryopreserved ASCT. All the apheresis products were kept in a conventional blood bank refrigerator at 4°C for 2 d before infusion. The median time to platelet count of >20 × 10(9) /L was 13 d (range 10-31). Also, the median time to absolute neutrophil count >0.5 × 10(9) /L was 11 d (range 9-21). All the 38 patients were engrafted and there was not graft failure in this study group. Twenty-nine of 38 (76.3%) patients are alive and without disease activity after a median follow-up of 31 months (range 6-77). Responses (complete and partial response) were seen in all the 38 patients. The median progression-free survival was 27 months with 95% confidence interval 23.52-30.48, whereas the median overall survival was 30 months. One hundred days transplant-related mortality was 0%. HDT and autologous transplantation without cryopreservation is an effective and safe method which simplifies the procedure and is feasible and cost saving in our patients.

Early diagnosis of systemic candidiasis in bone marrow transplant recipients.

OBJECTIVES: Systemic candidiasis, are common infections during the neutropenic phase. The aim of this study was to identify quantitative Candida species ribosomal DNA using TaqMan technology for diagnosing candidiasis and monitoring them during hospitalization. MATERIALS AND METHODS: During the prospective, cross-sectional study, from September 2006 to September 2007, a total of 375 clinical blood specimens were collected from 35 patients with hematologic disorders once a week pretransplant and posttransplant. Patients were evaluated for systemic candidiasis during hospitalization. Cultures from the throat, urine, feces, and sputum, along with sonography and computerized tomographic scans, were done when patients were febrile and not having a response to antibiotics. All samples were cultured on Sabouraud dextrose agar with chloramphenicol, and direct, microscopic examination was performed. Blood samples were cultured by bedside inoculation into BACTEC medium at 35 degrees C for 7 days. Clinical blood specimens were evaluated for Candida infections using the TaqMan-based PCR assay. RESULTS: Of the 35 recipients, 6 had multiple samples that were TaqMan-positive with Candida species probe, 3 had 1 PCR positive-result in their blood samples, and the 26 recipients showed negative results. Fungal rDNA was found in 2 patients before and after transplant. All 6 patients with systemic candidiasis had microbiologic and/or radiologic evidence of Candida infections. CONCLUSIONS: It seems that TaqMan-based PCR assay can serve as an accurate method for diagnosing and monitoring Candida infections. This is the first report of its kind that shows Candida infections can be present in the blood of the bone marrow transplant candidates, so closer observation of the recipients who are neutropenic and receive immunosuppressive drugs seems warranted to improve their chances for survival.

Results of hematopoietic stem cell transplant in Shiraz: 15 years experience in southern Iran.

OBJECTIVES: Over the past 2 decades, hematopoietic stem cell transplant has evolved from an experimental procedure to the standard of care, and it is integrated into the management of many diseases. Hematopoietic stem cell transplant was established at Shiraz University of Medical Sciences in 1993. Here, we describe 15 years experience with stem cell transplant at our center in southern Iran. We provide information on indication, donor type, conditioning chemotherapy regimen, outcome, survival, and long-term follow-up in our stem cell activity. PATIENTS AND METHODS: From May 1993 to October 2008, 423 patients underwent allogeneic (n=311) and autologous (n=112) stem cell transplants at our center. For allogeneic stem cell transplant, the conditioning chemotherapy regimen comprised busulfan, cyclophosphamide, and antithymocyte globulin for thalassemic patients; busulfan and cyclophosphamide for leukemia patients; and cyclophosphamide and antithymocyte globulin for patients with aplastic anemia. RESULTS: During this period, 155 B-thalassemia major patients (mean age, 9.5 years; range, 2-20 years) underwent allogeneic marrow transplant. Of 155 patients with a diagnosis of thalassemia major, 112 are alive (72%) with full engraftment after a median follow-up of about 8.1 years (range, 12-184 months). During this time, 127 leukemia patients including acute myelogenous leukemia (n=68), acute lymphoblastic leukemia (n=30) and chronic myelogenous leukemia (n=29), received allogeneic stem cell transplant. In this group, long-term, disease-free survival (cure rate) was 67%, 60%, and 62%. CONCLUSIONS: These data reflect the important role of hematopoietic stem cell transplant in improving survival for a variety of hematopoietic system disorders at our center in Southern Iran. In patients with B-thalassemia major hematopoietic stem cell transplant seems to be the treatment of choice, because it leads to a cure in all classes (Lucarelli risk group, I-III). Based on high success rates in patients with class II and III thalassemia with the addition of the antithymocyte globulin to conditioning regimen of stem cell transplant, we also recommend using this new method of conditioning in transplant of thalassemia patients.