Evaluation of Central Nervous System Relapse in Adults with Acute Lymphoblastic Leukemia (ALL) Receiving Hyper-CVAD Treatment in Seyyed Al-Shohada Hospital: Isfahan, 2014-2019.

Background: Recurrence of ALL in the central nervous system, CNS Relapse, is known as a poor prognostic factor. Few studies have been performed on the CNS Relapse in adults with ALL. This study aimed to evaluate the recurrence of acute lymphoblastic leukemia in the central nervous system, CNS relapse, in adults with ALL. Materials and Methods: Seventy newly diagnosed patients with acute lymphoblastic leukemia aged 15 years and older referred to Seyyed Al-Shohada Hospital in Isfahan between 2014 and 2019 were included in this study. All patients treated with the Hyper-CVAD regimen underwent prophylaxis for the central nervous system based on the risk of CNS relapse. All study participants with CNS relapse underwent intrathecal chemotherapy. Results: The median age of patients was 34 years. Four patients (5.7%) had primary central nervous system involvement. Out of 70 patients receiving the Hyper-CVAD regimen, 59 (84.2%) achieved complete remission. Of the 59 patients achieving CR, ten (16.94%) developed CNS relapse. The median duration of CR before CNS relapse was 21 weeks. Out of 10 patients with CNS relapse, seven (70%) achieved complete remission. Of seven patients achieving CR in the central nervous system, one had a second recurrence in the central nervous system, but finally achieved CNS complete remission. The median survival of patients after CNS relapse was four months. The results also showed that out of 10 patients with CNS relapse, four (40%) survived one year. Conclusion: This study shows that the prognosis of CNS relapse in adults with ALL has not improved much. Limited studies have been conducted on the recurrence of the central nervous system in adults with acute lymphoblastic leukemia. Therefore, further studies on CNS relapse after complete remission of ALL are required to clarify more details.

The Effect of Dextrose Hypotonic vs Saline Hydration on Methotrexate-Induced Nephrotoxicity in Male and Female Rats.

Background: High-dose methotrexate (HDMTX) as a cytotoxic agent might cause various side effects. Hyperhydration has been implemented as the major strategy to decrease the potential risk of toxicities induced by HDMTX. This study aims to assess the renoprotective effect of hydration with dextrose water (DW) 5% versus normal saline (N/S) 0.9% against methotrexate (MTX) induced nephrotoxicity. Materials and Methods: This experimental animal study has been conducted on 36 Wistar rats (200-250 g) categorized into six groups, including male (n = 6) and female (n = 6) rats receiving sodium chloride 0.9% saline plus MTX, DW 5% plus MTX, or MTX alone. By the fifth day after the MTX injection, biochemical indexes were measured. The rats were also sacrificed and renal specimens were evaluated microscopically to determine kidney tissue damage (KTD). Results: The groups were not significantly different with regard to blood urea nitrogen (BUN) (P = 0.5), creatinine (Cr) (P = 0.24), kidney weight (P = 0.34), and urine flow (UF) (P = 0.5), while KTD score was remarkably less in the hydrated groups (P < 0.001). Weight loss in DW-treated rats was significantly more than N/S-treated ones, and creatinine clearance (CrCl) and urine load (UL) of Cr were statistically similar between males and females in the control group, but significantly lower among the DW5% treated males. Conclusion: Based on the findings of this study, hydration with N/S was superior to DW5% for the prevention from HDMTX-induced nephrotoxicity. Besides, we found insignificant differences between male versus female rats in response to the hydration for HDMTX-induced renoprotection; however, females probably benefit more.

Prognostic Factors and Outcome of Patients with Adult Acute Lymphoblastic Leukemia Treated with the Hyper-CVAD Regimen: A Retrospective Study.

Aim: The Hyper-CVAD regimen has shown promising results for adult patients with acute lymphoblastic leukemia (ALL), as designed by the MD Anderson Cancer Center (MDACC). This treatment has resulted in a complete remission rate of 92% and a 5-year overall survival of 38%. However, given the diversity of patient demographics and institutional methods, outcomes may differ between various institutions. This study will compare the outcome of adult ALL patients treated with the Hyper-CVAD regimen in Iran with those obtained in the original series presented at the MDACC. Patients and Method. In this retrospective study, we evaluated the 2-year leukemia-free survival (LFS) and the 2-year overall survival (OS) of 70 ALL patients treated between 2014 and 2019 in the Seyed Al-Shohada Hospital in Isfahan, Iran. Results: In total, 59 ALL patients (84.28%) achieved complete remission (CR). The CR rate had statistical differences by bone marrow transplantation (BMT) and WBC count. The 2-year LFS and OS were 40% and 42%, respectively. There were significant differences in LFS and OS by BMT, myeloid marker, and WBC count. Conclusion: The outcome of the traditional Hyper-CVAD regimen in treating adult ALL was not satisfying. More efficient therapies should be applied for the treatment of adult ALL.

The feasibility of PETHEMA ALL-96 regimen on treatment of patients with acute lymphoid leukemia.

Background: Asparaginase-based treatment regimen for acute lymphocytic leukemia (ALL) is considered as feasible, but there is still a lack of data. In this study, considering the results of other regimen that were not optimum in previous studies. Here, we aimed to investigate the feasibility of PETHEMA ALL-96 treatment regimen. Materials and Methods: This is a retrospective feasibility study that was performed in 2019-2021 on 13 patients diagnosed with B-cell ALL. Patients were treated by PETHEMA ALL-96 regimen during induction, consolidation, reinduction, and maintenance phases. Patients were followed for 2 years after initiation of PETHEMA ALL-96 regimen for disease-free survival (DFS) and overall survival (OS) of all patients were evaluated after 2 years. Results: Data of 11 patients were analyzed. Within 28 days after treatments, all patients (100%) had no blasts in the bone marrow that was considered as complete remission (CR). The CR rate was 100% within 6 months and 12 months and 81.8% within 2 years after the treatments. Evaluation of OS, CR, and DFS regarding 6, 12, and 24 months showed 100% for all items after 6 and 12 months. After 24 months, the CR was 90.9%, the OS was 81.8% and the DFS was 90.9%. None of the patients died during the induction phase and during the 12 months study. No side effects were observed. Conclusion: The PETHEMA ALL-96 had high feasibility and survival rates with no side effects during the study course. It is believed that PETHEMA ALL-96 regimen has beneficial outcomes in young patients with ALL.

Bacterial spectrum and antimicrobial resistance pattern in cancer patients with febrile neutropenia.

BACKGROUND: Bloodstream infections are serious complications in neutropenic cancer patients. There has been a universal pickup in multidrug resistant (MDR) strains. For individuals who are at high risk for infections caused by MDR bacteria, a novel de-escalation strategy has been developed. Determine the bacterial spectrum and antibiotic resistance pattern in febrile neutropenic cancer patients was the goal of this investigation. MATERIALS AND METHODS: From 2019 to 2020, 60 cancer patients with febrile neutropenia who were sent to Isfahan's Omid Hospital were included in this retrospective analysis. Experiments were done on the antimicrobial susceptibility of isolated bacterial infections. RESULTS: The patients' average age was 43.35±15.59 years. Ninety-one percent (55/61) of the 60 patients had hematologic malignancies, and 8.3 percent (5/61) had solid tumors. The majority of the germs were gram-negative bacteria (66.7 percent). E. coli was the pathogen that was isolated the most frequently (26.7%), followed by Klebsiella (16.7 percent). In addition, the most prevalent identified Gram-positive bacteria was Staphylococcus epidermidis (21.7 percent). Third-generation cephalosporin (ESBL-E) resistance was present in 50% of E. coli, along with 50% resistance to cotrimoxazole, ciprofloxacin, and piperacillin, 31% resistance to amikacin, and 20% resistance to meropenem (CRE). They had an 80% sensitivity to amikacin and a 70% sensitivity to ciprofloxacin. Ten percent of our patients had antibiotic resistance in the antibiogram (XDR). CONCLUSION: In summary, most bacterial infections were resistant to different medications. The emergence and spread of Gram-negative bacteria that are resistant to antibiotics can be stopped by prudent antibiotic use.

Thalidomide for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Clinical Trial.

Background: Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2. Materials and Methods: An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission. Results: From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7-10.3), as compared with days 5.3 (95% CI, 1.7-8.9) with control (odds ratio 0.01; 95% CI, -1.58-1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55-27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05). Conclusion: This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.

Patient and Physician Perspectives in the Management of Immune Thrombocytopenia in Iran: Responses from the ITP World Impact Survey (I-WISh).

Data describing physicians' and patients' perspectives towards immune thrombocytopenia (ITP) management and impact of disease in Iran are limited. This ITP World Impact Survey was conducted between October 2019 and October 2020. Of the 114 patients included in the survey, 17 were aged ≤18 years. Forty-seven physicians, including 22 pediatric hematologists, participated in the survey. Fatigue and anxiety around stable platelet counts were frequent patient-reported symptoms at diagnosis and at survey completion. According to physicians, "watch-and-wait" was the preferred treatment option for mean (standard deviation) proportion of 50.1 (24.1) and 48.6 (21.8) of their adult and pediatric patients, respectively, following first diagnosis. Per adult and pediatric hematologists, the most prescribed treatments for newly diagnosed patients based on available answers were steroids (100%, n = 20/20; 89%, n = 16/18), respectively. Forty percent of adult (n = 10/25) and 38% of pediatric hematologists (n = 8/21) reported that ITP reduced patients' quality of life. Energy levels (46%, n = 52/112) and ability to concentrate on everyday activities (42%, n = 47/113) were the most affected aspects of patients' lives. This I-WISh study in Iran underlined the negative impact of ITP on patients.

A comparative study of the effects of multimedia training materials on mini CEX scores of internal medicine residents in Isfahan University of Medical Sciences.

BACKGROUND: Role of multimedia training materials on Mini-CEX scores of internal medicine residents. We aimed to assess the effect of multi multimedia training materials on Mini-CEX scores of internal medicine residents of Isfahan University of Medical Sciences. SETTINGS AND DESIGN: A quasi-experimental action research study on 1st, 2nd, and 3rd-year internal medicine residents were implemented. MATERIALS AND METHODS: The Mini-CEX test measures students' performance in six core skills necessary for medical practice. Mini-CEX scores of 135 internal medicine residents in 2017-2018 were compared before and after the training with prepared multimedia materials. We used repeated measured ANOVA and Mann-Whitney U test to compare the distribution of Mini-CEX scores across corresponding groups. Analysis was done using the SPSS software version 23 (IBM SPSS Statistics for Windows. Armonk, NY, USA: IBM Corp). RESULTS: The median Mini-CEX score (IQR) of students in preintervention and postintervention groups were 16.14 (5.19) and 19.62 (3.13), respectively. Findings of this study showed a significant increase in mini-CEX scores of the groups who used the multimedia learning material compared to those who did not use it (P < 0.001). CONCLUSIONS: Multimedia learning resources demonstrated a promising influence on internal residents' mini-CEX scores in this study. They demonstrate significantly greater performance after using multimedia learning materials compared to their same-year residents who did not benefit from it. This demonstrates the favorable effect of multimedia on the acquisition of practical skills such as obtaining a history or performing a physical examination.

The Prevention of Cisplatin-Induced Nephrotoxicity: A General Consensus Statement of a Group of Oncologist-Hematologists, Adult and Pediatric Nephrologists, Radiation Oncologists, Clinical Pathologists, Clinical Pharmacologists, and Renal Physiologists on Cisplatin Therapy in Cancer Patients.

Backgrounds: Most of the cancer patients with solid tumor are subjected to chemotherapy with cisplatin (CP) in clinic. However, the most side effect of CP is nephrotoxicity, which limits the treatment. The aim of study was to develop a general consensus statement for CP therapy in clinic to limit the drug-induced nephrotoxicity. Methods: A total of 30 oncologist-hematologists, adult and pediatric nephrologists, radiation oncologists, clinical pathologist clinical pharmacologist, and renal physiologist participated in a workshop, and in order to reduce the incidence of CP-induced nephrotoxicity, a general consensus was developed. Results: The developed general consensus was focused on some items such as age, sex, female hormone, nonsteroidal anti-inflammatory drugs (NSAID), renin-angiotensin system inhibitor drugs, glomerular filtration rate, hydration methods, contrasts, antioxidants, dextrose, and magnesium. Conclusion: The agreement between participants for CP therapy in clinic was achieved, and this general consensus was announced to be implemented in the hospitals.

Intravenous Administration of Cisplatin with Magnesium Sulfate Supplement May Prevent Kidney Toxicity in Rats: The Role of Gender and Magnesium Sulfate Dose.

BACKGROUND: Cisplatin (CP) is widely used to treat various kinds of malignancies, but to avoid its side effects of nephrotoxicity and hypomagnesemia, magnesium supplementation is a subject of debate. The current study was designed to determine the protective role of intravenous magnesium sulfate (MgSO4) against intravenous administration of CP in male and female rats. METHOD: In this case-control experimental study, 80 Wistar male and female rats in 12 groups of experiments were subjected to receive intravenous administration of CP accompanied with intravenous infusion of different doses (1, 3, and 10 mg/ml solution) of MgSO4 and were compared with the control groups. RESULTS: CP administration increased blood urea nitrogen (BUN), creatinine (Cr), kidney tissue damage score (KTDS), and kidney weight (KW), and they were attenuated by the mid-dose of MgSO4 supplementation in female rats. However, in male rats, the increase of Cr, BUN, KTDS, and KW induced by CP was ameliorated by low, mid-, and high doses of MgSO4 supplements. The levels of these markers were significantly different between male and female rats in the mid-dose of MgSO4-treated group (BUN: P=0.002, Cr: P=0.005, KTDS: P=0.002, and KW: P=0.031). CP reduced clearance of Cr (ClCr) in both male and female rats significantly compared to the control group of saline alone (P male = 0.002 and P female = 0.001), and the mid- and high doses of MgSO4 supplements improved ClCr in female rats. There were also sex differences in ClCr in mid- (P=0.05) and high (P=0.032) doses of MgSO4-treated groups. CP accompanied with the mid-dose of MgSO4 supplement reduced the KTDS (P male = 0.04 and P female = 0.004) and KW (P male = 0.002 and P female = 0.042) in both male and female rats significantly when compared with the CP-alone-treated group, while there were also significant differences between the sexes (KTDS: P=0.002 and KW: P=0.031). CP accompanied with three different doses of MgSO4 supplements did not improve the serum levels of lactate dehydrogenase, urine level of sodium, malondialdehyde, urine flow, and nitrite statistically when compared with the CP-alone-treated group. CONCLUSION: The renal protective effect of MgSO4 could be dose and gender related.

Rational, Design and Preliminary Results of a Cohort Study on Breast and Colorectal Cancer to Develop a Risk Assessment Model to Predict Future Cardiovascular Events. "Cardio Vascular Events in Breast and Colorectal Cancers (CIBC) Study".

Breast cancer (BC) and colorectal cancer (CRC) are among the most common cancers in Iran. We aimed to develop a risk assessment model to predict the development of cardiovascular events in these patients by performing a 5 year prospective cohort study on a newly diagnosed patients with BC or CRC before they receive any treatment. A multi-center prospective cohort study of 2700 newly diagnosed BC and CRC patients has been started in Iran since 2019 and will be continued until 2024. Demographics, socioeconomic status, life style behaviors, psychological characteristics and type of cancer treatments will be collected by standard questionnaires and blood pressure, obesity indices will be measured. Blood sampling, ECG, and echocardiography will be done in all patients at base line, 6 and 12 months, then at annual basis for five years. Incidence of heart failure, acute coronary syndrome, stroke and CVD related death are the primary outcome of this study. In this preliminary analysis, 70 patients with BC and 30 patients with CRC were enrolled in this study from April 2019 to November 2019. Mean age of BC and CRC patients was 48 ± 10.5 and 61 ± 13.2 respectively. 98.6% of patients in BC group and 60% of CRC groups were female. This study will be a platform for other cancers to develop CVD risk assessment charts that can cover other cancers. Patients who lie in the high risk category according to the newly developed risk assessment chart, should receive special management and preventive interventions.

T-cell immunophenotyping in COVID-19 pneumonia.

The COVID-19 epidemic is currently a global threat that has affected many parts of the world. Some patients require intensive care unit admission due to severe symptoms in the course of the disease. The severity of symptoms in this disease varies from person to person. The effectiveness of the immune response against viral infections depends on the number and activity of T-cells, which play an important role in eliminating virus-infected cells. In this study, we report two patients with COVID-19 pneumonia, one with moderate symptoms and the other with severe symptoms. Although a decrease of absolute lymphocyte count was seen in both patients, a more significant decline reported in the ICU-admitted patient. Expression of activated markers, HLA-DR, CD38, on CD8-positive T-cells was shown in a patient with more severe disease. On the other hand, partial loss of CD7 in the severe case was also observed. Hence, besides of the above parameters that already mentioned in other studies, loss of pan T-markers could be considered as a potentially valuable test for predicting disease severity. We suggest evaluating the predictability of these tests in COVID-19 in larger studies. This study was approved by the Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.MED.REC.1399.238).

Hydration with Mannitol and Dextrose May Promote Cisplatin-Induced Nephrotoxicity: Test of Five Protocols of Hydration during Cisplatin Therapy in Rat Models.

BACKGROUNDS: Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. METHODS: Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. RESULTS: Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. CONCLUSION: Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.

Association of lymphocyte subsets with mortality in severe COVID-19 pneumonia patients.

BACKGROUND: Few studies have investigated the alterations in the T and B cell counts and related subgroups in pulmonary infections especially COVID-19. Here, we aimed to evaluate total T and B lymphocytes and T cell subgroup counts to find the possible correlation between number of these cells and severity and mortality in COVID-19 patients. METHODS: This study was performed on 40 patients with severe COVID-19 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chest HRCT in August 2020. By the time of admission, T lymphocytes profile in peripheral blood was investigated using multicolor flow cytometry. The total number of T lymphocytes, CD4+ T cells, CD8+ T cells, and B lymphocytes were calculated. Expression of CD2, CD3, CD5, and CD7 as pan T cell surface markers and expression of CD38 and HLA-DR as activated markers on T lymphocytes were also evaluated. RESULTS: Nine patients (22.5%) died during the study and 16 patients (40%) were admitted to ICU. Deceased patients demonstrated lower amounts of T cell count and CD4+ T cell count (with a marginal difference (p = 0.07)) compared with survived patients at the time of admission. The chance of mortality was significantly higher for patients with CD7 loss (OR = 14.89). A marginally significant relationship was also indicated between CD4<200/ml and mortality (OR = 8.65), but no other significant relationships were observed between variables and ICU admission. CONCLUSION: Altogether, CD7 loss on T lymphocytes and CD4+ T cell count below 200/ml revealed a significant relationship with mortality. Considering T lymphocytes and T cell subgroup count could have a predictive value for patients suffering from COVID-19.

Validation of a newly developed questionnaire regarding clinical history in patients with breast and colorectal cancers.

BACKGROUND: Understanding the close interaction between the specialties of cardiology and oncology is necessary for early detection of cardiovascular disease (CVD) events in cancer patients. For the risk assessment of CVD in Breast and Colorectal Cancers (CIBC) study, in the current study we aimed to validate a questionnaire for the assessment of clinical history in patients with breast cancer and colorectal cancer (CRC). METHODS: We determined the content validity of the questionnaire using the 2 indexes of content validity ratio (CVR) and content validity index (CVI) to examine the specificity, simplicity, clarity, and transparency of the items. Content validity assessment was performed through a panel of experts including 2 oncologists, 5 cardiologists, 2 general practitioners, and 1 epidemiologist. The reliability of the questionnaire was estimated using Cronbach's alpha coefficient in 50 patients. Intraclass correlation coefficient (ICC) was used to examine the reproducibility of the questionnaire during 1 week. RESULTS: The CRC and breast cancer questionnaire were designed with 16 and 32 questions, respectively. To obtain acceptable CVR, 5 and 11 questions were removed from the CRC and breast cancer questionnaires, respectively. Cronbach's alpha was 0.70 in the breast cancer questionnaire and 0.94 in the CRC questionnaire. All questions had a CVI of higher than 80%. The ICC in the breast cancer questionnaire ranged between 0.71 and 0.96 and in CRC questionnaire ranged between 0.78 and 0.98. CONCLUSION: The validity and reliability of our newly developed questionnaire was desirable. The reliability of the breast cancer questions was acceptable and that of the CRC questions was excellent. Thus, thus questionnaire can be used in this group of patients regardless of whether the goal is cardiac care or not.

Survival of Post-Transplant Lymphoproliferative Disorder after Kidney Transplantation in Patients under Rapamycin Treatment.

Background: One of the important causes of mortality and morbidity in kidney transplanted patients is Post Transplant Lymphoproliferative Disease (PTLD), which is due to immunosuppression therapy and viral activity. It seems that Rapamycin, with dual antineoplastic and immunosuppressive effects, may have a pivotal role in the treatment of PTLD patients and preserving transplanted kidneys. Methods and Materials: Twenty patients with PTLD were enrolled. Immunosuppressive therapy was reduced or ceased, and Rapamycin was initiated at the time of PTLD diagnosis. We evaluated the effects of switching immunosuppressive drugs to Rapamycin on graft status, the response of tumor, and 6, 12 months, and 5-year survival in patients. Results: PTLD remission was achieved in 14 patients, while six patients died; no relapse was detected in recovered patients. The median of PTLD free time was 25 months, and the mean overall survival in patients with PTLD treated by Rapamycin was 84.8 (95% CI=61.3-108.23).The five-year survival rate was 67%, 12 months survival was 73.8%, and six months' survival was 80%. The response rate to Rapamycin and immunosuppression reduction alone was 46.6%. Four out of 13 Diffuse Large B-Cell Lymphoma patients achieved a complete response just only after the reduction of immunosuppressive drugs and the consumption of Rapamycin. Conclusion: The present study demonstrated the effectiveness of conversion from immunosuppressive medication, particularly of Calcineurin inhibitors to Rapamycin in PTLD patients. However, more research is needed to confirm the Rapamycin effect on patients with PTLD.

Reduced Weekly Subcutaneous Doses of Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Newly Diagnosed Multiple Myeloma.

OBJECTIVE: A combination of bortezomib, cyclophosphamide, and dexamethasone is highly effective in the treatment of newly diagnosed multiple myeloma. Neuropathy is a dose-limiting adverse effect of this regimen. Subcutaneous and weekly injection instead of biweekly intravenous administration are used to reduce neuropathy. In this study, patients treated with subcutaneous weekly reduced the dose of bortezomib to reduce neuropathy and cost of treatment. METHODS: This is an interventional study, including 16 patients. Enrolled patients received bortezomib 1 mg/m2 subcutaneously, cyclophosphamide 300 mg/m2 intravenously, and dexamethasone 40 mg intravenously days 1, 8, 15, and 22 of a 28 cycle. FINDINGS: The overall response rate (≥partial response [PR]) was 93.8%. Thirteen of 16 patients (81.3%) were in an acceptable PR and complete response. Two patients (12.5%) achieving a PR. Meantime to achievement, the best response was 71 (55-87) days. Median progression-free survival was 33 (2-56) months, and autologous stem cell transplantation was performed for 68.8% of patients. Five patients (31.25%) experienced Grade I and one patient (6.25%) Grade III (no Grade 2 or 4) of peripheral neuropathy. Dose reduction and drug discontinuation was required in one patient (6.25%). CONCLUSION: A reduced subcutaneous, weekly dose of bortezomib in combination with cyclophosphamide and dexamethasone is effective with manageable profile toxicity and acceptable cost.

COVID19 Prevention & Care; A Cancer Specific Guideline.

On March 11th 2020, the coronavirus outbreak was declared a pandemic by the WHO. One of the groups that is considered high risk in this pandemic are cancer patients as they are treated with a variety of immune system suppressor treatment modalities and this puts them in a great risk for infectious disease (including COVID-19). Therefore, cancer patients require higher level measures for preventing and treating infectious diseases. furthermore, cancer patients may bear additional risk due to the restriction of access to the routine diagnostic and therapeutic services during such epidemic. Since most of the attention of health systems is towards patients affected with COVID-19, the need for structured and unified approaches to COVID-19 prevention and care specific to cancer patients and cancer centers is felt more than ever. This article provides the recommendations and possible actions that should be considered by patients, their caregivers and families, physician, nurses, managers and staff of medical centers involved in cancer diagnosis and treatment. We pursued two major goals in our recommendations: first, limiting the exposure of cancer patients to medical environments and second, modifying the treatment modalities in a manner that reduces the probability of myelosuppression such as delaying elective diagnostic and therapeutic services, shortening the treatment course, or prolonging the interval between treatment courses.

A case report of sinusoidal diffuse large B-cell lymphoma in a STK4 deficient patient.

INTRODUCTION: Primary immunodeficiency diseases (PIDs), a rare group of gene defects with different manifestations, are at great risk of malignancy. The incidence of diffuse large B-cell lymphoma in the sinusoidal tract is quite rare with nasal congestion, stuffiness, and pain in maxillary sinus manifestation. Human serine-threonine kinase 4 (STK4) deficiency affects the immune system with recurrent bacterial and viral infections, mucocutaneous candidiasis, cutaneous warts, skin abscesses, T- and B-cell lymphopenia, and neutropenia. PATIENT CONCERN: In this study we describe the infrequent incidence and successful treatment of sinusoidal diffuse large B-cell lymphoma in a STK4 deficient patient with clinical manifestation of severe intractable headaches, unilateral swelling of her face, nasal congestion, stuffiness, and pain in maxillary. DIAGNOSIS: Clinical data including headaches, unilateral swelling of face, nasal congestion, stuffiness and pain in maxillary sinus with confirmed histopathology and magnetic resonance imaging finding confirmed sinusoidal diffuse large B cell lymphoma in a STK4 deficient patient. INTERVENTION: Six cycles of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone) were administered and after each cycle, G-CSF support was used. Chemotherapeutic drugs were administered with standard dose and no dose reduction was done during the treatment. IVIG treatment continued during the courses of chemotherapy. OUTCOME: The index patient achieved complete response at the end of chemotherapy courses and was in remission for about 8 months afterward, prior to the date of the present report. CONCLUSION: PID patient are often at increased risk of malignancies. Sinusoidal diffuse large B-cell lymphoma is quite rare and prognosis is variable. Early attention to patient's manifestation, suitable treatment, and monitoring manifestations caused by PID are critical.

Optimization of In Vitro Expansion and Activation of Human Natural Killer Cells against Breast Cancer Cell Line.

BACKGROUND: Regarding to the increase of cancer deaths in recent years and disability of common therapies to eradicate cancers, as well as expansion of Natural Killer (NK) cell therapy, it seems so vital to find new useful therapies against cancers. Breast cancer is the second main cause of cancer death among women. As it is impossible for a majority of patients to receive NK cell therapy, an attempt was made to establish a low-cost and efficient method for expanding and activating NK cells against breast cancer cell line (MCF7). METHODS: NK cells were isolated from Peripheral Blood Mononuclear Cells (PBMCs) applying either MACS based NK cell enrichment kit or antibodies and complement as cytotoxic method. Then, the NK cells were cultured in Stem Cell Growth Medium (SCGM) with feeder layer (irradiated PBMCs) along with PHA or OKT3. IL-2, IL-15 and IL-21 were used to expand NK cells and finally their cytotoxic activity was investigated by flow cytometry. RESULTS: Highly pure NK cells were obtained and no significant difference between the two isolation methods was found. Using IL-2 plus IL-15, the number of NK cells increased up to100 fold after 16 days. No significant effect was observed after IL-21 treatment. CONCLUSION: Our data indicated that cytotoxicity method can be considered a low-cost alternative for NK cell isolation kits. It seems that culturing NK cells for 14 days in either PHA or OKT3 supplemented SCGM medium would be more effective than culturing for 16 days in the presence of IL-21.