AML in Saudi Arabia: Analysis According to the European LeukaemiaNet 2017 Cytogenetic Classification.

INTRODUCTION: To the best of our knowledge, few studies have addressed the prognosis of patients with acute myeloid leukemia (AML) in Saudi Arabia. The present study retrospectively analyzed the prognostic factors in patients with de novo AML at a single institution owing to the observation of some differences with the reported data from the Western world. PATIENTS AND METHODS: Patients with de novo AML who had been referred to King Abdulla Medical City were included. All patients had undergone bone marrow aspiration, biopsy, flow cytometry, cytogenetics (conventional and fluorescence in situ hybridization panel performed at Mayo Clinic), molecular tests, and other routine tests. RESULTS: The data from 170 patients were reviewed. Of the 170 patients, 26 had had acute promyelocytic leukemia, 16 with AML had received less intensive therapy, 119 had received intensive induction, and 8 had refused treatment. The present analysis was limited to the 119 patients who had received intensive induction therapy. For the major cytogenetic categories, 17 of 27 patients with core binding factor leukemia (62.9%) were reassigned to the intermediate (n = 10; 37%) or unfavorable (n = 7; 25.9%) risk group according to the FLT3-ITD and NPM results. Of the 50 cases of normal cytogenetic findings, 2 (4%) were considered unfavorable, 12 (24%), favorable, 30 intermediate (60%), and 6 (12%) unknown. The median leukemia-free survival was 21.5 months. The median overall survival was 16.4 ± 2.2 months, with a 3-year survival rate of 37.2%. Multivariate Cox regression analysis revealed that the cytogenetics results (P = .002) and the presence of FLT-3 (P = .03) were independent prognostic factors for relapse-free survival. Performance status, response, relapse, and cytogenetics findings were independent prognostic factors for survival. CONCLUSIONS: The results from the present study revealed some differences in patient age and cytogenetic risk groups for patients with AML in our region and those in the Western world, including a younger median age, relevance of core binding factor leukemia, and a greater incidence of monosomies.

The Dana Farber consortium protocol (DFCP) vs. classic Hyper-CVAD for treatment of acute lymphoblastic leukemia in patients <50 Y. Single institution experience.

BACKGROUND: The use of intensive pediatric protocols for the treatment of ALL is being extended to older adults. AIM OF THE STUDY: Analysis of the efficacy and toxicity results of pediatric DFCP vs. classic Hyper-CVAD protocol for the treatment of patients with ALL < 50 Y. PATIENTS AND METHODS: A retrospective single center comparative analysis of DFCP & classic Hyper-CVAD for first line treatment of patients with ALL < 50 Y. RESULTS: 73 patients were included, 43 received DFCP and 30 received Hyper-CVAD protocol. CR rate was 90.7% for DFCP vs. 83.7 for Hyper-CVAD (p 0.7). 3 Y Leukemia free survival was 57.4% (70.9% for DFCP vs. 41.6% Hyper-CVAD P 0.1) while 3Y OS was 62.6%% for the whole group, 72.6% DFCP vs. 48.5% Hyper-CVAD, P 0.04. Those with age <21 Y, had significantly longer 3 Y LFS and OS (P 0.04, 0.02, respectively). TOXICITY: pancreatitis occurred in 5 patients with DFCP and it was related to Asparginase and in 1 patient on Hyper-CVAD related to gall stones. Osteonecrosis affected 5 patients on DFCP. IN CONCLUSION: pediatric protocols are feasible in patients younger than 50 Y and they are more active than classic adult protocols. Although modifications of adult protocols may improve their results, this had to be investigated in randomized controlled trials.

The Dana Farber Consortium Protocol for the Treatment of Adolescents and Young Adults With Acute Lymphoblastic Leukemia: A Single Institution Experience in Saudi Arabia.

BACKGROUND: Recent retrospective analyses and phase II trials have shown differential outcomes in adolescents and young adults when treated with pediatric compared with adult protocols. The aim of this study was to evaluate the efficacy and toxicity of the Dana Farber Consortium Protocol (DFCP) in Saudi young adults diagnosed with de novo acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: In this retrospective study we included 38 patients with de novo ALL who presented to King Abdulla Medical City in the period from June 2010 to March 2015 and received the DFCP (Princess Margret modified version). RESULTS: A total of 38 patients were included with a median age of 19 years. Two patients died during induction treatment, and 35 of 38 patients achieved complete remission (92.1%). With a median follow-up period of 22 months, at 1 and 3 years, leukemia-free survival was 80% and 68%, respectively, and overall survival was 88% and 72%, respectively. Age younger than 21 years showed a significant association with longer survival. Toxicities included febrile neutropenia in all patients during induction, typhilitis in 8/38 (21%), pneumonia in 10/38 (26%), and pancreatitis in 5/38 patients (13%), 3/38 (7.8%) during induction and 2/38 (5.2%) during intensification. Osteonecrosis affected 3/38 patients (7.8%), and was detected during screening in 2/38 (5.2%) of these patients. There were no fractures or surgical interventions, and no venous thromboembolism was recorded. CONCLUSION: Although it might be feasible to use pediatric-inspired protocols in this age group, toxicity cannot be overlooked, and the application of these protocols might require modification of drug doses or schedules relative to those used for younger children. Moreover, additional surveillance and supportive measures should be implemented to maximize benefits while minimizing toxicity.

Emergency Department Visits at the End of Life of Patients With Terminal Cancer: Pattern, Causes, and Avoidability.

Frequent emergency department visits (EDVs) by patients with terminal cancer indicates aggressive care. The pattern and causes of EDVs in 154 patients with terminal cancer were investigated. The EDVs that started during working hours and ended by home discharge were considered avoidable. During the last 3 months of life, 77% of patients had at least 1 EDV. In total, 309 EDVs were analyzed. The EDVs occurred out of hour in 67%, extended for an average of 3.6 hours, and ended by hospitalization in 52%. The most common chief complaints were pain (46%), dyspnea (13%), and vomiting (12%). The EDVs were considered avoidable in 19% of the visits. The majority of patients with terminal cancer visit the ED before death, mainly because of uncontrolled symptoms. A significant proportion of EDVs at the end of life is potentially avoidable.

Predictive Value of IHC4 Score for Pathological Response to Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer.

PURPOSE: This study aimed to explore the value of IHC4 in predicting pathological response after neoadjuvant chemotherapy in patients with hormonal receptor (HR)-positive breast cancer (BC). MATERIALS AND METHODS: In this retrospective exploratory study, data for 68 HR-positive BC patients who received neoadjuvant chemotherapy were recorded. IHC4 scores were calculated based on estrogen receptors/progesterone receptors, Ki-67 and HER2 status. Logistic and ordinal regression analyses in addition to likelihood ratio test were used to explore associations of IHC4 scores and other clinico-pathological parameters with pathological complete response (pCR) and pathological stage. RESULTS: Taking the 25th percentile as the cut-off, a lower IHC4 score was associated with an increased probability of pCR (low; 52.9% vs. High; 21.6%, OR=4.1, 95% CI= 1.28-13.16, p=0.018) and a lower pathological stage (OR =3.9, 95% CI=1.34-11.33, p=0.012). When the IHC4 score was treated as a continuous variable, a lower score was again associated with an increased probability of pCR (OR=1.010, 95% CI=1.001-1.018, p=0.025) and lower pathological stage (OR=1.009, 95% CI= 1.002-1.017, P=0.008). Lower clinical stage was associated with a better pCR rate that was of borderline significance (P=0.056). When clinical stage and IHC4 score were incorporated together in a logistic model, the likelihood ratio test gave a P-value of 0.004 after removal of the IHC4 score and 0.011 after removal of the stage, indicating a more significant predictive value of the IHC4 score for pCR. CONCLUSIONS: This study suggests that the IHC4 score can predict pathological response to neoadjuvant chemotherapy in HR-positive BC patients. This finding now needs to be validated in a larger cohort of patients.

Gastric carcinoma at Tanta Cancer Center: a comparative retrospective clinico-pathological study of the elderly versus the non-elderly.

BACKGROUND AND AIMS: To study the clinico-pathological features, treatments and outcomes of gastric carcinoma (GC) in the elderly (⩾65 years) and the non-elderly Egyptian patients. METHODS: This retrospective cohort study included 168 patients with histologically confirmed GC treated at Tanta Cancer Center between 2003 and 2007. RESULTS: Compared to the non-elderly, elderly patients had significantly higher proportion of tumors involving the cardia (p=0.034) and of adenocarcinoma NOS histology (p=0.032). Treatments were largely comparable in the two groups. Response to palliative chemotherapy was achieved in 44.4% of the elderly and 25.5% of the non-elderly patients (p=0.417). The median overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 6, 17 and 3 months, respectively. The median OS was 4 months in the elderly compared to 9 months in the non-elderly (p=0.005). The median DFS was 4 months in the elderly compared to 20 months in the non-elderly (p=0.004). The median PFS was 2 months in the elderly compared to 3 months in the non-elderly (p=0.685). In multivariate analysis, poor performance status was an independent predictor of poor OS, DFS and PFS. Non-curative or no surgery and lack of chemotherapy use were independent predictors of poor OS. Age was an independent predictor of poor DFS. CONCLUSIONS: Compared to the non-elderly, GC in the elderly has similar clinico-pathological characteristics and exhibits comparable outcomes with the same treatment options. Treatments should be tailored to each patient.

The pattern of infection and antibiotics use in terminal cancer patients.

BACKGROUND: Although cancer patients are susceptible to infection, there is no evidence-based published guideline on the appropriate use of antimicrobial treatment in this group of patients. METHODS: We retrospectively collected medical records of all terminal cancer patients who died in the oncology department over a 15-month period and were reviewed for the pattern of infection and causes of antimicrobial use during the patients' last admission of life. RESULTS: A total of 258 eligible patients were enrolled, there was an equal distribution of males and females (M/F: 129/129), and the mean age was 60.5 years. 221 patients admitted with fever (85%), 22 patients (8.5%) got fever after hospitalization and 15 patients (5.8%) did not suffer from fever. Among patients with fever, 46 patients (18.9%) had two infection episodes and 197 patients (81.1%) had only one infection episode. The culture results revealed positive in 98 patients (40%) with gram-negative organisms were the dominant organisms. The major infection sites were the respiratory tract, urinary tract and wound. 114 patients (47%) received one antibiotic and 129 patients (53%) received more than one. The mean duration of hospitalization was significantly longer for infected patients than for uninfected patients (8.00 vs. 18.15 days, p=0.0001). Outcome of antibiotic use revealed 42 patients (17.3%) with symptoms improved 71 patients (29.2%) with stationary symptoms and 130 patients (53.5%) revealed symptom deterioration. CONCLUSIONS: Our study revealed that antibiotic therapy for terminal cancer patients should be on a clear rationale. We need further study to clarify if there is survival effect with antibiotic use or not.

Target therapy in metastatic pheochromocytoma: current perspectives and controversies.

Most of the pheochromocytomas (PCCs) are benign neoplasms, but when they are malignant, they can be difficult to treat. Despite advances in diagnosis and imaging, it remains an untreatable tumor, when metastases develop. A deeper understanding of the alteration of the specific molecular pathways causing malignant PCCs might hopefully lead in the future to the development of multiple molecular-targeted therapies to treat it successfully. Clinical experience and the use of murine models of metastatic PCCs have helped introduce new experimental treatment options which will significantly help the PCCs community explore novel targeted therapies that have already shown promising results in many other types of tumors.

The Clinical Implications of Methylated p15 and p73 Genes in Adult Acute Lymphoblastic Leukemia.

BACKGROUND: Aberrant methylation of promoterassociated CpG islands is an epigenetic modification of DNA which is associated with gene silencing. It plays an important role in the leukemia pathogenesis. This phenomenon is frequently observed in acute lymphoblastic leukemia (ALL) and results in the functional inactivation of its associated genes. The aim of this study is to investigate the frequency and the prognostic impact of p15 and p73 genes methylation in adult acute lymphoblastic leukemia patients. PATIENTS AND METHODS: Methylation-specific polymerase chain reaction (PCR) was used to analyze methylation of the p15 and p73 genes in 51 newly diagnosed adult ALL patients. RESULTS: The methylation frequencies of p15 and p73 genes at diagnosis were 41.2% and 27.5% respectively, while concomitant methylation was detected in 14% of the patients. Concomitant methylation of p15 and p73 genes was associated with significant lower rate of CR compared to patients without methylation (57% versus 90%), p=0.008. Overall survival (OS) was not affected by p15 methylation, but was poorer with p73 methylation and the difference was near significant (p=0.059). For patients without meyhylation, the survival benefit was significant when compared to patients with p15, p73 or both genes methylation (p=0.047). The leukemia free survival was not affected by the methylation status of single gene p15 or p73, but tended to be worse in patients with methylated p15, p73 or both genes when compared to patients without methylation (p=0.08). CONCLUSION: Aberrant p73 promoter methylation is a potential prognostic factor in adult ALL patients. P15 methylation is frequent in Egyptian adult ALL patients, its concomitant methylation with p73 is of poor prognostic significance. Identification of these molecular targets improve risk assessment and selection of appropriate therapy. KEY WORDS: Methyaltion - p15 - p73 - Adult acute lymphoblastic leukemia.