Identifying Prognostic Factors That Influence Outcome of Childhood Acute Myeloid Leukemia in First Relapse in Saudi Arabia: Results of the Multicenter SAPHOS Study.

BACKGROUND: The outcome of childhood acute myeloid leukemia (AML) in first relapse (rAML) remains poor. Reported overall survival (OS) rates vary between high-income developed countries and those with fewer resources. The OS of rAML in high-income developing countries (HIDCs) has not been reported. PATIENTS AND MATERIALS: A multicenter study was performed in an HIDC. The outcome of patients with relapsed non-M3/non-Down syndrome AML was evaluated. Three-year OS was computed using the Kaplan-Meier method, and predictors of OS were analyzed using a Cox proportional hazards model. RESULTS: A total of 88 patients with non-M3/non-Down syndrome AML diagnosed between January 2005 and December 2012 with a first relapse were identified. Their 3-year OS was 22.6% ± 5.4%. Patients with inv(16) and t(8;21) had an OS of 75.0% ± 21.7% and 36.0% ± 16.1%, respectively. Worse outcomes were associated with "other intermediate" and 11q23 rearrangement AML (OS of 9.4% ± 8.7% and 10.7% ± 9.6%, respectively). Patients experiencing time to relapse (TTR) less than 1 year had shorter OS than those with a longer TTR (14.6% ± 5.4% vs. 41.1% ± 11.5%; P = .006). The outcome of patients after stem cell transplantation (SCT) in second complete remission (CR2) was superior compared with no SCT (50.9% ± 11.2% vs. 7.7% ± 4.6%; P = .001). TTR, risk group, CR2, and SCT in CR2 were the most significant predictors for survival. CONCLUSIONS: rAML remains a clinical challenge. Genetic variability in outcomes was observed. A majority of patients with inv(16) were successfully salvaged post-relapse, whereas patients with 11q23 rearrangement had a poor prognosis. Only one-third of those with t(8;21) rAML survived. Better access to SCT in HIDCs is needed.

Quantifying the Hawthorne effect using overt and covert observation of hand hygiene at a tertiary care hospital in Saudi Arabia.

INTRODUCTION: Although direct human observation of hand hygiene (HH) is considered the gold standard for measuring HH compliance, its accuracy is challenged by the Hawthorne effect. OBJECTIVES: To compare HH compliance using both overt and covert methods of direct observation in different professional categories, hospital settings, and HH indications. METHODS: A cross-sectional study was conducted in 28 units at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between October 2012 and July 2013. Compliance was defined as performing handrubbing or handwashing during 1 of the World Health Organization 5 Moments for HH indications (ie, opportunities). Overt observation was done by infection preventionists (IPs) who were doing their routine HH observation. Covert observation was done by unrecognized temporarily hired professionally trained observers. RESULTS: A total of 15,883 opportunities were observed using overt observation and 7,040 opportunities were observed using covert observation. Overall HH compliance was 87.1% versus 44.9% using overt/covert observations, respectively (risk ratio, 1.94; P < .001). The significant overestimation was seen across all professional categories, hospital settings, and HH indications. CONCLUSION: There is a considerable difference in HH compliance being observed overtly and covertly in all categories. More work is required to improve the methodology of direct observation to minimize the influence of the Hawthorne effect.

Clinical characteristics and outcome of childhood acute promyelocitic leukemia (APL) in Saudi Arabia: a multicenter SAPHOS leukemia group study.

BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia. Patients were treated based on the standard protocol used by the center following the PETHEMA or the C9710 treatment protocols. We modeled 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) vs. treatment and potential covariates of age at diagnosis, involvement of central nervous system (CNS), and white blood cell (WBC) levels. RESULTS: The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 × 109/l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74 ± 12%, 55 ± 19%, and, 36 ± 17% respectively. No significant difference was found by treatment protocol. WBC levels were significantly prognostic for all negative events, but treatment with C9710 significantly ameliorated negative WBC effects. Overall outcomes were comparable to those reported in developed countries. CONCLUSIONS: Access to modern care is likely to be a critical factor in successful and comparable outcomes of childhood APL across the globe. In the present study, utilizing a cytarabine-containing protocol improved outcome of high-risk pediatric patients with APL.

Treatment results in children with myeloid leukemia of Down syndrome in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%, and other aberrations in 29%. Complete remission, cumulative incidences of relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were 96.8%, 19.4%, 13.1%, and 67.7±8.4%; respectively. In the present study, multivariate analysis revealed favorable outcome (5-year EFS 86.7±8.8%) for patients with normal karyotype. The incidence and clinical characteristics of ML-DS in Saudi patients were comparable to other reports. However, there is a need to optimize risk stratification and treatment intensity to reduce CIR and toxic death rates to further improve outcomes of patients with ML-DS.

Clinical characteristics and outcome of childhood de novo acute myeloid leukemia in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acute myeloid leukemia (AML). Furthermore, survival outcomes from developing countries are reported to be inferior to developed nations. We hypothesized that risk- and response-based outcome in high-income resource-rich developing countries would be comparable to developed nations as access to care and supportive measures would be similar. A total of 193 children diagnosed with de novo AML between January 2005 and December 2012 were identified, of those 175 were evaluable for outcome. Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) groups. The complete remission (CR), early death, and induction failure rates were: 85.7%, 2.3%, and 12%; respectively. The 5-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 43.1% and 9.8% respectively; overall survival (OS) was 58.8±4% and event-free survival (EFS) 40.9±4.1%. The 5-year OS for LR, IR, and HR groups were 72.0±6.9%, 59.8±6.2%, and 45.1±7.4%; respectively (p=0.003); and EFS 50.5±8.0%, 46.3±6.4%, and 23.3±6.4%; respectively (p=0.001). This study demonstrated comparable outcomes to those reported from developed countries. This suggests that utilization of risk- and response-based protocols in developing countries can overcome ethnic and geographic variation, if access to care and supportive measures were similar.

Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia in Saudi Arabia: a multi-institutional retrospective national collaborative study.

BACKGROUND: Treatment of childhood acute lymphoblastic leukemia (ALL) has been available in Saudi Arabia (SA) for over 30 years; however, only limited data have been published from there. This study was conducted to establish processes for collaborative data collection and provide clinical characteristics and outcome of children with ALL in SA. PROCEDURE: Clinical data for patients diagnosed from 2004 to 2008 were retrospectively collected at eight institutions and entered remotely into a custom-built database. Statistics regarding clinical and genetic characteristics and treatment outcome were calculated. RESULTS: The 594 evaluable patients had a median age of 4.37 years and 56.4% were boys. Majority of patients had B-precursor ALL while 10.7% had T-ALL. CNS leukemia was present in 5.2% of patients. The distribution of common genetic abnormalities was similar to that reported from western populations, with 24.6% hyperdiploidy, 21% RUNX1-ETV6 positivity, 4.2% BCR-ABL1 positivity, and 2.5% with MLL gene rearrangement. Patients received risk-adapted therapy according to various protocols, although treatment strategies for the majority were similar. Five-year OS, RFS and EFS were 86.9%, 79.1%, and 73.3%, respectively. The OS for patients with pre-B ALL was significantly higher than for T-ALL (88.0% vs. 71.8%; P = 0.019, Log-Rank test). Patients with pre-B ALL categorized as low-risk by NCI/Rome criteria and those with hyperdiploidy had OS of 93.4% and 95.8%, respectively. CONCLUSIONS: The characteristics of childhood ALL in SA are similar to those observed in developed countries. Future prospective studies utilizing unified national protocols are needed to further improve the outcome of our patients.

Erlotinib in wild type epidermal growth factor receptor non-small cell lung cancer: A systematic review.

BACKGROUND: Targeting epidermal growth factor receptors (EGFR) is an innovative approach to managing non-small cell lung cancer (NSCLC) which harbors EGFR mutation. However, the efficacy of these agents like erlotinib in patients without the mutation is not known. METHODS: This systematic review included Phase III randomized clinical trials that compared single agent erlotinib to other management options in the setting of NSCLC with reported outcome data on patients with EGFR wild type (EGFRWT) tumors. Outcome data include overall survival (OS), progression free survival (PFS) and response rate (RR). Random effects meta-analysis was used to pool outcomes across studies. RESULTS: Three studies met the inclusion criteria. These studies included a total of 2044 patients with outcome data on 674 patients with EGFRWT tumors (33%). Meta-analysis revealed a statistically significant improvement in OS with erlotinib (hazard ratio of 0.780; 95% confidence interval: 0.654-0.930, P = 0.006). Data were not available to perform PFS or RR analysis. The quality of this evidence is considered to be moderate to high. CONCLUSION: Our study revealed a significant benefit of erlotinib in patient with EGFRWT tumors compared with other approaches. These findings add another therapeutic option to patients generally considered difficult to treat.

Use of complementary and alternative medicine by patients with cancer in Saudi Arabia.

BACKGROUND: The use of complementary and alternative medicine (CAM) is common among patients with cancer. However, the issue is not well-studied among the Saudi patient population. Our study aimed at determining the patterns of CAM use among patients with cancer in Saudi Arabia. METHODS: A cross-sectional study using interview-administered questionnaire was conducted in patients with cancer in the Oncology Department of King Abdulaziz Medical City for National Guards, Riyadh, Kingdom of Saudi Arabia. Patients were asked about CAM use including dietary supplement (DS) and non-DS remedies. Univariate and multivariate analyses were conducted to identify predicting factors for CAM use. RESULTS: A total of 453 adult patients were enrolled in the study, with a median age of 53.5 years (14.7-94.6), and the ratio of females to males was 271/182 (59.8%/40.2%). Of those, 410 patients (90.5%) used some type of CAM remedy. Non-DS remedies were used by 399 patients (88%) and were mainly of a religious nature including reciting the Quran (74.8%), prayer (16%), supplication (13%), and others (3.7%). However, 386 patients (85.2%) used DS including: Zamzam water (59.8%), honey (54.3%), black seed (35.1%), water with the Quran recited over it (29.8%), and other remedies. The majority of patients (90%) used CAM as a cancer treatment and the rest used it for various reasons, such as symptom control or supportive treatment. Only 18% of the patients discussed CAM use with their physicians, compared to 68% discussing it with religious clergypeople (Sheikhs).The univariate analysis revealed that only female gender is a predictor of CAM use, which remained significant in a multivariate analysis, in addition to current employment. CONCLUSIONS: The use of complementary therapies among Saudi patients with cancer is highly prevalent, with a predominance of interventions of religious background, indicating the strong influence of religion on peoples' lives, especially when people are faced with life-threatening illnesses.

Improved outcome for children with acute lymphoblastic leukemia after risk-adjusted intensive therapy: a single-institution experience.

BACKGROUND AND OBJECTIVE: Because of the need for more comprehensive information on the least toxic and most effective forms of therapy for children with acute lymphoblastic leukemia (ALL), we reviewed our experience in the treatment of children with ALL at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and King Fahad National Center for Children's Cancer and Research (KFNCCC&R) over a period of 18 years with a focus on patient characteristics and outcome. METHODS: During the period of 1981 to 1998, records of children with ALL were retrospectively reviewed with respect to clinical presentation, laboratory findings, risk factors, stratification, therapy and outcome. The protocols used in treatment included 4 local protocols (KFSH 81, 84, 87 and 90), and subsequently, Children's Cancer Group (CCG) protocols, and these were grouped as Era 1 (1981-1992) and Era 2 (1993-1998). RESULTS: Of 509 children with ALL treated during this period, 316 were treated using local protocols and 193 using CCG protocols. Drugs used in Era 1 included a 4-drug induction using etoposid (VP-16) instead of L-asparaginase. Consolidation was based on high dose methotrexate (MTX) 1 g/m(2) and maintenance was based on oral mercaptopurine (6-MP) and MTX with periodic pulses using intravenous teniposide (VM-26), Ara-C, L-asparaginase, adriamycin, prednisone, VP-16 and cyclophosphamide. International protocols were introduced in Era 2, which was also marked by intensification of early treatment, a wider selection of cytoreductive agents, and the alternating use of non-cross-resistant pairs of drugs during the post-remission period. The end-of-induction remission rate improved from 90% in Era 1 to 95% in Era 2, which was of borderline statistical significance (P=.049). The 5-year event-free survival (EFS) improved from 30.6% in Era 1 to 64.2% in Era 2 (P<.001). Improvement in outcome was achieved without any significant increase in morbidity or mortality, due to improvement in both systemic therapy and supportive care. The most important independent prognostic factors were intensity of therapy, poor risk category assignment and CNS disease at diagnosis. CONCLUSION: Outcome in children with ALL has improved because of intensification of treatment protocols and better supportive care.