Impact of COVID-19 on Management and Outcomes of Oncology Patients: Results of MENA COVID-19 and Cancer Registry (MCCR).

Introduction: Despite extensive studies of the impact of COVID-19 on patients with cancer, there is a dearth of information from the Middle East and North Africa (MENA) region. Our study aimed to report pertinent MENA COVID-19 and Cancer Registry (MCCR) findings on patient management and outcomes. Methods: MCCR was adapted from the American Society of Clinical Oncology COVID-19 Registry to collect data specifically from patients with cancer and SARS-CoV-2 infection from 12 centers in eight countries including Saudi Arabia, Jordan, Lebanon, Turkey, Egypt, Algeria, United Arab Emirates, and Morocco. The Registry included data on patients and disease characteristics, treatment, and patient outcomes. Logistic regression was used to assess associations with mortality. Results: Between November 29, 2020, and June 8, 2021, data were captured on 2008 patients diagnosed with COVID-19 from the beginning of the pandemic. Median age was 56 years (16-98), 56.4% were females, and 26% were current or ex-smokers. Breast cancer (28.5%) was the leading diagnosis and 50.5% had metastatic disease. Delays of planned treatment (>14 days) occurred in 80.3% for surgery, 48.8% for radiation therapy, and 32.9% for systemic therapy. Significant reduction in the delays of all three treatment modalities occurred after June 1, 2020. All-cause mortality rates at 30 and 90 days were 17.1% and 23.4%, respectively. All-cause mortality rates at 30 days did not change significantly after June 1, 2020; however, 90-day mortality increased from 33.4% to 42.9% before and after that date (p = 0.015). Multivariable regression analysis showed the following predictors of higher 30- and 90-day mortality: age older than 70 years, having metastatic disease, disease progression, and being off chemotherapy. Conclusion: Patients with cancer in the MENA region experienced similar risks and outcome of COVID-19 as reported in other populations. Although there were fewer treatment delays after June 1, 2020, 90-day mortality increased, which may be attributed to other risk factors such as disease progression or new patients who presented with more advanced disease.

Effects of zinc oxide nanoparticles on antioxidants, chlorophyll contents, and proline in Persicaria hydropiper L. and its potential for Pb phytoremediation.

Applications of nanoparticles and plants for efficient restoration of heavy metal-polluted water and soil are an emerging approach and need to be explored. Hydroponic study was performed to find the role of zinc oxide nanoparticles (ZnO NPs) in plant growth, antioxidative response, and lead (Pb) accumulation in Persicaria hydropiper. Seedlings were grown in Pb-polluted media amended with 5, 10, 15, and 20 mg L-1 ZnO NPs. Inductively coupled plasma spectroscopy (ICP) was used for Pb analysis in plant tissues. Pb significantly inhibited seedling growth, and ZnO NPs alleviated Pb-induced stress by promoting plant growth, and improved chlorophyll and carotenoid contents. Oxidative stress ameliorated in ZnO NPs exposed seedlings through enhanced production of free proline, phenolics, flavonoids, and activation of antioxidative enzymes. Pb accumulation boosted in ZnO NP treatments, and highly significant increase in Pb accumulation in roots (255.60±4.80 mg kg-1), stem (124.07±2.84 mg kg-1), and leaves (92.00±3.22 mg kg-1) was observed in T3 (15 mg L-1 ZnO NPs) for P. hydropiper. Contrarily, ZnO NPs at 20 mg L-1 dose suppressed plant growth, Pb accumulation, secondary metabolites, and antioxidative enzyme activities. Moreover, positive correlation was found in Pb accumulation with free proline and secondary metabolite contents in plant tissues. These results suggest that ZnO NPs at optimum concentration may augment efficacy of plants to remove heavy metal from polluted water through nanophytoremediation.

Hematopoietic stem cell transplantation in Saudi Arabia between 1984 and 2016: Experience from four leading tertiary care hematopoietic stem cell transplantation centers.

Saudi Arabia is the largest of the Arabian Gulf countries with a total population of 33.41 million as of 2017. This report summarizes the experience from four leading tertiary care hematopoietic stem cell transplantation (HSCT) centers in Saudi Arabia representing more than 90% of all HSCTs performed in the country. Between 1984 and 2016, a total of 6,184 HSCTs were performed. Of these, 3,586 HSCTs were performed in adults and 2,598 HSCTs were performed in pediatric patients. Malignancy was the main indication for transplantation (47%). While most transplants were performed from an identical sibling donor, HSCTs from cord blood, unrelated and, more recently, haploidentical donors have also been performed. Relative shortage of HSCT bed capacity is perceived to be a limiting factor in Saudi Arabia. Lately, more HSCT centers are emerging with rapid growth, which may significantly improve the access to HSCT in the country in the near future.

Pride and Prejudice during the COVID-19 Pandemic: The Misfortune of Inappropriate Clinical Trial Design.

Coronavirus Disease 2019 (COVID-19) is a rapidly evolving global pandemic for which more than a thousand clinical trials have been registered to secure therapeutic effectiveness, expeditiously. Most of these are single-center non-randomized studies rather than multi-center, randomized controlled trials. Single-arm trials have several limitations and may be conducted when spontaneous improvement is not anticipated, small placebo effect exists, and randomization to a placebo is not ethical. In an emergency where saving lives takes precedence, it is ethical to conduct trials with any scientifically proven design, however, safety must not be compromised. A phase II or III trial can be conducted directly in a pandemic with appropriate checkpoints and stopping rules. COVID-19 has two management paradigms- antivirals, or treatment of its complications. Simultaneous assessment of two different treatments can be done using 2 × 2 factorial schema. World Health Organization's SOLIDARITY trial is a classic example of the global research protocol which can evaluate the preferred treatment to combat COVID-19 pandemic. Short of that, a trial design must incorporate the practicality of the intervention used, and an appropriate primary endpoint which should ideally be a clinical outcome. Collaboration between institutions is needed more than ever to successfully execute and accrue in randomized trials.

Role of testosterone in COVID-19 patients - A double-edged sword?

COVID-19 affects males twice as frequently as females with significantly increased severity and mortality. Current data suggest a direct correlation between the lower level of serum testosterone, inflammatory cytokines, disease severity, and poor clinical outcomes among male patients with COVID-19. The gradual decline in total and free testosterone levels has a direct correlation with serious pulmonary complications requiring advanced care (ICU, ventilators, ECMO, etc.). SARS-CoV-2 utilizes Angiotensin-Converting Enzyme II (ACE2) for entry in the host cell, and Transmembrane Protease, Serine 2 (TMPRSS2) to prime spike protein of SARS-CoV-2. Testosterone induces ACE-2 expression, a critical pulmonary protective enzyme. Low testosterone levels in males have a direct correlation with the high probability of ICU admission and the worse disease outcome (ARDS, duration of ICU stay, mortality). On the contrary, however, high testosterone levels can lead to thrombosis which is also one of the fatal manifestations in COVID-19 patients. A critical evaluation of the serum testosterone and its relevance to COVID-19 is warranted to re-evaluate strategies to effectively triage, prioritize, and manage high-risk patients for ICU admission, survival outcomes, targeted solutions, and operational algorithms.

The Increasing Trends in Cases of the Most Common Cancers in Saudi Arabia.

BACKGROUND: Cancer epidemiology in Saudi Arabia (SA) differs from that of the USA with respect to types of common malignancies. Hematologic malignancies are among the top five cancers prevalent in SA, including lymphoma and leukemia. Most common malignancies in SA also include breast, thyroid, and colorectal cancer. We sought to evaluate the current trends of these most common cancers in SA. METHODS: Electronic search analysis pertaining to Hodgkin's lymphoma, leukemia, breast, colorectal, and thyroid cancer were carried out from two databases: The Saudi Cancer Registry (SCR) and the Surveillance, Epidemiology, and End Results (SEER). Data on prevalence and incident frequency were collected. Trends from 2001 to 2014 were calculated and compared between SCR and SEER. FINDINGS: Leukemia is the most common cancer type among males in SA, followed by colorectal cancer. Hodgkin's lymphoma has become the third most common malignancy among Saudi males. Percentage of women's breast cancer and thyroid cancer among total cancer cases have increased by 10.5% and 1.7% respectively from 2001 to 2014, making them the first and second most common cancers in women respectively. Trends of thyroid cancer among males has been stable. Colorectal cancer stands as third most common among Saudi females. INTERPRETATIONS: There have been significant changes in trends of incidence rate of the most common cancers in SA among both males and females over the past decade. Breast cancer rates have risen at an alarming pace. More epidemiological studies need to be conducted to evaluate etiological factors at environmental, molecular, and genetic levels.

Quantification of Global Health Impact.

Global Health Engagement is used as one of the instruments of power to win hearts and minds of our partner nations and allies worldwide. Global Health Engagement is dynamic process with myriads of dimensions, applications, and deliverables. Planned and executed correctly, it can yield huge dividends as per SCP and Theater Campaign Plan.

Trends and Patterns of Primary Hepatic Carcinoma in Saudi Arabia.

BACKGROUND: Primary hepatic carcinoma (PHC) is the 4th most common malignancy among males at King Faisal Specialist Hospital and Research center (KFSH & RC) and in Saudi Arabia. There has been a steady increase in the number of PHC cases since 1975 at KFSH & RC and the burden of hepatic carcinomas is growing in Saudi Arabia. The aim of this study is to explore the changing trends and patterns of PHCs at KFSH & RC and conduct a comparative analysis with local, regional and global trends. MATERIALS AND METHODS: Cancer incidence data was obtained from the King Faisal Specialist Hospital and Research Center Tumor Registry program as per the American College of Surgeons standards. Clinico-epidemiological data of 1174 liver cancer patients from KFSH & RC during 2000 to 2014 and Saudi Cancer Registry (SCR) between 2001-2015 with total of 5,796 cases was reviewed. Trends, patterns of occurrence and other prognostic factors of interest were sub-stratified by gender, age, stage, and grade. RESULTS: Temporal trends indicated a rising incidence of PHC from 2001 to 2014 in Saudi Arabia; from 323 cases in 2001 to 376 cases in 2015 as per SCR. A total of 2,779 new cases of PHC were seen at KFSH & RC between 1975 and 2014; the rate of PHC increased from 60 cases in 2004 to 80 cases in 2014. Majority of liver cancers were hepatocellular carcinomas (79.3%) followed by cholangiocarcinoma (11%), and hepatoblastoma (4.7%) with significantly higher incidence among males with a male to female ratio of 2:1 (p <0.01). The highest incidence by age was at 6th and 7th decade of life. Majority of patients were diagnosed in localized stage (44.6%) and had a past medical history (28.2%) of hepatitis (p < 0.001). The most common treatment for liver cancer at KFSH & RC was surgery (26.7%) followed by transplant (9.5%). CONCLUSION: Despite improvement in preventive measures, incidence rates of PHC has increased during the last decade with marked regional variation. Etiology of this escalating trend is multifactorial; predominantly, chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), heavy alcohol consumption, obesity, diabetes, and tobacco smoking. This exponential increase may also be due to early detection and diagnosis due to expanding health care delivery in the Kingdom. Further studies are indicated to comprehend the rising trends at the molecular and genetic levels.

Magnesium oxide nanoparticles and thidiazuron enhance lead phytoaccumulation and antioxidative response in Raphanus sativus L.

An in vitro study was conducted to evaluate the effects of thidiazuron (TDZ) growth regulator and magnesium oxide (MgO) nanoparticles on radish (Raphanus sativus L.) under lead (Pb) stress. Effects of TDZ and MgO on seed germination, growth, biomass, total phenolics and flavonoids, antioxidant potential, and Pb phytoaccumulation in different plant parts were assessed. Nanoparticles of MgO were synthesized with leaf extract of Sageretia thea (Osbeck) plant. Thidiazuron and MgO nanoparticles were added to growth media in individual and in combinations. Lead (50 mg L-1) was added to growth media. Thidiazuron and MgO nanoparticles increased plant growth, phenolic and flavonoid contents, free radical scavenging activity, and lead phytoaccumulation. The increase was highly significant in TDZ and MgO nanoparticle combination treatments (T5, T6). Treatment (T6) showed a sixfold increase in Pb accumulation (1721.73 ± 17.4 µg g-1 dry biomass) as compared to control (274.29 ± 4.23 µg-1g-1). Total phenolic and dry biomass showed significantly positive correlation in leaves (R2 = 0.73), stem (R2 = 0.58), and roots (R2 = 0.72). The correlation of Pb accumulation and phenolic contents was significantly positive in root (R2 = 0.80), stem (R2 = 0.92), and leaves (R2 = 0.69). Flavonoid showed a positive correlation with dry biomass and Pb accumulation. Antioxidant activity was highly increased in leaves followed by stem and root. Findings show that TDZ in combination with MgO nanoparticles can play a significant role in secondary metabolite production and Pb phytoaccumulation.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Stem Cell Transplantation Program in Countries with Limited Resources, Part II: Clinical, Technical, and Socioeconomic Considerations.

The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. Although this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state-of-the-art treatments, including transplantation, by providing financial, technological, legal, ethical, and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population and potentially provide long-term cost savings by circumventing the need for their citizens to seek care abroad. The costs of establishing an HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. In addition, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT, and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation for establishing HSCT programs, with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in resource-constrained settings.

Narrowing the gap for hematopoietic stem cell transplantation in the East-Mediterranean/African region: comparison with global HSCT indications and trends.

Hematopoietic Stem Cell Transplantation (HSCT) activity was evaluated in the African (AFR)/EMRO region and compared to the global activity for the years 2006-2013. Data were obtained from 1570 teams in the 6 WHO continental regions. Of these, 29 (1.85%) of all teams were active in 12 of the 68 AFR/EMRO countries. They reported 2.331 (3.3%) of the worldwide 71.036 HSCT, and a transplant rate of 32.8 (TR; HSCT/10 million inhabitants; worldwide 128.5). This reflects still the lowest regional TR despite an increase of 90% since 2006. HSCT activity in AFR/EMRO countries was characterized by a higher use of allogeneic compared to autologous HSCT, an almost exclusive use of family donors, including haploidentical family donors. These findings contrast with the prevalence of autologous over allogeneic HSCT, and a higher frequency of unrelated HSCT in other parts of the world. Of note, the increase by 200% in HSCT for hemoglobinopathies from 2006 to 2013 (72 per year) in the AFR/EMRO region. This reflects the specific role of HSCT for these disease categories with high prevalence and incidence in the AFR/EMRO region. This report provides information for the competent authorities to foster adequate infrastructure. It urges transplant organization to optimize their cooperation.

Current concepts on hematopoietic stem cell transplantation outcome registries; Emphases on resource requirements for new registries.

There is tremendous variability in size, scope, and resource requirements for registries depending on the number of patients and participating sites. The outcome registries are organized systems to collect uniform data using an observational study methodology. Patient registries are used to determine specified outcomes for a population for predetermined scientific, clinical, or policy purposes. Historically, outcome registries established in the development of hematopoietic stem cell transplantation (HSCT) have now evolved into myriads of locoregional and international transplant activity and outcome resources. Over time, these registries have contributed immensely in determining trends, patterns, and treatment outcomes in HSCT. There is wider variation in the goals, mission, objectives, and outcomes of the ongoing registries depending on the organizational structure. There is a growing trend toward overarching relationship of these registries to serve as complementary and interoperable resources for high potential collaborative research. In addition to capacity building, standardized, accredited, and optimally operational registries can provide unmatched and unparalleled research data that cannot be obtained otherwise. Moving forward, HSCT data collection, collation, and interpretation should be an integral part of the treatment rather than an option. Quality assurance and continuous quality improvement of the data are pivotal for credibility, measurable/quantifiable outcomes, clinically significant impact, and setting new benchmarks.

Hematopoietic stem cell transplantation in the Eastern Mediterranean Region (EMRO) 2011-2012: A comprehensive report on behalf of the Eastern Mediterranean Blood and Marrow Transplantation group (EMBMT).

OBJECTIVE/BACKGROUND: The Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group has accumulated over 31 years of data and experience in hematopoietic stem cell transplantation (HSCT), particularly in hemoglobinopathies, severe aplastic anemia, inherited metabolic and immune disorders, in addition to a wide array of hematologic malignancies unique to this region. A regional update in current HSCT trends is highly warranted. We studied the trends of HSCT activities in World Health Organization-Eastern Mediterranean (EMRO) region, surveyed by the EMBMT, between 2011 and 2012. METHODS: Retrospective analysis of the survey data mainly of cumulative number of transplants, types of transplants (autologous vs. allogeneic), types of conditioning such as myeloablative versus reduced intensity was conducted. Also, trends in leukemias, hemoglobinopathies, severe aplastic anemia, inherited bone marrow failure syndromes, amongst others were analyzed. RESULTS: Twenty-one teams from nine EMRO countries reported their data (100% return rate) to the EMBMT for the years 2011-2012, with a total of 3,546 first HSCT (1,670 in 2011; 1,876 in 2012). Allogeneic HSCT (allo-HSCT) represented the majority (62%) in both years. The main indications for allo-HSCT were acute leukemias (988; 46%), bone marrow failure syndromes (421, 20%), hemoglobinopathies (242; 11%), and immune deficiencies (157; 7%). There was a progressive increase in the proportions of chronic myeloid leukemia cases transplanted beyond first chronic phase (37 [7%] of all chronic myeloid leukemia cases in 2011 vs. 39 [29%] in 2012). The main indications for autologous transplants were multiple myeloma/plasma cell disorders (510; 39%), Hodgkin lymphoma (311; 24%), non-Hodgkin lymphoma (259; 20%), and solid tumors (163; 12%). Reduced intensity conditioning continued to show a progressive decrease over years (9.5% in 2011 vs. 7.9% in 2012), yet remained relatively low compared with contemporary practices in Europe published by EBMT. The vast majority (91%) of allo-HSCT source was from sibling donors with continued dominance of peripheral blood (64%) followed by bone marrow (33%).While umbilical cord blood transplants increased to 4% of allo-HSCT, matched unrelated donor remained underutilized and there was no haplo-identical transplant reported. Large centers with >50 HSCT/year, showed a continued increase in the total number of allo-HSCT over the past 2years that may be related to capacity building issues and require further studies. CONCLUSION: There is a discernable increase of HSCT rate in the EMRO region with a significant expansion in utilization of cord blood transplants and allogeneic peripheral blood-HSCT as a valuable source. However, further research of outcome data and the development of regional donor banks (cord blood and matched unrelated donors) may help to facilitate future planning to satisfy the escalating regional needs and augment collaboration within the EMBMT and globally.

Awareness and Perceptions of Clinical Trials in Cancer Patients and Their Families in Saudi Arabia.

Despite the increasing number of medical articles being published from the Middle East, clinical research is still lagging behind compared to other regions. Enrolling participants into clinical trials presents an important challenge. We wanted to explore the perception, knowledge, and willingness of cancer patients to participate in oncology clinical trials and to recommend strategies to overcome these challenges. A 31-item questionnaire was administered to cancer patients and their family members in an outpatient clinic. Two hundred four patients and family members were enrolled between December 2011 and February 2013. Fifty-eight percent of the participants were aware of clinical trials. Some misconceptions included the following: 22% believed that no clinical trials were conducted in the Arab world, 19% believed that clinical trials in the Arab world were not under any regulatory authority supervision, and 15% believed that local clinical trials are conducted on subjects without their consent. One third of patients assumed that clinical trials are executed on animals instead of humans, and greater than 40% believed that clinical trials are performed for new medications only. Finally, 61% of the survey participants who were aware of clinical trials expressed their willingness to participate in trials. This large cohort survey demonstrated that a relatively significant number of Saudi cancer patients and their families are aware of clinical trials and a similarly high number of participants are willing to participate in clinical trials. This leads us to believe that patients' awareness and perception of clinical trials are not a significant limiting factor in clinical trial recruitment in our region.

Incidence of thyroid cancer in the Kingdom of Saudi Arabia, 2000-2010.

BACKGROUND: Thyroid cancer is the second most common malignancy among females at King Faisal Specialist Hospital and Research Centre (KFSH&RC) and in Saudi Arabia, accounting for about 11% of all newly diagnosed female cancers in the country in 2008. Over the past several decades, an increasing incidence of thyroid cancer has been reported in the Kingdom of Saudi Arabia. There are no comprehensive clinical epidemiological data for the trends of thyroid cancer incidence compared to the global incidence. This report reviews the thyroid cancer incidence in KFSH&RC and compares that with Saudi Arabia, the Gulf region, North America and globally from 2000 to 2010. METHODS: Retrospective review of patients with thyroid cancer was carried out from 2000 to 2010, using the hospital Tumor Registry program as per the American College of Surgeons standards. Trends and patterns of all well-known prognostic factors were sub-stratified by age, stage and grade. RESULTS: A total of 2292 patients with thyroid cancer were treated at KFSH&RC, Riyadh, Saudi Arabia, from 2000 to 2010. Thyroid cancer constitutes about 9% of all malignancies and 12% of all female malignancies at KFSH&RC, which are significantly higher compared to the USA, where thyroid cancer represents only 2.9% of all malignancies and 4.6% of all female malignancies. Papillary adenocarcinoma was the most common histological subtype followed by papillary carcinoma, follicular variant. Median age at diagnosis was 40 for females and 44years for males. Overall Age-Standardized Incidence Rate (ASR) was 4.4/100,000 (6.8 for female and 2/100,000 for males) in the Kingdom in 2008. Median age at diagnosis was 38years and the highest incidence was in the 30-39year age group in KFSH&RC. About 48% of patients presented in the localized stage and 60% underwent combined modality treatment consisting of surgery, radiation and hormonal therapy. There was significantly increased incidence among females as compared to males. The age-adjusted thyroid cancer incidence rates from 2000 to 2010 varied three-fold more for females than for males. Considerable geographical variations were present in thyroid cancer incidence in Saudi Arabia. CONCLUSION: Thyroid cancer incidence rates have increased exponentially between 2000 and 2010 and there is significant geographical variation in the incidence of thyroid cancer throughout the Kingdom. Thyroid cancer has become the second most common cancer among young Saudi women with a male to female ratio at 0.3:1. Rising incidence of thyroid cancer in Saudi Arabia may be due to the increased detection and diagnosis of the thyroid cancers and not only an increase in the true occurrence of thyroid cancer. More studies are required to determine this significant difference at the molecular level.

Hematopoietic stem cell transplantation practice variation among centers in the Eastern Mediterranean Region (EMRO): Eastern Mediterranean Bone Marrow Transplantation (EMBMT) group survey.

INTRODUCTION: This practice survey is conducted to analyze clinical hematopoietic stem cell transplantation (HSCT) practice variability among centers in the WHO Eastern Mediterranean Region (EMRO), as represented by the Eastern Mediterranean Blood and Marrow Transplantation (EMBMT) group. METHOD: This internet based survey was completed by the medical program directors of the EMBMT centers; 17 centers participated. The survey collected data on various clinical aspects of HSCT practice. RESULTS: Consistency in pre HSCT cardiac (100%), pulmonary (82%) and viral screen (100%) was observed. Obtaining informed consent was universal. Pre-HSCT psychological assessment is practiced in 50% of the centers. All centers used single-bedded rooms with HEPA filters. Visitor policy during neutropenic phase and the use of gowns, masks or gloves when examining patients varied among centers. MRSA/VRE screen and use of low bacterial diet were applied in 65% and 82%, respectively. Anti-bacterial prophylaxis is employed in 58% (Auto-SCT) and 60% (Allo-SCT) of the centers. Drug choice varied (cotrimoxazole, ciprofloxacin, levofloxacin, piperacillin-tazobactam); 60% of the centers used penicillin prophylaxis in GVHD patients. PCP prophylaxis is applied in 58% (Auto-SCT) and 87% (Allo-SCT) of the centers; cotrimoxazole is usually used. Anti-viral prophylaxis with acyclovir or, less commonly, valacyclovir is used in 70% (Auto-SCT) and 93% (Allo-SCT) of centers. Anti-fungal prophylaxis is applied in 70% (Auto-SCT), 93% (myeloablative Allo-SCT) and 87% (reduced intensity [RIC] Allo-SCT). Fluconazole is used in all Auto-SCT and majority of Allo-SCT recipients; few centers used other agents (itraconazole, voriconazole, amphotericin B) in Allo-SCT. Prophylactic GCSF use varied among centers: Auto-SCT 77%, myeloablative Allo-SCT 33%, RIC Allo-SCT 27%. Use of ursodeoxycholic acid for venoocclusive disease (VOD) prophylaxis is variable: 60% (Allo-SCT) and 12% (Auto-SCT). Cyclosporine/methotrexate is the most commonly used GVHD prophylaxis in myeloablative Allo-SCT (93%); heterogeneity was seen in RIC SCT. Treatment of steroid refractory acute GVHD varied (ATG 53%, higher steroid dose 40%). CMV monitoring varied between antigenemia (53%) and PCR (40%) techniques. Pre-emptive anti CMV therapy is used in 86% of the centers, while 7% used routine CMV prophylaxis; 7% had no specific CMV management policy. CONCLUSION: Consistency was observed in areas of pre-SCT work up, use of single rooms, HEPA filters and GVHD prophylaxis. Heterogeneity is observed in other practice aspects including other isolation measures, anti-microbial prophylaxis, VOD prophylaxis, growth factor use and treatment of steroid refractory GVHD. Further studies are needed to probe the impact of such practice variations on post-transplant outcome and to ascertain the best clinical practice approach.

Allogeneic hematopoietic stem cell transplantation in adolescent and adult patients with high-risk T cell acute lymphoblastic leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is often recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (≥CR2) and sometimes in high-risk (HR) patients in first complete remission (CR1). Between January 1995 and July 2009, 53 patients with HR T-ALL underwent allo-SCT at our institution. Median age was 18 years (range, 14-51). Thirty-two patients (60.3%) were in CR1, 18 (34%) were in ≥CR2, and 3 (5.7%) were in relapse. The cumulative incidence of nonrelapse mortality at 5 years was 22.5%. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 40.2%, and that of chronic GVHD was 43.7%. The majority of relapses (88.9%) occurred within 1 year after SCT. The cumulative incidence of relapse (CIR) at 5 years was 35.6%. CIR was 29.8% in patients in CR1, 35.3% in patients in ≥CR2 and all patients transplanted in relapse had disease recurrence post-allo-SCT (P = .000). Overall survival (OS) and disease-free survival (DFS) at 5 years were 43.5% and 41.8%, respectively. The 5-year OS was 53.5% (95% CI 34.5%-72.5%) and 5-year DFS was 52% (95% CI 33%-71%) in patients who underwent allo-SCT in CR1, compared with 31.9% (95% CI, 9%-54.8%) and 29.4% (95% CI 7.6%-51.2%) in those who underwent allo-SCT in ≥CR2. On multivariate analysis, disease status at SCT remained significantly associated with OS (P = .007), DFS (P = .002), and CIR (P = .000). The presence of extramedullary disease at diagnosis had no effect on the different outcomes. Grade II-IV acute GVHD was significantly associated with a lower OS (P = .006) and DFS (P = .01). Our data indicate that allo-SCT represents an effective treatment for HR T-ALL, particularly when performed in CR1.

Hematopoietic stem cell transplantation in the Eastern Mediterranean Region (EMRO) 2008-2009: report on behalf of the Eastern Mediterranean Bone Marrow Transplantation (EMBMT) Group.

BACKGROUND: The Eastern Mediterranean Bone Marrow Transplantation (EMBMT) Group has accumulated over 25 years of data and experience in hematopoietic stem cell transplantation (HSCT), most particularly in hemoglobinopathies, severe aplastic anemia (SAA), and inherited metabolic and immune disorders, in addition to hematologic malignancies peculiar to the region and where recent updates in trends in activities are warranted. OBJECTIVES: To study trends in HSCT activities in the World Health Organization-Eastern Mediterranean (EM) region surveyed by EMBMT between 2008 and 2009. STUDY DESIGN: Retrospective analysis of the survey data, mainly of the cumulative number of transplants, types of transplants (autologous vs. allogeneic), types of conditioning as myeloablative (MAC) vs. reduced intensity conditioning (RIC) and trends in leukemias, hemoglobinopathies, SAA, inherited bone marrow failure syndromes amongst others. RESULTS AND DISCUSSION: Fourteen teams from ten Eastern Mediterranean Region Organization (EMRO) countries reported their data (100% return rate) to the EMBMT for the years 2008-2009 with a total of 2608 first HSCT (1286 in 2008; 1322 in 2009). Allogeneic HSCT represented the majority (63%) in both years. The main indications for allogeneic HSCT were acute leukemias (732; 44%), bone marrow failure syndromes (331, 20%), hemoglobinopathies (255; 15%) and immune deficiencies (90; 5%). There was a progressive increase in the proportions of chronic myeloid leukemia (CML) cases transplanted beyond the first chronic phase (3; 7% of all CML cases in 2008 vs 13; 29% in 2009). The main indications for autologous transplants were plasma cell disorders (345; 36%) Hodgkin disease (256; 27%), non-Hodgkin lymphoma (207; 22%) and solid tumors (83; 9%). RIC continued to show a progressive increase over the years (7% in 2007, 11% in 2008 and 13% in 2009), yet remained relatively low compared to contemporary practices in Europe published by EBMT. The vast majority (95%) of allo-HSCT sources were from sibling donors with a continued dominance of peripheral blood (PB) (1076; 63%), while cord blood transplant (CBT) increased to 83 (5% of allo-HSCT), matched unrelated donor (MUD) remained underutilized (1; 0%) and there were no haploidentical transplants reported. Large centers with >50 HSCT/year showed a plateau of the total number of allo-HSCT over the last 5 years that may be related to capacity issues and needs further study. CONCLUSIONS AND RECOMMENDATIONS: There is an overall increased rate of HSCT in the EMRO region with a significant increase in utilization of CBT and allogeneic PB-HSCT as a valuable source. However, further research on outcome data and development of regional donor banks (CB and MUD) may help facilitate future planning to satisfy the regional needs and increase collaboration within the group and globally.

Trends of hematopoietic stem cell transplantation in the Eastern Mediterranean region, 1984-2007.

Hematopoietic stem cell transplantation (HSCT) activity was surveyed in the 9 countries in the World Health Organization Eastern Mediterranean region that reported transplantation activity. Between the years of 1984 and 2007, 7933 transplantations were performed. The number of HSCTs per year has continued to increase, with a plateau in allogeneic HSCT (allo-HSCT) between 2005 and 2007. Overall, a greater proportion of transplantations were allo-HSCT (n = 5761, 77%) compared with autologous HSCT (ASCT) (n = 2172, 23%). Of 5761 allo-HSCT, acute leukemia constituted the main indication (n = 2124, 37%). There was a significant proportion of allo-HSCT for bone marrow failures (n = 1001, 17%) and hemoglobinopathies (n = 885, 15%). The rate of unrelated donor transplantations remained low, with only 2 matched unrelated donor allo-HSCTs reported. One hundred umbilical cord blood transplantations were reported (0.017% of allo-HSCT). Peripheral blood stem cells were the main source of graft in allo-HSCT, and peripheral blood stem cells increasingly constitute the main source of hematopoietic stem cells overall. Reduced-intensity conditioning was utilized in 5.7% of allografts over the surveyed period. ASCT numbers continue to increase. There has been a shift in the indication for ASCT from acute leukemia to lymphoproliferative disorders (45%), followed by myeloma (26%). The survey reflects transplantation activity according to the unique health settings of this region. Notable differences in transplantation practices as reported to the European Group for Blood and Marrow Transplantation over recent years are highlighted.