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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.

Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 15% of all newly diagnosed ALL in children and adolescents and is associated with worse outcomes compared to pre-B ALL. We aimed to decrease T-ALL relapses by intensifying our regimen. Methods: Patients with T-ALL were treated using two different regimens; before September 2014, patients were treated per St. Jude Total XV protocol; subsequently, a major change was adopted by adding two intensive blocks: FLAG and Re-Intensification (fludarabine, dexamethasone, cytarabine, etoposide and asparaginase). Cranial radiation was limited to patients with WBC >=100k/µl at diagnosis and/or patients with CNS2/CNS3 status. Results: Between June 2005 and April 2020, a total of 100 patients (76 males) were treated and followed for a median of 70 months (range, 14-181 months). Median age at diagnosis was 9 years (range,0.5-17.8 years). Forty-eight patients were diagnosed after September 2014 and received the augmented regimen; their median follow up was 46 months (range,14-74 months). The 5-yr-EFS estimates for patients who received the augmented regimen vs. standard regimen were 87%±4.9% vs 67%±6.8% (p=0.03); and the 5-yr-OS estimates were 87%±5.1% vs. 71%±6.3% (p=0.06) respectively. Treatment related mortality (TRM) were reported in 2 patients treated using our standard regimen but none for patients who received the augmented regimen. Conclusions: We implemented a novel approach with early intensification added to a backbone of modified St. Jude Total-XV regimen for patients with T-ALL that resulted in improved outcome with no treatment related mortality.

Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Introduction: Breast Cancer is the most common cancer worldwide and so in our region. In Jordan, almost 50% of patients are diagnosed before the age of 50. Knowledge of BRCA1/2 mutations has significant clinical impact on the management and prevention of breast cancer. In this study, we evaluate the prevalence of germline mutations in BRCA1/2 among high-risk Jordanian patients selected as per the updated NCCN guidelines. Methods: Jordanian breast cancer patients, stages I-IV, with a selected high-risk profile treated at our institution were invited to participate. Blood samples were obtained for DNA extraction, and BRCA sequencing and dosage analysis were performed at Leeds Cancer Center, Leeds-United Kingdom. BRCA1/2 mutations were classified as pathogenic/likely pathogenic and variant of uncertain significance (VUS). Clinical and pathological data were obtained from patients' medical records and a detailed 3-generation family history was also obtained by a genetic counselor. Results: A total of 517 patients were enrolled, genetic testing and counseling have been completed for all. Median age at diagnosis was 39 (range: 20-78) years. Among the whole group, 72 (13.9%) patients had pathogenic or likely pathogenic BRCA1 (n=24, 4.6%) or BRCA2 (n=48, 9.3%) mutations, while 53 (10.3%) others had VUS. Among 333 younger (≤40 years) patients, pathogenic/likely pathogenic mutations were observed in 44 (13.2%) patients and 36 (10.8%) others had VUS. Among 242 patients who had one or more close relatives with breast cancer, diagnosed at age 50 years or younger, 40 (16.5%) had pathogenic/likely pathogenic mutations (Table). Twenty (35.1%) of the 57 patients with triple-negative (TN) disease had pathogenic/likely pathogenic mutations; 16 (28.1%) were in BRCA1. Rate was significantly higher (55.6%, p Conclusions: BRCA1/2 mutations are not uncommon and may contribute to the pathogenesis of familial breast cancer among Jordanians. Young age, per se, has the weakest association with positive BRCA1/2 mutations while TN-disease, especially when associated with positive family history, has significantly higher mutation rate. The establishment of Clinical Cancer Genetics program made running such culturally-sensitive genetic testing and counseling more acceptable even in societies like ours. Table: Rates of positive BRCA1/2 mutation across different indications for testingVariableTotalPositive BRCA mutations*BRCA1BRCA2BRCA1/2P-ValueAge (years)≤4033315 (4.5%)29 (8.7%)44 (13.2%)0.53>401849 (4.9%)19 (10.3%)28 (15.2%)Age ≤ 50 years with one or more close relative with breast cancer at any ageYes2428 (3.3%)32 (13.2%)40 (16.5%)0.1No27516 (5.8%)16 (5.8%)32 (11.6%)Age ≤ 60 with triple negative diseaseYes5716 (28.1%)4 (7.0%)19 (35.1%) Citation Format: Hikmat Abdel-Razeq, Lama Abujamous, Amal Al-Omari, Abdelghani Tbakhi, Dima Jadaan. Genetic counseling and genetic testing for germline BRCA1/2 mutations among high risk breast cancer patients in Jordan: A study of 500 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-06.

Data compression is a challenging and increasingly important problem. As the amount of data generated daily continues to increase, efficient transmission and storage has never been more critical. In this study, a novel encoding algorithm is proposed, motivated by the compression of DNA data and associated characteristics. The proposed algorithm follows a divide-and-conquer approach by scanning the whole genome, classifying subsequences based on similarity patterns, and binning similar subsequences together. The data are then compressed in each bin independently. This approach is different than the currently known approaches: entropy, dictionary, predictive, or transform based methods. Proof-of-concept performance was evaluated using a benchmark dataset with seventeen genomes ranging in size from kilobytes to gigabytes. The results showed considerable improvement in the compression of each genome, preserving several megabytes compared with state-of-art tools. Moreover, the algorithm can be applied to the compression of other data types include mainly text, numbers, images, audio, and video which are being generated daily and unprecedentedly in massive volumes.

Haploidentical hematopoietic cell transplantation (HCT) is a valuable curative option for children with non-malignant diseases. Haploidentical HCT using post-transplant cyclophosphamide (PTCy) is a readily available option in the absence of an HLA- matched donor. We conducted a retrospective single-center study on the outcome of haploidentical HCT in children with non-malignant diseases. We gathered data from 44 patients underwent HCT in the period 2015 to 2020. The indications for HCT were bone marrow failure, primary immunodeficiency, metabolic disorders, and hemoglobinopathy. Median age at HCT was 4 years (range 0.7-20).The conditioning regimens were myeloablative (n=16), or reduced intensity (n=26). After a median follow-up of 20 months (range 4-71), 2-year overall survival was 89% and 2 year GvHD-free relapse-free survival (GRFS) was 66%. Incidence of primary graft failure was 13.6%. Cumulative incidence of grade II-IV acute and moderate/severe chronic GvHD were 20% and 6.4%, respectively. Younger age at HCT (p

10580 Background: Detection of pathogenic germline variants (PGVs) has a significant and growing impact on the management of patients with many types of cancer. Most research to date evaluated individuals of European background, which can result in skewed genetic testing criteria and variant interpretation. Additional data are needed from diverse populations. This study aimed to investigate a universal germline testing strategy and the pattern and frequency of PGVs among all newly diagnosed cancer patients at a single center in Jordan. Methods: In this prospective, observational study, consecutive patients newly diagnosed with cancer were classified as meeting or not meeting National Comprehensive Cancer Network (NCCN) germline genetic testing criteria. All patients underwent an 84-gene panel test, independent of age, stage or family history. Demographics and clinical history were collected and analyzed from information provided by the clinicians on the test requisition form. Descriptive statistics were employed, and statistical significance was determined by two-tailed Fisher’s exact test and unpaired t test. Results: In total, 1377 cancer patients of Arabic background were enrolled, of which 831 (60.3%) met NCCN criteria (Table). PGVs were identified in 210 (15.3%). Excluding the 29 patients who were carriers for autosomal recessive conditions, 192 PGVs were identified in 181 (13.1%) patients. PGVs were most commonly identified in APC (p.I1307K variant, 55, 28.6%), BRCA2 (35, 18.2%), BRCA1 (21, 10.9%), and TP53 (12, 6.3%). While patients who met NCCN testing criteria were more likely to have a PGV (p95% of whom might qualify for increased screening, targeted therapies, and/or clinical trials. [Table: see text]

Pattern matching is a fundamental process in almost every scientific domain. The problem involves finding the positions of a given pattern (usually of short length) in a reference stream of data (usually of large length). The matching can be an exact or as an approximate (inexact). Exact matching is to search for the pattern without allowing for mismatches (or insertions and deletions) of one or more characters in the pattern), while approximate matching is the opposite. For exact matching, several data structures that can be built in linear time and space are used and in practice nowadays. For approximate matching, the solutions proposed to solve this matching are non-linear and currently impractical. In this paper, we designed and implemented a structure that can be built in linear time and space ($O(n)$) and solves the approximate matching problem in $O(m + \frac {log_2n {(log_\Sigma n)} ^{k+1}}{k!} + occ)$ search costs, where $m$ is the length of the pattern, $n$ is the length of the reference, and $k$ is the number of tolerated mismatches (and insertion and deletions)., Comment: 15 pages double spaced

The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.

The response to the COVID-19 pandemic from the research and science community has been vigorous, with information being released faster than that of any other event in human history. Articles related to the virus were being rapidly published by January 2020. A small fraction of these publications comprised reports of prospective clinical trials (0.25%), and many of these trials have imparted conflicting conclusions, leading to confusion among the public and the scientific community. Additionally, the pandemic has raised many serious scientific and ethical concerns related to clinical research. In this review, we divided the conduct of clinical research trials into three steps and critically reviewed each step, along with the challenges and obstacles arising amid the ongoing crisis. The clinical research steps we reviewed include (1) clinical trial design factors such as social and scientific value, feasibility, single vs. multicenter trials, randomization, control groups, endpoints, off-label and compassionate use of medications, data analysis, and verifying the integrity of data; (2) ethical issues such as committee approvals, efficiency, virtual visits and remote monitoring, informed consent, shipping investigational products, and external monitoring and audits; and (3) publication and sharing of preprints, press releases, social media, and misinformation. The COVID-19 pandemic is adversely affecting existing clinical trials for other ailments and diseases, including cancer, with most trials being delayed or deferred. Although urgency is needed to communicate effective treatment and prevention strategies for COVID-19, research efforts should maintain the same high-quality core ethical principles that governed human subject research before the pandemic. Despite the catastrophic devastation caused by the pandemic, the adoption of more flexible, cost-effective methods of conducting clinical trials (without compromising ethical conduct, safety, or data integrity, while maintaining research efficiency) represents a potential silver lining. Streamlining clinical research will help to congruently address other important health issues, despite the ongoing COVID-19 crisis.

Introduction BRAF V600E is one of the most common mutations in Papillary Thyroid Cancer (PTC). Its clinical correlation has been extensively studied with contradictory results. The aim of this study is to evaluate the oncological impact of BRAF V600E mutation on a cohort of Middle Eastern PTC patients treated at a single institute.Methods Patients with histologically confirmed PTC that were treated surgically between 2006 to 2015 were included in the study. Formalin fixed paraffin embedded tumor blocks were sectioned and tested for BRAF V600E mutation. Short- and long-term oncological outcomes were collected. Results 128 patients (68% females) were included with a mean age of 38 years (±13.8). Median follow-up was 50 months. BRAF V600E mutation was found in 71% of patientsIThe BRAF negative tumors were significantly larger than the BRAF positive (3.47 cm versus 2.31 cm respectively, P = 0.009). All other clinicopathological characteristics were comparable between BRAF V600E mutation positive and negative groups. The two groups showed similar 5-year Disease-free (P= 0.37) and Overall survival rates (P = 0.94).Conclusion BRAF V600E mutation did not affect loco-reginal recurrence, distant metastasis, overall and disease-free survival. These results support the diversity of BRAF V600E significance among various ethnicities.

Mantle cell lymphoma (MCL) is a rare B-cell malignancy that remains challenging to treat with high rates of relapse. Frontline strategies range from intensive chemotherapy followed by consolidation with autologous stem cell transplant (ASCT), to less-intensive therapies including combination regimens. The treatment landscape for relapsed patients includes Bruton tyrosine kinase (BTK) inhibitors among other targeted treatments. Novel agents such as the selective BCL2 inhibitor venetoclax showed high response rates when used as monotherapy for refractory relapsed MCL. The rituximab, bendamustine, and cytarabine (R-BAC) regimen, while response rates were high, were not durable. Chimeric antigen receptor (CAR) T-cell products targeting CD19 have been efficacious in relapsed and refractory MCL patients. Brexucabtagene autoleucel (brexu-cel, formerly KTE-X19) was approved by US Food and Drug Administration (FDA) in July, 2020, for treatment of refractory and relapsed MCL. This article provides an overview for the available management strategies for relapsed MCL and examines the role of CAR T-cell in the current and future treatment of MCL.

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

Neutrophil recovery after autologous hematopoietic cell transplantation (auto-HCT) is affirmed with achievement of an Absolute Neutrophil Count (ANC) of ≥500/uL. There is growing evidence that neutrophils may be observed despite undetectable peripheral ANC counts following autologous hematopoietic cell transplant and are preferentially delivered to sites of inflammation. We report an interesting case that confirms neutrophil tissue delivery to the skin two days prior to evidence of blood engraftment after an auto-HCT.

Data compression is a fundamental problem in the fields of computer science, information theory, and coding theory. The need for compressing data is to reduce the size of the data so that the storage and the transmission of them become more efficient. Motivated from resolving the compression of DNA data, we introduce a novel encoding algorithm that works for any textual data including DNA data. Moreover, the design of this algorithm paves a novel approach so that researchers can build up on and resolve better the compression problem of DNA or textual data.

Key Points DM, an autoimmune inflammatory myopathy, can be associated with a number of malignancies, including, rarely, myelodysplastic syndromes. Allo-HCT presents a novel approach to treat refractory DM in patients with a coexisting malignancy through the GvA effect.

Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV-free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients' age at transplant >= 13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment.

Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses (SARS-FCoVs); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset of patients who presented with SARS during the 2003 outbreak. We established a gene signature that defines differential gene expression in patients who were sick with SARS vs. healthy controls and convalescent patients. We used a robust platform to conduct drug repositioning based on clustered gene expression and pathway enrichment to identify best matching drugs. We identified 55 agents of potential benefit. In most of these drugs we were able to establish a link to previous related research, use as antiviral, or at least a hypothetical role in treating SARS-FCoVs. Most notably, the heat shock protein 90 (hsp90) emerged as a major component that enables viruses to hijack infected cells through the process of autophagy. Almost half of the drugs identified could be linked to hsp90. As such, we propose using hsp90 inhibitors, mainly geldanamycin and its derivatives, to treat COVID-19.

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.