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Aim: The outcome of T-cell acute lymphoblastic leukemia (T-ALL) has improved with the use of pediatric-inspired protocols in the adolescents and young adults (AYA) population. There is limited literature regarding the outcome of T-ALL/lymphoblastic lymphoma (LBL) AYA patients treated with pediatric protocols. Methods: A total of 35 T-ALL/LBL-AYA patients ages between 14 and 55 years were treated with AYA-15 protocol. Results: At a median follow-up of 5 years the overall survival, disease-free survival and event-free survival are 71%, 62% and 49.6% respectively. Toxicities were within the expected range. Conclusion: Our single-center experience real-world data in treating T-ALL/LBL-AYA patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18–55 years.

Background: primary graft failure is a devastating complication after allogeneic transplant. Donor specific antibodies has been reported as a major risk factor contributing to graft failure. We retrospectively analyzed our haploidentical transplant registry to report the incidence and impact of DSA and anti-HLA on engraftment in a cohort of malignant hematologic disease conditioned with myeloablative regimens. Methods: retrospective analysis of consecutive cases with malignant hematologic disorders who received a myeloablative haplo-HSCT at a single center. Results: 107 patients were identified with a median recipient age of 22 and a median donor age of 31. Sixty-two patients had AML (58%), 29 had ALL (27%), and 16 (15%) had other malignancies. Sixty-one recipients (57%) had positive anti-HLA, 56 of them had the DSA results available, of these 17 patients had DSAs (15% of the total number of patients, or 28% of patients who have anti-HLA antibodies). The median cumulative MFI was 2062 (IQR: 1038 - 6500). Sixty three percent of the DSA were against class II HLA antigens, while 37% were against class I HLA antigens. The OS, CIR, aGvHD, and cGvHD did not differ between patients with and without anti-HLA antibodies, nor between patients with and without DSA. The gender of the recipient and donor, as well as the gender mismatch between recipient and donor, were statistically associated with the incidence of anti-HLA antibodies, but not with DSA. Three patients only developed GF (2.8%), one was primary (0.9%) and the other two had secondary GF (1.9%). None of the GF cases was in patients with anti-HLA antibodies or DSA. Conclusion: In our cohort, the presence of anti-HLA or DSAs did not affect the outcomes including the incidence of PGF following myeloablative haplo-HSCT for malignant hematologic disorders.

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.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

Secondary acute myeloid leukemia (sAML) includes AML as a complication of an antecedent hematological disorder or a therapy-related AML. Large registry-based data identified sAML as an independent poor-outcome type of AML post allogeneic hematopoietic cell transplantation (allo-HCT). In our study, we tried to define factors affecting outcomes of sAML post allo-HCT, and identify patients with sAML who may truly benefit from allo-HCT. We retrospectively analyzed the data of 64 patients aged (14-61 years) with sAML who received allo-HCT between September 2010 and February 2018 at our institute. Most of the patients were transplanted from matched related donors (MRD; 54, 84.4%). Our results showed that poor-risk cytogenetics were identified in 31 patients (48.4%), and their presence was an indicator of poor overall survival (OS) and disease-free survival (DFS

The relationship between cancers and thromboembolic events is well established. In our study, we aim to determine the burden of thromboembolic events in patients with solid tumors and identify the risk factors related to their development.Data on patients with solid tumors and thromboembolism between January 2013 and September 2014 were collected and analyzed.During the study period 174 patients were identified. Of which, 172 (98.9%) had venous thrombus embolism, 137 (79%) were diagnosed with deep vein thromboses, 67 (38.5%) with pulmonary embolism, 84 (48.3%) were symptomatic and 90 (51.7) were incidental at diagnosis. The most common patients and disease characteristics were female sex, high body mass index (BMI), metastatic stage, colorectal and breast primaries, and anti-neoplastic therapy. Our study confirmed the high burden of thromboembolic events in cancer patients and the relevant factors associated with its development.

Background. The one-stage assay is the most common method to measure factor VIII activity (FVIII : C) in hemophilia A patients. The chromogenic assay is another two-stage test involving purified coagulation factors followed by factor Xa-specific chromogenic substrate. Aim. This study aimed to assess the discrepancy and correlation between the chromogenic and one-stage assays in measuring FVIII : C levels in hemophilia patients receiving Extended Half-Life Elocta® as a recombinant extended half-life coagulation factor. Methods. We performed a study comparing the measurements of FVIII : C levels by the chromogenic versus the one-stage assays at different drug levels. Data of FVIII : C levels, dosage, and the time interval from administration to measurement were retrieved from the hospital records. The correlation, mean differences, and discrepancy between the two assays were calculated. The linear regression analysis was used to predict the time interval till reaching 1% FVIII : C. Results. Fourteen patients with 56 samples were included in the study. Of them, 13 patients were receiving Elocta® as a prophylactic, while one was receiving Elocta® on demand. One-third of these samples showed a discrepancy between the chromogenic and one-stage assays. The two assays were well correlated. Mean differences were significant at the individual and the time interval level. The time since the last Elocta® injection could significantly predict FVIII : C levels (β = 0.366, P<0.001). Conclusion. Our findings suggested a significant difference between both methods; the FVIII : C levels measured by the one-stage assay were less than those estimated by the chromogenic assay. However, the measurements of FVIII levels by the two assays were well correlated but discrepant in one-third of the samples. The levels of FVIII : C reach 1% after 5.4 days since the last Elocta® administration.

Introduction: Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests. Methods: Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring. Results: A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue. Conclusion: The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).

Background Treating adolescents and young adults (AYA) patients with acute lymphoblastic leukemia (ALL) using pediatric-inspired protocols have shown improvement in outcomes. Most data available in the literature of such protocols is derived from well-controlled clinical trials. This report aims to provide a real-world experience from using a pediatric-inspired protocol in ALL-AYA population in larger number of patients treated at a national tertiary care referral center. Methods Newly diagnosed Philadelphia negative ALL-AYA patients ages between 14 and 55 years of age were treated on an institutional protocol (AYA-15 protocol) adopted from a modified version of Children's Cancer Group (CCG) 1900 protocol. At the time of this publication, a total of 79 patients were treated using the AYA-15 protocol between 2015 and 2020). Event-free survival (FFS), disease-free survival (DFS), and overall survival (OS) were analyzed using cumulative incidence and Kaplan-Meier methods. Results The median age at diagnosis was 18 years (14–51 years) with 63% male patients. Complete remission (CR) at day 28 of induction was achieved in 88.6% of which 73.4% were minimal residual disease (MRD) negative. At a median follow up of 5 years, EFS, DFS and OS were 57.5%, 69.2% and 75.8% respectively. Toxicities were within the expected range with infections and transaminitis being the most common adverse events. Conclusion Our single-center experience real-world data in treating AYA-ALL patients with pediatric-inspired protocol demonstrates encouraging results of high survival rate and excellent tolerability for patients aged 18–55 years.

The antiphospholipid syndrome (APS) is an autoimmune disease that is characterized by thrombosis and/or pregnancy failure and associated with the presence of all or at least one of three standard antibodies (anti-phospholipid (aPL) antibodies, including lupus anticoagulant (LA), anti-cardiolipin (aCL), and anti-β2-glycoprotein I (anti-β2GPI)). A growing body of evidence recommends adding additional aPL antibodies, such as anti-phosphatidylserine (aPS), anti-prothrombin (aPT), and anti-annexin A5 (aAA5), to conventional laboratory tests (revised Sapporo criteria), especially in seronegative APS cases.We aimed to compare the diagnostic value, utility, and performance of these three additional antibodies along with the standard aPL antibodies in cases with confirmed and non-criteria APS (seronegative).This was a prospective observational study on 59 patients who presented with clinical features of APS at the hematology, medical, rheumatology, and obstetric clinics. LA was detected by standard coagulation tests, while other aPL, IgG, and IgM antibodies (aCL, aβ2GPI, aPS, aPT, aAA5) were detected with enzyme-linked immunosorbent assay (ELISA).Anti-PS antibody was more frequent compared to aPT and aAA5 in both confirmed cases (84.6%) and non-criteria (seronegative) (15.4%) APS. As a single test, the aPS antibody was significantly better (Our data support the findings of previously published studies and attribute the clinical significance of additional aPL antibodies, particularly aPS, in identifying non-criteria APS cases. In the future, along with conventional aPL antibodies, these additional antibodies should be included as standard laboratory tests in the revised Sapporo criteria.

Background: Iron deficiency (ID) and ID anemia (IDA) are common in the member states of the Gulf Cooperation Council (GCC). The unique genetic and lifestyle factors of the patient population in the region have necessitated the development of recommendations to help educate health-care professionals on appropriate diagnosis and management of ID/IDA. Methods: A panel of regional experts, including gastroenterologists and hematologists with expertise in the treatment of IDA, was convened to develop regional practice recommendations for ID/IDA. After reviewing the regional and international literature, the expert panel developed consensus recommendations for screening, diagnosis, and treatment of patients with IDA in the GCC region. Results: The recommendations proposed were customized to the patient population keeping in view the increasingly recognized burden of coeliac disease, high fertility and obesity rates, high prevalence of alpha- and beta-thalassemia traits, and poor tolerance and low treatment compliance with oral iron therapy. Conclusions: This consensus statement proposes recommendations for screening, diagnosis, and treatment of IDA in the GCC region.

Background Treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients using traditional adult chemotherapy protocols give low overall survival (OS) rates. Data are growing regarding the use of pediatric-inspired chemotherapy protocols in AYA patients with improvement in OS. Patients and Methods To assess efficacy and tolerability of using a pediatric-inspired protocol in AYA patients, we initiated our local prospective trial using a modified version of the Children’s Cancer Group 1900 protocol for newly diagnosed high-risk Philadelphia chromosome-negative ALL patients. Results A total of 40 patients were enrolled in the study (from 2015 to 2018). The median age was 18 years (range, 14-34 years). The complete remission rate after induction was 37 patients [93%] and after a median follow-up of 5 years, OS, disease-free survival (DFS), and event-free survival were 75%, 72%, and 60%, respectively. Use of this protocol was well tolerated with manageable toxicities. Pegylated asparaginase was given to all patients during the induction phase and was well tolerated. Conclusion The use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.

Patients between 14 and 22 years old are underrepresented in both adult and pediatric studies. We analyzed the outcomes of 94 consecutive patients aged between 14 and 22 who underwent myeloablative matched related-donor transplant while in first or second complete remission. We studied the impact of disease type, remission status, ELN risk group, ABO mismatch, time from diagnosis to transplant, patient and donor age, conditioning type, stem cell source, and the year of transplant on transplant outcomes. The cumulative incidences of relapse, NRM, OS, and DFS at 5 years were 42%, 10%, 59%, and 48%, respectively. Absence of ABO mismatch and donor age > 20 were associated with better OS and DFS on univariate and multivariate analysis. The cumulative incidence of aGVHD and cGVHD were 18% and 44%, respectively. Donor age > 20 and peripheral blood stem cell source were significantly associated with higher incidence of cGVHD on univariate and multivariate analysis. Younger patient age was significantly associated with higher incidence of aGVHD. In this age group, the determinants of survival seem to be dependent on donor variables rather on the traditional disease and patient related variables. Relapse still a significant factor for transplant failure while NRM was low.

Coagulation factor V plays a significant role in the blood coagulation cascade as part of the prothrombinase complex. Factor V deficiency (FVD) is a rare autosomal recessive bleeding disorder with a variable phenotypic expression which varies from being asymptomatic-to-severe bleeding episodes. The aim of this study was to perform molecular and clinical characterization of FVD in patients originating from Saudi Arabia. Eleven patients (two males and nine females) with confirmed FVD were recruited in the study with ages ranging between 5 and 53 years. A next-generation sequencing-based hematology panel encompassing 393 known genes was used. A total of six sequence variations in F5 gene were identified, including four missense mutations (p.Pro189Leu, p.Trp2004Arg, p.Met2148Thr, p. Arg2202Cys), a deletion (p.Arg872Lysfs*12) and a splicing variant (c.1118+5G>T). Four variants were identified for the first time in this study. Three patients were homozygous for their respective mutations and seven patients were heterozygous. We were not able to identify a pathogenic variant in one patient of the cohort. In-silico and three-dimensional structural analyses were performed to predict the possible impact and functional consequences of the identified variants. To our knowledge, this is the first study addressing factor V mutations in patients with Arab ancestry. Results have helped in providing a definitive diagnosis to the patients and carrier detection in extended family members. Overall, the hematology panel assay was an efficient platform, demonstrating a formidable approach for the molecular diagnosis of other suspected bleeding disorders.

Background: The relationship between cancers and thromboembolic events is well established. In our study we aim to determine the burden of thromboembolic events in patients with solid tumors and identify the risk factors related to their development.Methods: Data on patients with solid tumors and thromboembolism between January 2013 and September 2014 were collected and analyzed. Results: During the studied period 174 patients were identified, 172 (98.9%) of which had venous thrombus embolism. 137 (79%) were diagnosed with deep vein thromboses and 67 (38.5%) with pulmonary embolisms. 84 (48.3%) were symptomatic and 90 (51.7) were incidental at diagnosis. The most common risk factors were female sex, high Body mass index, metastatic stage, colorectal and breast primaries, and anti-neoplastic therapy.Conclusion: Our study confirmed the high burden of thromboembolic events in cancer patients and the relevant risk factors associated with its development.

The recommended therapy for severe aplastic anemia (SAA) in younger patients with a matched sibling donor (MSD) is allogeneic hematopoietic cell transplantation (allo-HCT). A number of conditioning regimens and protocols have been used for these patients. Here we report a homogeneous cohort of SAA patients receiving a uniform transplantation protocol. This study is a retrospective analysis of 82 consecutive patients with SAA who underwent MSD allo-HCT at a single center. The median duration of follow-up for survivors was 100 months, the 10-year overall survival (OS) was 87.5%, and the 10-year event-free survival was 75.3%. The OS was 97.4% for "mobilized" bone marrow (BM) graft recipients and 78.9% for "nonmobilized" BM graft recipients (P = .01. The cumulative incidence of acute graft-versus-host disease (GVHD) was 25.6%, that of chronic GVHD was 27.16%, and that of graft failure was 16.2%. Recipient age ≥30 years and transplantation at >6 months after SAA diagnosis were associated with a increased risk of events. In the presence of a fully matched sibling donor, allo-HCT with a mobilized BM graft and fludarabine-cyclophosphamide conditioning is an efficacious and safe approach. Early transplantation is associated with a better outcome, emphasizing the importance of not delaying transplantation in these patients. Prospective trials are needed to determine the optimal regimen.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

Acquired FXIII deficiency has been described in association with malignancies or autoimmune disorders. We report two cases of acquired FXIII deficiency associated with hematologic malignancies. The first patient is a 60-year-old male with CMML who presented 4 weeks after confirming his diagnosis with non-traumatic anterior abdominal wall hematoma. Workup revealed FXIII deficiency. He was treated with FXIII replacement and other supportive measures. The hematoma resolved and patient was maintained on factor replacement. Unfortunately, his disease transformed to AML and he succumbed to death after starting AML therapy despite achieving complete remission. The second patient is a 24-year-old male patient post haploidentical transplant for intermediate risk AML. He developed hemorrhagic cystitis day 36 post-transplant and non-traumatic subdural hematoma on day 60 post-transplant. Workup revealed FXIII deficiency. He was treated with factor replacement and the subdural hematoma resolved with improvement of the hemorrhagic cystitis. Both patients had RUNX1 mutation which regulates expression of F13A1 in megakaryocyte this can decreased platelet expression of F13A1 in patient with RUNX1 haplodeficiency which lead to platelet dysfunction. FXIII deficiency should be considered for patient with unexplained bleeding with normal routine workup.

Introduction Coronavirus disease (COVID-19) pandemic has started to affect Saudi Arabia in the beginning of March 2020 and is expected to cause significant morbidity to many patients, especially to elderly, who might require intensive care unit (ICU) support to survive as its lethality increases with the increasing age. Recent publications suggested the benefit of utilizing convalescent plasma from recovered donors as a therapeutic approach in treating COVID-19 patients. Convalescent plasma could provide our first-line defense for people with COVID-19, especially those who are older and at a much higher risk for complications., therefore, we developed a national protocol to investigate the safety, benefit and applicability at larger scale and at different health care facilities in Saudi Arabia (KSA). Objectives Primary endpoints are 1. ICU (or designated area for critical patients) length of stay 2. Safety of convalescent plasma> Secondary endpoints included: 1. 30 days mortality 2. Number of days on mechanical ventilation 3. Days to clinical recovery Method Eligible convalescent plasma donors will be invited to participate in trial. The arrangement for plasmapheresis will start after obtaining donor informed consent. The collected plasma will be treated with pathogen reduction system. The convalescent plasma units will be labelled, stored and shipped as per the standard transfusion medicine protocols. It will be used only for eligible patients' "recipients" as per the following eligibility criteria: 1. Inclusion criteria: - Confirmed case of SARS-CoV-2 infection with POSITIVE rRT PCR test -18 or older -Must have been requiring ICU care or severe or immediately life-threatening care (any one of the following): 1. Patient requiring ICU care/admission. 2. Severe disease is defined as: a. Dyspnea b. Respiratory frequency ≥ 30/min c. Blood oxygen saturation ≤ 93% d. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, and/or Lung infiltrates > 50% within 24 to 48 hours 3. Life-threatening disease is defined as: a. Respiratory failure b. Septic shock, and/or c.Multiple organ dysfunction or failure Exclusion criteria: 1. Negative or non-conclusive test COVID-19 rRT PCR test 2. Mild symptoms 3. Hospitalization not requiring ICU care/admission Eligible Patients will be infused with the convalescent plasma (200-400 ml / treatment dose)at least once & if possible, daily, for up to 5 sessions. Other supportive and therapeutic measures should continue according to the locally approved protocols with due diligence. Sample size was calculated with 80% power and 5% level of significance based on the recently published data to detect statistical difference in the study outcome. Therefore, we plan to recruit total of 575 patients. Convalescent plasma Recipient Group: 115 patients (recipients) who have COVID 19 as per the inclusion criteria. Comparative control Group: 460 Patients who are eitherCOVID 19 historical control or only consent for sharing their clinical and laboratory data Matching for age, gender, Hypertension, Diabetes and intubation status were done based on the propensity score. Continuous variables will be presented as the median and interquartile range (IQR). Statistical software SPSS 24.0 will be used. Demographic, Clinical, imaging and laboratory information of all enrolled patients will be retrieved from the hospital electronic/paper records system to be used for the outcomes analysis. Results 22 sites across KSA that participated in the study. Tertiary, secondary, academic and non-academic centers participated (real world data). There were no unusual safety issues related to convalescent plasma infusion since all mortalities in the plasma group were not related to plasma infusion which represent similar finding from other the published international reports. Keeping in-mind that our data is still maturing, 30 survival probability in the plasma group was 69% compared to 56% in the comparative group (p value = 0.066) (figure-1). This benefit to seem to be more noticeable in the COVID-19 cases who did not meet the criteria for life-threatening disease (figure-2). Conclusion Our study supports the safety of convalescent plasma in treating COVID-19 patients. Patients who are in the category of life-threating/end organs failure do not seem to benefit. There might be a benefit in the other subgroups. Disclosures No relevant conflicts of interest to declare.

Background The COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. Objective The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. Methods Eligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance. Results At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. Conclusions In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. Trial Registration ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681 International Registered Report Identifier (IRRID) PRR1-10.2196/23543

BACKGROUND The COVID-19 pandemic is expected to cause significant morbidity and mortality. The development of an effective vaccine will take several months to become available, and its affordability is unpredictable. Transfusion of convalescent plasma (CP) may provide passive immunity. Based on initial data from China, a group of hematologists, infectious disease specialists, and intensivists drafted this protocol in March 2020. OBJECTIVE The aim of this study is to test the feasibility, safety, and efficacy of CP in treating patients with COVID-19 across Saudi Arabia. METHODS Eligible patients with COVID-19 will be recruited for CP infusion according to the inclusion criteria. As COVID-19 has proven to be a moving target as far as its management is concerned, we will use current definitions according to the Ministry of Health (MOH) guidelines for diagnosis, treatment, and recovery. All CP recipients will receive supportive management including all available recommended therapies according to the available MOH guidelines. Eligible CP donors will be patients with COVID-19 who have fully recovered from their disease according to MOH recovery criteria as detailed in the inclusion criteria. CP donors have to qualify as blood donors according to MOH regulations except for the history of COVID-19 in the recent past. We will also test the CP donors for the presence of SARS-CoV-2 antibodies by a rapid test, and aliquots will be archived for future antibody titration. Due to the perceived benefit of CP, randomization was not considered. However, we will compare the outcome of the cohort treated with CP with those who did not receive CP due to a lack of consent or lack of availability. In this national collaborative study, there is a likelihood of not finding exactly matched control group patients. Hence, we plan to perform a propensity score matching of the CP recipients with the comparator group patients for the major characteristics. We plan to collect demographic, clinical, and laboratory characteristics of both groups and compare the outcomes. A total sample size of 575 patients, 115 CP recipients and 460 matched controls (1:4 ratio), will be sufficient to detect a clinically important hospital stay and 30-day mortality difference between the two groups with 80% power and a 5% level of significance. RESULTS At present, patient recruitment is still ongoing, and the interim analysis of the first 40 patients will be shared soon. CONCLUSIONS In this paper, we present a protocol for a national collaborative multicenter phase II study in Saudi Arabia for assessing the feasibility, safety, and potential efficacy of CP in treating patients with severe COVID-19. We plan to publish an interim report of the first 40 CP recipients and their matched comparators soon. CLINICALTRIAL ClinicalTrials.gov NCT04347681; https://clinicaltrials.gov/ct2/show/NCT04347681 INTERNATIONAL REGISTERED REPORT PRR1-10.2196/23543

Thrombocytopenia remains a life-threatening late complication of HCT with an incidence of 5-20%. Currently, there is no approved drug for the treatment of persistent thrombocytopenia post HCT and platelet transfusion is the maintain stay of treatment. Eltrombopag is approved for the treatment of thrombocytopenia associated with different diseases, however; data on eltrombopag treatment post HCT are limited.This is a retrospective cohort study evaluating the effect of eltrombopag on platelet recovery in patients with persistent thrombocytopenia post HCT. The primary endpoint was platelet recovery to ≥ 20,000/μL for 7 consecutive days without transfusion support after starting eltrombopag. Secondary endpoint was platelet recovery to ≥ 50,000/μL for 7 consecutive days.Twenty-one patients were included. Twelve (75%) of 16 patients became independent from platelet transfusions. Median time from starting eltrombopag to last transfusion was 60 days (range, 9-226 days). Ten (63%) of 16 transfusion dependent patients with platelet count20,000/μL achieved the primary endpoint. Seven (33%) patients of 21 included had successful platelet recovery (ie, ≥50,000/μL without transfusion support) and the median time to platelet recovery in patients who achieved it was 32 days (range, 13-265 days). Ten patients (48%) were able to successfully discontinue eltrombopag without recurrence of thrombocytopenia.Our findings demonstrated that eltrombopag appears to have a clinically significant impact on platelet recovery in persistent thrombocytopenic patients post HCT.

Aplastic anemia (AA) is a serious hematological disorder, which is solely cured by hematopoietic stem cell transplantation (HSCT). Haploidentical HSCT is an emerging modality with encouraging outcomes in several blood conditions. The present study aims to comprehensively assess the feasibility and safety of haploidentical HSCT in patients with severe and very severe AA. It is a systematic review and meta-analysis of studies related to haploidentical stem cell transplantation in idiopathic AA investigating rates of successful engraftment, acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), transplant-related mortality (TRM), and posttransplantation viral infections (including cytomegalovirus [CMV]) in patients with AA. The effects of reduced-intensity conditioning (RIC) and nonmyeloablative conditioning (NMA), as well as various GvHD prophylaxis regimens on these outcomes were evaluated. In total 15 studies were identified, (577 patients, 58.9% males), successful engraftment was observed in 97.3% of patients (95% CI, 95.9-98.7) while grades II-IV aGvHD and cGvHD were reported in 26.6% and 25.0%, respectively. The pooled incidence of TRM was 6.7% per year (95% CI, 4.0-9.4). RIC regimens were associated with higher proportions of successful engraftment (97.7% vs 91.7%, P = 0.03) and aGvHD (29.5% vs 18.7%, P = 0.008) when compared with NMA regimens with no differences in cGvHD or mortality incidence. When compared with methotrexate-containing regimens and other regimens, posttransplant cyclophosphamide-containing regimens reduced the rates of aGvHD (28.6%, 27.8%, and 12.8%, respectively, P = 0.02), CMV viremia (55.7%, 38.6%, and 10.4%, respectively, P < 0.001), and CMV disease in initially viremic patients (2.1%, 33.0%, and 0%, respectively, P < 0.001). We have concluded that Haploidentical HSCT was associated with promising outcomes in terms of successful engraftment and reduced complications. Future prospective trials are needed to identify the preferred conditioning regimen, GvHD prophylaxis, and graft source in the setting of haploidentical transplant for AA.

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in our institution between January 2005 and December 2015. We limited this retrospective review to patients who received a MA conditioning, were in complete remission (CR) at the time of transplant and who received a matched sibling transplant, all other patients were excluded to avoid heterogeneity. Seventy-seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR. The only variable that was statistically associated with EMR post allo-HCT was male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The median overall survival (OS) after relapse for all relapses was 10 months (95% CI 4.839–15.161). The median OS for BMR group was 8 months (95% CI 2.850–13.150) and 14 months for the EMR group (95% CI 5.776–22.224); however, this was not statistically significant, p-value = 0.4. Multivariate analysis revealed that gender, treatment modality, and time from allo-HCT to relapse (≥12 vs.

Hematopoietic Stem Cell Transplantation (HSCT) is the only potentially curative treatment option for the hematologic complications that occur in patients with Fanconi anemia (FA). In this study, we present a retrospective multicenter analysis from the Eastern Mediterranean Blood and Marrow Transplantation Group (EMBMT) of matched related donor HSCT for FA in adolescents and adults transplanted between 1988 and 2015. Forty-five patients received HSCT with a median age at transplant of 18 years, the interquartile range (IQR) (15–23.5); 25 (55.6%) patients were females and 20 (44.4%) were males. Conditioning regimen was fludarabine-based in 29 (64.4%) patients, irradiation-based in five (11.1%) patients, and the remaining patients received other combinations. Indication for HSCT was bone marrow failure in 39 (86.7%) and myelodysplastic syndrome in six (13.3%) patients. Stem cell source was bone marrow in 22 (48.9%), peripheral blood in 20 (44.4%), umbilical cord blood in one (2.2%), and combination of bone marrow and cord blood in two (4.4%) patients. Twenty-seven (60%) patients engrafted and five (11.1%) had primary engraftment failure. The median time to neutrophil engraftment was 14 days (range 10–21 days); median time for platelet engraftment was 17 days (10–33 days). The probability of developing grade II–IV acute GVHD for all patients was 7.0% and chronic GVHD 36.6%. No new malignancies were reported. The OS probability was 53.6% (95% CI, 38.3–68.9%) with a median follow-up of 13 months (95% CI, 1–240). Our HLA-matched related HSCT results in AYA patients with FA compare favorably with other reported international registry data.

Hematopoietic cell transplantation (HCT) activity is increasing at an unprecedented pace with > 50,000 allogeneic transplants occurring annually worldwide. Establishing a functional HCT donor registry can be very challenging with respect to ethnicities, financial, technical, and geopolitical issues. Extensive planning steps are essential to overcome the expected challenges while establishing the registry, and to maintain its functionality. A few strategies can help move past those challenges and push the development of such registries forward. Authorities involved in HCT donor registry establishment will have to balance the advantages and costs of such a project and accommodate the emerging alternatives such as cord blood or related haploidentical transplants. Miscalculations and incomplete understanding of the various aspects of the process can have tremendous impact on the optimization of a HCT donor registry especially in developing countries. Herein we present some challenges in establishing such a registry and present potential solutions.

Summary Autosomal recessive mutations in G6PC3 cause isolated and syndromic congenital neutropenia which includes congenital heart disease and atypical inflammatory bowel disease (IBD). In a highly consanguineous pedigree with novel mutations in G6PC3 and MPL, we performed comprehensive multi-omics analyses. Structural analysis of variant G6PC3 and MPL proteins suggests a damaging effect. A distinct molecular cytokine profile (cytokinome) in the affected proband with IBD was detected. Liquid chromatography-mass spectrometry-based proteomics analysis of the G6PC3-deficient plasma samples identified 460 distinct proteins including 75 upregulated and 73 downregulated proteins. Specifically, the transcription factor GATA4 and LST1 were downregulated while platelet factor 4 (PF4) was upregulated. GATA4 and PF4 have been linked to congenital heart disease and IBD respectively, while LST1 may have perturbed a variety of essential cell functions as it is required for normal cell-cell communication. Together, these studies provide potentially novel insights into the pathogenesis of syndromic congenital G6PC3 deficiency., Graphical abstract, Highlights • Multi-omics approaches identify unique signatures • Whole-exome sequencing reveals distinct cytokine profiles • Expression of GATA4, PF4, and LST1 is dysregulated, Pathophysiology ; Systems Biology ; Genomics ; Proteomics

There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual's best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as 'personalized-medicine-model'.

Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE) is commonly encountered in daily clinical practice. After diagnosis, its management frequently carries significant challenges to the clinical practitioner. Treatment of VTE with the inappropriate modality and/or in the inappropriate setting may lead to serious complications and have life-threatening consequences. As a result of an initiative of the Ministry of Health of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University Guideline working group, this clinical practice guideline was produced to assist health care providers in VTE management. Two questions were identified and were related to the inpatient versus outpatient treatment of acute DVT, and the early versus standard discharge from hospital for patients with acute PE. The corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Saudi Med J 2015; Vol. 36 (8): 1004-1010 doi: 10.15537/smj.2015.8.12024

Plasma cell leukemia (PCL) is a rare hematologic malignancy with very poor outcome. It is defined by the presence of >2 × 109/L plasma cells or >20% plasmacytosis of the differential white cell count in the peripheral blood. Primary PCL is first diagnosed in the leukemic phase, while secondary PCL corresponds to the leukemic transformation of a previously diagnosed multiple myeloma (MM). The incidence of PCL ranges between 2–4% of patients with MM and 0.9% of patients with acute leukemia. In this case series, we describe the clinicopathologic, immunophenotypic, and cytogenetic findings of four patients diagnosed with PCL within a ten-year period (2002–2012) at King Faisal Specialist Hospital and Research Centre (General Organization), Riyadh, Saudi Arabia. Keywords: Leukemia, Plasma cell, Plasma cell leukemia, Multiple myeloma

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder. The mutation in the ECGF1 gene causes severe deficiency of thymidine phosphorylase (TP), which in turn increases thymidine and deoxyuridine in the blood, serum, and tissue. The toxic levels of these products cause malfunction of the mitochondrial respiratory chain and mitochondrial DNA. Commonly, patients become symptomatic between 15 and 20 years of age (range 5 months to 35 years). The most commonly affected systems are gastrointestinal, followed by ocular, and nervous system. The disease is often fatal; high mortality rate is reported between 20 and 40 years of age. Treatment modalities that can increase thymidine phosphorylase activity and decrease thymidine and deoxy-uridine have shown symptomatic improvements in patients with MNGIE. Platelet transfusion, hemodialysis, peritoneal dialysis or allogeneic hematopoietic stem cell transplantation (HSCT) have been tried. The survival and long-term benefits of these measures are still not clear. Engrafted patients after stem cell transplantation have showed improvements in serum thymidine and deoxyuridine. We are reporting a case of MNGIE from Saudi Arabia, who underwent allogeneic hematopoietic stem cell transplantation. No MNGIE case has been previously reported from Saudi Arabia or the Gulf Arab countries. From the available literature, so far only 11 patients with MNGIE have undergone stem cell transplantation. Keywords: Mitochondrial neurogastrointestinal encephalomyopathy, MNGIE, Stem cell transplantation, Bone marrow transplantation

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) is commonly encountered in the daily clinical practice. Cancer is an important VTE risk factor. Proper thromboprophylaxis is key to prevent VTE in patients with cancer, and proper treatment is essential to reduce VTE complications and adverse events associated with the therapy. DESIGN AND SETTINGS: As a result of an initiative of the Ministry of Health of Saudi Arabia, an expert panel led by the Saudi Association for Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the Saudi Scientific Hematology Society with the methodological support of the McMaster University working group produced this clinical practice guideline to assist health care providers in evidence-based clinical decision-making for VTE prophylaxis and treatment in patients with cancer. METHODS: Six questions related to thromboprophylaxis and antithrombotic therapy were identified and the corresponding recommendations were made following the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: Question 1. Should heparin versus no heparin be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? Recommendation: For outpatients with cancer, the Saudi Expert Panel suggests against routine thromboprophylaxis with heparin (weak recommendation; moderate quality evidence). Question 2. Should oral anticoagulation versus no oral anticoagulation be used in outpatients with cancer who have no other therapeutic or prophylactic indication for anticoagulation? Recommendation: For outpatients with cancer, the Saudi Expert Panel recommends against thromboprophylaxis with oral anticoagulation (strong recommendation; moderate quality evidence). Question 3. Should parenteral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? Recommendation: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests thromboprophylaxis with parenteral anticoagulation (weak recommendation; moderate quality evidence). Question 4. Should oral anticoagulation versus no anticoagulation be used in patients with cancer and central venous catheters? Recommendation: For outpatients with cancer and central venous catheters, the Saudi Expert Panel suggests against thromboprophylaxis with oral anticoagulation (weak recommendation; low quality evidence). Question 5. Should low-molecular-weight heparin versus unfractionated heparin be used in patients with cancer being initiated on treatment for venous thromboembolism? Recommendation: In patients with cancer being initiated on treatment for venous thromboembolism, the Saudi Expert Panel suggests low-molecular-weight heparin over intravenous unfractionated heparin (weak; very low quality evidence). Question 6. Should heparin versus oral anticoagulation be used in patients with cancer requiring long-term treatment of VTE? Recommendation: In patients with metastatic cancer requiring long-term treatment of VTE, the Saudi Expert Panel recommends low-molecular-weight heparin (LMWH) over vitamin K antagonists (VKAs) (strong recommendation; moderate quality evidence). In patients with non-metastatic cancer requiring long-term treatment of venous thromboembolism, the Saudi Expert Panel suggests LMWH over VKA (weak recommendation; moderate quality evidence).