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Objective: To present the interim findings from a national study investigating the safety and efficacy of convalescent plasma (CP) containing detectable IgG antibodies as a treatment strategy for severe coronavirus disease 2019 (COVID-19). Trial Design and Participants: An open label, two-arm, phase-II clinical trial conducted across 22 hospitals from Saudi Arabia. The intervention group included 40 adults (aged ≥18 years) with confirmed severe COVID-19 and the control group included 124 patients matched using propensity score for age, gender, intubation status, and history of diabetes and/or hypertension. Intervention group included those (a) with severe symptoms (dyspnea; respiratory rate, ≥30/min; SpO2, ≤93%, PaO2/FiO2 ratio, 50% within 24–48 h), (b) requiring intensive care unit (ICU) care or (c) experiencing life-threatening conditions. The control group included confirmed severe COVID-19 patients of similar characteristics who did not consent for CP infusion or were not able to receive CP due to its nonavailability. Interventions: The intervention group participants were infused 300 ml (200–400 ml/treatment dose) CP at least once, and if required, daily for up to 5 sessions, along with receiving the best standard of care. The control group only received the best standard of care. Outcomes: The primary endpoints were safety and ICU length of stay (LOS). The secondary endpoints included 30-day mortality, days on mechanical ventilation and days to clinical recovery. Results: CP transfusion did not result in any adverse effects. There was no difference in the ICU LOS (median 8 days in both groups). The mortality risk was lower in the CP group: 13% absolute risk reduction (P = 0.147), hazard ratio (95% confidence interval): 0.554 (0.299–1.027; P = 0.061) by log-rank test. There was no significant difference in the days on mechanical ventilation and days to clinical recovery. Conclusion: CP containing detectable antibodies is a safe strategy and may result in a decrease in mortality in patients with severe COVID-19. The results of the completed trial with a larger study sample would provide more clarity if this difference in mortality is significant. Trial Registration: ClinicalTrials.gov Identifier: NCT04347681; Saudi Clinical Trials Registry No.: 20041102.

Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Background The role of fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) in indolent lymphoma has been minimally studied. Objective This study aims to assess the value of FDG-PET/CT in predicting the prognosis of indolent lymphoma. Methods We prospectively recruited 42 patients with indolent lymphoma. A total of 2 patients were excluded, and 40 underwent baseline PET/CT and follow-up at various time points. A total of 9 patients were observed only, 7 received 4 doses of rituximab alone, and 24 received chemoimmunotherapy. Metabolic response on follow-up PET/CT was assessed using the maximum standardized uptake value (SUVmax) and Deauville criteria (DC). We aimed to obtain the best SUVmax and DC to predict optimal survival rates, risk stratification, and optimize therapeutic strategies. The mean follow-up from the initial diagnosis was 33.83 months. Results SUVmax Conclusions We demonstrated the utility of PET/CT in indolent lymphomas. SUVmax (

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.

Introduction The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the 21st century. The World Health Organization declared the COVID-19 outbreak as a pandemic on March 11, 2020. Lockdowns were imposed in multiple countries affecting patient flow in hospitals. Methods This is a retrospective study conducted at King Fahad Medical City (KFMC), a tertiary care hospital in Riyadh, Saudi Arabia, which examined the differences in palliative care services during the initial four months of the COVID-19 pandemic compared to the respective four months in 2019 (March, April, May, June). Results A total of 319 patients were seen at the palliative care department from March to June 2020 during the COVID-19 pandemic (119 inpatient, 200 outpatient), compared to 346 patients seen during the corresponding months in 2019 (97 inpatient, 249 outpatient). Our main findings included more patients being discharged home, lesser transfers, shorter hospital length of stay, lesser imminent death protocols, and a higher palliative performance score (PPS) during the COVID-19 pandemic. Although there were more cancelations by the hospital for the outpatient department, a virtual clinic was started, and 84 patients were effectively seen. Around 87% of patients were fully satisfied (5/5) with the services provided by the virtual clinic. There were no positive COVID-19 cases in our healthcare workers in the palliative care department due to the high standard precautions applied at KFMC. Family meetings as well as administrative and academic meetings have been efficiently held virtually and may possibly become the standard of practice. Conclusion Palliative care services were successfully maintained during the COVID-19 pandemic at KFMC.

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

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, accounting for approximately 25% of all newly diagnosed patients (Swerdlow et. al. IARC, 2017). It is estimated that 40% of patients are refractory to, or relapse after treatment with chemo-immunotherapy (R-CHOP). Salvage therapy with autologous stem-cell transplantation (ASCT) can cure around 40% of those patients, nevertheless, the prognosis is poor for most patients with R/R DLBCL who are relapsed after, or ineligible for ASCT, and in those with suboptimal response to salvage chemotherapy. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate delivering monomethyl auristatin E (MMAE), a microtubule inhibitor. It was granted accelerated approval by the US FDA on June 2019 for treatment of R/R DLBCL after at least two prior therapies, in combination with bendamustine and rituximab. We herein report our experience on the use of polatuzumab in patients with R/R DLBCL. Methods: Retrospective-single center review on the use of polatuzumab vedotin as part of a compassionate program in patients with R/R DLBCL between June 2018 and July 2021. Inclusion criteria for the study were: age ≥ 18 years, R/R DLBCL [both de-novo and transformed lymphoma], 2 or more prior lines of therapy, and treatment with polatuzumab-based therapy for at least 1 cycle. Patients with CNS involvement were excluded. The compassionate use access program provided polatuzumab at a dose of 1.8 mg/kg, administered with or without bendamustine (up to two doses of 90 mg/m2,) and rituximab (375 mg/m2). Treatment was given every 21 days for up to 6 cycles. Results: we identified 3 patients with R/R DLBCL who were treated with polatuzumab-based therapy. The median number of prior therapies was 2 (2 - 5). The median IPI and CNS-IPI score were 2, (1 - 4) and 2, (2 - 5), respectively (Baseline characteristics are summarized in Table). The median number of Pola-BR cycles received was 3 (2 - 6). One patient completed 6 cycles of polatuzumab with bendamustine and rituximab and achieved partial response. The other two patients were taken of treatment at the time of progression on cycles number 1 and 3. Treatment options were limited after polatuzumab-based therapy. The patient who achieved partial response after 6 cycles of Pola-BR maintained that response for 11 months without additional treatment and died due to COVID-19 associated pneumonia. One patient been screened for Glofitamab compassionate use program, and one patient elected to receive no further therapy. Conclusions: Polatuzumab-based treatment in R/R DLBCL is a promising treatment in an otherwise difficult to treat patient population. The compassionate use program provides access in developing countries to an otherwise prohibitively expensive emerging therapeutic armamentarium in R/R DLBCL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Hodgkin lymphoma (HL) is an uncommon B-cell malignant neoplasm, with high curable rate for patients with localized disease or advanced.However, up to 30% of patients with HL are either refractory or relapsed after primary treatment. Salvage chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the standard of care for eligible patients in relapsed setting. Brentuximab vedotin and Bendamustine (BvB) combination have been recommended by National Cancer Center Network (NCCN) as one of the salvage regimens for patients with relapsed or refractory HL prior to transplant or who relapsed after hematopoietic stem cell transplant (HSCT). Evidence from retrospective and prospective studies in regards of BvB have shown remarkable progression free survival (PFS) with 2-years PFS ranging from 62.2% up to 93.7%, and overall survival (OS) ranging from 88.1% up to 95%, and complete remission (CR) rates ranging from 43% to 90%. The objective of this study is to assess patient response to BvB in the treatment of relapsed/refractory HL especially for patients beyond first salvage therapy unlike many other studies. Methods: A retrospective study was conducted in patients with relapsed/refractory Hodgkin lymphoma treated with BvB chemotherapy at single tertiary hospital from January 2016 until July of 2021. Data collection was done including patient demographics data, comorbidities, disease stage, lines of chemotherapy regimens taken, and PET scan response with Deauville score. Brentuximab was given as 1.8mg/kg on day 1, and bendamustine was given as 90mg/m 2 on day 1 and day 2. Cycle was repeated every three weeks. Result: A total of 16 patients with relapsed/refractory HL whom treated with BvB chemotherapy were analyzed. Median age is 29 years (22-70 years), 5 patients were female, and median number of lines of therapy prior to starting BvB is 2 (0-5). The median number of cycles of BvB was 5.5 (3-8 cycles). 2 out of 16 patients had a prior autologous HSCT (12.5%). 15 patients were assessed for response and one patient died before disease assessment. The overall response rate was 80% with 50% of patients achieving complete metabolic response on PET scan. After median follow up of 14.5 months, the median PFS was 13.4 months (Figure 1), and the median OS was not reached (Figure 2). 4 patients underwent HSCT (3 autologous, and 1 allogeneic). Conclusion: BvB combination is an effective outpatient-based salvage regimen for heavily pretreated patients with multiple lines chemotherapy in relapsed/refractory HL, as majority of patients in our study were beyond first salvage. As there is no standard salvage regimen in this setting, randomized trials are needed to compare efficacy and safety BvB with other established regimens. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: JAK2 GGCC 46/1 haplotype can be represented by four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782) which replace one cytosine and three thymidines by two guanosines and two cytosines, generating a "GGCC" combination. These four SNPs located on JAK2 introns 10, 12, 14, and 15, respectively, and are always inherited together, being in complete linkage disequilibrium. The 46/1 component of the name came from Jones et al. study where the haplotype structure of the JAK2 gene was mapped using 14 SNPs genotyped by the Wellcome Trust Case Control Consortium (WTCCC) in 1500 healthy blood donors. Two haplotypes (numbers 46 and 1) were found to be identical except for one SNP, and they have a combined frequency of 0.24 in healthy individuals. Numerous observational studies associate this haplotype with myeloproliferative neoplasms (MPNs), as well as splanchnic vein thrombosis (SVT) and non-splanchnic vein thrombosis (non-SVT). In contrast to 24% frequency noted in healthy population, the frequency goes up to 40-80% in JAK2 V617F mutated MPN, and in 64% of those with JAK2 exon 12 mutations (Anelli et al. IJMS, 2018). We herein report our study of JAK2 GGCC (46/1) Haplotype in unprovoked Venous Thrombotic Events (VTE) in patients with negative thrombophilia workup, including negative JAK2 V617F mutation. Methods: We retrospectively identified patients positive for one of the two SNPs (rs12343867 and rs10974900) and unprovoked venous thrombotic among adult patients with negative thrombophilia workup (including JAK2 mutation) treated at tertiary care center from January 2018 to January 2021. Results: We have identified 8 patients, Table (1), that were positive for JAK2 46/1 haplotype SNPs, of whom 62.5% were homozygous 2/2, 25% heterozygous 1/2, while only 12.5% harbor homozygous 1/1 (a normal variant of JAK2 haplotype). The median age 48.5 years (23-65), and the majority (87.5%) were females. Thrombosis site was noted to be SVT in half of the patients, while non-SVT was noted in the other half (12.5% had cerebral vein thrombosis, 12.5% had deep venous thrombosis, 12.5% had a pulmonary embolism, and 12.5% had jugular vein thrombosis). Half of the patients had more than one site venous thrombosis and the other half had only one site. Around 37.50% of the patients had recurrent venous thrombosis on top of therapeutic anticoagulation. Two patients (25%) had high hemoglobin (17.4/16.7) g/dl, but did not fulfill the criteria for polycythemia vera diagnosis (of whom one is a male smoker and one was a female). None of the patients had leukocytosis or thrombocytosis. By imaging, one patient had mild splenomegaly which could be related to SVT. Conclusion: We report on a potential correlation between unprovoked thrombotic events, mainly venous thrombotic events, with JAK2 46/1 haplotype in patients with a negative thrombophilia workup, a finding that merit further investigation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) 75 years or older, or unfit for intensive chemotherapy. As precision therapy in AML expanded with the addition of venetoclax among others in the therapeutic armamentarium of AML, efficacy and safety reports in ethnic minorities are limited, with a background of well recognized inter-ethnic differences in drug response. Phase III data from VIALE-A, as well as VIALE-C, was limited for the Arab population as no site opened in the Arab world. We herein report our experience on the use of venetoclax with azacitidine in patients with newly diagnosed or relapsed/refractory AML in the Arab population. Methods: Retrospective-single center review on the use of Azacitidine with venetoclax in older patients (aged ≥60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML and relapsed or refractory AML. All patients self-identified of Arabic ethnicity. Patients who received previous BCL2-inhibitor therapy were excluded. Patients who received at least one dose of treatment (Azacitidine ≥3 days, >14 days of venetoclax) were included in the intention to treat analysis. Patients typically received azacitidine 75 mg/m2 intravenously for 7 days with oral venetoclax 400 mg daily for induction, with appropriate dose adjustment for concomitant use of azoles. This is followed by the same regimen in consolidation, with adjustment according to response and side effects at the treating physician's discretion. The primary endpoint was overall survival. The secondary endpoints include response rate, safety, and relapse-free survival. Results: Between July 2019, and July 2021, we identified 19 patients; 13 (68%) had newly diagnosed AML (ND-AML), and 6 (32%) had relapsed or refractory AML (R/R AML). The median age was 70 years (17-82). In the ND-AML, most patients had an adverse ELN 2017 AML (69%) with 23% having either intermediate or adverse AML (Negative for CBF, NPM1, FLT3-ITD and biCEBPA, but missing NGS data for adverse mutations Tp53/ASXL1 and RUNX1). Only one patient was classified as intermediate-risk AML. The overall response rate in the ND-AML was 77%, with 46% achieving complete remission (CR), and 23% CR with incomplete count recovery (CRi) [Table]. One patient achieved PR after the first cycle (blast 7% by morphology and 1.5% by flow cytometry) and did not have a subsequent bone marrow evaluation, however had a full count recovery. Among the responders in the ND-AML cohort, 4 deaths were noted. One death was related to COVID-19 associated pneumonia, one due to graft failure (at day 42 post Haplo-SCT), one due to septic shock, and one was related to relapse disease. The overall survival and relapse-free survival for ND-AML were 5.6 months for both [Figure]. In the R/R AML, 66% had prior HMA exposure, and all patients did receive high-intensity chemotherapy. The median number of prior treatments was 3 (1-5). the response rate was 80% (4/5), with 60% achieving CR. All patients are still alive with a median follow-up of 7.6 months. One patient had progressive disease. One patient is early to evaluate and was not included in the response analysis [Table]. The 30-day mortality was zero in both ND-AML and R/R AML cohorts. Conclusions: In a majority of adverse risk ND-AML, and in heavily pretreated R/R AML, the response rate and overall survival is comparable to what has been previously reported. Our data support the use of this regimen in older patients with newly diagnosed AML, patients with relapsed or refractory disease, and those with adverse-risk features. This analysis is limited by the small number of patients, and by the lack of ELN 2017 favorable-risk AML. Future prospective and randomized studies are needed to clarify activity and safety in the Arab population, as well as in the high-risk AML subset. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: WIdiopathic aplastic anemia is a rare and life threatening disorder characterized by immune mediated hematopoietic stem cells dysfunction. The standard treatment strategy of severe aplastic anemia (SAA) has been hematopoietic stem cell transplant (HSCT) for children and adults younger than the age of 40 if an HLA matched sibling donor (MSD) is available. Immunosuppressive therapy (IST) is the mainstay of treatment for older patients or when MSD is not available. The response rate to IST with the use of horse anti-thymocyte globulin (ATG) is around 70%. Despite that, many patients suffer from relapse or clonal evolution. The use of alternative donor transplant (ADT) from matched unrelated donor (MUD) or HLA haploidentical donor (HID) is not commonly used in frontline setting. We herein, conducted a systematic review and meta-analysis of retrospective studies to compare the outcome of IST versus ADT as upfront therapy for SAA. Methods: WWe conducted a comprehensive search in PUBMED/MEDLINE and EMBASE (1998-2019) for retrospective studies that compared the outcome of ADT with IST as upfront therapy in patients with SAA. The study was conducting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We included the studies with 10 patients or more in each arm. Studies that included patients with inherited aplastic anemia or PNH are excluded. The primary outcome is the 5-year overall survival. Two authors independently screened the studies, extracted the data, and evaluated the quality of included studies and discrepancies were resolved by a third author. Study quality was evaluated by description of study characteristics, patients' characteristics, treatment details, and outcome. The odd ratio (OR) for 5-year survival was measured by Mantel-Haenszel test using random effect model. We also conducted another search and meta-analysis to compare upfront with salvage ADT. The meta-analyses were performed using Review Manager software version 5.3. Result: WWe screened a total of 697 articles (506 EMBASE, 191 PUBMED/MEDLINE). Five studies met our inclusion criteria included a total of 343 patients (176 in ADT group and 167 in IST group) for upfront ADT versus IST comparison and 6 studies with a total of 298 patients (198 in upfront ADT group and 100 in salvage ADT group) for upfront versus salvage ADT comparison. Included patients were of pediatric age group in 4 out of 5 studies. Xu ZL et al, included adult patients with median age 28 (18-49) years in upfront ADT arm and 32 (18-62) years in IST arm. Of those, only 10 patients in ADT group and 12 patients in IST group were above age of 40. In ADT versus IST comparison, the type of transplant was HID in three studies (total of 124 patients) and MUD/MMUD in two studies (total of 52 patients). The rabbit ATG was used in three studies, horse ATG in one study, and both types were used in one study (total of 68 patients received horse ATG and 99 patients received rabbit ATG). In term of disease severity, all included patients were SAA and very SAA (VSAA). Five studies were included in meta-analysis for 5-year overall survival. The pooled OR is statistically significant at 0.44 [95% CI 0.23-0.85] in favor of upfront ADT (Fig 1-A). The survival outcome was compared between upfront versus salvage ADT in 6 studies. The pooled OR is statistically significant at 0.31 [95% CI 0.15-0.64] in favor of upfront ADT (Fig 1-B). Conclusion: WThe pooled analysis of this study showed a potential survival advantage of upfront ADT over IST in patients with SAA who lack an HLA identical sibling donor. The use of ADT earlier in the disease course rather than as a salvage in young patients with severe disease, may improve survival. Data in older patients are limited, and at present, we cannot recommend ADT upfront in older patients. Given the limitations of our study including various types of IST, heterogeneity of patient population, health care systems, and retrospective nature of included studies; further studies are needed to confirm our findings. Disclosures Peffault De Latour: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Research Funding; 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. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Hoechsmann:Apellis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria. 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. DiPersio:Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

BackgroundThe management of Acute Myeloid Leukemia (AML) during pregnancy remains challenging as both the maternal and fetal outcomes should be considered. Several reports suggested that chemotherapy can be administered safely during the second and third trimester of pregnancy. However, the use of 5-azacytidine presents limitation due to lack of data.Case presentationA 28-years-old woman in the 26th week of gestation diagnosed with FLT3/ITD-mutated AML, complete remission was induced by Daunorubicin and Cytarabine, and subsequently with 5-azacytidine (75 mg/m2 daily for 7 days) with no fetal hematological or toxicity issues. Fetal ultrasound showed no aberrant morphology. Fetal size below the 5th percentile with normal umbilical artery dopplers, normal middle cerebral artery dopplers and ductus venosus doppler.Three weeks post 5-azacytidine, the team determined the most appropriate time for delivery after balancing the risks of prematurity and prevention of disease relapse since patient in hematological remission. The patient underwent elective lower segment caesarian section and had a baby girl delivered at 35 weeks of gestation weighing 1670 g without apparent anomalies.ConclusionTreatment using 5-azacytadine during last trimester of pregnancy resulted in no major fetal and maternal complications. These findings concluded that 5-azacytadine during the third trimester of pregnancy seems to be safe however, potential risks of this agent should be considered.

Introduction Respiratory viruses are an important cause of outbreaks of pneumonia in hematological malignancy patients. Recently, novel Middle East respiratory syndrome coronavirus (MERS-CoV) caused a cluster of life-threatening infections in Saudi Arabia (688 confirmed MERS-CoV infection cases with 282 deaths were reported to WHO by June 6, 2014 including 28% cases in HCW). Most patients had upper &/or lower respiratory tract symptoms but other features included abdominal pain, diarrhea, acute kidney injury & shock. Few hematology units were closed due to havoc. Here we report clinical features & outcome of 4 patients diagnosed at our unit during the peak period (mid-March through May 2015) including 2 who got chemotherapy (chemo) soon after recovery. Patient #1 A 62-yr-old male had free λ light chain multiple myeloma (MM) with spinal cord compression. After surgery & local radiation, he was sent to us with paraplegia & grade 4 infected sacral bedsore that needed inpatient care. He was started on CyBorD Cycle 2 on April 24, 2014. On May 2, he had a fever spike with shortness of breath (SOB) & cough. He was started on antibiotics. CXR revealed bilateral infiltrates & right sided pleural effusion. His O2 sat dropped & he needed CPAP. Oseltamivir was started & sputum was positive for MERS-CoV RT-PCR. He became afebrile with decreasing O2 requirement, CXR normalized & RT-PCR for MERS-CoV turned negative. Later he was able to receive 3rdcycle of CyBorD. Patient #2 A 65-yr-old lady came to us with B symptoms & huge organomegaly due to stage-IV DLBCL. On May 2, 2014 RCVP chemo was started. On day 6, she spiked fever with SOB, cough & was started on imipenem. CXR showed consolidation in right lower lobe. She needed 4L of O2/min. On May 10, 2014, she worsened with RR 32/min, O2 sat 79% on 15L O2/min & BP 79/47 mmHg. CXR revealed bilateral consolidation. She needed intubation & inotropic support in ICU. Vancomycin & oseltamivir were started & RT-PCR was positive for MERS-CoV on two nasopharyngeal swabs (NPS). LFT & RFT were normal but she continued to decline & died on May 13, 2014. Patient # 3 A 22-yr-old lady with past H/O AML t(8;21) was admitted on April 27, 2014 with 3 day H/O cough, fever & SOB. CXR had infiltrates in left lower lobe. She had severe pancytopenia & BMB confirmed relapsed AML. She had slightly raised LFT. Urine grew Ent. fecium. Antibiotics & voriconazole were used. She remained febrile over next 2 days. CT chest revealed extensive bilateral consolidation. She needed O2 up to 5L/Min for few days. RT-PCR for MERS-CoV was positive from NPS. She was initiated on oseltamivir. She became afebrile after 2 days & repeated RT-PCR for MERS-CoV was negative. Fludara, Ara-C (FA) chemo was started. She remained neutropenic for next 4 weeks but there was no recurrence of respiratory symptoms. BMB on day 28 of FA confirmed CR. CT chest revealed complete resolution of air space opacities. She was discharged with plan to undergo matched sibling donor Allo-HSCT. Patient #4 A 76-yr-old male with H/O HTN & CKD was diagnosed to have IgA κ MM. He was started on MPV chemo as inpatient due to logistic reasons. After 3 cycles of MPV, serum free κ chains decreased by 91% but remained on dialysis. On 21 April, 2014 he developed cough, SOB & fever. CXR revealed bilateral infiltrates & antibiotics were started. He worsened over next few days & CXR showed worsening bilateral consolidation. Eventually he needed intubation. He was treated with antimicrobials including voriconazole & oseltamir. RT-PCR for MERS-CoV was positive from NPS. Unfortunately he died few days later. Discussion: Patients with hematological malignancies are at increased risk of community & hospital-acquired infections. Recent outbreak of MERS-CoV infection has created a havoc among hematologists community. There is uncertainty about impact of MERS-CoV infection on continuation of chemo. We report 4 cases of hematological malignancies with MERS-CoV infection. Three of the 4 patients developed severe pneumonia & required intubation (2 died later) & one had milder form of pneumonia treated in isolation room. In addition to supportive care, all 4 received antimicrobials & oseltamivir. Chemo was safe soon after recovery from infection in the surviving 2 patients. We propose that during MERS-CoV epidemics, pneumonia can be treated with supportive care, antibiotics & oseltamivir. Chemo can be continued for the malignant disease soon after recovery. Further reports are needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.

e19562 Background: Central nervous system (CNS) relapse develops in 2-10% of patients with diffuse large B cell lymphoma (DLBCL) and has an adverse prognosis. Tools like IPI and CNS-IPI scores identify patients at high risk of systemic or CNS relapse based on the presence of established risk factors ( Schmitz et al. JCO 2016). International guidelines propose prophylactic intravenous high-dose methotrexate (HD-MTX) for patients at high risk of CNS relapse; however, limited data is backing this approach. Methods: We conducted a retrospective review of newly diagnosed DLBCL patients aged 18-75 years treated with curative intent at large academic medical centers in Riyadh, Saudi Arabia, between 2015-2018. Patients who were planned for CNS HD-MTX after cycles 2, 4, and 6 of R-CHOP and received at least one HD-MTX cycle were included. Results: We identified 35 DLBCL patients who received at least one R-CHOP cycle with one cycle of HD-MTX. The median IPI and CNS-IPI score were 3, (range = 0-4) and 3, (range = 0-5), respectively. The median number of R-CHOP cycles received was 6 (range 3-6) and HD-MTX 3 (range 1-6). The overall response rate was 91%, with 3 (9%) primary refractory patients per interim evaluation on cycle 3 of R-CHOP. Achieving complete remission after six cycles of RCHOP was noted in 80%, with four additional patients showed residual disease at the end of treatment evaluation. The entire cohort's overall survival was not reached, and five years estimated survival is 75%. With a median follow-up duration of 37.3 months, none of the patients relapsed after achieving CR at the end of treatment evaluation. The risk of systemic or CNS relapse in our cohort was 0%. In restricting the analysis to CNS-IPI of ≥ 4, a total of 13 patients with a median follow-up of 42 months were included; four patients did not achieve CR by the end of treatment, while nine patients continue to be in CR without any evidence of relapsed disease. Conclusions: High-dose methotrexate with high-intensity chemoimmunotherapy (R-CHOP) seems to be associated with an improvement in the expected rate of CNS relapse. Our data set is small, and a more extensive study evaluating HD-MTX's effectiveness in high-risk DLBCL is warranted.[Table: see text]

Introduction Outcomes of patients with hematological cancers and coronavirus disease 2019 (COVID-19) have been reported to be poor with high rates of hospitalization, mechanical ventilation with high case fatality rates, mortality being around 10% or higher. The mortality had been particularly higher among blacks and ethnic minority individuals. There is paucity of data on the outcomes of patients with autologous stem cell transplant and concurrent COVID-19 infections, especially from eastern mediterranean region, no similar studies have been reported so far. Methods Here we describe outcomes of five consecutive patients of middle eastern ethnic origin who had a history of autologous stem cell transplant and developed COVID-19 infection, who were admitted at our tertiary care center between April and June 2020 with a minimum of 10 days follow-up. Results A total of five patients were identified who had undergone autologous stem cell transplantation and had developed COVID-19 infection. There were 3 males and 2 females and the median age was 43 years (range 18-59). Indications for transplant were myeloma (n=3), relapsed Hodgkin lymphoma (n=1), and relapsed diffuse large b cell lymphoma (n=1). Three of five patients had other comorbidities. Median time from transplant was 9 months (range 3-33 months). Four of five patients were on active treatment or maintenance at the time of infection. One patient was on brentuximab, and three were on lenalidomide based therapy. Only one of the five patients had active disease at the time of infection while the rest were in remission. None of the patients had severe disease and four were discharged to home isolation and made full recovery, and one needed admission requiring minimal oxygen and eventually made full recovery. At a median follow up of 70 days (range 12-90) all patients were doing well with no sequelae. Conclusion Our study, albeit small, shows excellent outcomes among patients of middle eastern ethnic origin with hematological cancers who had undergone autologous stem cell transplantation and had developed COVID-19 infection, unlike other studies that have shown high mortality among patients with hematological cancers. However, our cohort is relatively younger, most of them were in remission at the time of infection which may have had a protective effect. At the same time, the majority had transplant within the last nine months and four-fifths of the patients were on some sort of immunosuppressive therapy whilst developing COVID-19 infection. It is possible that a dampened immune system due to transplant and recent therapy might have had a protective effect against cytokine storm or severe COVID-19, in our view. More studies are needed to examine this aspect further, however, these results are encouraging. Disclosures No relevant conflicts of interest to declare.

Introduction Outcomes of patients with hematological cancers and Corona Virus Disease-19 (COVID-19) have been dismal with high rates of hospitalization, admission to intensive care unit and high mortality of up to 20% compared to general population, more so pronounced among black and ethnic minorities. There is hardly any data on outcomes of patients with lymphoma and concurrent COVID-19 from eastern mediterranean region. From eastern mediterranean area no similar studies have been reported so far. Methods Here we describe outcomes of eleven consecutive patients who had history malignant lymphoma (either treated or currently on treatment) and now had developed COVID-19 infection, recently admitted at our tertiary care center between April and July 2020 with minimum of 10 days follow up. Results Total of eleven (n=11) patients were identified with COVID-19 who also had diagnosis of malignant lymphoma. There were 5 males and 6 females and median age was 31 years (Range 19-59). Diagnoses included five cases of diffuse large b cell lymphoma, two cases of primary central nervous system lymphoma, three cases of classical Hodgkin lymphoma, one case of low grade non Hodgkin lymphoma. Two cases were newly diagnosed and had not received any treatment while six patients were on active treatment and three patients had received treatment more than six months prior. Three patients were on Rituximab based therapy at the time of infection and two patients had prior autologous stem cell transplant. Seven patients had mild COVID-19 while four had severe form of disease. All patients were on supportive care and treatment included various options including chloroquine, antibiotics, convalescent plasma, interferon, enoxaparin, Tocilizumab depending on treating physician's discretion. Four patients had home isolation and recovered fully, while seven patients needed hospitalization of which three made full recovery while three needed admissions to intensive care unit (ICU) due to severe COVID-19. Out of three patients in ICU, two needed noninvasive ventilation, one needed mechanical ventilation. At the time analysis one ICU patient made complete recovery and discharged home while two others are still in hospital. After a median follow up of 37 days (range 10-87), no mortality has been recorded so far. Out of four patients with severe COVID-19, one was newly diagnosed and treatment naïve, and one was in remission for more than a year, the remaining two were on active rituximab based chemotherapy for lymphoma. However, 3 out of 4 patients had cleared COVID-19 by polymerase chain reaction testing. Conclusions Our results suggest that COVID-19 causes significant morbidity in patients with lymphoma like other studies, however there has been no mortality so far in our cohort with relatively long follow up, although some patients are still admitted at the time of analysis. One of the reason for lower mortality could be younger age group. Our study also suggests that over two thirds of the patients had only mild disease out of which majority of them were on some sort of therapy or had undergone recent transplant, making us wonder if recent immunochemotherapy may have some protective effect against cytokine storm or severe COVID-19 by having dampening role on immune system. Half of the patients who had severe disease were not on any therapy while the other two who were on active therapy, although still inpatients, had cleared the virus interestingly. Further studies needed to examine this further, our results from this ethnic community are encouraging. Disclosures No relevant conflicts of interest to declare.

Introduction Granulocyte Colony Stimulating Factor (GCSF) with cyclophosphamide based peripheral blood stem cell (PBSC) mobilization is a widely used strategy among patients with multiple myeloma (MM), however, it is associated with toxicity and morbidity including severe infectious complications needing hospitalization. Plerixafor with GCSF has been widely used for mobilization as a preemptive strategy or during second attempt at collection with encouraging results. Methods We describe our experience from a newly established transplant unit in the Eastern Mediterranean region. A retrospective chart review was done and all consecutive patients of MM who underwent PBSC mobilization by GCSF and plerixafor between 2017 to 2020 were included in the study. Patients received GCSF (filgrastim, 10 µg/kg/day) and if peripheral blood CD34 count was less than 20/µl on day 4, patients received the first dose of plerixafor (240 µg/kg/day) on the evening of Day 4. Daily apheresis started on Day 5 for a maximum of 4 days, or until enough stem cells collected for one or two transplants at physician's discretion. Results A total of seventeen PBSC collections were carried out among patients with myeloma (n=17). There were 10 males and 7 females. The median age was 53 years (range 38-71), and 8/17 were less than 50 years of age. 14/ 17 were of IgG myeloma subtype, 2/17 were light chain myeloma, 1/17 was IgA myeloma type. 6/17 patients had R-ISS stage 3 disease while rest (11/17) had R-ISS stage 2 disease. 15/17 patients were in first remission. Only 1/17 patients had high-risk cytogenetics. 12/17 patients had bortezomib based therapy while 5/17 had lenalidomide based therapy. 13/17 patients had GCSF alone mobilization while 4/17 had GCSF plus pre-emptive plerixafor. 9/17 had a single collection while 8/17 had 2 collections. All patients on plerixafor needed two collections. Median CD34 stem cell dose was 8.6 x10^6 cells/kg (range 3.4-20 x 10^6 cells/kg). No grade 2-4 adverse events were recorded with this strategy post-collection and none required hospitalization for any adverse events. All patients underwent melphalan based conditioning and autologous stem cell transplant, although only 12/17 received a full dose of 200 mg/m2. 13/17 patients had fresh stem cells infused while the rest had cryopreserved stem cells. Median time to neutrophil recovery was 11 days (range 9-27) while median time to platelet recovery was 12 days (range 10-37). Day 100 mortality was zero percent. Conclusions Our study demonstrates successful collection with high stem cell yield enough for two stem cell transplants with GCSF and preemptive plerixafor strategy, in patients with MM, thus saving patients toxic effects of cyclophosphamide including cytopenias, infections which at times are severe causing morbidity and mortality. Over two-thirds of patients collected with GCSF alone. No major adverse events post stem cell collection were noted and all our patients engrafted early thus reducing hospital stay. Although the use of plerixafor increases cost but failure of mobilization, second mobilization, and infections (at times severe), delayed engraftment have their own costs and implications. Our study at our new transplant unit confirms that this pre-emptive strategy is safe, effective and reasonable chemo free first line option with no major adverse events as demonstrated by other studies. Disclosures No relevant conflicts of interest to declare.

Myeloid neoplasm with eosinophilia and FIP1-like-1-platelet-derived growth factor receptor-alpha (FIP1L1-PDGFRA) rearrangement is a multi-organ disease with diverse clinical presentation. Thrombotic thrombocytopenic purpura (TTP) is characterized by the concomitant occurrence of often severe thrombocytopenia, microangiopathic hemolytic anemia, and a variable degree of ischemic organ damage. To our knowledge, only one case of eosinophilia with FIP1L1-PDGFRA rearrangement presented as a case of thrombotic thrombocytopenic purpura reported in the literature. We herein report a case of a young male patient with hypereosinophilic syndrome and FIP1L1-PDGFRA rearrangement who presented with asthma, transient ischemic attacks (TIA), and confusion. He had an acquired TTP that was successfully treated with plasma exchanges (PLEX), corticosteroids, rituximab, and later with the addition of imatinib mesylate (Gleevec, Novartis). He remains in complete remission on imatinib 100 mg daily for more than 28 months of follow-up.

Background: Hematology practice in developing countries has some unique issues including a higher prevalence of infectious disease markers. Epstein-Barr virus (EBV) is an oncogenic virus and implicated in Burkitt's lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma and leiomyosarcoma in the immunocompromised (Ito Y et al. 2009). Cytomegalovirus (CMV) infection/reactivation in patients with hematological malignancies causes serious morbidity and mortality. Saudi Arabia is a high income rapidly developing country, but seroprevalence of CMV and EBV is reportedly higher compared to developed countries (Ghazi 2002, Seale et al., 2006, Joseph et al., 2005). EBV & CMV co-infection is not infrequent & occurs most commonly in the immunocompromised host. A significantly higher prevalence of antibodies (Abs) against CMV & EBV in some disease groups compared to controls has been reported from the same communities (Ocak et al., 2006, Al-Hakami et al., 2016). Interestingly, CMV disease occurrence in sibling donor hematopoietic stem cell transplant (HSCT) is infrequent in our area in spite of the occurrence of CMV reactivations (Aljurf et al., 2009, Saovic et al., 1999). Hence, knowledge of seroprevalence of these viruses in hematological malignancies may be helpful in strategic planning for transplants & transfusions. It may help in establishing any plausible etiological linkage with certain hematological malignancies. Methods: We retrospectively examined the records of adult patients (>14 years) with hematological malignancies for CMV and EBV status (IgG and IgM Abs by chemiluminescence immunoassay). We identified 2,007 patients (1104 males and 903 females) and grouped them according to gender along with broad hematological malignancy categories (Table 1). We tried to establish if any disease category had extraordinary seropositivity for CMV (IgG ≥20 U/ml) or EBV (IgG ≥12 U/ml). We also studied the prevalence of IgM Abs in those tested positive for IgG Abs. Results: Of 2,007 patients (males significantly more than females, p = 0.001), age range 14-93 year (mean 47.2), 503 underwent testing for CMV status and 520 for EBV. Among these tested patients, there was no significant gender difference as 96.1% males were CMV positive, and 95.4% females were CMV positive. On the other hand, 96.9% males were EBV IgG Abs positive compared to 92.5% of females, which was 2.56 (95% CI; 1.12 - 5.96) times more likely to be positive in the studied male patient population (p = 0.021). Overall seroprevalence for CMV IgG Abs was 95.4%, and for EBV IgG Abs it was 95% (Table 1). Among those with CMV IgG Abs, 25/482 (5.1%) had very high antibodies titer (>180 U/ml), and 23/25 patients (92%) had lymphoid malignancies (11 NHL, 7 HL, 2 ALL, 3 MM) and 2 had CML. Among those with EBV IgG Abs 59/495 (11.9%) had very high antibodies titer (>750U/ml); and 46/59 (77.97%) of these patients had lymphoid malignancies (20 HL, 16 NHL, 6 ALL, 4 CLL, 1 MM) and 13/59 (22.03%) had myeloid neoplasms (6 AML, 5 CML, 1 MDS, 1 MPN). Six patients had very high titers for both EBV and CMV antibodies. In CMV IgG Abs positive patients only 1.03% (5/482) had IgM antibodies, and in EBV IgG Abs positive only 2.22% (11/495) had IgM antibodies. Table 1 shows the prevalence across the gender and in different disease categories. The highest seroprevalence for CMV was found in CLL, multiple myeloma and MDS patients (100%); and for EBV it was highest in MDS and MPN patients (100%). Relatively lower seroprevalence of EBV was noted in ALL patients group (86.2%), and lower seroprevalence of CMV was noted in MPN patients group (87.5%). However, overall, there was no significant difference across the disease categories for either CMV (p = 0.362) or EBV (p = 0.114). Conclusions: In this large study on our patients with hematological malignancies, we report very high seroprevalence of CMV and EBV Abs, reaching up to 100% in some disease categories. Among those with very high titer of EBV IgG Abs, the majority had lymphoid malignancies. Short of establishing any etiological linkage, we noticed 100% of MDS patients had both CMV and EBV Abs. Contrary to other reports, our male patients were more likely to be EBV positive compared to the females. Our results support the need for further studies to investigate possible cooperative linkage of EBV and CMV in carcinogenesis. Disclosures No relevant conflicts of interest to declare.

Bilharzial hepatic fibrosis is usually accompanied by marked enlargement of the spleen. Schistosoma hematobium and Schistosoma mansoni infestation is endemic in Africa and southern part of Saudi Arabia. Patients with acute myeloid leukemia (AML) present with clinical features resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells (including splenomegaly), or both. Co-occurrence of bilharzial splenomegaly and AML is intuitively possible. Spontaneous splenic rupture has been reported to be catastrophic in both conditions and rarely splenic rupture may be the first manifestation of AML. Splenectomy is a considerable option in symptomatic splenomegaly in schistosomiasis. An enlarged spleen may also serve as a sanctuary site for residual leukemic cells after chemotherapy. Splenectomy has been reported in pediatric AML after chemotherapy and selected adult patients with myelodysplastic syndrome and myeloproliferative neoplasm (MPN). However, to the best of our knowledge, this is the first report of successful outcome of splenectomy prior to induction chemotherapy in an AML patient who presented with huge symptomatic splenomegaly due to past history of schistosomiasis, had also shown refractoriness to platelet transfusion due to hypersplenism and vaginal bleeding. Splenectomy in such a scenario was a difficult decision but was feasible with adequate expertise, vigilance and blood products availability. The patient is alive in complete remission with good performance status more than 2½ years after therapy.

Objective: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients Methods: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC). Results: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR. Conclusion: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities..

Background: Indolent lymphomas (ind-LYM) are a subset of B-cell lymphomas, characterized by slow growth, protracted course without treatment and a tendency to reoccur after therapy. The management of ind-LYM is varied and evolving. To-date reliable tools for imaging based prognostication and treatment strategies are limited. We explored the utility of serial FDG PET scans (baseline (BL), interim/6 months (INT) end of therapy/1 year (EOT)), in managing ind-LYM). Methods: From an ongoing prospective study, examining the role of PET scan in ind-LYM at our institution, we performed an interim analysis of all patients hitherto enrolled in our study. Patients diagnosed as ind-LYM and having undergone serial PET scans from 2015 to date (N=40, males= 27, females =13) had median age of 59.68 ± 14.5 (28-82 at diagnosis. All PET scans were obtained per accepted protocols. SUVmax and Deauville scores (DS) were obtained from five target lesions. The average of composite SUV (cSUV) and composite Deauville scores (cDS) were computed for each patient. Statistical analyses (using t-test, mean delta change) were performed with the cSUV and cDS. Results: The types of ind-LYM were CLL/SLL (17), Follicular (15), mantle cell (3), marginal zone lymphoma (3), and 1 each of MALT and lymphoplasmacytic lymphoma. The data were analyzed for two arms of the study treatment chemotherapy arm (CHEMO-22/40) and Rituximab + observation arm (OBSR-18/40). At BL, patients on CHEMO had significantly higher cSUV and cDS compared to those who were on OBSR (SUV: 6.99 vs. 4.32 p-value 0.0124; cDS: 4.37 vs 3.71 p-value 0.0075 respectively). Although there was a delta change in the cSUV and cDS in both arms after INT and EOT, both treatment lines showed no significant difference in the SUV mean and DS (p-value: 0.754 and 0.5721, receptively). A 2-tailed T-test was used for delta change of cSUV. BL to INT cSUV was statistically significant (p-valve 0.05) and difference in cSUV was not significant for BL to EOT (p-valve 0.98). Difference in cDS was not significant between BL, INT and EOT. Conclusion: The higher cSUV/cDS at BL for the treatment arm may be due to disease profile at the time of presentation and/or selection bias. At EOT no difference in both estimates were noted. Both arms showed similar trends in delta change from BL-INT-EOT. Our findings suggest that SUV and DS at BL maybe an independent criterion for treatment selection in ind-LYM. Disclosures No relevant conflicts of interest to declare.

Background: Acute Myeloid Leukemia (AML) is a group of heterogeneous clonal disorder of myeloid progenitor cells. Relapsed and refractory AML represent a clinical and therapeutic challenge to hematologist because of chemotherapy resistant disease and are associated with poor outcome. Allo-SCT is the only potentially curative therapy for such patients and is only possible after achieving second remission. FLAG is used more commonly and is associated with around 50%. We hypothesize that pretreatment with azacytidine will improve the overall response rate and remission status. Objectives : The primary objective of this study is to evaluate the overall response rate (ORR) of pretreatment with azacytidine followed by FLAG for the treatment of relapsed/refractory AML. Methods: This is prospective phase II study of patients with diagnosis of refractory/relapse AML at King Fahad Medical City, Riyadh, Saudi Arabia between January 2015 and July 2018. Patient confirmed to be relapse/refractory AML based on bone marrow biopsy results were included. Eligible patients received pretreatment with azacytidine for 5 days (days -5 to -1). The FLAG protocol was started on the next day after the completion of 5-azacytidine. G-CSF was started on day 0 (24 hours after last 5-azacytine dose) and continued for a total of seven days (days 0 to 6). Fludarabine and cytarabine was started on next day after G-CSF start day and continued daily for 5 days (days 1 to 5). Patients were followed up with daily clinical examination and labs until next bone marrow examination at count recovery up to day 35. The bone marrow sample was analyzed for cell cycle and global DNA methylation status before and after azacytidine treatment. The ORR is the proportion of the treated patients who achieved CR or Cri. The toxicity was graded base on the frequency of Adverse Events (the NCI-CTCAE version 4.0 scoring system). Results: Sixteen refractory/relapsed AML patients (5 females; 11 males) admitted to our Center from January 2105 to July 2018 were included in the study. Twelve patients were evaluable after exclusion of three patients from analysis based on exclusion criteria. One patient died during induction. The mean age was 39.38 ± 15.11 years. The mean WBC, hemoglobin, platelets, peripheral blood blasts, bone marrow blasts were 26.44 ± 23.15, 7.43 ± 1.55, 61.81 ± 85.20, 49 ± 30.36, and 57.36 ± 29.23 respectively at diagnosis. The mean bone marrow blasts were 42.09 ± 29.75 at relapse/refractory disease. Seven patient had normal Cytogentics. One patient had BCR (9q43), PML (15q22), RUNX1T1(8q22) & MLL (11q23) genes. Another one had EGR1 (5q31) deletion, while t(8;21) was found in another patient. One patient was positive for 7q31 deletion. Four out of twelve patients had abnormal molecular cytogentics including FLT3 -ITD, CEBPA, FLT3 -TKD mutation and KITD816V. No patient has extramedullary disease at diagnosis or relapse settings. Seven out of twelve patients had primary refractory disease while five patients had relapsed disease with 6 months' median duration of remission (Range 1.25-84). Nine patient received 3+7 induction regimen at diagnosis while three had ICE protocol. Eight out of twelve patients showed complete response (67%). Four out of five relapsed patients achieved complete response (80%) whereas four out of seven (57.14%) achieved complete response in refractory disease. Eight patients were referred for stem cell therapy. The most common toxicity was cytopenia and bacterial infections. One patient has left arm cellulitis whereas one had arthritis with myositis. All patients were successfully treated with antibiotics, one patient died during study period because of severe invasive fungal infection. Conclusion Our phase II study preliminary results indicate that the addition of Azacitidene prior to standard therapy can improve the overall response rate and remission status in relapsed/refractory AML. This may provide an opportunity to responding patients to proceed to curative therapy with stem cell transplant. Disclosures No relevant conflicts of interest to declare.

Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by microvascular platelet deposition and thrombus formation with resulting microangiopathic hemolytic anemia and thrombocytopenia. Deficiency of the von Willebrand factor cleavage metalloprotease, also known as ADAMTS 13, has been implicated as an important etiological factor in TTP. Few small studies have been reported on Saudi patients with TTP until now. Our aim was to analyze the clinical features, laboratory characteristics and treatment outcomes with TTP patients treated at our large tertiary care center. Methods This is retrospective data of 24 patients with diagnosed of TTP who were treated at King Fahad Medical City, Riyadh, Saudi Arabia between October 2006 and April 2015. Patient suspected as a case of TTP on the basis of clinical features with the evidence of microangiopathic hemolysis and thrombocytopenia were included in this study although data related to pentad of TTP was collected and wherever logistically possible ADAMTS13 levels and inhibitor titer were determined. The primary aim was outcome assessment by overall response rate (ORR) in the treated patients through Kaplan-Meier method. Paired sample t-test was applied to determine the mean significant difference among platelets (plt), hemoglobin (Hgb) & LDH on day 1 and day 7 of treatment. Results Twenty-four TTP patients (18 females; 6 males) admitted to our hospital from 2006 to 2015 were analyzed. The mean age was 33.5±13.9 years. Twenty-two (91%) of the patients presented with neurologic features, seven (29%) had fever, ten (42%) had renal impairment that normalized with treatment and four (20.83%) had increased troponin-T or cardiac symptoms. There were 22 patients (91.7%) with the triad of TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; only 2 (8.2%) had the classical pentad of TTP. Among the plausible etiology, idiopathic (51.8%) was the most common followed by acquired autoimmune abnormalities (29.2%). Plasma ADAMTS 13 activity was determined in 19 patients. Eight patients (42.1%) had severe ADAMTS 13 deficiency (activity< 5%); 5 (26.3%) had moderate decrease of ADAMTS 13 activity (activity: 5-10%); another 3 (15.8%) had low ADAMTS 13 activity and 3 (15.8%) patients had normal ADAMTS 13 (>50%) most likely due to sampling post plasma infusion in emergency situations. Median platelet count on Day 1 was 14x10^9/L, and Day 7 was 119x10^9/L (P value< 0.001), Median Hgb on Day1 was 8.25 gm/dl and Day 7 was 9.35 gm/dl (P value< 0.007), Median LDH on Day 1 was 1211 IU/L and Day7 was 278.92 IU/L (P value< 0.001) respectively. All patients received plasma exchange whereas 23 (95.8%) patients received adjunctive corticosteroids. Five patients (20.8%) were early refractory to standard treatment with therapeutic plasma exchange (TPE). Thirteen (54.2%) patients received rituximab either due to refractoriness to TPE on ~ day 7, or earlier due to cardiac or neurological manifestations at treating physician's discretion. Average hospital stay was 27 days (range 1-131). Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. On long term follow up of 22 months (median, Range 1-113), overall survival was 80%. Three patients died during acute episode because of very sever disease or delayed arrival to our center. One patient died later on because of other comorbidities while in CR. Conclusion Thrombotic thrombocytopenic purpura is a life threatening condition and immediate treatment with plasma exchange along with steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of our patients. Combination of very severe CNS manifestations and delayed arrival contributed to mortality significantly. More awareness is needed for early diagnosis and early referral to higher centers. Disclosures No relevant conflicts of interest to declare.

Background: Blood products transfusion is universally the most executed procedure in hospitals around the world. Still there is a general lack of interest among the physicians in training, both at undergraduate and postgraduate level. A lot more enthusiasm development is needed to motivate medical students to get interested in making TM their future career. In fact medical students are not taught enough during undergraduate courses. International studies have indicated that there is often little exposure to TM beyond 1-2 lectures in undergraduate medical training. Our regional anecdotal observations at undergraduate level had indicated that the students, inducted with different educational background (bachelor in biochemistry, pharmacy, dental health, radiology and medical laboratory) were not motivated enough to get involved on-the-bench and in the donation area, eventually reflecting in a poor performance in the examinations when it comes to TM questions. Methods: In this prospective study involving 22 volunteering year 4 medical students, we investigated that if motivational didactic lectures by senior faculty members at undergraduate level can enhance enthusiasm level for TM related training among our students. During motivational talk, emphasis was placed on wide scope and opportunities in TM field. We also tested the basic essential knowledge related to transfusion medicine focused on pre-transfusion testing, blood donation and informed consent procedure in Results: Among 22 medical students, median pre-test score was 6.75 (Range 3-9), median post-test score was 9.75 (Range 6.5-10) & the median percentage positive change in the score was 22.5% (Range 0-60 %). Detailed analysis revealed that students with medical laboratory background at the time of admission to medical school had the least change in the score. In post-talk assessment all of the respondents indicated that they were motivated to do a proactive rotation in blood bank. All respondents also showed their enthusiasm to work on the bench (blood grouping, cross-matching, antibody screen and DAT), participate in donor history questionnaire assessment of responses, and attending complete blood donation process. Conclusion: We demonstrate effectiveness of motivational didactic multi-media teaching by senior faculty member in enhancing enthusiasm level for TM related training among the students at our place. We recommend that transfusion medicine specialists should gain expertise in medical education and collaborate with colleagues who are experts in medical education. We like to disseminate our results to make changes in standardized curriculum and to improve teaching strategies. TM leaders should come forward to enhance enthusiasm level for TM related training among medical students to prevent extreme shortages of TM specialists in future. Disclosures No relevant conflicts of interest to declare.

Introduction: Baseline (PETb) and end of therapy (PETe) FDG PET is standard of care in the management of hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). The role of interim PET (PETi) in HL is well established while its role in DLBCL is not well defined. We evaluated the utility of triPET (PETb, PETi and PETe ) in management of these two lymphomas. Methods: Retrospective review of PET archives revealed a total of 37 pts (HL=22, DLBCL=15). TriPET were acquired per accepted protocol. SUVmax and Deauville scores (DSc) were obtained from five target lesions, the average i.e. composite SUVmax & DSc were computed for each pt. Statistical analyses were performed with the composite maxSUV (cSUV) and Deauville scores (cDSc) (using EXCEL). Following statistics were performed (separately and combined in HL and DLBCL); mean+SD, PPV and NPV for complete response (CR) Vs. progressive disease (PD) on PETi using the following variables 1. cSUV and 2. cDSc and 3. delta change (DELT). Median progression free survival (PFS) was the clinical endpoint for response. Results: The mean PFS in our group was 17 and 15 months in HL and DLBCL respectively. Using cut off thresholds for intP to predict CR at cSUV=80%,. In HL: for cSUV- PPV 67%, NPV 95%; for DELT of cSUV PPV 100%, NPV 95%; for cDSC-PPV 30%, NPV 100%. In DLBCL: for cSUV- PPV 25%, NPV 100%; for DELT of cSUV PPV 33%, NPV 100%; for cDSC- PPV 50%, NPV 100%. Conclusion: The results from our series suggest that PETi has a role not only in HL but in DLBCL as well. Our modest cohort suggests that a negative PETi in DLBCL had a NPV of 100% across cSUV, cDSc and DELT, with regards to CR. Our data also suggests that PETe is not needed if PETi is -ve. While in HL subset, our results concur with results from other groups, this needs to be validated in a larger series. Disclosures No relevant conflicts of interest to declare.

The International Prognostic Score (IPS) is the standard stratification system for survival in patients with classical Hodgkin's lymphoma (cHL). However, the IPS only applies to patients with advanced stage disease and it does not offer risk stratification for classical Hodgkin's lymphoma patients diagnosed with limited disease [i.e., stages I and IIA, without constitutional symptoms and no bulky disease. Furthermore, early interim positron emission tomography (PET) has been shown to have a prognostic value superior to that of the IPS in patients with advanced-stage cHL in an analysis (Gallamini et al). Lymphopenia (750 per ul (Tadmore et al) and high tumor-associated macrophages (TAM) are reported to be negative prognostic factors for survival in classical Hodgkin's lymphoma (Koh et al). More recent studies suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL patients treated with multitude of chemotherapies (Porrata et al, Tadmor et al). It is intriguing to investigate the significance of the ALC/AMC ratio in relation to PET negativity after treatment. Out of 164 cases of cHL treated at our center with ABVD +/- radiation therapy, we identified 70 patients who were evaluated by PET Scan. Median age was 26 years (range 14-80), 33 (47%) were stage IV, Median IPS was 3 (range1-6). We tested correlation of a high ALC/AMC ratio (>2.1) with achievement of a negative PET scan after ABVD chemotherapy. We arbitrarily chose cut-off value of >2.1 (Tadmore et al) from the multiple values reported recently, as this multicenter study had the largest number of patients. A total of 45 patients achieved a negative PET scan. Mean ALC/AMC ratio was 2.39 (range0.19-14.6). ALC/AMC ratio of >2.1 did show a trend for better OS in addition to a negative PET scan. A Spearman correlation test of a negative PET result showed a positive correlation with ALC/AMC ratio of >2.1 though it was weak. This study suggests that the ALC/AMC ratio may be a simple, inexpensive, and independent prognostic factor in cHL outcome and may have a role in the stratification of cHL patients in addition to the International Prognostic Score, TAM content and acheivement of a negative PET scan early post chemotherapy. However we plan to define our own best cut off value for ALC/AMC ratio by ROC and AUC analysis as ALC/AMC Ratio of ≥2.1 did not discriminate survival advantage very well and it may be a reason for weaker correlation with likelihood of a negative PET. Further larger studies are needed to confirm our findings. Disclosures No relevant conflicts of interest to declare.

In our clinical practice, international prognostic score (IPS) comprising of seven parameters has been in use for prognostication of advance stage Hodgkin's lymphoma (HL). Simple scoring system, that can stratify patients and or predict outcome both in early stage and advance stage HL, would be both helpful and practical to apply in daily practice. This is a retrospective study to find out whether recently reported absolute monocyte count (AMC) and absolute lymphocyte : monocyte ratio (LMR) at diagnosis are valid parameters for predicting prognosis of classical Hodgkin lymphoma (cHL) patients treated with ABVD at our center. Among many cut-off values for ALC/AMC ratio reported in literature (1.1, 1.5, 2.1, 2.8, 3.5) we chose the cut off of ≥2.1 as reported in the largest series by Tadmore et al. Data from patients' records were collected after approval by local institutional review board. All studies were performed in accordance with the principles of the Declaration of Helsinki. Patients were included into this study if they had histopathological diagnosis of cHL, no human immunodeficiency virus infection, availability of data on all clinical and laboratory features and treatments given, as well as outcome, and follow-up. Only patients treated with ABVD as initial chemotherapy with or without subsequent radiation therapy were included as this chemotherapy regimen is currently considered the standard of care in North America and at our institution. Response criteria were based on the guidelines from the International Harmonization Project on Lymphoma revised by Cheson et al. We excluded 4 patients with Nodular Lymphocyte Predominant HL(NLPHL), as NLPHL is considered to be a different disease entity. Hence we found 164 patients with cHL treated at King Fahad Medical City, Riyadh from 2006, through July 2015 with ABVD. Out of 164 patients we identified nodular sclerosis 116/164 (70%) and mixed cellularity 31/164 (19%) were the most common. The median age of the patients was 26 years (range, 14-86 years); 70 (41.6%) patients had bulky disease, 84 (52.1%) had extranodal disease; Median IPS was 3; Pre-Treatment ALC median was 1635/ul (range 192-825), AMC median was 841/ul (range 60-9600), and Pre-Treatment ALC/AMC Ratio (LMR) median was 2.168 (range 0.28-19.81). Overall survival was for ALC/AMC Ratio of >=2.1 was 97.5% and 92.8% for ALC/AMC Ratio of 45 | 24 | (14.6) | | Gender | Male | 88 | (53.7) | | Female | 76 | (46.3) | | Stage of disease | Early | 15 | (9.1) | | Advanced | 149 | (90.9) | | Bulky | No | 94 | (57.3) | | Yes | 70 | (42.7) | | Stage IV | No | 92 | (56.1) | | Yes | 72 | (43.9) | | Histopathology | Lymphocyte Rich | 6 | (3.7) | | Classical | 11 | (6.7) | | Mixed Cellularity | 31 | (18.9) | | Nodular Sclerosis | 116 | (70.7) | | Extranodal | No | 80 | (48.8) | | Yes | 84 | (51.2) | | Albumin | =40 | 23 | (14.6) | | Hemoglobin | =10.5 | 105 | (64.0) | | WBC | =15 | 37 | (22.6) | | IPS Score | | 5 | (3.0) | | 1 | 34 | (20.7) | | 2 | 42 | (25.6) | | 3 | 42 | (25.6) | | 4 | 32 | (19.5) | | 5 | 7 | (4.3) | | 6 | 2 | (1.2) | | ALC | =600 | 140 | (89.7) | | ALC | =0.6 | 134 | (85.9) | | AMC | =750 | 86 | (55.1) | | ALC/AMC Ratio | =2.1 | 84 | (53.8) | Table. Disclosures No relevant conflicts of interest to declare.

Acquired Hemophilia (AH) may lead to fatal bleeds. Relapse remains a major challenge as 1/3 of patients with AH do not achieve durable CR with immunosuppressive therapies (IST). Patients’ acceptance for cyclophosphamide (being a chemotherapeutic agent) for treating AH remains poor as compared to biological agent rituximab (R) and steroids (St). However, when fixed number of doses of R are utilized along with prolonged courses of St, considerable morbidity is seen. In quest of durable remission and prevention of relapse, we hypothesized that a strategy of targeting antibody producing B cells along with inhibitor (Inh) monitoring and titrated number of R doses earlier in the course of therapy with one additional dose beyond complete disappearance of Inh may result in better chances of prolonged remission and even cure. Here we report excellent outcome with our strategy used for three consecutive patients including a patient with multiple relapses and high titer Inh (819 BU) in whom all other therapies had failed to produce durable remission. Median time to CR from addition of R was 6 weeks (range 3-6). With a median follow up of 16-72 months none has relapsed yet. CASE #1 A student was diagnosed to have bleeding diathesis in November 2007 in Kuwait at the age of 13 years and was treated with FFP, FVIII, rFVIIa and St. He presented in December 2007 to pediatric hematology complaining of swellings in the muscles, hematuria, hematemesis, severe abdominal pain and bruising for the last 2 weeks. He had tenderness in hypogastrium and right iliac fossa, multiple skin bruises with multiple swellings over extremities. Eventually he was diagnosed to have AH with FVIII Inh of > 850 BU. He had intra-abdominal and multiple joint bleeds on imaging. He was managed with rFVIIa, IVIG, St and cyclophosphamide. Because of persistent low FVIII level (0.17%) he was given 4 doses of R along with prolonged steroid course. This resulted in normalization of FVIII level and Inh disappearance. However, soon he suffered 3 quick relapses with bleeding treated with 2 doses of R, St and IVIG. He returned in relapse with right thigh swelling, hematuria, and epistaxis in February 2013 (FVIII < 1 % and Inh 57.6 BU). He was treated again with rFVIIa and a dose of R. He was then referred to our team with Inh 115.2 BU. After giving him rFVIIa and starting St we added R on a weekly basis and prednisolone 1mg/kg daily. Inh disappeared after the 6th dose. He received the additional R dose (#7) on April 14, 2013. At this point, we could start immediate tapering of his 40 mg prednisolone dose and discontinued by July 2013. His FVIII level later rose to 200 % with undetectable Inh. He is off St since September 2013. He remains in CR after more than 16 months of his last dose of R. CASE #2 This 20-year-old lady presented to ER in March, 2013 with sudden onset swelling of the right hand, bluish discoloration and moderate wrist pain for 3 days. She gave past history of migratory joints swelling. Her mother had thrombocytopenia for the last 7 years. She had a tender warm swelling of right hand with bluish discoloartion, remarkably decreased ROM of the right wrist. She was admitted under internal medicine with possible diagnosis of CTD. Investigations revealed an ANC of 1.16x10^9/L; and an isolated prolonged PTT of 102.9 seconds that after mixing with pooled normal plasma (1:1) was 91.9 seconds. FVIII level was 0.20% and FVIII Inh was 22.4 BU. Based on further investigations a diagnosis of SLE with APLA and AH was made. rFVIIa was given, and by rheumatology team prednisolone 40 mg daily along with HCQ 400mg started on 17 March 2013 (prednisolone was tapered to discontinuation by October 2013). As bleeding manifestations continued, R 500mg weekly doses were started on 27th March 2013. After a few days of the 3rd dose, her Inh had disappeared and FVIII level had normalized. We gave her 4th dose after it according to our strategy and then started quick prednisone tapering. Patient remains in CR under follow up. CASE #3 A 28-year-old female was diagnosed to have acquired hemophilia after severe postpartum bleeding in February 2008 with FVIII Inh titer of 49.92 BU. After rFVIIa, with ongoing prednisolone her Inh level rose to 230 BU and she refused to consent for cyclophosphamide. She required 7 weekly doses of R after which Inh disappeared. Then one additional (8th) dose of R was given. Later she had an early abortion and then twin pregnancy in August 2012 without relapse. She remains in CR 6 years after her last treatment. Disclosures Off Label Use: Rituximab is a genetically engineered monoclonal antibody that targets a specific protein, known as CD20 found on the surface of normal and malignant B-lymphocytes. Use of Rituximab treatment for other than FDA approved indications include a rare condition of acquired factor VIII inhibitors in individuals without inherited hemophilia as an autoimmune phenomenon that may lead to life-threatening bleeding. Due to the low incidence rate of acquired inhibitors, published data consists of only case reports, and reviews.