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Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. The only and curative option for PMF is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib is highly effective in reducing constitutional symptoms and spleen volume, and has been found to improve survival. Ruxolitinib decreases the activity of type I T-helper cells, leading to decreased release of cytokines including tumor necrosis factor-α, interleukin-1 (IL-1), IL-6, interferon-γ, and production of IL-12, which can be a risk factor for opportunistic infections. In this report, we describe three cases of tuberculosis reactivation shortly after initiation of ruxolitinib therapy followed by a literature review.

Background: The coronavirus disease‐2019 (COVID‐19) caused by SARS Coronavirus 2 (SARS‐CoV‐2) is a potentially lethal infection. Cancer patients, and specifically hematopoietic cell transplant (HCT) recipients are severely immunocompromised and may be at a higher risk of a complicated course with this infection. We aimed to study the COVID-19 outcomes and severity in post HCT patients. Methods: We retrospectively reviewed post-HCT patients diagnosed with COVID-19 between March 15, 2020, and December 1, 2020 at 10 transplant centers across the Middle East. Results: We identified 91 patients with confirmed SARS-CoV-2 infection across 10 transplant centers. 52 patients were post allo-HCT while the remaining 39 patients were post auto-HCT. The median time from transplant was 14.9 months. Mortality rate was 4.4%. Hospital admission rate was 53%. ICU admission rate was 14%. Mechanical ventilation rate was 10%. Oxygen supplementation rate was 18%. Time from HCT to COVID-19 > 6 months was associated with lower admission rates and lower rates of the “severity” composite endpoint. Antibody responses was seen 67% of evaluable patients. Conclusion: In this series of HCT recipients, we report overall favorable clinical outcomes for patients with COVID-19 and provide preliminary insights into the clinical course of this disease in this specific population. Funding Statement: None Declaration of Interests: None. Ethics Approval Statement: The hospitals’ Institutional Review Board approved the study.

Background Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is associated with a high fatality rate (34%), which is higher in the presence of co-morbidities. The aim of the current study was to assess the clinical course and the outcome in hematological or oncological malignancy cases, diagnosed with MERS-CoV. Methods This is a case series of hematological /oncological cases, diagnosed with MERS-CoV, in a tertiary care setting in 2015. The cases were identified based on the World Health Organization (WHO) MERS-CoV case definition. The demographic, clinical, and outcome data were retrieved from the patients’ medical charts and electronic health records. Results In total, nine hematological or oncological cases were identified, diagnosed with MERS-CoV. The baseline malignant condition was hematological malignancy in seven patients, as well as colon cancer and osteosarcoma in one patient each. Six (67%) patients were male. The median age was 65 years (range 16–80 years). Co-morbidities included chronic kidney disease (n = 3.33%), diabetes mellitus (n = 3.33%), and hypertension (n = 2.22%). The presenting symptoms were shortness of breath (n = 6.66%), fever (n = 5.55%), cough (n = 2.22%), and diarrhea (n = 2.22%). Chest x-rays indicated bilateral infiltrates in 6 patients (66%). The PCR (polymerase chain reaction) test was repeated in six patients to confirm the diagnosis. The mortality rate was 100%, and the median time to death was 26 days (range 15–77 days). Conclusion MERS-CoV infection in this small cohort of hematology or oncology patients has a 100% mortality rate, regardless of the status of the underlying disease. The confirmation of the diagnosis may require repeated testing. Additional studies are required to verify the findings and to elucidate the disease pathogenesis in cancer patients.

Objectives Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. Methods Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach. Results Of 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I2 = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I2 = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I2 = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively. Conclusions Cumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.

Non-myeloablative haematopoietic progenitor cell transplantation (HPCT) from matched related donors (MRD) has been increasingly utilized in sickle cell disease (SCD). A total of 122 patients received 300 cGy of total body irradiation (TBI), alemtuzumab, unmanipulated filgrastim-mobilized peripheral blood HPC and sirolimus. The median follow-up was four years; median age at HPCT was 29 years. Median neutrophil and platelet engraftment occurred on day 22 and 19 respectively; 41 patients required no platelet transfusions. Overall and sickle-free survival at one and five years were 93% and 85% respectively. Age, sex, pre-HPCT sickle complications, ferritin and infused HPC numbers were similar between graft failure and engrafted patients. Mean donor myeloid chimaerism at one and five years post HPCT were 84% and 88%, and CD3 was 48% and 53% respectively. Two patients developed grade 1 and 2 skin graft-versus-host disease (GVHD) with no chronic GVHD. Median days of recipients taking immunosuppression were 489; 83% of engrafted patients have discontinued immunosuppression. Haemoglobin, haemolytic parameters and hepatic iron levels improved post HPCT. Pulmonary function testing, hepatic histology and neurovascular imaging remained stable, suggesting cessation of further sickle-related injury. Fourteen patients had children. In this largest group of adult SCD patients, this regimen was highly efficacious, well-tolerated despite compromised organ functions pre HPCT, and without clinically significant GVHD.

Context: Blood donation is an essential lifesaving procedure. There is a continuous effort to supply the high demand in hospitals. Aims: To assess the current status, knowledge, and attitudes of female health care students in King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS) regarding blood donation. Settings and Design: A cross-sectional study was done with students in the female campus of KSAU-HS in Riyadh. Methods and Material: The sample was categorized based on the college and year of study. A self-administered questionnaire was distributed during the first semester of the 2018–2019 academic year to an estimated 20%–25% of students per batch. Statistical analysis used: Statistical Package for Social Sciences version 22 (SPSS Inc., Chicago, IL). Results: A total of 302 students completed the questionnaire with a median age of 21 years and a range of 18–30 years. Only 14.6% of the sample previously donated blood, with half of this group donating more than once. Just less than half (48.7%, n = 147) have been exposed previously to a university campaign related to blood donation. The majority (74.5%, n = 225) knew their blood type, small proportions (16.6%, n = 50) and (10.9%, n = 33) reported knowing family members or friends requiring blood products. More than half (57.6%) of the students admitted not having sufficient knowledge regarding blood donation, and the majority (75.1%) were not aware of the quantity of blood collected during a donation. Two-thirds, 31.4% and 32.1% agree and strongly agree, respectively, that blood donation is a duty that every individual should perform. Just more than half (53%) of the students strongly agreed that they are motivated to donate blood on moral or religious grounds. Conclusion: The proportion of prior blood donation in the sample was low. This is due, in part, to inadequate knowledge about the donation process. Given that many students felt motivated to donate, it is possible that raising awareness through educational interventions could increase donations in female health care students.

PURPOSE Programmed death-ligand 1 (PD-L1) is a marker for checkpoint inhibitor use in the management of solid tumors, especially in non–small-cell lung cancer (NSCLC). Our study was aimed at determining the patterns of PD-L1 expression and cluster of differentiation 8 (CD8) immunostains in patients with NSCLC in the Arab population. METHODS Archival tumor tissue from patients with a confirmed diagnosis of NSCLC were obtained and stained for PD-L1 with antibody 22C3, using immunohistochemistry staining and giving the tumor proportion score (TPS) as a percentage from 0%-100% of stained tumor cells. Tumors were categorized into negative expressers (TPS < 1%), low positive (TPS, 1%-49%), and high positive (TPS, 50%-100%). Correlation of expression with clinical and pathologic features, including CD8-positive (CD8+) lymphocyte density, was also analyzed. RESULTS Two hundred patients with NSCLC were included in the study from 6 centers in Saudi Arabia and Algeria. Median age was 65 years (28-93 years), and the majority were men (75%) with stage 4 NSCLC (64%). The TPS was high in 37 patients (18%), low in 60 patients (30%), and negative in 103 patients (52%). In a univariate analysis, the following were significant predictors of any PD-L1 expression (> 1%): male sex, being Saudi national patients, high expression of CD8+, and presence of tumor-infiltrating lymphocytes. In the multivariate analysis, only high expression of CD8+ cells (≥ 2+) was significant, with an odds ratio of 4.4 (95% CI, 1.5 to 12.9; P = .003) CONCLUSION PD-L1 expression in our population is similar to the published literature and correlated with the density of CD8+ cells. Validation of the predictive value of this marker in our population and identifying easier and reliable methods to test for it are warranted.

Background Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with cytarabine and methotrexate (hyper-CVAD) is a commonly used regimen in adults with acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL). Adult patients fit for pediatric-inspired protocols have an excellent outcome with chemotherapy alone. However, it is unclear whether patients receiving hyper-CVAD should undergo allogeneic hematopoietic cell transplantation (HCT) as postremission therapy. Our aim was to examine the role of HCT at first complete remission (CR1) in adult ALL/LBL after hyper-CVAD. Patients and Methods Adult patients with newly diagnosed ALL/LBL receiving frontline hyper-CVAD from 2008 to 2018 were identified and records retrospectively extracted. Results A total of 85 patients were identified and included for further analysis. The median (range) age was 23 (14-68) years, and 56 (66%) were male. A total of 24 (28%) had adverse cytogenetics, and 48 (56%) had at least one risk factor. All patients received hyper-CVAD as induction; induction failure was seen in 10 (12%). A total of 38 patients continued the hyper-CVAD course, while the remaining 47 received HCT in CR1. Three-year event-free survival (EFS) and overall survival for the entire cohort were 51.4% and 61.6%, respectively. Median follow-up of alive patients was 39.9 (3.8-123.8) months. At multivariable analysis for EFS, induction failure was associated with worse outcome (hazard ratio [HR], 4.8; 95% confidence interval [CI] 1.7-13.7; P = .003), whereas HCT in CR1 improved outcome (HR, 0.42; 95% CI 0.18-0.97; P = .044). Furthermore, HCT in CR1 was the only prognostic factor for overall survival (HR, 0.3; 95% CI 0.11-0.85; P = .023). Conclusion HCT at CR1 resulted in a favorable EFS and overall survival in ALL/LBL patients after hyper-CVAD frontline therapy. Given that hyper-CVAD is a widely used protocol for adult patients, further examination of this observation is warranted.

Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Background Multiple myeloma has witnessed significant advances due to the approval of many novel agents. However, in spite of all these new developments, multiple myeloma remains an incurable disease with inevitable relapse in the majority of patients. Venetoclax is a selective antiapoptotic protein B-cell lymphoma 2 inhibitor that induces cell death in multiple myeloma cells, particularly in those harboring t(11,14)(q13;q32). We report two cases of patients with multiple myeloma with t(11,14)(q13;q32) who were treated with venetoclax/carfilzomib/dexamethasone with rapid initial response; however, the response was short-lived. Cases presentation Patient 1 was a 50-year-old Saudi man with International Staging System stage III kappa light chain multiple myeloma with normal karyotype diagnosed in May 2013. He received bortezomib/thalidomide/dexamethasone treatment and underwent autologous hematopoietic stem cell transplant. Three years later, he presented with disease progression and received multiple lines of chemotherapy, including carfilzomib/lenalidomide/dexamethasone. Venetoclax/carfilzomib/dexamethasone was started after acquiring t(11,14)(q13;q32) 5 years into his disease course. He achieved complete remission, with disease progression after cycle 6. Patient 2 was a 48-year-old Saudi man with International Staging System stage III immunoglobulin G kappa multiple myeloma with t(11,14)(q13;q32) diagnosed in May 2017. He received bortezomib/thalidomide/dexamethasone treatment and underwent autologous hematopoietic stem cell transplant. Eighteen months later, he had disease progression, and he received multiple lines of chemotherapy, including carfilzomib/dexamethasone. He was shifted to venetoclax/carfilzomib/dexamethasone in April 2019 and had an initial clinical response; two months later, he progressed to plasma cell leukemia with rapid deterioration to multiorgan failure. Conclusions Acquired t(11;14)(q13;q32) is unreported in the multiple myeloma literature. In the era of targeted therapy, it is essential to repeat the cytogenetic and multiple myeloma fluorescence in situ hybridization panel with each disease progression. Multiple myeloma remains a challenging hematological malignancy despite advances in personalized/precision medicine.

Systemic mastocytosis with an associated hematological neoplasm (SM-AHN) is a rare diagnosis commonly associated with myeloid disorders. Herein, we describe the case of a 53-year-old female diagnosed with systemic mastocytosis (SM) in conjunction with renal light chain amyloidosis (AL) and smoldering myeloma. Although cytokines such as IL-6 may play a role in the proliferation of plasma cells, delays in the diagnosis of SM and paucity of relevant studies cast uncertainty on whether the associated disease is secondary to the mast cells or etiologically independent. To our knowledge, this is the first case of confirmed renal AL disease in conjunction with SM. We review and summarize the available literature describing SM in association with plasma cell disorders.

Recent advancements in cancer care, coupled with early detection and an aging population have resulted in significant growth of cancer survivors. Long term follow up of such survivors is essential given the heightened risk for development of late effects such as secondary neoplasms, cardiovascular disease or psychosocial dysfunction among others. As more patients with hematologic malignancies are cured or managed over protracted periods of time, awareness of such issues is paramount for the practicing clinicians for optimal patient management. In this review, we describe the genesis of the field of cancer survivorship, and then it's gentle metamorphosis into multiple sub-fields currently by presenting literature relevant to late effects commonly seen in Hodgkin lymphoma, non-Hodgkin lymphoma, chronic leukemia and multiple myeloma. We will discuss the strengths and pitfalls of the existing models of survivorship care in hematologic malignancies and conclude with expert perspective on how to move the field forward.

Graft vs host disease impacts overall survival post allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia/lymphoma

Background Diagnosis of COVID-19 infection in cancer patients is critical to co-manage their underlying disease and infection appropriately. Our study aimed at evaluating the sensitivity and specificity of screening patients with cancer for COVID-19 infection. Methods All oncology patients receiving care at Department of Oncology at King Abdulaziz Medical City in Riyadh were screened using the acute respiratory infection (ARI) survey. Nasopharyngeal and throat swap for polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was performed on patients who have high ARI score (i.e. ≥ 4), or any patient requiring elective/emergency hospitalization, undergoing a procedure as well as screening asymptomatic patients receiving chemotherapy between April 1st and July 30, 2020. Institutional Review Board approval was obtained. Descriptive and inferential analyses were done and sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated considering the COVID-19 PCR as the gold standard. Results During the study period, a total of 473 patients were included with a median age was 56 years (14- 104), 51% were female, 73% had solid tumors, and 66% received treatment within the last 3 months. These patients underwent 688 PCR tests along with ARI survey screening. Testing was done in the outpatient, inpatient, and emergency department setting in 41%, 40% and 19% of the patients, respectively. Majority of tests were screening of asymptomatic patients and only 23% were tested for suspected infections with ARI ≥ 4. A total of 54 patients (8%) had positive PCR for COVID-19 infection. The prevalence of infection varied from month to month ranging from 1.09% in April up to 19.70% in June and correlated with the average daily and active case load at a national level. The diagnostic yield of the ARI score also correlated with infection burden nationally. The PPV and NPV of the ARI as a screening tool was 18.24% (0-31.8) and 95.6% (86.36-98.86%) with the PPN fluctuating considerably in parallel with the prevalence of COVID-19 result. Similarly, the sensitivity and specificity of the ARI were 55.77% (0-70.59) and 79.4 (69.19-92), respectively. Conclusion The yield of screening asymptomatic patients with cancer varies based on the community burden of COVID-19 infection. As universal screening can cause delays to patient care, it should be tailored based on the individual patient risks and infection burden in the region.

Histiocytic disorders are an exceptionally rare group of diseases with diverse manifestations and a paucity of approved treatments, thereby leading to various challenges in their diagnosis and management. With the discovery of novel molecular targets and the incorporation of targeted agents in the management of various adult histiocytic disorders, their management has become increasingly complex. In an attempt to improve the understanding of the clinical features and management of common adult histiocytic disorders (Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and hemophagocytic lymphohistiocytosis), we created this document based on existing literature and expert opinion.

Background. Refractoriness to platelet transfusion is an understudied phenomenon in critically ill patients. Our objective was to evaluate the prevalence, risk factors, and clinical outcomes of platelet refractoriness among patients in a tertiary-care intensive care unit (ICU). Methods. A retrospective cohort study included all patients (age >14 years) who were admitted to a tertiary-care medical-surgical ICU between 2011 and 2016 and received ≥2 platelet transfusions during their ICU stay. We calculated platelet increment (PI) and corrected count increment (CCI). Results. A total of 267 patients were enrolled in the study, collectively receiving 1357 transfusions with a median of 4.0 (interquartile range: 2.0, 6.0) transfusions per patient. The median pretransfusion platelet count was 31000.0 × 106/L (interquartile range: 16000.0, 50000.0). The median PI was 6000 × 106/L. The prevalence of platelet transfusion refractoriness was 54.8% based on PI p = 0.02), but not with mortality. Conclusions. Platelet transfusion refractoriness was highly (>50%) prevalent in ICU patients. However, it was not associated with increased mortality.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous disease with a variable prognosis. The International Prognostic Index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network-IPI (NCCN-IPI) have been developed and validated to predict prognosis in DLBCL. However, patients from the Middle East and North Africa (MENA) region were under-represented in such scores, and it is unclear whether ethnic background contributes to different disease biology or response to therapy. Following due Institutional Board Review approval, DLBCL patients diagnosed from January 2010 until December 2015 from the MENA region were retrospectively reviewed. A total of 122 were identified and further analyzed. There were 74 males (61%), and the median age at diagnosis for the cohort was 64 years (range: 18-98 years), with a median follow-up duration of 32.9 months (range: 0.2-123.7 months). Estimates of three-year progression-free survival found a significant difference among risk groups using all three prognostic models but were more discriminating among the groups using NCCN-IPI and R-IPI vs. IPI (p = 0.019 and 0.014 vs. 0.039, respectively). For overall survival estimates at three years, the NCCN-IPI was the best model compared to R-IPI and IPI (p = 0.0013 vs. 0.05 and 0.04, respectively). In conclusion, we validated that the IPI and its subsequent iterations were predictive of outcome in DLBCL patients from the MENA region; however, the NCCN-IPI appeared the most prognostic. These results warrant further confirmation.

Preemptive therapy (PET) for cytomegalovirus (CMV) reactivation post allogeneic hematopoietic stem cell transplantation (SCT) was shown to decrease the incidence of CMV disease. However, the optimal PET threshold is elusive.To examine the efficacy of PET initiation at a viral threshold of 1000 copies/mL (1560 IU/mL) in a patient population with high prevalence of CMV seropositive status.A single center retrospective review of patients that underwent allogeneic SCT was done.A total of 195 allogeneic SCT recipients were included with median follow up of 18.1 (0.7-95.6) months. A total of 178 (91 %) of patients had a positive CMV PCR with median days to initial reactivation post SCT of 17 (1-1187); 129 patients had peak CMV titer1000 copies/mL (low titer) whereas the remaining 49 patients had a peak titer ≥ 1000 copies/mL (high titer). 120 (93 %) of patients with low titers cleared spontaneously with median time to clearance of 40 days (4-188). One patient in the high titer group developed CMV disease. At multivariable analysis; age at SCT HR 1.02 (1.004-1.04; 0.017), malignant vs. benign condition HR 9.4 (2.47-61; 0.0005) and cGVHD HR 0.37 (0.2-0.65; 0.0005) were significant for OS.CMV reactivation post SCT was very common in patients with high prevalence of seropositive status. A PET threshold of 1000 copies/mL (1560 IU/mL) appears desirable as it was associated with spontaneous clearance in over 90 % of patients while minimizing treatment related toxicity. Validation of these observations is warranted.

The prognosis of acute myeloid leukemia (AML) remains poor. Among 180 patients, the median age was 53 (14-88) years. The overall 2-year disease free survival (DFS) was 28.6% (+/- 3.4), 47.7% (+/- 6.6%) for ≤ 40, 23.6% (+/- 5.8%) for 41–60 and 11.7% (+/- 4.2%) for ≥61 (p< 0.0001). The overall 2-year survival (OS) was 45.3% (+/- 3.8%), 78.6% (+/- 5.5%) for ≤40, 43.5% (+/- 6.9%) for 41–60 and 15.8% (+/- 4.8%) for ≥61 (p< 0.0001). Induction outcome of ≥61 was best in high dose chemotherapy (HDC) group (p < 0.0001). Only those ≤40 had durable DFS and OS. HDC appears to improve the outcome of older AML patients.

Background Hypomethylating agents (HMA), azacitidine, and decitabine are frequently used in the management of myelodysplastic syndromes (MDS). However, there are no clinical trials that have directly compared these agents. We conducted a systematic review and indirectly compared the efficacy of azacitidine to decitabine in MDS. Methods We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) through June 28, 2018, without language or time restrictions. Studies were screened by two independent reviewers, and differences were resolved by consensus. The fixed effect model and adjusted indirect comparison methods were used to pool relative risks (RR) of major outcomes of interest (mortality, response rate, quality of life, hematologic improvement, hospitalization, leukemia transformation, transfusion independence). Results Only four trials met the eligibility criteria. Two trials compared azacitidine to the best supportive care (BSC) and included 549 patients, and the other two compared decitabine to BSC and included 403 patients. The risk of bias was unclear overall. Compared to BSC, azacitidine was significantly associated with lower mortality (RR = 0.83, 95% CI 0.74–0.94, I 2 = 89%) whereas decitabine did not significantly reduce mortality (RR = 0.88, 95% CI 0.77–1.00, I 2 = 53%). Both drugs were associated with higher partial and complete response compared to BSC. Indirect comparisons were not statistically significant for all the studied outcomes, except for complete response where azacitidine was less likely to induce complete response compared to decitabine (RR = 0.11, 95% CI = 0.01–0.86, very low-certainty evidence). Conclusions Azacitidine and decitabine are both associated with improved outcomes compared to BSC. The available indirect evidence comparing the two agents warrants very low certainty and cannot reliably confirm the superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patient preferences, adverse effects, drug availability, and cost.

Background: Allogeneic HSCT for adult patients with sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. At our center, we adopted a non-myeloablative (NMA) conditioning regimen in adult patients with severe SCD. Herein, we are reporting our outcome data of up to 5-years of follow up post HSCT. Methods: Following IRB approval, adult patients that underwent HSCT from 2015 to 2020 for severe SCD with at least 6 months of follow up were included. Indications for HSCT were; presence of recurrent vaso-occlusive crisis (VOC), end organ damage, multiple joint AVN, recurrent priapism, transfusion dependency, or RBC alloimmunization. Conditioning regimen consisted of alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1. Pre-transplant preparation consisted of Hydroxyurea at maximum tolerated dose for 2-3 months. Peripherally mobilized stem cells targeting 10x106/kg of CD34 cells were used. For GVHD prophylaxis sirolimus was started on day -1 and continued for one year with tapering off if lymphoid chimerism is > 50%. EFS was defined as time from HSCT to graft failure or death from any cause whereas OS was defined as time from HSCT to death or last documented follow up. Results: A. Baseline Characteristics: A total of 110 patients were included with a median (range) age of 27 years (14-43), 59% of patients were male. Baseline median hemoglobin and hemoglobin S (HbS) was 95 g/L (64-121) and 74 % (17 -97), respectively. Regular hydroxyurea use was among 108 (98%) and 109 (99%) of patients required at least ≥ 1 transfusion annually. Narcotic pain killers were used regularly in 21 (19%) of patients. Median pre-HSCT ferritin was 1062 and iron chelation was used in 36 (33%). The most common indications for HSCT were (overlapping) recurrent VOC in 93%, ACS in 36%, stroke in 28% and RBC allo-immunization in 26%. Furthermore, 18 patients had 3 indications, 45 had 2 indications while the remaining 47 patients had one indication. Furthermore, 10 (9%) patients had Moya-Moya disease, 5 (5%) had sickling hepatopathy and or liver cirrhosis with total bilirubin up to 670 mmol/L and 1 (1%) patient had end stage renal disease on peritoneal-dialysis. A total of 61 (55%) donors were SC trait and underwent GCSF mobilization without major adverse events as previously reported (Damlaj et al., BMT 2018). 8 (7%) and 15 (14%) had major and minor ABO incompatibility, respectively. The remaining characteristics are found in table 1 B. Transplant Characteristics and Post HSCT Outcome: Median infused CD34x106/kg was 12.4 (6.4-24.9) and 108 (98%) patients had successful engraftment. A total of 12 patients experienced GF; 2 as primary and 10 as secondary within a median time of 129 days (40-583). Outcome post GF was as follows; recurrence of SCD in 6 (50%), aplastic bone marrow in 6 (50%) of whom 4 underwent a second allogeneic HSCT with Flu-Cy-ATG platform and all from MRD. Among second HSCT recipients, 3 are still alive and in SCD free disease status. Among patients with GF, 5 (42%) had minor ABO incompatibility while the remaining 7 (58%) were ABO matched HSCT. Mild acute skin GVHD (grade I to II) occurred in 3 cases and 4 cases developed autoimmune haemolytic anemia that resolved with steroids. Only one patient had CNS bleeding 2 years post-transplant in a background of history of stroke and Moya-Moya disease. A total of 53 (48%) patients successfully discontinued sirolimus while an additional 40 (35%) are on active taper. There were a total of 4 successful pregnancies in 3 patients; 3 pregnancies completed to term while 1 miscarried. Median follow up for the cohort is 16.8 (2-66) months. Estimated 2-year EFS and OS was 87.3% (+/- 0.036) and 97% (+/-0.017). All deaths were due to GF. There was no difference in outcome (EFS or OS) between patients receiving graft from normal vs. SC trait. Post HSCT Hb and chimerism results are shown in table 2. Conclusions: Herein, we present a large real-life experience demonstrating feasibility and favourable outcome of NMA HSCT in adult patients with severe SCD including patients with significant organ dysfunction or neurologic vasculopathy. Successful pregnancies and long-term discontinuation of immune suppression was possible. Longer follow up is warranted to ascertain stability of graft function over time. Disclosure: The authors declare they have no relevant conflicts of interest Disclosures No relevant conflicts of interest to declare.

We present the largest to date of a case series of nine patients with hematological and oncological malignancies who were infected with Middle East Respiratory Syndrome Coronavirus (MERS-CoV). MERS-CoV is a novel beta-coronavirus with a high fatality rate in comorbid patients. The majority of MERS cases globally were reported from Saudi Arabia (1983 cases, including 745 related deaths with a case-fatality rate of 37.5%) according to the WHO update of February 2019. All were clinically stable before acquiring the virus. Most of the cases had an active disease as relapse or refractory with three cases being neutropenic. The clinical presentation and radiological features of the patients were variable and inconsistent (Table 1). Diagnosis was confirmed with RT-PCR assays targeting upstream of the E gene and the open-reading frame gene 1a which had to be done repeatedly and required an average of 3 (with max. of 7) samples for a test to be positive (Table 2). All the patients developed respiratory failure, were admitted to the critical care unit (ICU) and required mechanical ventilation. The length of hospital stay ranged from 15 - 48, with an average of 24 days. Unfortunately, all nine patients died within days after admission to the ICU. In addition, the time from diagnosis to death has an average of 9 days ranging from 2-24 days, respectively. In conclusion, MERS CoV infection in hematology/oncology patients has a very poor prognosis regardless of the status of the underlying disease. The clinical presentation is not distinctive and confirming the diagnosis requires numerous respiratory samples. Measures to prevent nosocomial outbreaks should include proper compliance with personal protection equipment by health-care workers when managing patients with suspected and confirmed MERS-CoV infection and prompt isolation of infected patients. Future research is required to enhance our understanding of the disease and to evaluate superior diagnostic and therapeutic options. Disclosures No relevant conflicts of interest to declare.

B-cell prolymphocytic leukemia (B-PLL) is a very rare tumor of monoclonal B-cells representing

Background Screening for vancomycin-resistant Enterococcus (VRE) is performed at many transplant centers, but data on the impact of VRE colonization and bloodstream infection (BSI) on hematopoietic cell transplantation (HCT) outcomes remain conflicting. Methods Consecutive adults with acute myeloid leukemia who underwent allogeneic HCT between 2004 and 2014 were retrospectively reviewed. Patients were screened by perirectal PCR swabs targeting vanA and vanB twice weekly while inpatient. Results Of a total of 203 patients (median age 54 years), 73 (36%) were VRE colonized prior to HCT, 23 (11%) became colonized within the first 100 days, and 107 (53%) remained non-colonized through day 100 post HCT. A landmark analysis on HCT day 0 revealed no significant difference in overall survival according to pre-transplant colonization status (P=.20). However, patients with subsequent VRE colonization within the first 100 days of HCT had a significantly worse survival on both univariable (P=.04) and multivariable (P=.03) analyses. During the first 30 days post HCT, 11 (5% of total and 11% of the VRE colonized) patients developed VRE BSI. Ten (91%) of these had screened positive for VRE colonization before the bacteremia. Age ≥60 years, HCT-comorbidity index ≥3, and VRE colonization were independent risk factors for VRE BSI on multivariable analysis (P=.04, .03, .003, respectively). Only 1 (9%) patient with VRE BSI died within the first 100 days post HCT. Conclusion VRE colonization is a surrogate marker and not an independent predictor of worse outcomes post HCT. VRE BSI is associated with increased morbidity, but does not impact post-HCT survival.

Plasmablastic lymphoma (PBL) is a rare and aggressive mature B-cell neoplasm typically seen in conjunction with an immunosuppressed state such as HIV infection. It is associated with a poor outcome with median survival spanning a few months. The optimal front line treatment regimen for patients with PBL is unknown and is further more elusive at the relapsed or refractory setting. Recently, it was shown that PBL expressed PD-L1 and PD-1 in the immune infiltrate and around one quarter strongly expressed PD-L1 within the tumor and immune cells. Herein, we report a case of a 34 year old HIV negative female with refractory PBL following treatment with combinational chemotherapy and plasma cell directed therapy. Subsequently, she received the checkpoint inhibitor therapy nivolumab with significant disease regression but with residual disease so she proceeded with a matched sibling allogeneic transplant. In conclusion, given the poor outcome and the newly reported evidence of PD-L1 expression in patients with PBL, further exploration of check point inhibitor therapy is warranted.

Background Pain is the main source of distress in patients with sickle cell disease (SCD). Unmanageable pain, often termed ‘crises’, may prompt unexpected visits to the emergency department (ED) or other acute healthcare facilities. One study from the Eastern Province in Saudi Arabia reported that 64% of patients with SCD present to the ED more than three times over a 6-month period. Outpatient follow-up may have a role in preventing ED visits, but this has not been fully explored in Saudi Arabia. This study aimed to assess the relation between outpatient follow-up and future ED visits due to painful crises in patients with SCD. Methods This retrospective, observational study utilized data from the electronic medical record system at King Abdulaziz Medical City, National Guard Health Affairs in Riyadh. The study included adult patients with SCD who presented at least once to the ED due to a painful crisis between January 2016 and December 2017. The time between ED visits due to painful crises was set as the outcome variable. Cox regression analysis with random effects model (frailty model) was used to determine the effect of outpatient follow-up at 15 days, 30 days, and 90 days on the time to next ED visit. Baseline characteristics and previous history of sickle cell complication were included in the model as confounders. Results Eighty patients with SCD presented a total of 463 times to the ED due to painful crises. 54% of these visits required admission and resulted in a total length of stay of 1474 hospital days and 49 ICU days. Attendance at a hematology outpatient clinic within 30 days from discharge significantly reduced the hazard of an ED visit due to a painful crisis compared with no follow-up (hazard ratio 0.70, 95% CI 0.52–0.94, p=0.02). Conclusion Appropriate outpatient referral at discharge may be associated with decreased ED visits. These benchmark results invite further investigation into the effects of outpatient management on preventing painful crises in patients with SCD.

Objectives The prevalence of concomitant myeloid neoplasms was recently reported to be unexpectedly high among adults without non-Langerhans cell histiocytosis (non-LCH); however, the coexistence of non-LCH with RUNX1 genetic aberration has not been reported previously. Methods Herein, we report a 23-year-old woman with severe pancytopenia diagnosed with non-LCH following presentation with pancytopenia and marrow examination showing histiocytosis positive for CD45, CD68, CD136, and lysozyme but negative for CD1a, langerin, and S100. Results Whole-exome sequencing showed RUNX1 mutation and NF1 mutation. In the ensuing 6 months, she developed hepatosplenomegaly, and repeat bone marrow evaluation was diagnostic of acute myeloid leukemia (AML). Repeat mutational analysis showed again presence of RUNX1 mutation. She underwent induction therapy but died of septic shock. Conclusions The demonstration of RUNX1 mutation in both non-LCH and AML bone marrow specimens at differing time points is suggestive of a biologic association of both distinct disease entities.

The prognostic impact of CD20 expression and rituximab therapy in classical Hodgkin lymphoma (cHL) is unclear. Among 310 patients, CD20 was expressed in 66 (22%) cases. The 3-year PFS was 75.1% for CD20+and 70% for CD20− (p = 0.36). The 3-year PFS was 84.7% for the rituximab group and 67.8% for the no rituximab group (p = 0.23). Only constitutional symptoms and positive interim PET/CT were significantly associated with worse outcome, HR 3.2 (1.14–9.01; p = 0.028) and 4.3 (2.27–8.1; p < 0.0001), respectively. Neither CD20 expression nor rituximab use significantly impacted outcome.

Therapy of chronic myeloid leukemia (CML) has been completely transformed by the development of tyrosine kinase inhibitors (TKIs). However, a subset of patients will fail TKI therapy due to resistance or intolerance. Omacetaxine mepesuccinate (OM), a protein translation inhibitor, is currently the only approved therapy that does not directly target the kinase domain. It has activity for CML patients irrespective of the phase or underlying kinase domain mutation status.We searched the MEDLINE database for articles published in English on homoharringtonine or omacetaxine from 1970 to present. This article reviews the pharmacokinetics of OM and its clinical evolution for the treatment of CML pre- and post TKI development. Toxicity profile, drug administration and future directions are also discussed.OM represents a unique addition to the CML therapeutic armamentarium with its distinct mechanism of action and activity. The adverse event profile is manageable and with subcutaneous administration at the approved dose, cardiac toxicity is no longer a concern. The recent approval of home administration will facilitate access to this therapy and increase patient compliance. We conclude with specific scenarios where OM use should be considered in CP and AP-CML patients in the era of TKI therapy.

Background Respiratory syncytial virus (RSV) infection causes significant morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. Although ribavirin and immunoglobulins are common components of therapy, the role of adjunct corticosteroids is not established. Objectives We sought to evaluate corticosteroid utilization in the setting of post-allo-SCT RSV infection in our center and assess post-transplant outcomes including pulmonary function decline. Methods Patients with a history of RSV infection from 2008 to 2014 seen at our institution were identified. Treatment and outcome data were retrospectively collected. Forced expiratory volume at 1 s (FEV1) and carbon monoxide diffusion capacity (DLCO) were collected pre- and post-RSV infection. Results During the observation period, RSV was isolated in 53 of 552 patients undergoing allo-SCT (10%) and 45 had evaluable therapy data. RSV-related mortality in this cohort was 4/45 (9%). Twenty-one (47%) were on corticosteroids prior to RSV diagnosis, of whom 11 (24%) had a dose increase post symptom onset. Eight (18%) patients were started on corticosteroids at the time of RSV infection. Corticosteroid therapy at symptom onset was associated with a higher rate of upper respiratory infection (URTI) to lower respiratory infection (LRTI) progression risk ratio (RR) 2.49 (1.21–5.13; P = 0.016), hospital admission RR 2.05 (1.24–3.37; P = 0.005), or intensive care unit admission RR 2.91 (1.89–5.01; P = 0.002). No significant difference was seen with FEV1 and DLCO decline (P = 0.3 and 0.24, respectively) or mortality (P = 0.26). Conclusion Adjunct corticosteroid use in the setting of RSV infection did not improve RSV-related outcomes including long-term pulmonary function. Our results do not support the routine use of corticosteroids; however, this finding does need to be verified in a larger cohort of patients.

High-dose salvage chemotherapy followed by haematopoietic stem cell transplantation (HCT) is the standard of care in transplant eligible relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL).1 Approximately, half of patients receiving HCT will achieve long-term remissions, but relapse remains the most common cause of treatment failure. A number of prior studies investigated the value of pre-HCT positron emission tomography (PET) scan as a predictor of outcome. Considerable heterogeneity is noted within these studies due to methodology of PET interpretation, timeline of the scan prior to HCT and whether further clinical decisions were based on the scan results.2, 3, 4, 5 In light of the above, we examined the impact of pre-HCT PET/CT graded on the five-point scale Deauville criteria on the post-HCT outcome.

Background: Although the prevalence of genetic hematological disorders varies widely between geographical regions, region-specific hematological reference ranges have not been defined in Saudi Arabian adults. Methods: A multicenter retrospective cross-sectional study was conducted with 1127 participants who completed their pre-employment screening and recruitment process between January 2013 and December 2016. Data related to the demographic and hematological indices were extracted. Results: The mean age was 28.0±5.2 years (range 19.4-72.8 years) and gender was distributed equally (47.5% female vs. 52.5% male). The WBC reference range was 3.3-11.4 ×109/L; hemoglobin 111-174 gm/l; platelet 163-412 ×109/L; MCV 80-95.7 fl, and neutrophils 1.2-8.8 ×109/L. A robust regression model was used to evaluate the effect of the participant's characteristics on the hematological indices. Except for WBC, the rest of the hematological indices were significantly influenced by gender, region, and age. The 2.5 percentile hemoglobin values were 135 gm/L in males and 104 gm/L in females, while platelet values were 173 x109/L in females and 159 x109/L in males. Conclusion: The study defined local hematological reference ranges, which were mostly lower than reported in international studies used in our center. Hematological values were mainly influenced by gender and region. A community nationwide screening study is required to create reference ranges specifically for the Saudi population. Disclosures No relevant conflicts of interest to declare.

Introduction: The chemotherapeutic agents are effective in destroying cancerous cells for patient with hematological malignancies, but can damage the germinal cells. Hence, the infertility is the therapy-induced complication, which can be transient or permanent, depending on type of treatment protocol used and other factors. The aim of the study was to assess the fertility status among patients treated for Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL). Methods: A chart review was done for patients followed up in hematology clinic. All male patients treated for hematological malignancies during the period from 2004-2014 were assessed. The infertility status was assessed using WHO infertility criteria. The fertility status was defined based on semen analysis or having a child post chemotherapy. The data was captured for type of protocol, number of cycles, fertility status, having a child pre and post chemotherapy, and sperm bank utilization. Results were summarized as frequency and percentages. Data was analyzed using SAS. Results: 400 medical charts were reviewed. 208/400 were included based on age inclusion criteria (18-60 years). 59/208 included based on available fertility data, of which 31 were diagnosed with HL, 21 NHL, 4 acute lymphocytic leukemia, and 3 acute myeloid leukemia. Only HL and NHL were considered for further analysis. 9/31 (29%) with HL and 1/21 (4.7%) with NHL had infertility prior to starting chemotherapy based on semen analysis with no follow-up fertility assessment done post-treatment. The final sample consisted of 42 patients who had data available on their fertility status post-treatment (22 HL and 20 NHL) (Figure 1). The mean age was 38 ± 8 years. 25(68%) had advanced disease. Among HL, 8/22 (36.36%) were fertile (7 conceived a child and 1 with normal semen analysis) (Figure 2). This includes 6 out of 9 (66.7%) patients who received ABVD protocol alone, 0 out of 6 who received ABVD + BEACOPP protocol, and 2 (28.6%) out of 7 who received salvage chemotherapy. Among the NHL, 11/20 (55%) were fertile (8 conceived a child and 3 with normal semen analysis) (Figure 2). This includes 7 out of 11 (63.6%) who received CHOP +/-Rituximab protocol, 3 out of 5 (60%) who received CHOP + other chemotherapy (MTX/CVP), 1 out of 3 (33.3%) who received only other chemotherapies (Hyper CVAD/MTX) (Figure 2). 9 out of 22( 41%) HL and 6 out of 20 NHL patients had sperm banking done, and only two utilized their sperms with one successful conception in a patient with NHL (Figure 3). Conclusion: Although the sample size is very small, we found a trend that may suggest HL to affect fertility and that ABVD protocol may not be as safe as it thought to be on fertility. The advanced stage of the disease being the majority may have influenced this finding. We found the documentation of fertility status among patients receiving chemotherapy to be scarce. Hence, it is important to educate physicians and dedicate a protocol for assessment of fertility pre- and post-treatment with encouragement to utilize sperm banking. Disclosures No relevant conflicts of interest to declare.

Response-adapted therapy in advanced classical Hodgkin lymphoma (cHL) using interim functional imaging (IFI) is under active investigation.We retrospectively examined patients with advanced cHL receiving 2 front-line regimens stratified by IFI results at our institution. Time to endpoint analysis was estimated using the method of Kaplan-Meier with log ranks. Cox regression modeling was computed for multivariable analysis.A total of 124 patients with advanced cHL with a median follow up of 40.9 months were included. A total of 84 (67.7%) received ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), whereas the remaining 40 (32.3%) received ABVD/eBEACOPP (escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). A positive IFI was seen in 36 (29%) patients. The corresponding 3-year progression free survival (PFS) stratified by IFI was 81.7% (95% confidence interval [CI], 70.1%-88.8%) versus 48.3% (95% CI, 30.4%-64.1%) (P .0001) for patients with negative or positive scan, respectively. Escalation to eBEACOPP from ABVD following a positive IFI resulted in a significantly higher 3-year PFS at 58.7% (95% CI, 0.3-0.79) versus 39.7% (95% CI, 0.18-0.61) respectively (P = .00015). Overall survival (OS) was similar across the groups (P = .44) irrespective of therapy received. At multivariable analysis, IFI was the only predictor of PFS with a hazard ratio of 4.6 (95% CI, 1.9-10.8; P = .0008) whereas therapy escalation had a hazard ratio of 0.66 (95% CI, 0.14-3.4; P = .62).IFI is an independent predictor of PFS in advanced cHL and can guide therapeutic decisions in the real world. Given the inferior outcome seen in patients with a positive IFI, novel approaches of therapy are warranted.