Background: Aautologous hematopoietic stem cell transplants (HSCT) is the standard of care for newly diagnosed patients with multiple myeloma (MM) who are eligible for autologous transplantation. Although cryopreservation is routinely employed, autologous HSCT can be performed using non-cryopreserved stem cells. Methods and materials: A retrospective study of patients with MM who received autologous HSCT between the 10th of October 2010 and the 31st of January 2022 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed. Results: Over 11 years and 113 days, a total of 135 autologous HSCTs were performed for 119 patients with MM at our institution. Single autologous HSCTs were performed for 119 patients, while 16 of these patients received either planned tandem autologous transplants or second autografts due to either progression or relapse of their myeloma. The median age of patients with MM at autologous HSCT was 51.5 years. At presentation of their MM, the following high-risk (HR) features were encountered: stage III disease according to the revised international scoring system (RISS) in 12.3%; adverse cytogenetics in 31.93% of patients; advanced bone disease in 60.50%; and renal dysfunction or failure in 11.76% of patients. A total of 104 autologous HSCTs (77.04%) were performed without cryopreservation while 31 autografts (22.96%) were performed using cryopreserved apheresis stem cell products. Additionally, 54 autologous HSCTs (40.00%) were done at outpatient while 81 autografts (60.00%) were performed in an inpatient setting. Survival for 100 days post-HSCT for all patients with MM who received autologous transplants including those done at outpatient was 100%. The 4 years overall survival (OS) an progression-free survival (PFS) for patients with MM who received non- cryopreserved or fresh autologous HSCTs were 82% and 68% respectively. Conclusion: Autologous HSCT without cryopreservation is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation with cryopreservation. Non- cryopreserved autologous grafts allow the performance of autologous transplants in an outpatient setting to save beds and reduce costs.

Introduction The optimal treatment for young patients with high-risk newly diagnosed multiple myeloma (NDMM) remains a challenge. Methods We retrospectively evaluated 58 NDMM patients younger than 55 years treated in our center from 2010 to 2021 with the current recommended protocols. Results After a median follow-up of 48 months, median overall survival (OS) was not reached; however, approximately 25% of them died within 4 years after diagnosis. Advanced disease stage, presence of extramedullary disease, elevated LDH, and less than very good remission before autologous hematopoietic stem-cell transplantation adversely affected patient survival. Based on these factors, we created a risk-assessment scoring system that sufficiently discriminated young NDMM patients at risk of poor outcome. The 4-year OS was superior for patients with zero to two factors to those with three to five factors (86% vs 44%, p<0.001). Conclusion The proposed scoring system could be reliably used at diagnosis and at interim disease evaluation in aiming for personalized treatment for young NDMM patients.

Background Disease chemosensitivity to salvage treatment is a major predictive factor for a favorable outcome after autologous stem cell transplantation (ASCT) for patients with refractory lymphomas. Therefore the importance of effective and safe salvage regimens is indisputable. Methods We retrospectively compared the outcomes in terms of safety and efficacy, in 67 (HL:36, NHL:31) patients, with a median age of 34,5 (16-75)ys, who received as 1st salvage either DICEP [Dose Intensified Cyclophoshamide (1750 mg/m2), Etoposide (350 mg/m2), Cisplatin (35 mg/m2), days 1-3, (n=23)] or the widely used regimen ESHAP (n=44). Rituximab was additionally given to all CD-20 positive lymphoma patients. The statistical analyses based on the student's T-test, Kaplan Meir method and log rank test. Results In a total, 34 patients were evaluated with primary induction failure (PIF), 14 with early relapsed ( The overall response (>50% tumor reduction) rate was significantly superior for the DICEP regimen, reaching 83% (19/23 patients) vs. 60% (26/44 patients) for ESHAP group (p=0,04). Eleven out of 23 patients (48%) from the DICEP group and 14/44 (30%) from the ESHAP group achieved complete metabolic remission according to PET/CT criteria. The median hospitalization period was 20(5-25) days for the DICEP compared to 10(10-19) days for the ESHAP group. However, for the ESHAP group, an additional median of 21 (6-28) hospitalization days were required, since 12/18 non-responders patients admitted for a 2nd salvage treatment before ASCT. All but two patients (due to refractory disease) underwent ASCT. The 2-ys overall survival from disease diagnosis and the 2-ys progression free survival from 1st salvage treatment were similar for the two groups (95% vs. 88% and 70% vs. 78% for DICEP and ESHAP groups respectively). Two heavily pretreated patients from the ESHAP group developed secondary myelodysplastic syndrome post ASCT. Conclusion In our study both regimens demonstrated a safe profile. The extremely high response rates for DICEP regimen, finally resulted in less exposure to chemotherapeutic agents before proceeding to ASCT, that might led in less early and long term severe toxicity. Nevertheless, only prospective trials with large series of patients can clarify the role of DICE in the salvage treatment setting.

Introduction: Gut dysbiosis is an imbalance of the gut microbiome. The presence of dysbiosis can be a cause of systemic inflammation in the body or can be a contributing factor to it. Chronic systemic inflammation is a common feature of CLL, creating an environment in which CLL cells have a survival advantage. NF-κB and STAT3, master transcriptional regulators of pro-inflammatory markers, like IL-1 and IL-6, are reported to be involved in this process as are the Toll-like receptors (TLRs), key innate immunity receptors that are implicated in CLL pathophysiology. With increasing evidence for the role of dysbiosis in chronic inflammation, as well as the role of systemic inflammation in CLL, it seems relevant to prove the presence and the possible role of microbiome in the pathophysiology of CLL, to unravel the complex interaction between microbiome, nutrition and the host in patients with CLL. Our research investigate the hypothesis that dysbiosis i.e. the loss of "health-promoting" commensal gut microbes and/or the overgrowth of pathogenic bacteria distinguishes untreated patients with CLL versus aged-matched unaffected individuals. Methodology: Eight untreated CLL patients were with no history of gastrointestinal disorders, other malignancies and have not been on antibiotics for 4 weeks prior to samples collection. Two of them were not followed for logistical reasons. Six healthy volunteers matched for sex and age were also enrolled in the study. Stool samples from six patients and additional six matched healthy controls were collected and stored in a -40 freezer immediately until they were used for DNA isolation. Total genomic DNA was extracted using the Qiamp DNA stool mini kit and sequenced using Next Generation Sequencing and then analysis were done as per the manufacturer recommendations. Results: Our data indicates a reduced diversity and variability in bacterial phyla of gut microbiota in CLL patients as compare to healthy controls. Lower diversity with increase in certain bacterial types is a well-accepted sign of gut dysbiosis, which have been shown in many disorders such as; type-2 diabetes, obesity, and various autoimmune and neurological diseases. An increase in Proteobacteria numbers has been recognized as the signature of gut dysbiosis which we confirmed in our cohort of patients. Proteobacteria, Firmicutes and Bacteriodetes were also the most abundant bacterial phyla in CLL patients of our study which were reported previously in breast cancer patients. An elevated Firmicutes to Bacteroidetes ratio with altered gut microbiota in CLL patients compared with healthy subjects was also suggested in clinical studies involving obese individuals with insulin resistance. We have observed in CLL patients of this study relative increase in the numbers of Firmicutes and reduction in Bacteriodetes which is considered to be an inverted ratio as compared to healthy individuals which were also reported in ulcerative colitis, colonic and ileal crohn's disease as compared to healthy subjects. . Our finding of gut dysbiosis in this study is linked the association between CLL, inflammatory processes and dysbiosis. The microbiota may play a role in promoting malignancy through chronic inflammation, by disturbing the balance of cell proliferation, death and by initiating unwanted innate and adaptive immune responses. Conclusion: Restoring gut microbiota might open a new avenue for future researches as potential therapeutic intervention in CLL patients. Figure Disclosures No relevant conflicts of interest to declare.

Introduction Patients with Hodgkin (HL) or Non-Hodgkin Lymphoma (NHL) who have either bulky masses at relapse or residual disease post salvage therapy, have poor outcome even after autologous stem cell transplantation (ASCT). Involved field radiotherapy (IFRT) to the bulky/residual disease sites is widely used to minimize the risk of relapse post ASCT. However, the proper time for IFRT remains controversial. IFRT delivery before ASCT could cause toxicity which might delays the ASCT increasing the risk of disease progression. Moreover, the pre-ASCT IFRT may also damages the marrow niche impairing thus the engraftment. On the contrary, the IFRT early after ASCT as adjuvant therapy (adj-IFRT) offers the advantage of irradiation delivery after sufficient disease response, without affecting the engraftment, maximizing potentially a favorable outcome, with lower irradiation in restricted areas. Aim In this study we sought to investigate the safety and the efficacy of the adj-IFRT in autografted patients for relapsed/refractory HL or NHL. Methods We evaluated retrospectively 23 patients (HL=12, NHL=11), aged of 34(16-76) years, who underwent ASCT, for primary refractory (n=15) or relapsed (n=8) disease, and received adj-IFRT post ASCT. They had previously salvaged with a median of 2 lines of therapy. Patients with bulky mass at relapse or localized residual disease post salvage treatment, were candidates for adj-IFRT. Results All patients had chemosensitive disease before ASCT. However, 15(80%) had residual disease while 4(20%) were in complete remission. The preparative regimens were: single agent Melphalan (n=9), Busulfan-Etoposide-Melphalan (n=7), BEAM (n=4) and Bendamustin-Etoposide-Cytarabine-Melphalan (n=3). Filgrastim was given at 5mcg/kg after the 5th day of graft infusion till neutrophills recovery, while anti–bacterial, -fungal, -viral and –PCP prophylaxis were administered from the conditioning regimen initiation till the completion of adj-IFRT. The engraftment was successful. No patient had any toxicity or active infection before adj-IFTR. Though we planned to give adj-IFRT within 3 months post ASCT, finally it was delivered after a median of 4,5 (2-7) months; the median irradiation dose was 30 (24-36) Gy The adj-IFRT was well tolerated. No patient experienced toxicity grade>3 and none required hospitalization. Currently, 19/23 patients are alive and well; the 5-ys overall and progression free survival rates are 70% and 64% respectively. Four patients died; 2 due to relapsed disease and 2 heavily pretreated patients due to secondary myelodyspalstic syndrome. Conclusion In this study, the use of adj-IFRT post ASCT was well tolerated and safe. The promising survival rates in these poor risk patients suggest that the adj-IFRT is also an effective approach. Well designed clinical trials are needed to clarify the role of adj-IFRT in the ASCT setting.

Background: Damage associated molecular patterns (DAMPs) are considered important contributors to acute Graft vs Host Disease (aGvHD) pathogenesis. Uric acid (UA), a DAMPs family molecule, upon its release from damaged tissues post high dose chemo/radio therapy, triggers activation of donor derived T-cells. Currently, only two published studies evaluated the association between UA levels at day 0 and aGvHD occurrence, with totally conflicting results. Given that aGvHD is a dynamic process which takes place during the whole early post-transplant period, contrasting to previous studies, we evaluated serum UA levels not only once but in 4 different time points during the early transplant period, at days -7, 0, +7, +14, and investigated its correlation to aGvHD incidence, non-relapse mortality (NRM) and survival rates. Methods: We retrospectively evaluated 57 patients (pts), with a median age of 36.8 years (range, 17-62), who underwent allogeneic stem cell transplantation (alloSCT) from full matched sibling donors for malignant (n=48) or non-malignant (very severe aplastic anemia =9) hematological diseases. A median of 5.6 x106/kg CD34+ cells were infused after a myeloablative (n=34) or reduced intensity (n=23) regimen. At the time of alloSCT, 42 pts were in remission (CR1: 30, CR2: 10, >CR2: 2). All pts received either allopurinol or rasburicase from the day of conditioning initiation till day -1. The ROC-curve method, t-test, Kaplan-Meir method, and log-rank test were used for the univariate while the binary logistic regression method for the multivariate statistical analysis. Disease phase [early (CR1) vs. intermediate (CR2) and advanced (>CR2 or presence of residual disease)], donor gender, patient and donor age, UA levels at day -7, 0, +7, +14, type of conditioning regimens and number of infused CD34+ cells were tested as possible factors that can affect aGvHD incidence. Results: Median UA levels were 3.2, 2.4, 2.2 and 2.9 mg/dl at days -7, 0, +7 and +14 respectively; using the ROC curve method the cutoff point was determined at 4.4 mg/dl for day -7 and 2.2 mg/dl for days 0, +7 and +14. Overall, 20/57 (35%) pts developed aGvHD; 18 (31%) were assessed as gr ≥II, while 10 (17%) as gr III-IV. The incidence of the aGvHD gr ≥II was higher for pts with UA levels ≤ 4.4 mg/dl at day -7 (14 vs 4) and for pts with UA levels ≥2.2 mg/dl at days 0 (12 vs. 6 pts) and +14 (13 vs. 5 pts) however these differences did not reach statistical significance. UA levels at +7 day had no impact on aGvHD incidence. In multivariate analysis, only the number of CD34+ >6x106/kg was an adverse factor for aGVHD gr≥II (p=0.04) while intermediate & advanced disease phase along with a number of CD34+ cells >6x106/kg, proved to be significant contributors for severe aGvHD (gr III-IV) occurrence (p<0.03). We observed a better 4 years overall survival for patients with UA levels < 2.2 mg/dl at day +14 (85% vs. 55%, p=0.06). Fifteen pts succumbed to NRM causes; 8/15 deaths were attributed to aGvHD complications. The NRM was higher in patients who had UA levels ≥2.2 mg/dl at day +14 (32% vs. 15%) though this difference was not significant (p=0.2). Conclusions: The present study bears the limitations of a small series of pts and it's retrospective nature. However, it has the advantage of evaluation of UA levels, as an aGvHD mediator, at multiple time points during the peri-transplant period. Our results, though not of strong statistical significance, demonstrated that UA levels might affect aGvHD incidence as well as survival and the NRM rates post alloSCT. Definitely, well designed prospective clinical trials are warranted to clarify the role of UA on alloSCT outcome. Disclosures No relevant conflicts of interest to declare.

Background: The significant advances which have been achieved in the field of allogeneic transplantation (alloHCT) have resulted in better post-transplant outcome and prolonged survival. Therefore, complications other than the Graft vs. Host disease (GvHD) or disease recurrence have become increasingly important. The post-transplant metabolic syndrome (PT-MS), caused by several factors (i.e. immunosuppressive agents, chemo-radiotherapy, anti-viral, and biologic therapies) is a well known post-transplant complication in pediatric allografted long-term survivors however, only a few studies have evaluated the prevalence of the PT-MS in adults. In this retrospective study, we sought to evaluate the incidence, risk factors and impact of the PT-MS on alloSCT outcome. Methods: From 1/2011 to 12/2018, 54 patients (34 males and 20 females) with adequate clinical and laboratory data and a minimum follow-up of 6 months were included in the study. Median age was 35.6 years (range, 16-67) and following a myeloablative (n=34) or reduced intensity (n=20) regimen patients received either a mobilized peripheral blood stem cell (n=45) or marrow (n=9) graft originating from full-matched siblings (n=46) or haploidentical (n=8) donors. Calcineurin inhibitors plus either short-term Methotrexate or Mycophenolate Mofetil were given as GvHD prophylaxis. Diagnosis of PT-MS was based on NCEP-ATPIII criteria; for patients with unknown data for abdominal circumference, a modified criterion of body mass index (BMI) ≥25kg/m2 was utilized instead. The independent t-test, logistic regression analysis and log-rank tests were used for statistical analysis. Results: Twenty-four (44%) patients (14 males, 10 females) fulfilled the criteria for PT-MS. Twenty had been diagnosed after the 1st trimester, 3 patients after the 2nd and in addition 1 after the 3rd trimester post alloSCT. Twenty out of 24 (83%) patients had elevated glucose, 19/24 (80%) had BMI>25kg/m2, 18/24 (75%) elevated triglycerides levels, 14/24 (60%) low HDL levels and 13/24 (55%) hypertension. Six (25%) had a known history of MS before alloSCT (10 patients had no available data to assess for MS diagnosis prior to alloSCT). Interestingly, in 8/24 (33%) patients who had PT-MS diagnosed early, either in the 1st or 2nd trimester, the syndrome was completely reversible beyond the 6-month post alloSCT follow-up period. In the aforementioned statistical models, patients' gender, age, BMI, type of conditioning regimen and GvHD co-existence were evaluated as potential predisposing factors for the PT-MS. In univariate and multivariate analysis only BMI>25kg/m2 and age>35 years were detected as significant risk factors (p< 0.01) for development of PT-MS. The PT-MS did not adversely impact survival or the NRM incidence post alloSCT. Conclusions: In our study, in agreement with other publications, we demonstrate that the PT-MS is not an uncommon complication in the early post-transplant period however, for approximately 1/3 of patients the syndrome was reversible. For patients with high risk features (BMI>25kg/m2, age> 35 years, known history of diabetes-mellitus, dyslipidemia, hypertension) apart of close monitoring, specific diet and encouragement for exercise might help reduce the incidence and severity of PT-MS. Nevertheless, prospective and well design trials are warranted to determine the incidence, severity and impact of PT-MS on alloSCT outcome for adult patients. Disclosures No relevant conflicts of interest to declare.

Abstract Background Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL for which optimal treatment is controversial. We retrospectively reviewed the files of patients with NLPHL diagnosed and followed up at our institution and describe clinical characteristics and outcome and explore prognostic factors for progression-free survival (PFS) and overall survival (OS). Methods We included consecutive patients diagnosed with NLPHL and followed at King Fahad Specialist Hospital, Damamm (KFSH-D), a referral center for the Eastern Province of Saudi Arabia. Primary aim of this study was to determine clinical outcomes (PFS and OS) according to treatment strategy, i.e. radiotherapy (+/- Rituximab) (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), Rituximab monotherapy (R), and active surveillance (AS). Secondary aim was an exploratory analysis of candidate prognostic factors for PFS and OS. PFS was defined as time (months) from date of diagnosis to disease progression or death from any cause. Event time distributions were estimated using the method of Kaplan-Meier and groups were compared using the log-rank test. We used univariable and multivariable PFS analyses for candidate prognostic factors. Results From 1/2006 to 12/2017 data on 49 patients treated at KFSH-D, aged 16 years (y) or older, with a diagnosis of NLPHL and with sufficient treatment and follow-up (F/U) were analyzed. Median age at diagnosis was 29y (range, 16-56), 76% were male. Histology was typical in 86% (n=42), variant in 8% (n=4), and with transformed histology at diagnosis in 6% (n=3) of cases. Disease characteristics: 63% (n=31) of patients were stage I/II and 37% (n=18) stage III/IV, B-symptoms 12%, extranodal disease 10%, splenic involvement 8%, bulky disease (≥5 cm) 12%, and bone marrow involvement 4% of patients. The German Hodgkin Study Group (GHSG) score was intermediate-risk and high-risk in 53% (n=26) and 24% (n=12) of patients, respectively. Management strategy (MS), depending on physician's preference, was RT (16%, n=8), CT (43%, n=21), CMT (27%, n=13), R (6%, n=3), and AS (8%, n=4). For patients induced with chemotherapy +/- RT, ABVD-like (+/- Rituximab) (n=25) or CHOP (+/- Rituximab) (n=9) were used in all cases. The overall response rate (ORR) for 45 patients who received treatment was 91% (complete responses (CR), 69%), 98% ORR when cases with transformed histology at diagnosis were excluded. Median F/U was 36 months (m), (range, 8-127). Overall, outcome was excellent, with 3- and 5-y PFS estimates of 80% and 75%, respectively (Figure). Overall survival was 100% with no deaths observed (Figure). The current PFS is 98%. Transformation at relapse/progression was observed in 2 patients at 36m and 45m, respectively, and remain disease free at 24m and 35m, respectively, following salvage treatment and auto-SCT. The 5-y cumulative risk of transformation (excluding cases with transformed histology at diagnosis) was 6%. Two secondary cancers were observed. Exploratory univariate analysis revealed high-risk GHLG score (P=0.001), bulky disease (P=0.001), splenic involvement (P=0.01), transformed histology at diagnosis (P=0.02), and non-RT MS (P=0.001) as risk factors for shorter PFS. In the final multivariate model, the GHLG score (P=0.01) and non-RT MS (P=0.004) were the only a risk factor for shorter PFS. In pairwise comparison, excluding patients with transformed histology at diagnosis and patients on AS, for patients with stage I/II disease, RT-based therapy was associated with improved 5-y PFS rates compared to CT-based therapy, (P = 0.02). For patients with stage III/IV disease 5-year PFS rates did not differ between RT-based and CT-based therapy (P= 0.4). For patients treated with CT, ABVD +/- Rituximab (n=13) vs CHOP +/- Rituximab (n=8) induction produced similar PFS rates at 5-years (P=0.9). Conclusion In this single center retrospective study, NLPHL had an excellent outcome. MS had an impact on PFS but not OS. High-risk GHLG score and omission of upfront RT were adversely prognostic factors for PFS. Large prospective trials are warranted to determine the optimal treatment approach for this rare B-cell lymphoma. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

All-trans retinoic acid (ATRA), a carboxylic acid form of vitamin A, was a revolutionary discovery in the treatment of acute promyelocytic leukemia (APL) that was found largely by chance in late 80s. The molecular hallmark of APL is the presence of a balanced reciprocal translocation resulting in the PML/RAR-α gene fusion, which represents the target of ATRA therapy. ATRA is considered to be a safe drug. Pseudotumor cerebri (PTC) is a rare neurological adverse event of ATRA that was mainly reported in pediatric population. It is characterized by neurologic and ocular signs and symptoms of increased intracranial pressure in the absence of any intracranial pathology or secondary causes of intracranial hypertension. Herein we report four cases of young female patients who were diagnosed with APL and experienced PTC with ATRA treatment. In three cases fluconazole was taken concurrently. Symptoms completely subsided with the temporary withdrawal of ATRA and discontinuation of fluconazole. PTC symptoms did not recur after reintroducing ATRA. In conclusion, we report a case series of young female patients that is suggestive of young age, female gender and concurrent use of fluconazole to be associated with increased risk of developing PTC with ATRA treatment. Fluconazole should not be used concurrently with ATRA. We also conclude that the drug could be safely reintroduced once the symptoms had resolved.