Use and safety of prophylactic endoscopy from a single center serving urban and rural children with portal hypertension

Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTN. This is a retrospective study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 to 07/01/2019. Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p < 0.001) with no difference in immediate complications (1% vs 2%, p = 0.173) or 2-week complications (1% vs 2%, p = 0.097). No deaths were related to variceal bleeding or endoscopy. Kaplan–Meier Survival Curve suggests improved transplant and shunt free survival in the primary prophylaxis group (log-rank p < 0.001). Primary and secondary endoscopic prophylaxis should be considered safe for the prevention of variceal hemorrhage in pediatric portal hypertension. There are differences in outcomes in primary and secondary prophylaxis, but unclear if this is due to patient characteristics versus treatment strategy. Further study is needed to compare safety and efficacy to watchful waiting.

Study of endoscopic esophageal variceal ligation cases in Tishreen University Hospital: دراسة لحالات ربط دوالي المري تنظيرياً في مشفى تشرين الجامعي

Objective: The aim of this study is to estimate the effectiveness and complications of performing EVL in cirrhotic patients, and to assess the outcome of rebleeding events after EVL. Patients and Methods: An Observational Descriptive Study conducted for the period from January 2020 to January 2021 at Tishreen University Hospital in Lattakia- Syria, 45 Cirrhotic patients with esophageal varices who underwent 69 EVL sessions whether done as prophylactic or therapeutic followed up for three weeks. Results: The median age was 57 years, 66.70% of patients were male. The most common etiology was cryptogenic cirrhosis (40%), and 44.4% of patients had esophageal varices grade III. The most common indication for performing EVL was primary prophylaxis (46.4%). Initial control of bleeding was achieved in 95.2% of emergency procedures. The mortality rate during follow- up was 2.2%. Chest pain was the most common complication of EVL (31.9%). The incidence of re- bleeding events after EVL was 7.24%, more frequently in emergency procedures. Re- bleeding was significantly associated with alcoholic liver disease, poor liver condition (Child- Paugh C class), emergency procedures, coagulation disorders (low levels of PLT and high levels of INR) and presence of large varices (grade III and IV). Conclusion: EVL is feasible, safe, and effective for the management of esophageal varices in patients with end stage liver disease.

Transarterial Chemoembolization Combined With Endoscopic Therapy Is Beneficial for Unresectable Hepatocellular Carcinoma With Esophagogastric Varices

BackgroundThe efficacy of transarterial chemoembolization (TACE) combined with endoscopic therapy for unresectable hepatocellular carcinoma with esophagogastric varices remains unclear.MethodsThe study has been registered on ClinicalTrials.gov with the number NCT05017922 (https://register.clinicaltrials.gov). Eligible patients were divided into combined group (received TACE plus endoscopic therapy) and control group (only received TACE). The occurrence of death and bleeding episodes during the follow-up was recorded. Kaplan–Meier analysis was used to compare outcomes between the two groups. Cox proportional hazard model was used to determine independent predictors for the survival.ResultsEighty-nine patients were included, 42 in the combined group, others in the control group. During the follow-up, 51 patients died, the 1-year, 2-year, and 3-year survival rates were 64.9%, 45.5%, and 34.5%. The cumulative survival was significantly higher in the combined group than in the control group (p = 0.027); the 1-year, 2-year, and 3-year survival rates were 75.5%, 55.9%, 43.8% and 55.0%, 35.9%, 26.6%, respectively. Forty-four patients experienced bleeding, the bleeding rate was significantly higher in the control group than in the combined group (77.4% vs. 56.8%, p = 0.016). Multivariate analysis showed that treatment, hemoglobin, portal vein tumor thrombosis, and aspartate aminotransferase were independent predictors for overall survival; the first three factors were also independent predictors for bleeding-free survival. Patients who received primary prophylaxis had longer overall survival (p = 0.042) and bleeding-free survival (p = 0.029) than those who received secondary prophylaxis.ConclusionsTACE combined with endoscopic therapy significantly improved survival and reduced bleeding rates in unresectable hepatocellular carcinoma with esophagogastric varices patients. Portal vein tumor thrombosis was a strong negative prognostic factor for both overall survival and bleeding-free survival. Primary prophylaxis improved survival benefits compared with secondary prophylaxis.

Total Oral Anticoagulation for Classic PNH As Primary Prophylaxis Strategy in a Complement Inhibitor Restricted Scenario: A Retrospective Analysis

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is associated with thrombosis and bone marrow failure. Thrombosis is the leading cause of death and morbidity, with 29-44% of patients presenting at least one thrombotic episode during their disease's natural course. Treatment with complement inhibitors is a strategy associated with reducing up to 80% of thrombosis risk, and improving survival of PNH patients. However, the high cost of these therapies limited their access in Low and Middle-Income Countries (LMIC). Mexico, like other LMIC, experience low access to complement inhibitors. Hence, we established a primary thromboprophylaxis strategy in classic PNH. The primary objective of the present study is to analyze thrombosis-free survival and all-cause mortality in patients with classic PNH subjected to this prophylaxis strategy compared to historical controls. Methods. Single-center, retrospective, case-control study. We included patients treated from 1991 to 2021, diagnosed with classic PNH (clone size ≥50% determined by flow cytometry). We defined the treatment group as patients who received total oral anticoagulation as primary prophylaxis. We excluded patients who had presented thrombosis prior to classic PNH diagnosis, sub-clinic PNH, bone marrow failure, platelets &lt;50x10 3/µ, and patients who failed to maintain a therapeutic (2 to 3) INR value three months after starting total oral anticoagulation with vitamin K antagonists (VKA). We collected data regarding clone type (II, III, or mixed), clone size, LDH values (&lt;1.5 vs ≥1.5 x ULN), platelet count, thrombosis occurrence, thrombosis site, bleeding cases and their severity according to the international society on thrombosis and haemostasis (ISTH) classification, and causes of death. Results. We found 44 patients with classic PNH diagnosed from 1990 to 2021. Median age at diagnosis was 39 years (28 -51), 50% were female, median LDH value 1669 U/L (926-2,241), and median clone size 95% (80-99). Clone type III was most prevalent, with 61.36% cases, followed by mixed type II-III with 38.64%; we found no type II clone patients. Median follow-up was 21.03 years. Four patients developed a site of thrombosis; three cases (75%) presented simultaneous venous and arterial thrombosis, and one (25%) venous only. The most common site for thrombosis was the portal vein (n=3), followed by supra-hepatic veins (n=1). A total 19 patients (43.2%) received primary prophylaxis with total oral anticoagulation, 17 (89.5%) used VKA and 2 (10.5%) direct oral anticoagulants. We found no differences regarding age, LDH value, clone size and clone type between the treatment and control groups. There were no cases of thrombosis in the treatment group, while 5 patients (20%) in the control group developed thrombosis at some point (p=0.038, Table 1). Thrombosis-free survival was not reached in the treatment group, vs 12.78 years (IC95%,6.19-19.37) in the control group (p=0.026, Figure 1). Bleeding episodes occurred in 15.8% (n=3) of the treatment group patients, all of them minor according to the ISTH classification. The global survival was 85% at 15 years in the anticoagulation group vs 74% at 15 years in the control group, (p=0.071, figure 2). Mortality was 15.8% (n=3) in the treatment group vs 28.0% (n=7) in the control group, p=0.338. The only cause of death in the treatment group was progression to aplastic anemia. Causes of death in the control group were thrombosis (28.6%, n=2), aplastic anemia (28.6%, n=2), acute leukemia (14.2%, n=1), sepsis (14.2%, n=1) and digestive tract bleeding (14.2%, n=1). Discussion and conclusions. Thrombosis is the most frequent cause of morbidity and mortality in classic PNH patients. In 2003, Hall et al. found that primary prophylaxis with full-dose oral anticoagulation drastically reduced the thrombotic risk in these patients (0 vs. 36.5%, p=0.01). Meanwhile, complement inhibitor has become the mainstay therapy, thromboprophylaxis with oral anticoagulation has virtually stopped in countries where this therapy is accessible. The present study replicated the Hall et al. results, and demonstrated that primary thromboprophylaxis is safe and effective in reducing the risk of thrombosis. In LMIC, where access to complement inhibitors is limited, the use of thromboprophylaxis could abate thrombosis and should be taken in consideration in all patients. Hence, the clonal progression would become the leading cause of death. Figure 1 Figure 1. Disclosures Apodaca Chavez: Abbvie: Speakers Bureau; Asofarma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rangel-Patiño: Abbvie: Speakers Bureau; Bristol: Consultancy. Demichelis: Jazz: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; ASH: Research Funding; Astellas: Consultancy; Gilead: Consultancy; Abbvie: Consultancy, Speakers Bureau; Bristol/Celgene: Consultancy, Speakers Bureau; AMGEN: Consultancy, Speakers Bureau.

Low-Risk Polycythemia Vera Treated with Phlebotomies: Clinical Characteristics, Hematologic Control and Complications in 358 Patients from the Spanish Registry of Polycythemia Vera

Introduction: Current recommendations for patients with low-risk polycythemia vera (PV) include hematocrit (Htc) control with phlebotomies and primary prophylaxis of thrombosis with low-dose aspirin. There is scarce information regarding the hematological control, the incidence of complications and the need for cytoreduction in PV patients treated with phlebotomies only. Methods: A total of 358 patients with low-risk PV (&lt;60 years old and without history of thrombosis) from the Spanish Registry of Polycythemia Vera were included in the present study. PV-related symptoms and blood counts were collected at 6, 12, 18, 24, 36, 48 and 60 months from diagnosis while the patients were treated with phlebotomies only. The duration of the treatment with phlebotomies, the indication of starting cytoreduction and the incidence of thromboembolic and hemorrhagic events during the cytoreduction-free period was also analyzed. Results: Baseline characteristics at the time of diagnosis are described in Table 1. Table 2 summarizes the main hematological and clinical characteristics under treatment with phlebotomies. Inadequate control of the Htc (&gt; 45%) was reported in 61-70% of the patients, leukocytosis &gt;15x10 9/l in 10% and thrombocytosis &gt;1000x10 9/l in 5%. In addition, about 20% of the patients had pruritus and 10% had microvascular symptoms. Of the 358 patients included, 275 (77%) required cytoreduction, 261 (73%) with hydroxyurea and 14 (4%) with IFN. The main indication of cytoreduction was thrombocytosis (20%), followed by age &gt;60 years old (15%) and microvascular symptoms (13%). Median duration of cytoreduction abstention was 4.7 (0.1-30.4) years being significantly longer in patients younger than 50 years (6 and 2 years for patients younger and older than 50 years, respectively, p&lt;0.0001). With a follow-up of 1659 person-years under phlebotomy only treatment, 14 thrombosis were observed (arterial n=9, venous n= 5), 12 hemorrhages (major n=4, minor n=8) and 4 solid tumors (1 melanoma and 3 non-cutaneous carcinomas). The incidence of complications during the cytoreduction-free period by person-years was: 0.8% for thrombosis, 0.2% for major hemorrhage and 0.2% for second neoplasia. The median follow-up until last visit including the time after starting cytoreductive therapy was 8.4 (0.2-39) years. Of 14 deaths observed, none occurred during the phlebotomy period. Half of the patients died from PV related reasons but the other 50% were not related. The median survival estimation by K-M was 36.5 years. Disease progression was documented in 27 (7.5%) patients, 26 of them to myelofibrosis, 1 to myelodysplastic syndrome and none to acute leukemia. Progression to myelofibrosis occurred during the cytoreduction-free period in 5 patients (1.4%) after a median of 5.8 years (Range: 4.9-8.9). Conclusions The incidence of thrombotic and hemorrhagic complications was very low in this series of low-risk patients treated with phlebotomies, even though only 30-40% of patients maintained the Htc &lt;45%. The data from the present study show that low-risk patients have different therapeutic needs than other PV patients and support the development of new treatment strategies. Representing the Spanish Group of Myeloproliferative Disorders. GEMFIN Figure 1 Figure 1. Disclosures Bellosillo: Qiagen: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding; Thermofisher Scientific: Consultancy, Speakers Bureau. Ferrer Marin: Cty: Research Funding; Incyte: Consultancy, Research Funding; Novartis: Speakers Bureau. Garcia Gutierrez: Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding.

Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Martinelli: Jazz Pharmaceuticals: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau; Celgene /BMS: Consultancy, Speakers Bureau; Abbvie: Consultancy; Daichii Sankyo: Consultancy; Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy.

Risk of Febrile Neutropenia in Very Elderly Patients Aged ≥80 Years Who Received R-CHOP Regimen: A Nationwide Analysis in Japan

Background: Despite the aging society, few studies have evaluated risk factors for febrile neutropenia (FN) in the very elderly. This may be due to the difficulty of conducting a prospective study in the presence of comorbidities and a limited number of patients. We retrospectively analyzed risk factors for FN in the first cycle of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in the very elderly aged ≥ 80 years using a nationwide inpatient database in Japan. Study Design and Methods: This study was a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. The database includes discharge abstracts and administrative claims data from &gt;1200 acute-care hospitals and covers around 90% of all tertiary-care emergency hospitals in Japan. We identified patients aged ≥ 80 years old with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first cycle of R-CHOP regimen between July 2007 and March 2017 from the database. The initial dose intensity (IDI, %) was calculated as the average ratio of the actual dose to the 100% dose of cyclophosphamide and doxorubicin. IDI less than 80% was defined as reduced IDI. Multivariable logistic regression analysis fitted with a generalized estimating equation accounting for within-hospital clustering was performed to identify factors associated with the occurrence of FN. P&lt;0.05 was considered statistically significant. Results: We identified 1,819 patients aged ≥ 80 years old with DLBCL who were newly diagnosed and treated with R-CHOP. The median age was 83 years (interquartile range: 82-85). A total of 73 (4%) patients received antimicrobial prophylaxis, and 270 (15%) received primary prophylaxis with G-CSF. Reduced IDI of R-CHOP regimen was performed in 1,444 (79%) patients, including 697 patients with 60-80% of IDI and 747 patients with 40-60% of IDI. FN occurred in 115 of the 1,819 patients (6.3%) with a median of 10 days (interquartile range: 8-12) after the administration of cyclophosphamide. Antimicrobial prophylaxis, primary prophylaxis with daily G-CSF, and pegfilgrastim were not significantly associated with a lower occurrence of FN in the very elderly patients (odds ratio 0.69 [95% confidence interval 0.30-2.21], 1.39 [0.73-2.64], 1.43 [0.73-2.81], respectively). Reduced IDI was significantly associated with a lower occurrence of FN (40-60%: odds ratio 0.54 [0.32-0.92]). Advanced-stage lymphoma (&gt;stage 2) and placement of central venous catheter was significantly associated with the occurrence of FN (odds ratio 1.59 [1.02-2.49], 3.19 [1.81-5.62], respectively). Conclusion: The present nationwide study showed that IDI was reduced in most of the very elderly patients with DLBCL in a real-world clinical practice. The proportion of the very elderly patients who developed FN tended to be lower than those in previous studies with younger patients, which may be explained by reduced IDI in the very elderly. Whereas, prevention strategies with G-CSF for FN may be less effective in the very elderly. Disclosures Matsuda: Ono Pharmaceutical: Other: Lecture fee; Kyowa Kirin: Other: Lecture fee. Jo: Tsumura: Other: Lecture fee, Research Funding; AstraZeneca: Other: Lecture fee; Sanofi: Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee. Shimura: Eisai: Other: Lecture fee. Honda: Otsuka Pharmaceutical: Other: Lecture fee; Ono Pharmaceutical: Other: Lecture fee; Nippon Shinyaku: Other: Lecture fee; Jansen Pharmaceutical: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Takeda Pharmaceutical: Other: Lecture fee. Masamoto: MSD K.K.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Yasunaga: Pfizer: Consultancy, Other: Lecture fee; Novartis: Consultancy, Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Tsumura: Other: Lecture fee. Kurokawa: MSD K.K.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau.

A Randomized Placebo-Controlled Trial of Primary Prophylaxis with Weekly Alendronate Against Glucocorticoid-Induced Osteoporosis in Lymphoma Patients Treated with Steroid-Containing Chemotherapy.

Introduction: Many lymphoma patients receive high doses of glucocorticoids as part of standard therapy, and several recent observational studies have highlighted a possible risk of glucocorticoid-induced osteoporosis (GIO) and excess bone fracture risk. As a substantial fraction of lymphoma patients become long-term survivors, studies that focus on mitigating the negative effects of treatment toxicities on survivorship are important. The objective of the SIESTA trial was to determine if primary prophylaxis with oral alendronate (ALN) is safe and effective against (GIO) in lymphoma patients. Methods: SIESTA was a single-center randomized and double-blinded phase 2 study performed at the Department of Hematology, Aalborg University Hospital, Denmark, enrolling lymphoma patients that were planned for glucocorticoid-containing chemotherapy regimens such as (R-)CVP and all variants of (R)-CHOP. Patients were randomized to weekly oral ALN 70mg or placebo with a treatment duration of 52 weeks. Study assessments included bone mineral density (BMD) measurements at baseline, after completion of chemotherapy at 4-6 months (EOT), and after 12 months, as well as vertebral fracture assessment (VFA) at baseline and at 12 months. The primary study endpoint was change in lumbar spine T-score from baseline to 12 months. Key secondary endpoints were change in T-score from baseline to 12 months at total hip and femoral neck levels, vertebral compression fractures and early T-score changes. Biomarker analyses were exploratory. The target recruitment was 60 patients in a three-year period. Results: A total of 59 patients (36 Diffuse large B-cell lymphoma, 15 follicular lymphoma, 8 other) were enrolled with 22 of 30 patients in the ALN arm and 23 of 29 patients in the placebo arm completing the study (efficacy group). Patient characteristics in the two arms were balanced with exception of more advanced stage diseases (Ann Arbor stage III-IV) in the ALN arm (70·0% vs 41·4%), and a lower median baseline T-score at the lumbar spine in the ALN arm (median T-score -0·6 vs 1·0). Patients in the ALN group received a median of 3,291 mg prednisone versus 3,398 mg for the placebo group. Median change in T-score from baseline to 12 months at the lumbar spine level (primary endpoint) was +0·2 for the ALN arm and -0·2 for the placebo arm (P=0·013) (figure 1), with stronger effect for female patients (median change; ALN +0·25; placebo -0·25) (figure 2). ALN had no effect on BMD for total hip (P=0·30) and femoral neck (P=0·58) at 12 months (figure 1). ALN had no significant early effects on BMD for any measured sites (4-6 months). No new fractures were observed. Nine patients experienced AEs related to the upper gastro-intestinal (GI) system (7 grade 1-2, 2 grade 3-4) with 5 AEs being assessed as related to the study treatment (3 in the ALN group and 2 in the placebo group). One patient (placebo group) discontinued study treatment due to upper GI AE (bleeding ulcer). Biomarker analyses (C-terminal telopeptide cross links (CTX) as marker of bone resorption and N-terminal propeptides of collagen type 1 (P1NP) as marker for bone formation) showed reduced bone resorption for ALN treated patients opposed to the placebo treated patients. From baseline to EOT the mean change in CTX was -0.17 in the ALN group and 0.10 in the placebo group respectively (P&lt;0.001). From baseline to 12 months the mean change in CTX was -0.19 in the ALN group and 0.00 in the placebo group respectively (P=0.002). Interpretation: ALN was a safe and effective primary prophylaxis against GIO in lymphoma patients planned for glucocorticoid-containing chemotherapy regimens. The treatment effects were clinically meaningful across all patient subgroups, but the largest effect size was observed in females. Biomarker analyses supported reduced bone resorption for ALN treated patients. Figure 1 Figure 1. Disclosures Vestergaard: Novo Nordisk Foundation: Other: Head of Research at Steno Diabetes Center North Jutland funded by the Novo Nordisk Foundation, Research Funding. El-Galaly: Abbvie: Other: Speakers fee; ROCHE Ltd: Ended employment in the past 24 months.