Palpable Spleen Research Articles

Clinical Presentation And Etiology of Acute Hepatitis In Children: An Experience From A Tertiary Centre of Bangladesh

Background: The prevalence of Acute hepatitis is still high in developing countries even though the availability of vaccines, prophylactic measures and improved sanitation. Objective: To investigate clinical features, biochemical parameters and etiology of acute hepatitis among hospitalized children in a tertiary care center. Method: This cross sectional study was conducted in the Department of Pediatrics Dhaka Medical College Hospital between June 2021 to July 2022.A total of 120 children aged bellow 15 years who presented with acute hepatitis were included in the study. Results: Most of the studied children were in 5-10 years age group 73(61%).Most of the children presented with jaundice 112 (93.3%), nausea & vomiting 105(87.5%),low grade fever 73(61%),upper abdominal pain 79(65.8%), pruritus 15(12.5%), melena 12(10%), pale stool 10(8.3%), anicteric 8(6.6%). On physical examination tender hepatomegaly was found 110(91.6%) cases, just palpable spleen 8(6.6%), hepatic encephalopathy 6(5%), ascites 4(3.3%) cases. Among the studied patients 102 (85%) were having herbal or homeopathic medicines at the time of admission. All of patients had increase serum bilirubin and ALT and most of them 79(65.8%) had ALT between 500-1500 IU/L.AST was also raised. Increase prothrombin time/INR 17(14.1%) and low serum albumin was seen in7 (5.8%) cases. Majority cases were HAV 81 (67.5%), followed by HEV 10 (8.3%), non A and non B 9(7.5%), HBsAg & anti-HBcIgM were found with positive 4 (3.3%) cases, HAV with HEV co-infection 3 (2.5%). Other than viral hepatitis Salmonella positive 5(4.1%), drug induced hepatitis due to anti-TB and valproic acid 3(2.5%) cases,3(2.5%) cases Wilson’s disease and 2(1.7%) following Wasp bite. Conclusions: The study found the common presenting features of acute hepatitis were jaundice, anorexia, nausea, vomiting, fever, abdominal pain, tender hepatomegaly and ascites. Acute hepatitis due to HAV was the commonest followed by HEV. Vaccination programme should be taken by government to control hepatitis A in children. J Dhaka Med Coll. 2023; 32(1) : 32-37

The Outcome of Patients with Leukemia Presenting with Hyperleukocytosis Requiring Leukapheresis. The Experience of King Fahad Specialist Hospital in Dammam, Saudi Arabia

Background: Patients with acute and chronic leukemia presenting with hyperleukocytosis are at risk of developing leukostasis which has serious and life-threatening complications. Leukapheresis is usually performed to reduce the complications of leukostasis in patients presenting with hyperleukocytosis and clinical manifestations compatible with leukostasis. Methods and materials: A retrospective study of patients with acute and chronic leukemia who received leukapheresis for hyperleukocytosis between the 1st of January 2013 and the 31st of December 2023 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed. Results: Over a period of 11 years, a total of 50 patients with acute and chronic leukemia presenting with hyperleukocytosis and clinical manifestations of leukostasis; 32 patients with acute leukemia (AL) and 18 patients with chronic myeloid leukemia (CML); received leukapheresis at our institution. Among the 32 patients with AL who received leukapheresis, 24 patients (75%) had acute myeloid leukemia (AML), 7 patients (21.88%) had acute lymphoblastic leukemia (ALL) and 1 patient (3.13%) had bilineage acute leukemia (BAL). At presentation of their AL: 3 patients (9.38%) had fever, 9 patients (28.13%) had infections, 4 patients (12.5%) had palpable spleen or liver, 6 patients (18.75%) had palpable external lymph nodes, and 9 patients (28.13%) had extramedullary disease (EMD). After receiving induction and consolidation cycles of chemotherapy, 11 patients (34.38%) of AL patients received allogeneic hematopoietic stem cell transplantation (HSCT). At the end of the follow-up, 17 patients (53.1%) with AL were alive while 15 patients (46.9%) were dead. The 8-year overall survival (OS) for all patients with AL subjected to leukapheresis was 47%. The 5 years OS for patients with AL who subsequently received HSCT and those who did not receive allogeneic HSCT were 70% and 40% respectively. The mean white blood cell (WBC) count of CML patients subjected to leukapheresis was 465.5 × 109/L, 11 patients (61.11%) had clear signs of leukostasis, and 8 patients (44.44%) had splenomegaly at presentation. Regarding the disease stage at presentation, 14 CML patients (77.78%) had chronic phase (CP), 2 patients (11.11%) had accelerated phase (AP) and 2 patients (11.11%) had blast phase (BP). Regarding the fate of CML patients at the end of the study were: 15 (83.33%) were alive, 1 (5.56%) dead, and 2 (11.11%) were unknown as they lost follow-up. However, the 10-year OS of patients with CML subjected to leukapheresis was 90%. Conclusion: Patients with acute or chronic leukemia presenting with hyperleukocytosis and either ongoing or impending leukostasis should have urgent cytoreductive chemotherapy and leukapheresis to prevent life-threatening complications. Although the outcome of AL patients presenting with leukostasis is generally poor, prompt cytoreductive therapy and leukapheresis, followed by induction chemotherapy and allogeneic HSCT may improve the outcome. Also, urgent cytoreduction including leukapheresis improves the outcome of patients with CML presenting with hyperleukocytosis and leukostasis.

Plasmodium ovale infection in Sri Lanka: distant exposure and incidental detection of hyperparasitemia: a case report

BackgroundPlasmodium ovale malaria, which was previously endemic to tropical Africa and the Southwest Pacific islands is now being reported from parts of Asia. In Sri Lanka, the indigenous transmission of malaria has not been documented since October 2012. Since then, there have been several imported cases of malaria, including P.ovale, which have been detected sporadically. The reporting case of P. ovale was imported and detected incidentally in 2021, with several atypical presentations.Case presentationA 40-year-old Sri Lankan medical doctor developed continuous fever with chills, rigors, and dysuria a day following removal of a large lipoma at the root of the neck under general anaesthesia. When the fever has been responding to antibiotics, on the 4th postoperative day a mild thrombocytopenia on complete blood count was detected. A blood smear which was done on the 5th postoperative day incidentally found a malaria parasite and confirmed as Plasmodium ovale with a density of 6535 parasites/microliter on the same day. He never had malaria in the past, but he had worked in South Sudan 1 year ago and visited India six months ago. On the 6th postoperative day, he was treated with chloroquine, and hyperparasitemia reduced rapidly by the next day. As the fever recurred with clinical deterioration, he was treated with different antibiotics. During the course of the illness, he did not develop pallor, or icterus except for a palpable soft spleen. The parasite count was zero on the 9th postoperative day and his fever subsided on the next day. Further, he was treated with primaquine to prevent future relapse and transmission.ConclusionA long incubation period, incidental detection of P ovale in a blood smear, and hyperparasitaemia are the atypical presentations of this case. Postoperative bacterial infection and stress may have reactivated the dormant malaria (hyponozoites) in this patient with an unusual picture. Coinfection of malaria with bacterial sepsis is a challenge in the management of the patient. As the Anopheles mosquito vector exists in Sri Lanka, the risk of indigenous transmission is high from such imported cases of P. ovale.

Patient Characteristics, Treatment Patterns, and Health Outcomes in a Real-World Population of Patients with Myelofibrosis Treated with Fedratinib

Introduction: Myelofibrosis (MF) is a type of myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, progressive anemia, and debilitating constitutional symptoms. Fedratinib (FEDR) is a selective Janus kinase-2 inhibitor (JAK2i) approved for the treatment of adult patients with intermediate (int)-2 or high-risk primary or secondary MF. Patients with MF have a median overall survival of 5-7 years; however, prior to FEDR approval, ruxolitinib (RUX) was the only approved JAK2i for MF treatment, with the majority of patients discontinuing RUX within 3 years of treatment initiation (Harrison C, et al. Ann Hematol 2020;99:1177-1191). Given the current availability and use of FEDR, the primary study objective was to describe demographics, clinical characteristics, and treatment patterns of patients with MF receiving FEDR in real-world practice settings after prior RUX treatment. A secondary objective was to assess changes in MF-related symptoms and spleen size during FEDR treatment. Methods: We report interim data from a medical records review of adult patients with MF who received FEDR treatment after RUX discontinuation (due to treatment refractoriness, relapse, or intolerance) in Canada (CAN), Germany (GER), and the United Kingdom (UK). Data collection is ongoing, and we present data abstracted from March through May 2023. Patients were required to have an int-2 or high-risk MF diagnosis at FEDR initiation and to have initiated FEDR after date of first availability in each country (CAN: Sep 21, 2020, GER: Feb 9, 2021, UK: Nov 1, 2021) up to 6 months prior to data abstraction. Patients who received allogenic, hematopoietic cell transplantation after initial MF diagnosis or participated in a JAK2i trial were excluded. Spleen size evaluation through palpation at FEDR initiation and at least once within the first 6 months of FEDR use was required. Study outcomes measured were patient characteristics, treatment patterns, MF-related symptoms, and spleen size evaluations. Descriptive statistics are reported. Results: A total of 58 patients (CAN: 13, GER: 32, UK: 13) were included in the analysis. Median age at MF diagnosis and FEDR initiation was 67.9 and 71.8 years, respectively. 65.5% of patients were male, and 91.4% were White. Most patients were diagnosed with primary MF (60.3%) and had JAK2 V617F mutation (84.5%). Among patients who had a bone marrow biopsy (n = 51), 58.8% had grade 2 bone marrow fibrosis. Mean baseline Charlson Comorbidity Index score was 2.5. Median time from MF diagnosis and RUX treatment discontinuation to FEDR initiation was 34.0 months and 0.7 months, respectively. Most common reasons for FEDR initiation were splenomegaly (75.9%), RUX failure (67.2%), and to achieve symptom control (63.8%) (Table). Over a median follow-up of 12.1 months after FEDR initiation, 19 patients (32.7%) discontinued FEDR treatment with a median treatment duration of 7.7 months. Among the 39 patients taking FEDR at data abstraction, median treatment duration was 12.5 months. At FEDR initiation, 48.3% and 51.7% had int-2 risk and high-risk MF, respectively. The most common MF-related symptoms presented were fatigue (74.1%), abdominal discomfort (63.8%), and night sweats (46.6%) (Table). 62.1% of patients initiated FEDR treatment at the recommended therapeutic dose of 400 mg, and 74.1% were receiving 400 mg at end of follow-up/treatment discontinuation. Among patients with ≥ 1 FEDR dose change, titration to therapeutic dose (68.4%) was the most common reason for their first dose change. MF-related symptoms decreased in the first 6 months of FEDR treatment, including fatigue (74.1% [at FEDR initiation] reduced to 52.8% [at 6 months after FEDR initiation]), abdominal discomfort (63.8% reduced to 11.3%), and night sweats (46.6% reduced to 3.8%). The proportion of patients with severe (palpable spleen:> 20 cm) and moderate splenomegaly (palpable spleen: 11-20 cm) decreased from FEDR initiation to 6 months after initiation (severe splenomegaly: 32.8% to 7.5%, moderate splenomegaly: 55.2% to 15.1%) (Figure). Conclusion: Thepatients included in this study exhibited a significant level of illness . In this interim analysis, patients treated with FEDR following RUX treatment failure showed resolution of MF-related symptoms and a marked decrease in splenomegaly in the initial 6-month period, demonstrating the real-world effectiveness of FEDR treatment in patients with MF.

Is the Eutos Long Term Survival (ELTS) Score a Useful Marker to Predict Outcome in Children with Newly Diagnosed Chronic Myeloid Leukemia (CML) in Chronic Phase (CP)? the Experience of the International Registry of Childhood CML

Aims. CML is a very rare disease in children. The present work aims to describe the characteristics of children with CML in chronic phase (CP) and to determine the outcome of this pediatric population. Methods. We retrospectively analyzed children with CML in CP registered in The International Registry of Childhood Chronic Myeloid Leukemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735) which represents the largest cohort of children with CML. Results. Between January 2011 and March 2021, 576 CML patients less than 18 years of age at diagnosis were registered. We retrospectively selected 535 (92.8 %) children in CP according to the European leukemia net (ELN) criteria at diagnosis. Boys accounted for 58% of all patients with a boy to girl ratio of 1.25. The median age at diagnosis was 12.4 years (range, 8 months to 18 years). The most common symptoms at presentation were asthenia, weight loss and abdominal pain in 46%, 25% and 23% of the patients, respectively. CML in CP was diagnosed incidentally in 80 (16%) children when a blood assessment was performed for medical reasons. At diagnosis, thrombosis was observed in only one patient whilst 20% of the children presented with bleeding. Bleeding signs were associated with a higher frequency of palpable spleen (p=0.0007), higher leukocyte (p<0.0001) and platelets (p=0.02) counts, and a lower hemoglobin level (p=0.02). Clinical signs of leukostasis were observed in 88 (16.5%) patients. At diagnosis, spleen was palpable in 76% of the patients with a median of 9 cm (range, 1 to 32) below the costal margin. The median leukocyte count was 222 G/L (quartile 95-353). There is no statistical difference between boys and girls in terms of frequency of signs of leukostasis, frequency of splenomegaly, spleen size, median of the leucocyte count and hemoglobin level but the median of the platelet count was significantly higher in girls (p<0.0001). The majority (67%) of the children was allocated to the low-risk group according to the Eutos Long Term Survival (ELTS) score. First line therapy consisted of imatinib in 482 children with a median follow up of 4.6 years (IQR. 2.2-8.4). Among them, 208 (43%) children remained on imatinib with a median follow up of 2.9 years (IQR. 1.5-5.6). The main reason for switching (38.7% of the switches) was failure to achieve hematologic, cytogenetic or molecular response. Among the patients treated with imatinib first line, 15 (3.1%) children died and the probability of overall survival at 36 months was 97.4% (95% CI: 95-99%) (Figure 1). ELTS score was calculated for 406 of these patients: the 3-year survival rate was 98.1.% (95% CI: 96.3-100%), 94.4% (95% CI: 89.1-99.9%) and 95% (95% CI: 88.5-100%) in the low-, intermediate- and high-risk group, respectively (p logrank=0.009). Nineteen of these patients (3.9%) switched from imatinib to another treatment due to progression (accelerated or blastic phase). Progression free survival (PFS) rate at 3-years was 97.1% (95% CI: 94.9-99.2%), 91.7% (95% CI:84.5-98.3%) and 72.0% (95% CI: 59-87.9%) in the ELTS low-, intermediate- and high-risk group, respectively (p logrank<0.001) (Figure 2). Conclusion. The analysis of clinical and biological parameters of the largest cohort of children with CML in CP demonstrated that pediatric CML is characterized by a bulky disease (large splenomegaly, high leucocyte counts). However, these characteristics did not translate in a low rate of response and the outcome was similar to adults. While the ELTS score can identify children with the poorest outcome, a refined prognostic score specific for the pediatric population needs to be established and validated.

Prospective Identification of Variables As Outcomes for Treatment (PIVOT): A Phase II Clinical Trial of Hydroxyurea for Children and Adults with HbSC Disease

Introduction: HbSC is a common form of sickle cell disease especially prevalent in West Africa. Despite experiencing similar clinical events as those with sickle cell anemia (HbSS or HbSβ 0 thalassemia), individuals with HbSC disease have received much less attention because disease complications occur less frequently and often manifest later in life. Retrospective reports suggest that hydroxyurea might benefit people living with HbSC disease, but rigorous prospective data are unavailable to describe potential treatment benefits, long-term safety, and appropriate study endpoints. We designed a Phase II clinical trial of hydroxyurea for children and adults with HbSC disease with the following aims: 1) to measure possible laboratory toxicities of hydroxyurea; 2) to assess the clinical effects of hydroxyurea on sickle-related clinical and laboratory parameters; and 3) to identify study endpoints that are suitable for a future definitive Phase III trial of hydroxyurea for HbSC disease. Methods: Prospective Identification of Variables as Outcomes for Treatment (PIVOT, Trial ID PACTR202108893981080) is a double-blind, randomized, placebo-controlled Phase II trial of hydroxyurea. Inclusion criteria included people with HbSC disease, age 5 to 50 years, receiving care at Korle Bu Teaching Hospital, Accra, Ghana. Exclusion criteria included treatment with hydroxyurea or other disease-modifying treatment or participation in a therapeutic trial in the previous 6 months, hospitalization >10 times in the past 12 months, pregnancy, severe chronic kidney disease or other underlying illness making participation ill-advised, previous myelosuppressive therapy or stem cell transplant, or inability to take hydroxyurea. After written informed consent, participants underwent initial screening for 2 months before randomization to placebo or hydroxyurea (donated by Addmedica, Inc, Paris) with a goal of treating ~100 participants in each arm for one year. Randomization is stratified by age and sex to ensure equal numbers of children and adults with balanced baseline characteristics in each arm. The primary study outcome is cumulative hematological toxicities after 12 months of treatment. Here we report the baseline characteristics of the enrolled cohort. Results: From April 2022 to June 2023, a total of 243 patients with HbSC disease (123 children, 120 adults) consented and began screening (Figure); after ~10% screen failures, 217 (112 children, 105 adults) were eligible for randomization. The average age (mean ± SD) at enrollment was 21.9 ± 14.6 years and 47% were female. Baseline medical history documented that almost all study participants (93%) reported previous hospitalization, while 87% had previous vaso-occlusive events, 78% had malaria, 21% reported transfusion, and 1 patient had a stroke. Baseline labs included hemoglobin = 11.0 ± 1.3 g/dL, HbF = 1.8 ± 1.5 %, ANC = 3.7 ± 1.8 x 10 9/L, and platelets 269 ± 115 x 10 9/L. Additional baseline laboratory studies include whole blood viscosity, ektacytometry, and point-of-sickling. Baseline assessment revealed a palpable spleen in 6 children (5%) and 1 adult (1%), but abdominal ultrasonography documented splenic tissue in 97% of children and 83% of adults with an average volume of 116 ± 71 mL (range 13 - 354 mL) and 222 ± 165 mL (range 4 - 707 mL), respectively. TCD examinations on children revealed an average maximum time-averaged mean velocity of 111 ± 19 cm/sec with 98% normal exams, 1% conditional, 0% abnormal, and 1% inadequate. Retinopathy was identified in 46% of children and 85% of adults, including both proliferative and non-proliferative findings. Near Infrared Spectrometry (NIRS), 6-minute walk, and Quality of Life were also collected. Discussion: Individuals with HbSC endure a substantial number of life-altering clinical complications and early mortality. Better treatments for this large group of people are desperately needed, and hydroxyurea is an obvious choice due to its low cost and ease of oral administration. Better understanding of the rate and severity of disease manifestations across the age span is needed to more completely understand the best time to treat this group to mitigate complications. Now fully enrolled, PIVOT will provide invaluable insights into the effects and potential benefits of hydroxyurea on clinical and laboratory outcomes among people living with HbSC disease.

Comparison of Clinicopathological Parameters, and Treatment Responses in Younger and Older Chronic Myeloid Leukaemia Patients Treated with Imatinib

Introduction: Differences in baseline characteristics and response to treatment in different age groups of patients with chronic myeloid leukaemia (CML) in resource-limited countries have not been extensively studied. We aimed to determine the differences in clinicopathological parameters at diagnosis and response to imatinib in adult CML patients with younger (under 60 years; YCML) and older (60 years and older; OCML) age treated at our institution from March 2001 to March 2021. Methods: A retrospective analysis of consecutive adult CML patients receiving imatinib was performed. Clinicopathological parameters and treatment response were reviewed and analysed using hospital medical records and electronic data reports. Results: The median age at diagnosis was 50 years. OCML patients (n=17) had significantly more comorbidities. The YCML group (n=50) generally had a palpable spleen >5cm from the costal margin, mild anaemia, hyperleukocytosis and thrombocytosis. A starting dose of 400 mg/day was observed in 84% of YCML and in 65% of OCML. Cumulative complete cytogenetic response was 50% in YCML versus 70.6% in OCML, p=0.158. OCML tended to have a higher percentage of major molecular response (MMR) (52.9% versus 32%) and a shorter time to MMR, 22 months (range 5-70) versus 35 months (range 8-53). OCML experienced more haematological and non-haematological treatment-related adverse events after imatinib therapy. Conclusion: Although OCML patients had more comorbidities and treatment intolerances, overall long-term treatment response was comparable to YCML. In OCML, a more personalised approach to initial and subsequent dosing of imatinib may be considered.

Pharmacokinetic-Guided Hydroxyurea to Reduce Transfusion Requirements in Ugandan Children with Sickle Cell Anemia: Baseline Data from the Alternative Dosing and Prevention of Transfusions (ADAPT) Trial

Background: Children are the primary recipients of blood transfusions in sub-Saharan Africa where the demand for safe blood far exceeds the supply. Without disease-modifying therapy, sickle cell anemia (SCA) causes excess morbidity, mortality, and healthcare resource utilization, specifically requiring a high reliance on blood transfusions. Hydroxyurea is a safe and effective medication for the treatment of SCA that decreases blood transfusion use in this population, which may offset the costs of improving hydroxyurea access. The widespread use of hydroxyurea in Africa is limited in part by challenges determining an individual's optimal dose; pharmacokinetic (PK) dosing of hydroxyurea may streamline the dosing process, maximizing the clinical benefits and minimizing toxicities. We designed the Alternative Dosing And Prevention of Transfusions (ADAPT) trial to analyze the reduction in transfusion use with hydroxyurea and as a pilot evaluation of the feasibility of PK-guided hydroxyurea dosing in Uganda. Methods: ADAPT (NCT05662098) is a prospective, single-center, open-label cohort study at Jinja Regional Referral Hospital in Uganda. Children 1-10 years old with HbSS were eligible to enroll; those already receiving hydroxyurea or scheduled blood transfusions, or with malignancy, HIV, tuberculosis, or other chronic illnesses were excluded, and those who received a transfusion within 30 days were temporarily excluded. All participants completed a 3-month screening period during which they underwent baseline evaluations and hydroxyurea PK testing. For PK testing, a 500 mg hydroxyurea test dose was administered, and serum was collected 30, 60, and 180 minutes after the dose. Hydroxyurea concentrations were determined via chemical derivatization and high-performance liquid chromatography in Uganda. Area-under-time-concentration-curves (AUC) and Bayesian estimation were then used to calculate the optimal hydroxyurea dose based on target medication exposure. Those for whom hydroxyurea PK evaluation was completed successfully with a dose recommendation between 15-35 mg/kg/day started on their PK-guided hydroxyurea dose; otherwise, participants started on the default dose of 20 mg/kg/day. All participants will be treated on hydroxyurea for a minimum of 12 months during which time both treatment groups will follow the same laboratory monitoring and dose adjustment protocol to achieve the maximum tolerated dose. The primary study endpoint is the incidence rate ratio of blood transfusion use during screening versus treatment. Secondary endpoints include characterization of blood transfusions (indications, risk factors, adverse reactions), feasibility of PK testing, and laboratory and clinical adverse events comparing children started on PK-guided versus default dosing. Results: From June 2022 to January 2023, 106 participants were enrolled, exceeding the projected enrollment pace and goal. The average age (mean ± SD) at enrollment was 4.6 ± 2.3 years, and 50% were female. Per family-reported history, most participants had previously received a blood transfusion (78%) with 15% reporting at least 6 lifetime transfusions. Five percent had a prior stroke. A majority also had a history of pain events (86%), malaria (79%), and dactylitis (74%). Only 2% had previously used hydroxyurea. At enrollment, the median weight-for-height z-score was -0.19 (interquartile range -1.03-0.32), and baseline exam demonstrated a palpable spleen in 20%. Abdominal ultrasonography was completed on all participants, and the spleen was identified in 75% of participants with a mean volume of 132 ± 99 mL. Transcranial Doppler exams were completed on 105 participants (99%) during screening with 13% conditional and 6% abnormal results. Baseline labs (mean ± SD) documented hemoglobin = 7.7 ± 1.3 g/dL and HbF = 10.3 ± 7.1 %. Of 106 children enrolled, 1 died from acute chest syndrome in screening and 2 were withdrawn after moving away from the clinic; 103 successfully initiated hydroxyurea treatment. Conclusion: ADAPT has fully completed enrollment and will prospectively evaluate the effectiveness of hydroxyurea treatment on reducing transfusion use in Ugandan children with SCA, a finding with both individual and public health implications. ADAPT will also provide pilot data regarding the feasibility of PK-guided dosing of hydroxyurea to facilitate safe, effective hydroxyurea use in Africa.

SAT545 Erythropoietic Thyroid Nodule in the Setting of Myelofibrosis

Abstract Disclosure: L.M. Vasquez: None. J.M. Bruder: None. M. Koops: None. J. Trejo: None. Background: Extramedullary hematopoiesis is frequently seen in non-osseous locations but not endocrine organs, this is a case of hematopoesis in a thyroid nodule. Clinical Case: A 79-year-old man with myelofibrosis diagnosed at age 66, CAD post CABG, atrial fibrillation on anticoagulation and HFrEF was referred to the endocrinology clinic due to enlarging left lobe thyroid nodule. He was diagnosed with a goiter at age 72 but denied compressive symptoms. He had no history of radiation to his neck or family history of thyroid cancer. On physical exam, the left thyroid lobe was visibly enlarged with slight right tracheal deviation without lymphadenopathy. TSH level was normal. Thyroid ultrasound demonstrated a 6.4 x 4.0 x 4.8 cm, complex cystic-solid, taller than wide nodule in the left lobe and a sub-centimeter cystic nodule in the right lobe. FNA showed hematopoietic elements, including maturing cells in three lineages of hematopoiesis. On repeat ultrasound 5 years later. The left nodule increased in size to 7.3 x 5.4 x 4.4 cm and highly suspicious (TR4 and TR3) by Ti-RADS criteria. Repeat FNA of the nodule showed many red blood cells with few hematopoietic cells, flow cytometry did not show any abnormal populations. No thyroid follicular cells were reported. Myelofibrosis was diagnosed by bone marrow biopsy many years prior. He had maintained a stable CBC without palpable spleen or hepatomegaly. Given this history without thyroid dysfunction or reported symptoms, surgery was not pursued. External beam radiation was a treatment option should the nodule cause symptoms. He continued to have mild anemia not requiring blood transfusions. He passed away 2 years later in hospice care after hospitalization for severe heart failure decompensation. Conclusion: Extramedullary hematopoiesis involving the thyroid is rare but has been reported(1). This type of extramedullary hematopoiesis. can be treated with surgery or low-dose radiation because of the radiosensitivity of hematopoietic tissue (2). This was a potential treatment modality if compressive symptoms arose, but they did not. This case illustrates a situation in which surgical intervention on highly suspicious nodules would not have been the optimal treatment choice. Reference: 1. Jan I., Weng M., Wang C., et al. Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature. Journal of the Formosan Medical Association. (2018) 117, 1108-1114. 2. Taher A, Vichinsky E, Musallam K et al., authors; Weatherall D, editor. Guidelines for the Management of Non-Transfusion Dependent Thalassaemia (NTDT) [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Chapter 11, EXTRAMEDULLARY HEMATOPOIESIS. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190455/ Presentation Date: Saturday, June 17, 2023

SAT243 A Rare Triad

Abstract Disclosure: H. Liaqat: None. F. Pasha: None. L. Chavez: None. Introduction: Hypercalcemia contributing to and directly causing pancreatitis is a well-known etiology in literature. Possible mechanisms identified include increased intrapancreatic conversion from trypsinogen to trypsin leading to damage of the pancreas and deposition of calcium in the pancreatic duct followed by pancreatic duct obstruction. The etiology of hypercalcemia-induced acute pancreatitis is usually hypercalcemia of malignancy. Less than ten cases of sarcoid-induced hypercalcemia leading to acute pancreatitis have been reported in the literature. Case Report: We present a case of a 39-year-old male who presented with complaints of generalized fatigue 60, pound weight loss, severe abdominal pain and sensation of lumps in his groin and neck. Examination revealed cervical and inguinal lymphadenopathy and a palpable spleen. Blood work revealed elevated lipase, creatinine, and hypercalcemia up to 14.8 mg/dl. Initial imaging revealed massive hepatosplenomegaly, hilar adenopathy and bilaterally miliary nodules in the lungs. Further workup of hypercalcemia revealed suppressed PTH, normal levels of PTHrP, and 25 hydroxyvitamin but elevated ACE levels and 1,25 dihydroxy vitamin D. Presentation and workup was concerning for sarcoidosis, and diagnosis was confirmed with a liver biopsy. The patient was treated initially with IV fluids, calcitonin, and steroids with resolution of his hypercalcemia and eventually pancreatitis symptoms. Case Discussion: Less than ten cases of sarcoid-induced hypercalcemia leading to acute pancreatitis have been reported in the literature, making this an extremely rare triad. The mechanism remains similar to other causes of hypercalcemia that lead to pancreatitis. Despite steroids not being recommended during an acute pancreatitis episode, this is one of the uncommon instances where steroids would be the preferred approach to tackle sarcoid-induced hypercalcemia. Other calcium-lowering therapies can be used short term like calcitonin and zoledronic acid. Presentation: Saturday, June 17, 2023

Real-world analysis of ruxolitinib in myelofibrosis: interim results focusing on patients who were naïve to JAK inhibitor therapy treated within the JAKoMo non-interventional, phase IV trial

Ruxolitinib (RUX) is a Janus kinase 1/2 inhibitor (JAKi) approved in the EU for treating disease‑related splenomegaly or symptoms in adults patients with myelofibrosis (MF). This is an interim analysis of JAKoMo, a prospective, non‑interventional, phase IV study in MF. Between 2012–2019 (cutoff March 2021), 928 patients (JAKi-naïve and -pretreated) enrolled from 122 German centers. This analysis focuses on JAKi-naïve patients. RUX was administered according to the Summary of Product Characteristics. Compared to the COMFORT-I, -II, and JUMP trials, patients in JAKoMo were older (median 73 years), had poorer Eastern Cooperative Oncology Group (ECOG) performance statuses (16.5% had ECOG ≥ 2), and were more transfusion dependent (48.5%). JAKoMo represents the more challenging patients with MF encountered outside of interventional studies. However, patients with low-risk International Prognostic Scoring System (IPSS) scores or without palpable splenomegaly were also included. Following RUX treatment, 82.5% of patients experienced rapid (≤ 1 month), significant decreases in palpable spleen size, which remained durable for 24 months (60% patients). Symptom assessment scores improved significantly in Month 1 (median –5.2) up to Month 12 (–6.2). Common adverse events (AEs) were anemia (31.2%) and thrombocytopenia (28.6%). At cutoff, 54.3% of patients had terminated the study due to, death, AEs, or deterioration of health. No new safety signals were observed. Interim analysis of the JAKoMo study confirms RUX safety and efficacy in a representative cohort of real-world, elderly, JAKi-naïve patients with MF. Risk scores were used in less than half of the patients to initiate RUX treatment.Trial registration: NCT05044026; September 14, 2021.

Real-World Use of Fedratinib for Myelofibrosis Following Prior Ruxolitinib Failure: Patient Characteristics, Treatment Patterns, and Clinical Outcomes

BackgroundThere is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. Patients and MethodsThis retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. ResultsTwenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). ConclusionFedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib.

Splenic Lesions as a Soft Pointer Towards the Diagnosis of Enteric Fever: A Case Series.

To the Editors: Enteric fever is a major public health problem in developing countries.1 The highest incidence is in children between 5 and 9 years-of-age.2 Splenic abscess (SA) is a rare extra-intestinal complication of salmonellosis with a reported incidence of 0.29%–2%.3,4 Salmonella SA is rare but carries a high risk of morbidity and mortality if unrecognized and untreated.5 This case series presents 3 cases of enteric fever complicated with splenic lesions. Case 1: A 5-year-old female patient presented with fever, pain in the abdomen, vomiting and loose stools for 10 days. On examination, she had a tender abdomen with hepatomegaly. She was started on ceftriaxone due to suspicion of enteric fever. Ultrasonography (USG) of the whole abdomen on admission day was normal. Widal serology on day 11 of illness was positive (1:320 for Titre of H antibody and Titre of O antibody). Blood culture grew nalidixic acid-resistant Salmonella typhi (Table 1). Because she continued to remain febrile, azithromycin was added on day 7 of the hospital stay, and a repeat USG was performed on day 10 of the stay, showing SA (1.4 × 2.1 × 2.3 cm) at the lower pole. USG-guided needle aspiration was performed, and antibiotics continued. She became afebrile over the next few days, was started on oral cefixime and discharged. TABLE 1. - Baseline Characteristics, Clinical, Lab and Management Details of Cases Patient Characteristics Case 1 Case 2 Case 3 Age at presentation (years) 5 12 4 Symptoms (duration in days) Fever Yes (10) Yes (21) Yes (10) Pain abdomen Yes (8) Yes (18) Yes (3) Vomiting Yes (8) No Yes (3) Loose stools Yes (8) No No Per abdomen examination Tenderness Yes Yes Yes Hepatomegaly (liver span) Yes (11 cm) Yes (12 cm) Yes (12 cm) Splenomegaly No Palpable spleen tip No Investigations at admission Haemoglobin (gm/dL) 9.3 11 11.5 TLC (per mm3) 7,800 8,260 5800 DLC (N%/ L %/ M %) 74/20/3 76/14/4 56/33/10 Platelet count (per mm3) 39,000 3,69,000 1,54,00 CRP (mg/dL) 97 36 43 Widal test (titres) Positive (1:320) Negative Positive (1:320) Antibiotics (days) Ceftriaxone (14) f/b cefixime (7) Azithromycin (14) Ceftriaxone (14) f/b cefixime (7) Ceftriaxone (14) f/b cefixime (7) Follow up USG 1 × 1.06 × 1 cm abscess, 1-month postdischarge. Resolution of splenic abscess, 2-month postdischarge Resolution of splenic abscess Resolution of splenic granuloma Typhoid vaccine status Unvaccinated Unvaccinated Unvaccinated CRP, C-reactive protein; DLC, Differential leukocyte count; f/b indicates followed by; TLC, Total leukocyte count; USG, ultrasonography. Case 2: A 12-year-old male presented with 3 weeks of high-grade fever and left abdominal pain. Examination revealed tenderness and palpable spleen tip. Ceftriaxone was initiated empirically. Widal serology was negative, and the blood culture was sterile. Other investigations to evaluate for the etiology of fever, including tuberculosis, were negative. USG abdomen revealed 3 SA, the largest 2.5 × 2.2 cm in splenic parenchyma. Ultrasound-guided aspiration of the largest abscess was performed. Pus culture grew Salmonella paratyphi A. Ceftriaxone was continued as per the sensitivity report. Subsequently, he became afebrile and was started on cefixime and discharged. Case 3: A 4-year-old female presented with fever for 10 days, pain in the abdomen, and vomiting for 3 days. She was started on intravenous ceftriaxone empirically, keeping a possibility of enteric fever. Due to persistent abdominal pain, USG of the abdomen was performed, which revealed multiple hypo-echoic foci in the spleen suggestive of splenic granuloma. Blood investigations revealed a positive Widal test (1:320 dilution titers for Titre of H antibody and Titre of O antibody) and blood culture grew Salmonella typhi. She became afebrile by day 4 of the hospital stay. She was given 7 days of intravenous ceftriaxone, followed by 7 days of cefixime. USG whole abdomen repeated 1-week post-discharge, showed no splenic granuloma. Salmonella SA is rare but carries a high risk of morbidity and mortality if unrecognized and untreated.5 Diagnosis is often delayed in children due to its rarity and nonspecific symptoms. USG abdomen is usually the first investigation performed in suspected cases, and sensitivity can be as high as 90% in the hands of an experienced operator. Percutaneous needle aspiration and antibiotics for 2–3 weeks may be sufficient in many cases, though the actual duration of antibiotics required is not known. The splenic abscess could be a pointer toward the diagnosis of enteric fever in high-burden settings like India. Though radiologic clearing can require 2–3 months, patients usually become asymptomatic after 2–3 weeks of adequate antibiotics and drainage.

Jaktinib in patients (pts) with myelofibrosis (MF) who were intolerant to ruxolitinib (RUX): An open-label, single-arm phase 2b study.

7061 Background: As the first approved Janus kinase inhibitor (JAKi) for pts with symptomatic MF, RUX showed superiority in spleen volume reduction with increased anemia and thrombocytopenia. However, there are few treatment options after RUX intolerance. Jaktinib, an oral novel JAK and ACVR1 inhibitor showed promising efficacy in Jaki-naïve pts with intermediate or high risk MF with mild side effects. Here we present the results of MF pts who were intolerant to RUX and received jaktinib 100 mg bid from a phase 2b study. Methods: Pts who had primary or post-ET/PV MF and were previously treated with RUX for ≥28 days who either required RBC transfusions or required more frequent transfusions on RUX, or had grade 3/4 anemia, thrombocytopenia or hematoma when receiving RUX, and with palpable spleen ≥5 cm were included. The primary endpoint was the proportion of pts with spleen volume reduction of ≥ 35% from baseline (SVR35) at week (wk) 24, assessed centrally on the basis of MRI/CT images. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with ≥ 50% reduction in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), anemia response, safety, etc. Results: A total of 45 patients received jaktinib 100 mg bid. The full analysis set (FAS) for efficacy included 44 pts who had completed the 24-week treatments and evaluations or terminated prior to wk 24, and excluded one pt because of incorrect diagnosis of MF. The median baseline TSS was 9.5, hemoglobin (Hb) was 79.5 g/L, and platelets was 132.5×109/L. While on RUX, 21 pts (48%) required RBC transfusion and all pts experienced those grade 3 hematological toxicities. In FAS, the SVR35 rate at wk 24 was 43% (19/44). Over the study phase, the best spleen response rate was 55% (24/44). The median time to achieve the first SVR35 was 12 weeks. Response was maintained in 80% pts for at least 24 weeks and median duration was not reached. At wk 24, 62% of the evaluable pts achieved a ≥ 50% improvement in TSS from baseline. Of 31 pts with baseline Hb ≤ 100 g/L, 13 (42%) had a ≥20 g/L Hb increase. Of 19 pts who required RBC transfusion at baseline, 11 (58%) had a 50% decrease in RBC infusion frequency. Of 9 transfusion-dependent pts at baseline, one became transfusion-independent. In the safety set (n = 45), the median jaktinib exposure time was 280 days. The most common grade ≥3 TEAEs were anemia (31%), thrombocytopenia (22%), pneumonia (18%), neutropenia (16%) and leukopenia (16%). Treatment discontinuation due to TEAEs occurred in five pts (11%). A dose reduction or temporary interruption due to TEAEs were reported in 12 pts (27%). Conclusions: Jaktinib demonstrated promising activities in MF pts who was intolerant to RUX by substantially reducing spleen volume, ameliorating MF-related symptom burdens, and elevating Hb levels. Jaktinib could be a viable treatment for MF pts with anemia in this setting. Clinical trial information: NCT04217993 .

Original research article: Study of effectiveness of homeopathic remedies in treatment of malaria

Background: One of India's biggest public health issues is malaria. Malaria is frequently linked to poverty, but it also contributes to it and hinders economic growth. The risk affects approximately half of the world's population (3.3 billion), making it the sixth largest cause of mortality globally.Objectives: The study's goal was to determine the function of a set of predetermined homoeopathic medications in the treatment of malaria.Methods: Out of 180 assessed cases, 36 individuals in all were enrolled. The research included patients who had the typical clinical signs and symptoms of malaria and had tested positive for the malaria parasite in a blood test. Based on typical malaria symptoms, experimental medications were chosen from the mainstream homoeopathic literature. Using a student t test calculator online, statistical analysis was performed. p value less than 0.05 recognized as a significant.Results: Of 36 individuals who tested positive for malaria, the majority (41.66%) had temperatures over 102°F. Just 8 patients had palpable spleens. (22.22%) In 21 individuals, mild body & muscular aches were detected. (58.33%). 22 individuals had mild fatigue and moderate sweating. (20) and (61.11%), respectively. Thirteen individuals (36%) reported experiencing nausea and vomiting. The mean MSS score at the beginning of the treatment was 12.2±1.6, and at the conclusion it was 6.9±3.4 (p 0.05). ESR value decreased as well and results were statistically significant. According to indications, the most often given medications were arsenic album (n=12, 33.33%)

Congenital syphilis as the cause of multiple bone fractures in a young infant case report

BackgroundThe differential diagnosis of multiple unexplained bone fractures in a young infant usually includes child abuse or bone disease such as osteogenesis imperfecta. Bone abnormalities can occur in 60–80% of cases with congenital syphilis and may be the sole manifestation. However, this frequent manifestation of this rare disease such as congenital syphilis is frequently disregarded. We describe a case of a young infant with multiple long bone fractures diagnosed with congenital syphilis.Case presentationThis 2-month-old male patient was referred to our hospital because of fractures of the ulna and distal radius bilaterally and noisy breathing with the suspicion of osteogenesis imperfecta. After thorough examination, the infant had anemia and a palpable spleen. We performed a screen for congenital infections among other investigations, which revealed positive non-treponemal and treponemal antibodies for syphilis. Hence the diagnosis for Congenital Syphilis was made.We performed a lumbar puncture (LP) which showed mild pleocytosis. The patient was treated with intravenous aqueous penicillin G 200 000 UI/KG per day for 10 days. In addition, a single dose of intramuscular penicillin G benzathine 50 000 UI/KG was given due to the abnormal result of CSF.On follow up admission 6 months later, the new syphilis serology had much improved and the new LP revealed no abnormal findings.ConclusionsWe present this case report in order to remind of a common manifestation of congenital syphilis, a rare disease which needs to be included in the differential diagnosis of multiple unexplained fractures in early infancy. In our case the fractures were symmetric and bilateral and they were accompanied by anemia and mild hepatosplenomegaly which led to the investigation of congenital syphilis as a possible cause. However, two thirds of infants with congenital syphilis are asymptomatic at birth. All women should have a proper syphilis screening during pregnancy.

Spleen size in homozygous sickle cell disease: trends in a birth cohort using ultrasound.

To provide ultrasound baselines for spleen length in homozygous sickle cell disease (HbSS) and in normal controls with a HbAA genotype. The Jamaican cohort study identified 311 babies with HbSS and 246 matched HbAA controls during the screening of 100,000 consecutive deliveries in Kingston, Jamaica from 1973 to 1981. Ultrasonography commenced in 1988 when the youngest patients were aged 6 years at which time deaths, emigrations and default had reduced the numbers to 206 HbSS and 89 controls. It continued annually until 2000. The spleen was visualized in all HbAA controls but in only 1103/2138 (52%) scans in HbSS. Where available, mean splenic lengths were significantly lower in HbSS (77-103 mm in males, 70-83 mm in females) compared to normal controls (89-101 mm in males, 86-95 mm in females). Assessed by statistical modelling after adjusting for body height, the splenic ratio (splenic length/body height) declined over the age range 12-20 years in HbSS, consistent with progressive splenic fibrosis. Genetic factors known to inhibit sickling, α thalassemia and fetal hemoglobin level (HbF) significantly reduced the decline in splenic ratio. Clinical splenomegaly was an insensitive measure of splenic enlargement as only 50% of patients aged 18 years and above with spleens measuring ≥150 mm on ultrasonography had palpable spleens. An age-related decline in splenic length occurred in HbSS and occurred more slowly with genetic factors known to inhibit sickling. The standards provided may be of value in assessing minor degrees of subclinical acute splenic sequestration. These are the first standards available for splenic length in HbSS. They may be useful in detecting red cell sequestration, not apparent from clinical splenomegaly and also provide a model for identifying factors inhibiting vaso-occlusion.

Characteristics and Clinical Outcomes in Patients (Pts) With Polycythemia Vera (PV) Receiving Ruxolitinib (RUX) After Hydroxyurea (HU): A Longitudinal Analysis From REVEAL

Background: Resistance or intolerance to first-line HU occurs in ~24% of pts with PV; RUX is a recommended second-line treatment (tx). In the large, real-world, multicenter, prospective Observational Study of pts with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159), demographics, disease burden, clinical management, and pt-reported outcomes data of pts with PV were collected from 227 community or academic centers between 2014 and 2019. This analysis describes the characteristics and clinical outcomes of pts with PV who switched to RUX after HU tx. Methods: This analysis included pts (≥18 y) with a clinical diagnosis of PV who were treated with HU at least 3 mo prior to study enrollment and did not switch to an alternative therapy during the observation period (index: study enrollment date) or who switched to RUX after previous HU tx (index: RUX initiation date). Descriptive statistics were used to describe demographics, disease characteristics, and tx patterns. Blood count, Myeloproliferative Neoplasm-Symptom Assessment Form total symptom score (MPN-SAF TSS), and spleen length measurements were analyzed at index and at 3 and 12 mo post index for pts who switched to RUX. Results:Characteristics of pts who switched to RUX vs who were treated with HU Out of 2510 pts enrolled in REVEAL,1053 were eligible for this analysis and comprised of 906 pts treated with HU and 147 who switched to RUX (Table 1). Median age for both groups at index was similar (RUX, 67 y; HU, 70 y); 44.2% and 51.8% were women in the RUX and HU groups, respectively. In RUX vs HU, median (range) time to index date from PV diagnosis was 6.9 (0.3-36.3) vs 4.8 (0.1-36.5) y. The median (range) duration of HU tx prior to index date was 27.6 (0.1-221.0) mo in the RUX and 26.7 (3.0-435.7) mo in the HU group. Main reasons for HU discontinuation prior to RUX tx were lack of efficacy (n=53, 36.1%), adverse events (n=47, 32.0%), and disease progression (n=10, 6.8%). Pts who switched to RUX vs HU had higher mean (SD) MPN-SAF TSS (27.5 [17.7] vs 17.3 [15.1]) and higher percentage of pts (n=40, 27.2% vs n=84, 9.3%) with a palpable spleen. At index, 26 (18.1%) vs 65 (7.8%) pts who switched to RUX vs HU had an elevated white blood cell (WBC) count, with mean (SD) of 16.1 (16.3) vs 9.2 (6.2) ×109/L, respectively. Mean (SD) number of phlebotomies (PHL) 6 mo prior to index date was 1.3 (2.3) in the RUX and 0.7 (1.45) in the HU groups. In RUX vs HU, 27.2% vs 19.3% had a thrombotic event (TE) history prior to index date. Tx patterns and clinical outcomes in pts who switched to RUX (n=147) Ninety-two pts (62.6%) received the recommended initial dose of RUX (10 mg BID); additional initial doses were 5 mg BID (n=19), 20 mg BID (n=16), 15 mg BID (n=10), and other (n=10). Seventy-two (49.0%) required a dose modification. The median (range) RUX tx duration was 22.6 (3.0-54.5) mo; most pts (89.1%) received RUX for ≥6 mo. At the end of study, 118 pts (80.3%) were still on RUX. Compared with index, MPN-SAF TSS, proportion of pts with palpable spleen, and spleen length decreased at 3- and 12-mo follow-up (Table 2). The number of pts with hematocrit >0.45 L/L decreased from 49 at index to 19 and 16 at 3 and 12 mo, respectively (Table 2). The number of pts with WBC counts >10×109/L decreased from 87 at index to 66 and 48 at 3 and 12 mo, respectively (Table 2). Pts with no blood count test at 3- or 12-mo follow-up more likely had controlled hematocrit/WBC at index. Mean (SD) number of PHL decreased from 1.3 (2.3) at index (6 mo prior) to 0.5 (1.3) after 6 mo; 110 pts (74.8%) no longer required PHL 12 mo after index date. The TE rate after index date was numerically lower in RUX vs HU (2.7% vs 4.2%) after a median follow-up of 26 and 44 mo, respectively. Conclusion: This analysis of REVEAL, the largest real-world cohort of PV pts to date, demonstrated that pts who switched from HU to RUX had more severe disease burden vs those who were treated with HU. RUX tx resulted in significant improvements in PV-related symptoms, correlating with reduction in spleen size and sustained improvement in hematologic parameters. This resulted in a reduction of PHL within 6 mo, with most pts becoming PHL-free at 12 mo. There was also a trend towards lower rates of TEs with RUX. This longitudinal analysis validates the efficacy of RUX for the tx of PV after HU exposure in the real-world and suggests monitoring of PV pts on HU to identify those who are likely to benefit from transition to RUX in order to meet tx goals and become PHL-free. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence, Description, and Timing of Serious or Opportunistic Infections in Patients with Hairy Cell Leukemia Treated with Purine Nucleoside Analogues

Background: Hairy cell leukemia (HCL) is an uncommon B-cell malignancy characterized by pancytopenia on presentation. While the purine nucleoside analogues (PNAs) cladribine and pentostatin have resulted in long overall survival, infections remain a major cause of mortality. PNAs are known to be immunosuppressive, and in combination with the inherent infection risk of HCL, patients are vulnerable to serious and/or opportunistic infections throughout the disease course. Furthermore, there is prolonged CD4+ lymphopenia post-PNA treatment for 1-3 years. We thus conducted a comprehensive retrospective review at an academic center to (1) describe the incidence and types of infections seen in HCL and (2) determine how treatment with pentostatin versus cladribine may affect infection risk. Methods: We reviewed charts of all HCL patients that were seen at The Ohio State University between January 1 2012 and June 30 2020. Patients with less than 1 year of follow up were excluded. We defined our infections of interest as (1) serious i.e. requiring hospitalization or (2) opportunistic i.e. organisms commonly seen in immunosuppression. These patients’ baseline demographics, disease characteristics, bone marrow biopsies, and treatment histories were abstracted from medical records. Time to infection was calculated from the start of HCL treatment to the onset of infections, treating death without infection as a competing risk. The cumulative incidence of infection was estimated, and the associations with patient characteristics were evaluated using Fine and Gray sub-distribution hazard models accounting for competing risks. Overall survival was calculated from diagnosis to date of death or last contact. Kaplan-Meier method was used to estimate the survival functions and corresponding 95% confidence intervals. Results: Our study included 149 patients with a median follow up time of 6.9 years (range 1.3 - 48.8) and a 10-year estimated overall survival of 99% (95% CI: 93 - 100%). Median age at diagnosis was 51 years (range 22 - 80) and most patients (n = 117, 78.5%) were male. A total of 138 (92.6%) had classical HCL and 11 (7.4%) had variant HCL. There was a total of 70 incidents of infection, with 52 patients (35%) experiencing at least one infection and 18 (12%) with a second infection. Forty-six infections (66%) were serious and 24 (34%) were opportunistic. Most infections were likely to be seen 2 months prior to (n = 10, 14%) or 2 months after (n=14, 20%) initial treatment. The cumulative incidence of infection increased during the 50 days after starting treatment (Figure 1). Based on infection site, clinical presentation, and/or laboratory findings, 36 infections (51%) were classified as bacterial, 14 (20%) were viral, 8 (11%) were fungal, and 1 was concurrent viral and bacterial. Eleven (16%) infections did not have a confirmed organism. Sixty-seven (96%) infection cases had resolved; the outcomes in 2 cases were unknown, and 1 case resulted in death. Organisms were confirmed in 38 cases and are listed in Table 1. We examined baseline factors that could be associated with increased risk of infection, including sex, age at diagnosis, variant histology, total number of HCL treatment courses, prior infection, and a palpable spleen at diagnosis: none of these were associated with increased risk. Using cladribine as a reference, no treatment agents (including newer, non-PNA therapies) were associated with lower or higher infection risk. Examining the PNAs specifically, treatment with pentostatin versus cladribine was not associated with a significant difference in infection incidence (HR 1.12, 95% CI: 0.48 - 2.63). Conclusions: In our large institutional cohort of patients with HCL, a considerable fraction (35%) of patients experienced serious or opportunistic infections. The majority of these were in the 2 months before or after initial treatment. We did not identify any demographic or disease factors associated with infection, although this is limited by the small sample size. Notably, treatment with either cladribine or pentostatin was not associated with a significant difference in infection incidence. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Updated Results from the Momentum Phase 3 Study of Momelotinib (MMB) Versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor

Updated Results from the Momentum Phase 3 Study of Momelotinib (MMB) Versus Danazol (DAN) in Symptomatic and Anemic Myelofibrosis (MF) Patients Previously Treated with a JAK Inhibitor