Vitamin B12 deficiency is commonly known to cause hematological, neurological, and gastrointestinal disturbances including anemia, pancytopenia, sub-acute combined degeneration, and glossitis, among others. Hemolytic anemia is a rare but possible presentation of vitamin B12 deficiency. We present a case series of three elderly females with different past medical histories but with similar presentations of severe anemia. Initial investigation revealed pancytopenia and hemolytic anemia. Further evaluation indicated vitamin B12 deficiency and subsequently, pernicious anemia, as confirmed by low serum vitamin B12 levels and positive intrinsic cell antibody respectively. These findings directed the diagnosis toward vitamin B12 deficiency-induced hemolytic anemia, a rare clinical entity. All three patients responded to treatment with intramuscular vitamin B12 injections, showing significant improvement in their pancytopenia and hemolytic anemia. This case series highlight the importance of considering vitamin B12 deficiency as a potential cause of hemolytic anemia in patients presenting with pancytopenia and ineffective hematopoiesis. Further research is necessary to illuminate the therapeutic implications of this rare condition.
e16251 Background: In patients (pts) with new-onset diabetes (NOD) above the age of 50 years, 1% are diagnosed with pancreatic adenocarcinoma (PDAC) within three years. Based on this, NOD has been proposed as an important factor for early diagnosis of PDAC. Research has been directed towards investigating NOD vs Type 2 diabetes and association with PDAC. Limited data exists on its impact on the survival outcomes amongst PDAC pts. Methods: We retrospectively analyzed clinical data of 150 pts diagnosed with a pancreatic mass at three hospitals from 2014 to 2021. NOD group consisted of pts diagnosed with Diabetes or Pre-Diabetes defined as HBA1c > 6.5% and 5.7-6.4%, respectively, within the three years prior to PDAC diagnosis. Primary aim of the study was the characterization of the impact of NOD on clinical outcomes. Results: 83 pts [mean age 68.32 yrs, 58% males, 61% white] were identified with biopsy proven PDAC, out of which, 9 (11%) pts had pre-existing Diabetes, 21 (25%) pts met the criteria for NOD group. In the NOD group whose weight was available (n = 15), 11 pts (79%) had experienced weight loss within one year of the NOD diagnosis with a median age of 68.46 yrs. No significant differences were noted between race (P = 0.36), age (P = 0.9), sex (P = 0.9), tumor location (P = 0.17), and chemotherapy received (P = 0.9) between the two groups. When comparing survival outcomes, no significant differences were noted in the metastatic cohort (n = 42, PFS HR 0.77, P = 0.4, OS HR 0.9 P = 0.7) including in the subgroup analysis for pts receiving FOLFIRINOX n = 20, PFS HR 0.59, P = 0.28, OS HR 0.66 P = 0.4) or Gemcitabine based treatment (n = 9, PFS HR 1.31, P = 0.7, OS HR 0.46 P = 0.3). In the resected cohort (n = 20), pts in the NOD group did worse than pts who did not meet the criteria with PFS 10 months vs. 18.3 months (P = 0.0058, HR 7.78), a similar trend was noticed in the OS 15.2 months vs. 28.2 months (P = 0.08 HR 2.98), but it did not reach statistical significance. Conclusions: Consistent with current literature, NOD preceding PDAC is distinct from Type 2 diabetes associated NOD, characterized by weight loss and occurring at a later age. Pts with NOD preceding PDAC were shown to have worse survival outcomes in the resected cohort. Larger studies need to be conducted in this context as this could have significant implications for PDAC screening and treatment.
TPS11572 Background: Talimogene laherparepvec (TVEC), an oncolytic HSV expressing huGMCSF, may be synergistic with trabectedin (T) and nivolumab (N) in treating advanced sarcoma. Objectives: (1) To evaluate the best overall response by RECIST v1.1, progression-free survival rate (PFS), and overall survival rate, (2) To determine the incidence of conversion of an unresectable tumor to a resectable one, and (3) To evaluate the incidence of adverse events related to the drug combination. Methods: This is an open label phase 2 study. A total of 40 patients will receive T (1.2 mg/m2 CIV over 24 hours q3 weeks), N (240 mg IV over 30 min q 2 weeks) and TVEC (intratumorally q 2 weeks according to tumor size). Eligible patients are those with histopathologically confirmed diagnosis of locally advanced, unresectable or metastatic sarcoma including desmoid tumor and chordoma, previously untreated or treated, with measurable disease by RECIST v1.1, and at least, one accessible tumor for intratumoral injection of TVEC. Currently, 31 of the 40 patients have been enrolled. Statistical Considerations: Continuous variables will be summarized by the sample size (n), mean, standard deviation, first and third quartiles, minimum and maximum. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Safety (incidence and severity of adverse events and significant laboratory abnormalities) will be performed on all patients (ITT population). Patient incidence of all treatment emergent AEs will be tabulated by system organ class and preferred term. Clinical trial information: 03886311 .
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), first identified in December 2019 in Wuhan, China, has rapidly spread worldwide, is now a public health emergency, and has been declared a pandemic. While SARS-CoV-2 is known to cause significant pulmonary disease, ranging from pneumonia to acute respiratory distress syndrome (ARDS), various extrapulmonary manifestations of COVID-19 have also been reported. Growing evidence suggests that COVID-19 leads to a hypercoagulable state leading to micro and macro-vascular angiopathies. We present a case of an 80-year-old male without a previous history of prothrombotic disorders who developed descending aortic thrombosis, approximately 40% stenosis, at the level of the diaphragmatic hiatus and acute limb ischemia secondary to COVID-19 requiring emergent surgical intervention. After 12 days of persistent ischemic left lower extremity imaging despite thrombectomy, bypass, and therapeutic heparin, the patient's limb was deemed non-salvageable and underwent left above-knee amputation. Transthoracic echocardiogram revealed normal left ventricular function, moderate pulmonary hypertension, and no evidence of atrial septal defect, aortic root abnormalities, or intraventricular thrombi. Evaluation of autoimmune and inflammatory vasculitis was negative. While further study into the prothrombotic nature of this condition still needs to be pursued, the thromboembolic risk of COVID-19 represents an urgent need for appropriate anticoagulation for venous thrombosis. Arterial thrombosis requires other kinds of management to avoid the severe adverse effects of emboli and related ischemia. This current case highlights the need for randomized control trials testing different prophylactic strategies. Further evidence is also required for the role of amputation surgery when initial interventions for revascularization fail to restore blood flow.
Autoimmune hemolytic anemia (AIHA) is related to an underlying condition in an estimated 50 to 60%, while the remaining is idiopathic, as a result of a combination of immune activation, deficiency, or dysregulation. AIHA is associated with viral infections, autoimmune disorders, immunodeficiencies, lymphoproliferative disorders, and pregnancy. AIHA has predictive properties and may be a harbinger of future lymphoproliferative disorders in up to 20% of AIHA cases. Autoimmune hemolytic anemia (AIHA) has been associated with lymphoproliferative disorders particularly chronic lymphocytic leukemia and non-Hodgkin lymphoma. Rarely is it seen in Hodgkin disease. In the following report, we describe the presentation of AIHA, ultimately resulting in the diagnosis of nodular sclerosis Hodgkin lymphoma (stage III). From the limited reports and reviews available, it is understood that advanced Hodgkin (stage III or IV) of nodular sclerosis (NS) or mixed cellularity (MC) types portend a stronger affiliation to AIHA. The majority of AIHA-associated Hodgkin lymphoma presents as stage III or IV disease with the hemolysis being the presenting symptom, as in this case. The mainstay of AIHA therapy has been corticosteroids; however, this first-line regimen appears to be less effective when treating AIHA in the setting of HL. The exact mechanism of AIHA related to HL is unclear, and it may be thought to be that tumor cell produced autoantibodies. Other hypotheses include paraneoplastic phenomena or more, perhaps immunity to tumor cells may cross-react with antigens on the red cells. Although these mechanisms require further investigation, the relationship of the AIHA and HL represents a piece to a larger puzzle between autoimmune disorders and lymphoproliferative conditions.
11520 Background: Sarcoma cells are most immunogenic earlier in the disease. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first-line therapy. Methods: Eligible patients include previously untreated male or female patients, ≥ 18 years of age with locally advanced unresectable or metastatic soft tissue sarcoma (STS), with measurable disease by RECIST v1.1. Immune checkpoint inhibitors I (1 mg/kg i.v. q 12 weeks) and N (3 mg/kg i.v. q 2 weeks) were given with T (1.2 mg/m2 i.v. q 3 weeks), a tumoricidal agent that depletes growth-promoting macrophages in the tumor microenvironment. Primary endpoint: Objective response rate by RECIST v1.1; Secondary endpoints: (1) Progression-free survival (PFS) at 6 months, (2) Overall survival (OS) at 6, 9, 12, 24, and 48 months, and (3) Incidence of adverse events. Results: Efficacy analysis: There were forty-one evaluable subjects. Best overall response rate was 19.5%; disease control rate 87.8%. The median OS was >12.5 months; median PFS was >6.0 months (6-month OS rate: 75%; 6-month PFS rate: 50%). Safety analysis: Grade 3 TRAEs include fatigue (n = 5), increased TSH (n = 3), decreased TSH (n = 1), adrenal insufficiency (n = 1), hyperglycemia (n = 1), dehydration (n = 1), hyponatremia (n = 2), bipedal edema (n = 2), increased AST (n = 8), increased ALT (n = 19), increased ALP (n = 2), increased CPK (n = 3), port site infection (n = 2), psoriasis exacerbation (n = 1), anemia (n = 6), thrombocytopenia (n = 2), and neutropenia (n = 2). Grade 4 TRAES include neutropenia (n = 1), thrombocytopenia (n = 2), and increased CPK (n = 2). Conclusions: These data suggest that combinatorial therapy with Ipilimumab, Nivolumab and Trabectedin (1) may have synergistic activity in achieving disease control, and (2) is safe with manageable toxicity for patients with previously untreated STS. Clinical trial information: NCT03138161 . [Table: see text]
