A Case of Symptomatic Supratherapeutic International Normalized Ratio on Rivaroxaban.

Rivaroxaban is a direct oral anticoagulant that works by inhibiting factor Xa. Direct anticoagulants have largely replaced direct vitamin K inhibitors (VKAs) due to the decreased risk of major hemorrhages and the lack of need for regular monitoring and dose adjustments. However, there have been multiple reports of elevated international normalized ratio (INR) and bleeding incidents in patients on rivaroxaban, which brings into question the potential need for monitoring. We report a case of an INR of 4.8 in a rivaroxaban-naïve patient who presented with gastrointestinal bleeding and a significant drop in hemoglobin four days after starting rivaroxaban. We present possible pharmacologic explanations. We propose the idea that specific subgroups of patients may be at risk for true INR elevations and may benefit from routine monitoring of their INR while on rivaroxaban.

Early orbital involvement in a rare diagnosis of Burkitt-like lymphoma with 11q aberration.

Burkitt-like lymphoma with 11q aberration is a rare condition that poses a diagnostic challenge due to similarities with Burkitt's lymphoma. Due to the rarity of cases, no specific guidelines exist for therapy, and it is treated the same way as Burkitt's lymphoma. We present such a case with initial orbital involvement, an unusual manifestation. Our patient achieved remission with induction chemotherapy, although he will need regular follow-up given the paucity of information on long-term monitoring in these patients.

Carfilzomib-Induced Tumor Lysis Syndrome and Biventricular Heart Failure in a Patient With Multiple Myeloma.

Carfilzomib is a proteasome inhibitor (PI) used in multiple myeloma (MM) that is resistant to other therapies. Despite its efficacy and potency, carfilzomib has been associated with kidney injuries, cardiovascular toxic effects, and hematological adverse events. Tumor lysis syndrome (TLS) following the use of PIs in MM, a malignancy not known to cause TLS, has seldom been reported. We present a case of a patient with a known diagnosis of MM who received prior therapy including bortezomib, a first-generation PI, developing worsening heart failure and new onset TLS days after the administration of carfilzomib.

Eculizumab in the Treatment of Gemcitabine-Induced Atypical Hemolytic Uremic Syndrome.

Gemcitabine-induced hemolytic uremic syndrome is an often-missed condition. We present a case outlining the successful management of a patient with metastatic cholangiocarcinoma treated with gemcitabine who subsequently developed hemolytic uremic syndrome. Early recognition and stopping gemcitabine are essential in this patient population. Complement inhibitors have been used, and our patient improved on eculizumab therapy.

Venetoclax and Azacitidine in the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm Refractory to Conventional Therapy.

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematological malignancy associated with poor prognosis and limited treatment options. No guideline-directed therapy existed until the approval of tagraxofusp in 2018 by the Food and Drug Administration. Multiple clinical trials are undergoing as treatment options continue to evolve. We report a case refractory to tagraxofusp and pivekimab sunirine with subsequent remission achieved on venetoclax and azacitidine therapy.

Ponatinib-Induced Cerebrovascular Accident (CVA).

Ponatinib is a highly potent tyrosine kinase inhibitor shown to have excellent outcomes in the treatment of acute and chronic leukemias. Despite its high efficacy, ponatinib has been shown to carry an increased risk for cardiovascular adverse events, not attributable to a known mechanism. We present a case of a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) who developed a cerebrovascular condition while receiving maintenance therapy with the lowest treatment dose of ponatinib for a prolonged duration.

Mutant PPM1D- and TP53-Driven Hematopoiesis Populates the Hematopoietic Compartment in Response to Peptide Receptor Radionuclide Therapy.

PURPOSE: Hematologic toxic effects of peptide receptor radionuclide therapy (PRRT) can be permanent. Patients with underlying clonal hematopoiesis (CH) may be more inclined to develop hematologic toxicity after PRRT. However, this association remains understudied. MATERIALS AND METHODS: We evaluated pre- and post-PRRT blood samples of patients with neuroendocrine tumors. After initial screening, 13 cases of interest were selected. Serial blood samples were obtained on 4 of 13 patients. Genomic DNA was analyzed using a 100-gene panel. A variant allele frequency cutoff of 1% was used to call CH. RESULT: Sixty-two percent of patients had CH at baseline. Persistent cytopenias were noted in 64% (7 of 11) of the patients. Serial sample analysis demonstrated that PRRT exposure resulted in clonal expansion of mutant DNA damage response genes (TP53, CHEK2, and PPM1D) and accompanying cytopenias in 75% (3 of 4) of the patients. One patient who had a normal baseline hemogram and developed persistent cytopenias after PRRT exposure showed expansion of mutant PPM1D (variant allele frequency increased to 20% after exposure from < 1% at baseline). In the other two patients, expansion of mutant TP53, CHEK2, and PPM1D clones was also noted along with cytopenia development. CONCLUSION: The shifts in hematopoietic clonal dynamics in our study were accompanied by emergence and persistence of cytopenias. These cytopenias likely represent premalignant state, as PPM1D-, CHEK2-, and TP53-mutant clones by themselves carry a high risk for transformation to therapy-related myeloid neoplasms. Future studies should consider CH screening and longitudinal monitoring as a key risk mitigation strategy for patients with neuroendocrine tumors receiving PRRT.

Utility of bone marrow aspirate and biopsy in staging of patients with T-cell lymphoma in the PET-Era - tissue remains the issue.

The role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computerized tomography (PET-CT) in evaluation of bone marrow involvement (BMI) in patients with T-cell lymphoma (TCL) is poorly understood. We investigated whether PET-CT could replace bone marrow aspiration and biopsy (BMAB) in TCL. Sixty patients with newly diagnosed TCL who underwent both diagnostic PET-CT and BMAB were identified. BMI was tissue-confirmed in 15 (25%) cases, however only 8 of these 15 showed BMI on PET-CT (sensitivity of 53.3%, specificity of 100%). BMI by BMAB was associated with lower progression-free survival (PFS) (p = 0.038) and overall survival (OS) (p = 0.003) while PET-CT BMI was associated only with OS (p = 0.02). BMI detected by BMAB in the setting of a negative PET-CT had similar inferior prognosis as BMI identified on PET-CT. Thus, PET-CT in TCL misses BMI in almost half of the cases detected by BMAB and hence cannot substitute BMAB in evaluation of TCL.