During the last decade, many new treatment options for chronic lymphatic leukemia (CLL) have become available, one of them being covalent-binding Bruton’s tyrosine kinase inhibitors (cBTK inhibitors [cBTKis]). There are currently three cBTKis approved for treatment of CLL/SLL: acalabrutinib, ibrutinib, and zanubrutinib. In relapsed and heavily pretreated patients, BTK inhibitors achieve a median PFS of 4 years, and in frontline, around 80% of CLL patients are still in remission and alive after 4 years of treatment with BTK inhibitors. Despite their efficacy, 40% of patients have to discontinue BTK inhibitors because of side effects or treatment resistance. We present the efficacy of the novel noncovalent BTKi in a patient with CLL who developed covalent BTKi-resistant disease with CNS localization. Pirtobrutinib appears to be effective in patients with ibrutinib resistance, even with CNS localization. Clinical responses may take several months to become evident.
Objectives Polycythaemia vera (PV) is associated with substantial arterial and venous thrombotic risk, particularly in patients with prior thrombosis and inadequate haematocrit (HCT) control. Although ruxolitinib is an established second‐line treatment after hydroxyurea failure or intolerance, some patients remain difficult to manage. We report a case of highly thrombotic, treatment‐challenging PV in which pacritinib‐based salvage therapy was used after inadequate disease control with hydroxyurea and ruxolitinib. Case Presentation A 44‐year‐old man was referred with portal vein thrombosis and a history of premature myocardial infarction and cerebrovascular accident. Investigations demonstrated JAK2V617F‐positive PV with borderline low erythropoietin and bone marrow panmyelosis. Despite antiplatelet therapy, anticoagulation, hydroxyurea and subsequent ruxolitinib, the patient experienced further thrombotic complications, including recurrent cerebrovascular events, bilateral limb ischaemia and left ventricular thrombosis. Ruxolitinib was escalated to 25 mg twice daily and combined with low‐dose hydroxyurea; however, HCT control remained suboptimal, with recurrent need for venesection. In February 2025, ruxolitinib was replaced with pacritinib 200 mg twice daily while hydroxyurea and warfarin were continued. During follow‐up, the patient achieved improved HCT control, no longer required venesection and had no further documented thrombotic events. Pacritinib was well tolerated. Conclusion This case describes a patient with high‐risk, refractory PV and recurrent arterial and venous thrombosis in whom pacritinib‐based salvage therapy was associated with improved HCT control, cessation of venesection and absence of further thrombosis during follow‐up. Although off‐label and hypothesis‐generating, this experience supports further evaluation of pacritinib in selected patients with treatment‐challenging PV.
Leukemic transformation of polycythemia vera (PV) to acute myeloid leukemia (AML) with a predominantly erythroid blast population is rare and carries a poor prognosis, particularly when driven by a TP53 mutation. We report a 55-year-old man with JAK2 V617F-positive PV, previously noted on surveillance biopsy to harbor a TP53 mutation and Grade 2 marrow fibrosis, who presented three years later with pancytopenia, schistocytosis, hyperferritinemia, hypofibrinogenemia, and altered mental status. The initial clinical presentation raised concern for thrombotic thrombocytopenic purpura (TTP), while the presence of rare circulating blasts and coagulopathy also prompted consideration of acute promyelocytic leukemia (APML). Empiric plasma exchange, corticosteroids, and all-trans retinoic acid were initiated. ADAMTS13 activity and PML-RARA FISH subsequently returned negative. The patient deteriorated with multiorgan failure and expired before leukemia-directed therapy could be initiated. Postmortem bone marrow results demonstrated greater than 90% erythroid blasts with TP53 protein overexpression, a TP53 p.C238Y mutation (VAF 66%), and a triploid karyotype with 7p and 19p abnormalities, consistent with pure erythroid leukemia (PEL) arising from an antecedent myeloproliferative neoplasm. This case highlights the diagnostic challenges posed by overlapping clinical features of TTP and APML, including limitations in immunophenotypic assignment of the erythroid lineage. Importantly, it provides a longitudinally documented example of a TP53 mutation detected three years before overt transformation and describes a previously unreported presentation mimicking both TTP and APML.
Acute myeloid leukemia (AML) is rare in infancy, with monocytic subtypes such as acute myelomonocytic leukemia often demonstrating extramedullary involvement. This report describes a 10-month-old male infant presenting with firm bilateral testicular enlargement and multiple parietal scalp nodules, accompanied by leukocytosis and circulating blasts in peripheral blood. Bone marrow examination confirmed French–American–British (FAB) M4 AML. Scrotal ultrasound demonstrated heterogeneous masses, and computed tomography identified scalp chloromas without bone erosion. The patient received AML chemotherapy, resulting in resolution of extramedullary lesions and achievement of remission. This case underscores the importance of early hematologic evaluation in infants with bilateral testicular masses to prevent misdiagnosis. It illustrates the rare occurrence of concurrent testicular and scalp chloromas as the initial manifestation of infant AML.
A middle-aged man presented with myalgia, fever, hematemesis, and melena. He was found to have acute kidney injury, acute coronary syndrome, thrombocytopenia, and Coombs-negative hemolytic anemia, raising concern for thrombotic microangiopathy (TMA). While awaiting confirmatory testing, empirical plasma exchange was initiated. Initially, minimal red blood cell fragmentation was observed, which later progressed to florid fragmentation. Despite supportive care, his clinical status deteriorated requiring hemodialysis. The presence of TMA, along with ADAMTS13 metalloprotease activity above the diagnostic threshold, worsening kidney function, and negative stool Shiga toxin testing suggested complement-mediated TMA (C-TMA). Stool PCR testing revealed rotavirus. Eculizumab was initiated, resulting in rapid normalization of hematological parameters and eventual renal recovery. Genetic testing identified a heterozygous PLG c.1735G > A (p.Gly579Arg) variant classified as a variant of uncertain significance (VUS). The importance of serial review of peripheral blood smears and the diagnostic challenge of differentiating TTP, STEC-HUS, and C-TMA are the key learning points.
