Case Reports in Hematology最新文献

T-cell large granular lymphocytic leukemia (T-LGLL) is an uncommon lymphoproliferative disorder that typically follows a slow clinical course. Symptoms often remain subtle until cytopenia or infection develops. Severe infection secondary to neutropenia represents the major cause of mortality. We describe an uncommon case involving an 81-year-old woman diagnosed with T-LGLL whose agranulocytosis was followed by recurrent infections. Immunosuppressive agents such as methotrexate, cyclophosphamide, and tacrolimus-commonly recommended by current guidelines-were administered but failed to improve neutropenia. Administration of fludarabine, a purine analog listed as a second-line option in the NCCN guidelines, led to a prompt rise in neutrophil counts and a concomitant decline in LGL levels. To our knowledge, no prior Japanese report has documented successful use of fludarabine monotherapy for T-LGLL-related neutropenia, prompting us to describe this case.

Acquired Factor V (FV) deficiency due to inhibitors is a rare coagulopathy that presents significant diagnostic and therapeutic challenges. We report the case of an 81-year-old male with persistent gross hematuria and severe coagulopathy, marked by prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and critically low FV activity (< 1%). Initial mixing studies corrected the coagulation abnormalities, suggesting a deficiency rather than an inhibitor; however, standard therapies failed. Fresh frozen plasma (FFP) did not elevate FV levels, and recombinant activated Factor VII (rFVIIa) did not resolve his symptoms, raising suspicion for a non-neutralizing inhibitor that depletes FV by increasing clearance. Clinical improvement was achieved with platelet transfusions, and his FV level normalized after treatment with rituximab and intravenous immunoglobulin (IVIG). PT and aPTT improved from 60 and > 200 to 12 and 32, respectively. It has remained normal with subsequent maintenance immunosuppression with rituximab. This case illustrates the diagnostic complexity created by non-neutralizing FV inhibitors, which accelerate factor clearance without directly impairing activity. It highlights the critical need for integrating clinical and laboratory findings to guide tailored treatment in managing rare coagulopathies.

Background: Central nervous system (CNS) involvement is an infrequent complication of chronic lymphocytic leukemia (CLL), occurring in less than 1% of cases. We report a case of a 63-year-old male with a history of CLL previously treated with ibrutinib but discontinued early due to intolerance. As a result, the patient was then treated with obinutuzumab plus venetoclax, achieving undetectable minimal residual disease (MRD) but relapsed after 2 years with CNS involvement.

Case presentation: The patient initially presented to the emergency department with confusion and altered mental status. Magnetic resonance imaging (MRI) of the brain revealed abnormal subcortical hyperintensities and leptomeningeal enhancement concerning leukemic infiltration. Lumbar puncture confirmed malignant CD5+ CLL cells in the cerebrospinal fluid (CSF), and a bone marrow biopsy revealed 50%-60% CLL involvement. Zanubrutinib 320 mg daily was initiated. The patient exhibited marked cognitive improvement within full resolution after four weeks of therapy. Follow-up MRI after 8 weeks showed full resolution of CNS, lesions with repeat LP demonstrating CSF cleared of CLL cells. He remains in complete remission with continued daily zanubrutinib 6 months follow-up; no significant adverse effects were observed.

Conclusion: This case highlights the rare occurrence of CNS involvement in CLL and is the first to demonstrate successful CNS disease eradication with zanubrutinib monotherapy.

Loxoscelism can cause local as well as systemic manifestations. Hematologic complications of brown recluse spider venom can be life-threatening. Here, we present two cases of loxoscelism-mediated hemolysis that highlight the variable clinical presentations and treatment options available based on severity and pathophysiology of hemolysis.

Background: Unstable hemoglobin leading to chronic hemolysis is a rare yet an important cause of hemolytic anemia and can be easily missed if not thought of during evaluation. Hemoglobin Sun Prairie is an extremely rare α-globin mutation associated with hemolytic anemia.

Case: We report a 22-year-old female from Nepal who presented with easy fatigability and jaundice since her childhood with worsening of symptoms for 2 months. Examination revealed pallor, icterus, and splenomegaly. Investigation showed anemia with low mean cell volume (MCV), reticulocytosis, indirect hyperbilirubinemia, and raised lactate dehydrogenase (LDH) level. Workup for etiology of hemolysis, including autoimmune, nutritional, RBC enzyme deficiency, and osmotic fragility, was negative. Hemoglobin electrophoresis was inconclusive. Whole-exome sequencing identified a pathogenic mutation in HBA2 gene, confirming Hemoglobin Sun Prairie. To our knowledge, this represents the first reported case of Hemoglobin Sun Prairie from Nepal.

Conclusion: This case highlights the importance of genetic testing in an unexplained hemolytic anemia. Genetic testing such as whole-exome sequencing would help in the early identification of rare causes of hemolytic anemia which can guide in the genetic counseling and prevent unnecessary investigations and interventions.

Background: Central nervous system (CNS) involvement by cutaneous T-cell lymphomas (CTCL) is exceptionally rare and is associated with a poor prognosis. Folliculotropic mycosis fungoides (FMF) is a rare subtype of CTCL and often has more aggressive clinical behavior compared to classic MF. The risk factors for CNS progression in patients with primary CTCL are not well understood.

Case summary: We present the case of a 75-year-old male with a history of Stage IA FMF, who developed progressive neurologic and functional decline over six months. Workup revealed marked eosinophilia, and CSF analysis showed monoclonal T-cell population with positive T-cell receptor (TCR) gene rearrangement. Flow cytometry further showed an atypical CD4+ T-cell population with loss of CD7, consistent with the immunophenotype of patient's cutaneous MF, supporting secondary CNS involvement. An MRI of the brain showed T2 hyperintensity in the pons and right middle cerebellar peduncle, with low signal intensity throughout the bone marrow of the skull, concerning for CNS progression of FMF. The patient was started on high-dose steroids, which led to improvement in eosinophilia. Due to transaminitis, high-dose methotrexate therapy was deferred, and the patient was initiated on intrathecal (IT) chemotherapy with methotrexate and cytarabine. Following five cycles of IT chemotherapy, the patient's neurologic status significantly improved, and CSF analysis showed resolution of the atypical T-cell population.

Conclusion: This case highlights the rare occurrence of CNS progression of FMF, even in the absence of lymphatic involvement and with well-controlled skin manifestations, and underscores the role of IT chemotherapy in managing this complication.

Hodgkin lymphoma (HL) presenting with initial skeletal symptoms as a paraneoplastic phenomenon is extremely rare. Herein, we report the case of a 26-year-old man with nodular sclerosis classical HL (NSCHL) who presented with low back pain as the initial symptom. Imaging studies were unremarkable except for right S1-S2 sacral marrow edema on MRI, and multiple biopsies showed only inflammatory changes, resulting in a tentative diagnosis of chronic recurrent multifocal osteomyelitis. Later in the course of the disease, after performing routine series of MRIs, lymphadenopathy was finally detected. Core biopsies of the axillary and pelvic lymph nodes subsequently confirmed the diagnosis of HL. Complete resolution of bone lesions was observed following lymphoma treatment. This case highlights the diagnostic challenges of HL, particularly when it presents with rare skeletal paraneoplastic manifestations.

Multiple myeloma (MM) is the second most common hematologic malignancy, and patients with relapsed/refractory MM (RRMM) face limited treatment options and a poor prognosis. Recently, CAR-T cell therapy targeting G-protein-coupled receptor, class C group 5 member D (GPRC5D) has shown promising efficacy and safety in preclinical studies, offering new hope for patients with RRMM. We report the successful treatment of a 48-year-old female patient with relapsed/refractory nonsecretory MM. The patient had high-risk factors, including 1q21 amplification and TP53 deletion, and had relapsed after seven lines of therapy, including autologous hematopoietic stem cell transplantation, proteasome inhibitors, immunomodulatory agents, PD-1 inhibitors, and CD38 monoclonal antibodies. She also developed extramedullary disease. Eventually, she received CAR-T cell therapy targeting GPRC5D, which led to the complete disappearance of extramedullary lesions and a sustained complete remission lasting up to 17 months. In conclusion, CAR-T cell therapy targeting GPRC5D is highly effective and well-tolerated in patients with RRMM, especially those with high-risk factors. Further studies with larger cohorts and longer follow-up periods are needed to validate the clinical application of GPRC5D-targeted CAR-T cell therapy in RRMM, particularly for patients who have failed BCMA-targeted therapies.

Pure red cell aplasia (PRCA) is a rare hematologic disorder characterized by normocytic anemia and severe reticulocytopenia. The co-occurrence of PRCA and myeloproliferative neoplasm (MPN) with JAK2 and MPL mutations is exceptionally rare. This case involves a patient who initially presented with anemia and thrombocytosis. Following a diagnosis of PRCA, the treatment with immunosuppressive therapy effectively increased her hemoglobin levels. Genetic testing revealed the presence of JAK2 V617F and MPL W515L mutations. The bone marrow biopsy results indicated MPN-U, followed by a subsequent biopsy revealing myelofibrosis secondary to MPN-U. Subsequently, ruxolitinib was administered. This case highlights the significance of pathological examination and genetic mutation testing in achieving precise differential diagnoses in MPNs. Additionally, it demonstrates effective management strategies for patients diagnosed with PRCA and MPN with JAK2 and MPL mutations. The use of ruxolitinib and cyclosporin A has been shown to be beneficial for such patients. And the use of ruxolitinib decreases the dosage of cyclosporin A, indicating that ruxolitinib may have a therapeutic effect on PRCA.

Patients with multiple myeloma (MM) have an inherent risk for secondary myeloid malignancies. Innovative approaches to treatment are needed when these hematologic malignancies co-occur. Venetoclax (VEN), a BCL2 inhibitor, has been used in combination with Azacitidine in acute myeloid leukemia, in the trial setting in high-risk myelodysplastic syndrome (MDS), and in t(11; 14) MM in the salvage setting. Here, we present a case report of concurrent treatment of high-risk MDS and t(11; 14) MM in a patient, using VEN-based therapy. Following diagnosis with IgG t(11; 14) MM, the patient received treatment with Lenalidomide, Bortezomib, and Dexamethasone and achieved a very good partial response. She subsequently proceeded to autologous stem cell transplant and thereafter continued on Lenalidomide maintenance. Relapsed disease was noted 3 years following transplant, with a concurrent diagnosis of a high-risk MDS (mutations in NRAS and DNMT3A). Given the known efficacy of VEN in her concomitant malignancies, we elected to use a VEN-based regimen, at a lower dose of VEN than has been shown to be efficacious in t(11; 14) MM. Bone marrow biopsy demonstrated response from the perspective of both malignancies, until she had relapsed disease with a mixed phenotype acute leukemia ∼ 19 months after relapsed MM/diagnosis of high-risk MDS. Overall, this case demonstrates successful treatment of both hematologic malignancies at a lower dose of VEN than previously shown to be efficacious in t(11; 14) MM.