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Cureus May 2024The hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is a syndrome with apoptosis deficiency that results in the impairment of a regulatory...
The hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is a syndrome with apoptosis deficiency that results in the impairment of a regulatory pathway with consequent immune and inflammatory responses. Fever, cytopenias, splenomegaly, and hemophagocytosis are cardinal signs. It may be familial or secondary to infection, autoimmunity, or neoplasia. Impaired natural killer (NK)-cell cytotoxicity is the hallmark of HLH. All genetic defects in familial HLH are related to granule-dependent cytotoxicity. The authors present a 50-year-old black female patient with a history of drepanocytosis who attended the emergency department due to fever, asthenia, lethargy, and hypogastric pain. Her laboratory workup on admission revealed severe pancytopenia. She was ultimately diagnosed with HLH due to sepsis of urinary origin, with a fatal outcome. HLH is a rare and life-threatening syndrome. The delay in its diagnosis due to the variability of the clinical and laboratory findings constitutes the main obstacle to a successful prognosis, as illustrated in this case report.
PubMed: 38910771
DOI: 10.7759/cureus.61015 -
Cureus May 2024Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms....
Vitamin B12 deficiency is a common condition that is often asymptomatic, though in severe cases may cause megaloblastic anemia and even neurologic symptoms. Occasionally, the clinical presentation can include pancytopenia and thus mimic a more concerning myelodysplastic syndrome (MDS) until corrected by B12 supplementation. In this unusual case, we present a patient with B12 deficiency who presents with severe macrocytic anemia, neutropenia, lymphocytosis, and a bone marrow morphology consistent with MDS.
PubMed: 38910768
DOI: 10.7759/cureus.60837 -
Cureus May 2024The development of Hodgkin's lymphoma (HL) is a known complication in patients with human immunodeficiency virus (HIV) infection. Extranodal involvement, specifically...
The development of Hodgkin's lymphoma (HL) is a known complication in patients with human immunodeficiency virus (HIV) infection. Extranodal involvement, specifically primary bone marrow Hodgkin's lymphoma (PBMHL) is a rare manifestation that has been reported in HIV-positive patients and may represent a distinct entity from HIV-associated HL. We present a case of PBMHL presenting with hemophagocytic lymphohistiocytosis (HLH) in an HIV-positive patient. The 55-year-old male with HIV/AIDS presented with abdominal pain, diarrhea, and fever, leading to hospital admission. Despite initial treatment, he deteriorated, prompting re-admission and investigation revealing pancytopenia and elevated inflammatory markers, suggestive of HLH. Subsequent bone marrow biopsy unexpectedly revealed PBMHL. Treatment with HLH-directed therapy and the HLH-94 protocol resulted in significant clinical improvement. This case underscores the importance of recognizing atypical lymphoproliferative presentations in HIV/AIDS patients and the need for interdisciplinary collaboration in complex cases.
PubMed: 38910743
DOI: 10.7759/cureus.60864 -
Cureus May 2024Rhupus syndrome is an autoimmune disorder that combines the symptoms of lupus and rheumatoid arthritis. It is a rare condition that affects the connective tissues of the...
Rhupus syndrome is an autoimmune disorder that combines the symptoms of lupus and rheumatoid arthritis. It is a rare condition that affects the connective tissues of the body such as the joints, muscles, and skin. The symptoms of rhupus syndrome can be similar to those of lupus, including joint pain, fatigue, and skin rashes. However, rhupus syndrome can also cause symptoms of rheumatoid arthritis, such as joint stiffness and swelling. Treatment for rhupus syndrome usually involves a combination of medications and lifestyle changes to manage symptoms and improve the overall quality of life. A 24-year-old female patient was referred by a local physician for evaluation of pancytopenia. Her history dates back to six months when she developed progressive fatigue, dyspnea on mild exertion, and polyarthralgia. Initial laboratory investigations revealed pancytopenia, positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Bone marrow examination confirmed the diagnosis of aplastic anemia. She was started on cyclosporine with an aim to maintain a trough level between 200 and 250 ng/mL. She responded well with hematological recovery in three to four months. This case highlighted the excellent response to cyclosporine hematologically and clinically in rhupus syndrome complicated with aplastic anemia. Further studies are required to establish the long-term efficacy of cyclosporine in this patient population.
PubMed: 38910697
DOI: 10.7759/cureus.60875 -
Virology Journal Jun 2024We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due...
We describe the case of a 57-year-old male with jaundice, abdominal distension and fatigue. He was diagnosed as chronic active Epstein-Barr virus infection (CAEBV) due to intermittent elevated liver enzymes, hepatosplenomegaly and pancytopenia, with persistent positive of EBV biomarkers in blood and also positive in liver tissue. The patient was reinfected by SARS-CoV-2 within 2 months companied with CAEBV. The patient's second infection with SARS-CoV-2 led to the aggravated liver dysfunction with pneumonia and re-admission. After receiving symptomatic treatment, the patient showed significantly improvement of symptoms with partially restoration of liver function. After discharge, the patient's health status continued to deteriorate and eventually died. The instances of SARS-CoV-2 co-infection with the original chronic virus are not uncommon, but the exact mechanism of EBV and SARS-CoV-2 coinfection and the relationship between them are still unclear. Since co-infection of SARS-CoV-2 with original chronic virus might affect each other and lead disease aggravated and complicated, it is necessary to differentiate in the diagnosis of disease and it is important to be aware of the re-infection signs of SARS-CoV-2 in people with chronic virus infection diseases, as well as the risk of co-infection of SARS-CoV-2 with other viruses.
Topics: Humans; Male; COVID-19; Epstein-Barr Virus Infections; Middle Aged; Reinfection; Coinfection; SARS-CoV-2; Herpesvirus 4, Human; Chronic Disease; Fatal Outcome
PubMed: 38910238
DOI: 10.1186/s12985-024-02418-7 -
Journal of Clinical Oncology : Official... Jun 2024SHR-A1811 is an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase...
Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2-Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2-Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial.
PURPOSE
SHR-A1811 is an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload. We assessed the safety, tolerability, antitumor activity, and pharmacokinetics of SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors.
METHODS
This global, multi-center, first-in-human, phase I trial was conducted at 33 centers. Patients who had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies were enrolled. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg once every 3 weeks. The primary end points were dose-limiting toxicity, safety, and the recommended phase II dose.
RESULTS
From September 7, 2020, to February 27, 2023, 307 patients who had undergone a median of three (IQR, 2-5) previous treatment regimens in the metastatic setting received SHR-A1811 treatment. As of data cutoff (February 28, 2023), one patient from the 6.4 mg/kg group experienced dose-limiting toxicities (pancytopenia and colitis). The most common grade 3 or higher adverse events (AEs) included decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. Serious AEs and deaths occurred in 70 (22.8%) and 13 (4.2%) patients, respectively. SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer, and 45.9% (39/85 with evaluable tumor responses) of the 98 nonbreast tumors.
CONCLUSION
SHR-A1811 exhibited acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in heavily pretreated advanced solid tumors. The recommended phase II dose of 4.8 or 6.4 mg/kg was selected for various tumor types.
PubMed: 38900984
DOI: 10.1200/JCO.23.02044 -
Frontiers in Neurology 2024Patients with neuromyelitis optica spectrum disorder (NMOSD) coexisting with both Sjögren's syndrome (SS) and pancytopenia are exceptionally rare. There is no study on...
Patients with neuromyelitis optica spectrum disorder (NMOSD) coexisting with both Sjögren's syndrome (SS) and pancytopenia are exceptionally rare. There is no study on the treatment of such patients. We presented a case of AQP4-IgG seropositive refractory NMOSD patient combined with SS and pancytopenia with significant response to inebilizumab. In 2017 the 49-year-old female patient was diagnosed with SS and pancytopenia without any treatment. In August 2022, she had a sudden onset of lower limbs weakness, manifested as inability to walk, accompanied by urinary incontinence. After receiving methylprednisolone and cyclophosphamide, she regained the ability to walk. In February 2023, she suffered from weakness of both lower limbs again and paralyzed in bed, accompanied by retention of urine and stool, and loss of vision in both eyes. After receiving methylprednisolone and three plasmapheresis, the condition did not further worsen, but there was no remission. In March 2023, the patient was admitted to our hospital and was formally diagnosed with AQP4-IgG seropositive NMOSD combined with SS and pancytopenia. After receiving two 300 mg injections of inebilizumab, not only the symptoms of NMOSD improved significantly, but also the symptoms of concurrent SS and pancytopenia. In the cases of AQP4-IgG seropositive NMOSD who have recurrent episodes and are comorbid with other autoimmune disorders, inebilizumab may be a good choice.
PubMed: 38899058
DOI: 10.3389/fneur.2024.1371515 -
Blood Cells, Molecules & Diseases May 2024Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per...
Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
PubMed: 38889660
DOI: 10.1016/j.bcmd.2024.102860 -
Frontiers in Immunology 2024This study aims to discuss the clinical manifestations and treatment of Familial hemophagocytic lymphohistiocytosis (FHL) caused by a mutation in the UNC13D gene. (Review)
Review
OBJECTIVES
This study aims to discuss the clinical manifestations and treatment of Familial hemophagocytic lymphohistiocytosis (FHL) caused by a mutation in the UNC13D gene.
METHODS
A 6-year-old female child presented with unexplained febricity, splenomegaly, pancytopenia, hemophagocytic lymphohistiocytosis in bone marrow, decreased NK cell activity, soluble CD25 levels > 44000ng/ml. Genetic sequencing revealed a mutation in the UNC13D gene. Additionally, the patient experienced intermittent fever with seizures characterized by involuntary twitching of the left upper limb. Head magnetic resonance imaging (MRI) showed white matter lesions.
RESULTS
According to the HLH-2004 diagnostic criteria revised by the International Society of Histiocytosis the patient was diagnosed with FHL. Despite receiving HLH-2004 treatment, the disease relapsed. However, after a salvage allogeneic Hematopoietic Stem Cell Transplant (HSCT), febricity, abnormal blood cells, and neurological symptoms significantly improved.
CONCLUSIONS
Prompt performance of allogeneic HSCT is crucial upon diagnosis of FHL, especially when neurological involvement is present.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Hematopoietic Stem Cell Transplantation; Female; Child; Transplantation, Homologous; Mutation; Membrane Proteins; Treatment Outcome
PubMed: 38887297
DOI: 10.3389/fimmu.2024.1391074