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Medicine Mar 2024Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering...
Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ± 11.3 mL/min/1.73 m2; SU: 8.6 ± 2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ± 19.0 mL/min/1.73 m2; SU: 9.5 ± 1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ± 9.9 vs 52.3 ± 14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ± 8.1 [CKD] vs 14.1 ± 7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ± 5.8 vs 19.3 ± 4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ± 20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ± 15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.
Topics: Humans; Female; Gout; Uric Acid; Methotrexate; Retrospective Studies; Treatment Outcome; Symptom Flare Up; Polyethylene Glycols; Gout Suppressants; Renal Insufficiency, Chronic; Urate Oxidase
PubMed: 38457582
DOI: 10.1097/MD.0000000000037424 -
European Journal of Case Reports in... 2024During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown...
INTRODUCTION
During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma.
CASE DESCRIPTION
A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal.
CONCLUSIONS
This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia.
LEARNING POINTS
Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.
PubMed: 38455694
DOI: 10.12890/2024_004339 -
Aplastic anemia secondary to adjuvant Osimertinib therapy: a case report and a review of literature.Frontiers in Oncology 2024Aplastic anemia is a rare hematological disorder characterized by suppressed hematopoiesis and pancytopenia. Although several drugs have been associated with aplastic...
Aplastic anemia is a rare hematological disorder characterized by suppressed hematopoiesis and pancytopenia. Although several drugs have been associated with aplastic anemia, its occurrence in response to Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is extremely rare. We present a case report of a 63-year-old patient with locally advanced non-small cell lung cancer (NSCLC) who developed aplastic anemia following adjuvant treatment with Osimertinib. Extensive investigations ruled out infectious etiology, and the absence of bone marrow involvement or other identifiable causes suggested a drug-induced etiology, specifically Osimertinib. This case report emphasizes the importance of recognizing this adverse event and considering it as a potential complication of Osimertinib therapy. Vigilant monitoring and prompt management are essential for optimizing patient outcomes. Further studies are needed to better understand the risk factors, underlying mechanisms, and management strategies for Osimertinib-induced aplastic anemia in the adjuvant settings.
PubMed: 38454933
DOI: 10.3389/fonc.2024.1275275 -
Indian Journal of Pathology &... Feb 2024Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its...
Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its rapidly fatal course, it warrants a timely and correct diagnosis. We present a case of a 44-year male who came with a short history of fever, generalised weakness, revealed pancytopenia with occasional circulating blast in the peripheral blood smear. Bone marrow aspirate was dry tap,biopsy revealed panmyelosis with myelofibrosis with increased (22%) blasts. Flowcytometric immunophenotyping, cytogenetics and molecular tests were undertaken. Together with clinical details, immunophenotypic profile, cytogenetics and molecular studies, the diagnosis of Acute panmyelosis with myelofibrosis was made and managed accordingly. 32 The WHO 2017 describes APMF as an acute panmyeloid proliferation with increased blasts (≥20% in the bone marrow or peripheral blood) and accompanying marrow fibrosis. APMF is rare with poor prognosis thus, must be differentiated especially from Acute megakaryoblastic leukemia to arrive at the correct diagnosis which will help reduce/prevent the early mortality by providing timely chemotherapy followed by upfront hemopoietic stem cell transplantation.
PubMed: 38427772
DOI: 10.4103/ijpm.ijpm_391_23 -
Cureus Jan 2024Myelodysplastic syndrome (MDS) is characterized by failure to initiate hematopoiesis or impaired maturation of cells, often presenting with pancytopenias with or without...
Myelodysplastic syndrome (MDS) is characterized by failure to initiate hematopoiesis or impaired maturation of cells, often presenting with pancytopenias with or without associated fatigue, infections, or inappropriate bleeding and bruising. Karyotype analyses of MDS patients commonly show deletion of the q arm of chromosome 7, suggesting loss of this region is likely implicated in the insufficient hematopoiesis seen in MDS. The predisposition to deletion of 7q is commonly inherited, with clinical presentation in early childhood associated with pancytopenia or hematological malignancy. In this case, we present a 66-year-old female who was incidentally found to be pancytopenic in the emergency department while being evaluated for dyspnea, with a bone marrow biopsy later confirming a diagnosis of MDS with monosomy 7. Sporadic loss of 7q can occur at any stage in life without any family history of hematological disease. Our patient has no known personal or family history of MDS, with normal blood counts during hospitalization three years prior, suggesting de novo loss of 7q occurring at greater than 60 years of age.
PubMed: 38420066
DOI: 10.7759/cureus.53159 -
Journal of Ayub Medical College,... 2023Aplastic anaemia is a rare bone marrow failure syndrome and is defined by pancytopenia associated with a hypo-cellular bone marrow with no increase in reticulin and the...
BACKGROUND
Aplastic anaemia is a rare bone marrow failure syndrome and is defined by pancytopenia associated with a hypo-cellular bone marrow with no increase in reticulin and the absence of any abnormal infiltrate. The objective of the study was to determine the frequency of Aldehyde Dehydrogenase type 2 (ALDH2) deficiency in patients with Aplastic Anaemia and investigate its correlation with patient and disease characteristics. It was a descriptive cross-sectional study conducted at Armed Forces Bone Marrow Transplant Centre Rawalpindi from 01-08-2022-01-02-2023, over 6 months.
METHODS
A total of 56 patients who were diagnosed with aplastic anaemia during this period, fulfilling inclusion criteria were enrolled. Patients were genotyped as GG (homozygous) and GA (heterozygous). GG had normal ALDH2, while GA were patients with ALDH2 deficiency. Data was collected on the patient's demographics, type and severity of anaemia, type of hematopoietic stem cell transplant (HSCT) and frequency of ALDH2 deficiency. Results were analyzed for ALDH2 deficiency and its correlation with patient and disease characteristics was investigated.
RESULTS
A total of 56 patients were included in the study. The median age of the patients was 28 years (20-39). According to the type of aplastic anaemia, 2 (3.6%) had Fanconi anaemia and 54 (96.4%) had acquired aplastic anaemia. In our study, 18 (32.1%) patients had undergone HSCT while the remaining 38 (67.9%) could not undergo HSCT. The frequency of the presence of ALDH2 deficiency was 2 (3.6%). There was no statistically significant correlation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant.
CONCLUSIONS
We concluded from our study the frequency of ALDH2 was rare in patients with aplastic anaemia. There was no statistically significant correlation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant.
Topics: Adult; Humans; Young Adult; Aldehyde Dehydrogenase, Mitochondrial; Anemia, Aplastic; Cross-Sectional Studies; Genotype; Pakistan
PubMed: 38404093
DOI: 10.55519/JAMC-03-12025 -
Life (Basel, Switzerland) Jan 2024Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it...
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, to some extent, a process of exclusion. AOSD has life-threating complications ranging from asymptomatic to severe, such as macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with cytokine storm production and monocyte/macrophage overactivation and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. For the treatment of MAS-HLH, the Histiocyte Society currently suggests high-dose corticosteroids, with the possible addition of cyclosporine A, anti-interleukin (IL)-1, or IL-6 biological drugs; the inclusion of etoposide is recommended for the most severe conditions. In all cases, a multidisciplinary collaboration involving the resources and expertise of several specialists (e.g., rheumatologist, infectiologist, critical care medicine specialist) is advised. Herein, we provide a detailed description of the clinical case of a previously healthy young woman in which MAS developed as a dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge; the condition was finally resolved by applying the HLH-94 protocol (i.e., etoposide in combination with dexamethasone).
PubMed: 38398704
DOI: 10.3390/life14020195 -
Pathogens (Basel, Switzerland) Jan 2024Shortly after the establishment of African swine fever virus (ASFV) genotype II in 2007, cases of acute fatal infection were observed. However, after several years of...
Shortly after the establishment of African swine fever virus (ASFV) genotype II in 2007, cases of acute fatal infection were observed. However, after several years of circulation in the Eurasian region, the clinical signs of the disease changed. Currently, this disease can occur acutely, subclinically, chronically, or asymptomatically. Cases of the complete recovery of infected pigs, and the disappearance of ASFV from their tissues and secretions have been described. This form of the disease first appeared in Armenia at the end of 2011. This virus was described and identified as the Dilijan2011IMB strain. The goal of our research was to study the main features of clinical, pathological, immunological, virological, and genetic parameters involved in the development of new forms of African swine fever (ASF). Chronic ASF was characterized with low titers of the virus and a decrease in the intensity of hemadsorption. Additionally, a reduced intensity in clinical symptoms and pathoanatomical results was noted. The absolute, but not the relative number of immune cells changes; the neutropenia (in bone marrow and spleen), lymphopenia (in bone marrow), lymphocytosis (only in spleen), lymphoid cell depletion (in bone marrow), and pancytopenia (in bone marrow) observed in the chronic form of ASF were less pronounced compared to in the acute form. When comparing the late stage of chronic ASF to the acute form, the key cytological indicators in the spleen, lymph nodes, and blood were less severe in the chronic stage. Bone marrow failure in the chronic form, expressed in a pronounced decrease in all cell types, generally coincided with the data in the acute form of ASF. The same data were obtained after assessing serum TNF-alpha levels. Thus, we can conclude that the chronic form of ASF occurs due to a less pronounced immune response, as well as a decrease in virus titers in the blood and tissues of infected pigs.
PubMed: 38392868
DOI: 10.3390/pathogens13020130 -
Indian Journal of Pathology &... Apr 2024Hemophagocytic lymphohistiocytosis (HLH) is a severe and frequently underdiagnosed disorder of systemic immune dysregulation resulting in hypercytokinemia and...
Hemophagocytic lymphohistiocytosis (HLH) is a severe and frequently underdiagnosed disorder of systemic immune dysregulation resulting in hypercytokinemia and histologically evident hemophagocytosis, We report a case of a 34-year-old man who presented with breathlessness, generalized weakness, and fever of unknown origin with pancytopenia. Clinically the patient was admitted for febrile illness, and treated symptomatically but his general condition worsened leading to death within 21 hours of admission. A complete autopsy was performed. The deceased had a significant past history of repeated episodes of fever, weight loss, and axillary lymphadenopathy over a period of 8 months with multiple hospital admissions. He was also diagnosed with enteric fever (Widal test and Typhi IgM positive) at the start of these episodes. Hemogram during this period revealed persistent pancytopenia. Serum ferritin, serum triglycerides, and liver function tests were consistently deranged. Investigations for the etiology of fever and blood cultures were negative while the bone marrow aspirate revealed a normocellular marrow. CT abdomen-pelvis showed mild hepatomegaly with enlarged retroperitoneal lymph nodes. Infective endocarditis, lymphoma, and bronchopneumonia were being considered the clinical diagnoses. The significant autopsy findings were hepatosplenomegaly with retroperitoneal lymphadenopathy and multiple gastric ulcers. On microscopy, the liver, spleen, bone marrow, and lymph nodes showed characteristic hemophagocytosis. Post-mortem histopathological examination clinched the diagnosis of HLH and fulfilled six out of eight diagnostic criteria of the HLH-2004 protocol. We discuss the clinical course and diagnosis of this unique case and strive to create awareness about secondary HLH induced by common diseases, such as enteric fever.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Male; Adult; Autopsy; Typhoid Fever; Fatal Outcome; Bone Marrow; Lymph Nodes; Liver; Spleen; Hepatomegaly
PubMed: 38391303
DOI: 10.4103/ijpm.ijpm_162_22 -
Respirology Case Reports Feb 2024In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis....
Steroid reduction-resistant pulmonary involvement with Sweet's syndrome suspected of being vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome: A case report.
In cases of Sweet's syndrome with pulmonary involvement, fever of unknown origin, and macrocytic anaemia, VEXAS syndrome can be considered in the differential diagnosis. A 67-year-old man who was taking prednisolone for a fever of unknown origin and Sweet's syndrome was referred to us because of an abnormal chest shadow. Computed tomography revealed a nonfibrotic hypersensitivity pneumonitis-like opacity, and blood test results indicated macrocytic anaemia. His pulmonary symptoms spontaneously improved but again exacerbated approximately 1 month later. Methylprednisolone pulse therapy improved his condition, but he had recurring fever flare and pulmonary involvement post-treatment. A peripheral blood gene test planned at a specialized institution was not performed, making the diagnosis difficult. We attempted careful tapering of methylprednisolone, but his macrocytic anaemia led to pancytopenia and he unfortunately died of sepsis due to neutropenia.
PubMed: 38384745
DOI: 10.1002/rcr2.1288