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Hematology. American Society of... Dec 2023Hematopoietic cell transplantation (HCT) can cure blood dyscrasias and reduce the risk of hematologic cancers in patients with inherited bone marrow failure syndromes...
Hematopoietic cell transplantation (HCT) can cure blood dyscrasias and reduce the risk of hematologic cancers in patients with inherited bone marrow failure syndromes (IBMFS). However, because of its high mortality rate, HCT is generally reserved until patients with IBMFS manifest life-threatening cytopenias or myeloid malignancy, at which point outcomes are poor. Screening tests that accurately predict transformation and enable timely intervention are lacking. These unknowns and risks limit the use of HCT in patients with IBMFS, sometimes until significant disease-related sequelae have occurred. A major goal for IBMFS is to reduce cellular therapy-related complications to the point that earlier intervention can be considered before significant transfusion exposure, occurrence of comorbidities, or malignant transformation. In recent decades, disease-specific allogeneic HCT trials have yielded significant improvements in outcomes in IBMFS conditions, including Fanconi anemia and dyskeratosis congenita. This is in large part due to marked reductions in conditioning intensity to address the increased sensitivity of these patients to cytotoxic chemotherapy and radiation. The success of these approaches may also indicate an ability to leverage intrinsic fitness defects of hematopoietic stem and progenitor cells across IBMFS disorders. Now with advances in tracking somatic genetic evolution in hematopoiesis and tailored minimal intensity conditioning regimens, this question arises: is it time for preventative HCT for IBMFS?
Topics: Humans; Anemia, Aplastic; Bone Marrow Diseases; Congenital Bone Marrow Failure Syndromes; Hemoglobinuria, Paroxysmal; Bone Marrow Failure Disorders; Pancytopenia; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning
PubMed: 38066900
DOI: 10.1182/hematology.2023000470 -
Annals of African Medicine 2023Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit...
BACKGROUND
Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit myelopoiesis and are major mediators of tissue damage. The primary goal of this study was to determine the IL-6 and IL-8 levels in children with AA, as well as their relationship to illness severity and immunosuppressive medication response.
MATERIALS AND METHODS
The IL-6 and IL-8 levels were tested in 50 children aged 3-18 years who had AA. As controls, 50 healthy age and sex matched individuals were used. A sandwich enzyme-linked immunosorbent assay kit (solid-phase) was used to measure IL-6 and IL-8 levels quantitatively. The concentrations of IL-6 and IL-8 in pg/mL were used to represent the results. Immunosuppressive medication was given to the patients in accordance with the British Committee for Standards in Haematology Guidelines 2009.
RESULTS
The patients' average age was 11.3 ± 3.7 years. Patients with AA had significantly higher IL-6 and IL-8 levels than controls (278.88 ± 216.03 vs. 4.51 ± 3.26; P < 0.001) and (120.28 ± 94.98 vs. 1.79 ± 0.78; P < 0.001), respectively. The IL-6 and IL-8 levels were also investigated with respect to AA severity, with statistically significant differences (P < 0.01) between different grading strata. Patients with very severe AA (VSAA) had the highest IL-6 levels (499.52 ± 66.19), followed by severe AA (SAA) (201.28 ± 157.77) and non-SAA (NSAA) (22.62 ± 14.63). For IL-8 levels, a similar trend (P < 0.01) was detected, with values of 209.81 ± 38.85, 92.12 ± 78.0, and 9.29 ± 10.68 for VSAA, SAA, and NSAA, respectively. After 6 months of immunosuppressive treatment (IST), mean levels of IL-6 and IL-8 in responders and nonresponders were again assessed. The mean IL-6 level in the responders' group (46.50 ± 45.41) was significantly lower, when compared to the nonresponders' group (145.76 ± 116.32) (P < 0.001). Similarly, the mean IL-8 level in the responder's group (33.57 ± 27.14) was significantly lower, compared to the nonresponder's group (97.49 ± 69.00) (P < 0.001).
CONCLUSIONS
Children with AA had higher IL-6 and IL-8 levels than normal age- and sex-matched controls. Increased levels were linked to the severity of the condition, suggesting that IL may have a role in AA. IL levels can be monitored in AA patients during IST, which can assist in predicting response to IST.
Topics: Child; Humans; Adolescent; Anemia, Aplastic; Interleukin-6; Interleukin-8; Treatment Outcome; Immunosuppressive Agents; Immunosuppression Therapy; Patient Acuity
PubMed: 38358144
DOI: 10.4103/aam.aam_106_22 -
Mikrobiyoloji Bulteni Oct 2023Malaria is a parasitic disease transmitted by infected female Anopheles mosquitoes. There are five species of Plasmodium species that can infect humans. Of these...
Malaria is a parasitic disease transmitted by infected female Anopheles mosquitoes. There are five species of Plasmodium species that can infect humans. Of these species, especially P.falciparum and P.vivax pose the greatest threat to human health. In the 2014 report of the World Health Organization, it was reported that there were no locally acquired cases of malaria in 16 countries including Türkiye. Malaria cases originating from outside the country and imported due to migration, travel and working abroad are reported as import cases. In this report, a case of non-imported malaria followed with a preliminary diagnosis of leukemia was presented. A 14-year-old female patient who was admitted to a health institution with complaints of high fever, headache, chills, nausea-vomiting, and diarrhea that had been going on for two weeks, was pre-diagnosed as leukemia and was referred to Manisa Celal Bayar University Faculty of Medicine, Hafsa Sultan Hospital, Department of Pediatric Hematology and after pancytopenia was detected in the complete blood count. The anamnesis of the patient revealed that she had no history of international travel and that she had been prescribed medications such as paracetamol, amoxicillin, and metoclopramide for flu-like complaints while working in the Southeastern Anatolia, Aegean, and Mediterranean Regions of Türkiye. Bone marrow aspiration was performed for the etiological examination of pancytopenia. Giemsa-stained blood smears, rapid diagnostics, and real-time quantative polymerase chain reaction (qRt-PCR) analyses were performed in the medical parasitology laboratory and malaria was suspected in both bone marrow and peripheral blood smears. P.vivax erythrocytic forms and gametocytes were present in abundance in smear preparations stained with Giemsa, and rapid diagnosis kit was positive for P.vivax. The strain was genotyped as P.vivax by qRt-PCR analysis. For the treatment of the patient, airalam (artemether + lumefantrine) tablets were provided with 2 x 4 daily posology for three days after the diagnosis, and primaquine was provided after one week of the diagnosis as 1 x 2 tablets (1 x 15 mg) for 14 days, and the patient was discharged without complications following the treatment regimen. The fight against malaria continues uninterruptedly since the establishment of the Republic of Türkiye. Tropical diseases, especially malaria, is of great importance for Türkiye due to numerous reasons such as its location in the subtropical region where Anopheles mosquitoes are capable of malaria transmission, it is situated at the crossroads on the migration routes between continents where human traffic is busy, there are many people who go abroad for work and most importantly rising temperatures due to climate change. For this reason, this case report is important to emphasize the importance of malaria for the country and to increase the awareness of clinicians and laboratories about malaria and the possibility of autochthonous malaria transmission in Türkiye.
Topics: Adolescent; Animals; Female; Humans; Leukemia; Malaria; Malaria, Vivax; Pancytopenia; Plasmodium; Travel
PubMed: 37885398
DOI: 10.5578/mb.20239958 -
BMJ Case Reports Aug 2023Pancytopenia due to systemic lupus erythematosus (SLE) is rarely reported, and among those reported, it is mostly due to immunologically mediated cell destruction....
Pancytopenia due to systemic lupus erythematosus (SLE) is rarely reported, and among those reported, it is mostly due to immunologically mediated cell destruction. Pancytopenia due to bone marrow fibrosis secondary to SLE is an extremely rare entity. Myelofibrosis secondary to SLE per se is reported only in 21 cases in the literature. Ours probably is the 22nd case report on SLE with myelofibrosis. Primary presentation of SLE with bleeding manifestation is also a rare phenomenon. Partial to complete regression of myelofibrosis is noted following treatment in secondary myelofibrosis caused by SLE. We report a case of a woman in her late 40s who presented to us with bleeding manifestations of petechial rash and menorrhagia, which on further evaluation showed pancytopenia due to myelofibrosis secondary to SLE. Our case underlines multiple features like primary bleeding manifestation and regression of myelofibrosis following treatment which is rarely reported in association with SLE.
Topics: Female; Humans; Primary Myelofibrosis; Pancytopenia; Lupus Erythematosus, Systemic; Menorrhagia
PubMed: 37591626
DOI: 10.1136/bcr-2023-255229 -
Revista Espanola de Enfermedades... Nov 2023This case reports illustrates a 44-year-old Caucasian male with ileal Crohn´s disease under combined immunosuppression that first presented with unspecific...
This case reports illustrates a 44-year-old Caucasian male with ileal Crohn´s disease under combined immunosuppression that first presented with unspecific constitutional symptoms, newly pancytopenia and elevated inflammatory markers. The infectious screening was negative except for an ileal abscess that resolved with conservative antibiotic therapy. Due to concerns for lymphoproliferative disease in a patient under anti-TNF and azathioprine, a myelogram was performed that ruled out dysplastic changes. After abscess resolution the symptoms relapsed with evening fever, nocturnal sudoresis and worsen pancytopenia. A more thorough work-up was performed with bone marrow and ileal biopsies that demonstrated numerous intra-and-extracellular leishmania amastigote forms, which confirmed the diagnosis of visceral leishmaniasis infiltrating the small bowel. The patient recovered after adequate treatment and withheld of immunosuppression during follow-up.
PubMed: 38031908
DOI: 10.17235/reed.2023.10097/2023 -
Cureus Aug 2023Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease...
Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLD found that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients, 64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LT needs among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population. Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.
PubMed: 37700968
DOI: 10.7759/cureus.43356 -
Frontiers in Immunology 2023Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often...
INTRODUCTION
Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often accompanied by nonspecific cutaneous, articular, neurological, and renal manifestations. Diagnosing cryoglobulinemia through biological testing can be time-consuming and sometimes yields negative results, making diagnosis challenging. There are also other potentially life-threatening complications that can significantly impact prognosis and delay urgent treatment, including digestive manifestations and heart failure.
CASE PRESENTATION
We report the case of a 60-year-old male patient with a medical history of rheumatoid arthritis. He was admitted to the Nephrology Department for investigation of necrotic vascular purpura, acute kidney injury, and pancytopenia. Laboratory tests revealed consumption of the C3 and C4 complement fractions and the presence of mixed-type III cryoglobulinemia. Despite the initiation of the treatment, the patient rapidly developed multiple severe organ failures, including renal, cardiac, respiratory, and finally digestive complications. Acute colic ischemia led to emergency surgery and the patient was transferred to the Intensive Care Unit. Despite surgical intervention and hemodynamic support, the patient experienced multi-visceral organ failure and died two hours after admission.
DISCUSSION
Mixed cryoglobulinemia vasculitis may result in rare cases of acute and life-threatening organ damage, such as cardiac or respiratory failure with pulmonary hemorrhage, gastrointestinal ischemia, and neurological disorders. These severe manifestations are associated with a poor prognosis and it is crucial to promptly initiate an aggressive therapeutic strategy.
Topics: Male; Humans; Middle Aged; Cryoglobulinemia; Vasculitis; Complement C4; Prognosis; Multiple Organ Failure; Ischemia
PubMed: 37901234
DOI: 10.3389/fimmu.2023.1271584 -
Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.Blood May 2024We report on the first-in-human clinical trial using chimeric antigen receptor (CAR) T-cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies...
We report on the first-in-human clinical trial using chimeric antigen receptor (CAR) T-cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies (clinicaltrials.gov NCT04136275). Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T-cells. CAR-37 T-cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4/5 patients. Tumor responses were observed in 4/5 patients, with 3 complete responses, 1 mixed response, and 1 patient whose disease progressed rapidly and with relative loss of CD37 expression. Three patients experienced prolonged and severe pancytopenia, and in two of these patients, efforts to ablate CAR-37 T-cells (which were engineered to co-express truncated EGFR) with cetuximab, were unsuccessful. Hematopoiesis was restored in these two patients following allogeneic hematopoietic stem cell transplantation. No other severe, non-hematopoietic toxicities occurred. We investigated the mechanisms of profound pancytopenia and did not observe activation of CAR-37 T-cells in response to hematopoietic stem cells in vitro or hematotoxicity in humanized models. Patients with pancytopenia had sustained high levels of IL-18, with low levels of IL-18 binding protein in their peripheral blood. IL-18 levels were significantly higher in CAR-37-treated patients relative to both cytopenic and non-cytopenic cohorts of CAR-19-treated cohorts of patients. In conclusion, CAR-37 T-cells exhibited anti-tumor activity, with significant CAR expansion and cytokine production. CAR-37 T-cells may be an effective therapy in hematologic malignancies as a bridge to hematopoietic stem cell transplant.
PubMed: 38781564
DOI: 10.1182/blood.2024024104 -
Ophthalmic Plastic and Reconstructive...Sweet's syndrome (acute febrile neutrophilic dermatosis) is an uncommon inflammatory condition most often associated with painful skin lesions of the head, neck, and...
Sweet's syndrome (acute febrile neutrophilic dermatosis) is an uncommon inflammatory condition most often associated with painful skin lesions of the head, neck, and upper extremities. To the authors' knowledge, this case report is the only published record of the necrotizing clinical variant of Sweet's syndrome in the periorbital space. This case follows a 91-year-old female who presented with generalized cutaneous eruptions of tender erythematous plaques, including a necrotic plaque of the left upper eyelid, and pancytopenia. A biopsy of an inner thigh lesion was consistent with Sweet's syndrome. Initially diagnosed with preseptal cellulitis, the patient experienced marked clinical improvement with corticosteroids. This, coupled with the histopathologic findings of her thigh biopsy and the absence of eyelid margins, led to the diagnosis of periorbital necrotizing Sweet's syndrome. Although cases of Sweet's syndrome in the periorbital region are rare, these diagnoses should not be overlooked and may be critical to patient care.
Topics: Humans; Female; Aged, 80 and over; Sweet Syndrome; Skin Diseases; Cellulitis; Face
PubMed: 37486325
DOI: 10.1097/IOP.0000000000002463 -
BMC Pediatrics Aug 2023Lysinuric protein intolerance is a rare inherited metabolic disease due to autosomal recessive mutations of the SLC7A7 gene. The affected patients commonly present with...
BACKGROUND
Lysinuric protein intolerance is a rare inherited metabolic disease due to autosomal recessive mutations of the SLC7A7 gene. The affected patients commonly present with protein-rich food intolerance, failure to thrive, hepatosplenomegaly, muscle hypotonia and lung involvement due to impaired intestinal absorption and excessive urinary excretion of dibasic amino acids. Presentation with splenomegaly and cytopenia without other features has not been reported. Here we report a Sri Lankan girl with lysinuric protein intolerance presenting with pancytopenia and splenomegaly mimicking acute leukaemia.
CASE PRESENTATION
Two years and six months old Sri Lankan girl presented with persistent pancytopenia following a viral illness. She was asymptomatic without vomiting, diarrhoea, abdominal pain or irritability. Physical examination revealed pallor and isolated firm splenomegaly of 2 cm. Growth parameters and other system examinations were normal. Full blood count revealed anaemia, leukopenia and thrombocytopenia. The blood picture showed a mixture of hypochromic microcytic and normochromic normocytic red cells with occasional pencil cells and macrocytes. Bone marrow examination was normal except for occasional megaloblasts; however, serum vitamin B12 and red blood cell folate were normal. The metabolic screen showed a high anion gap compensated metabolic acidosis, high lactate and ketosis. Genetic mutation analysis using whole exome sequencing revealed compound heterozygous variants of the SLC7A7 gene, confirming the diagnosis of lysinuric protein intolerance.
CONCLUSION
We report a child with lysinuric protein intolerance presenting with pancytopenia and splenomegaly without other disease features. This case report adds to the heterogenic presentations of lysinuric protein intolerance, which is considered a multifaceted disease.
Topics: Child; Female; Humans; Infant; Pancytopenia; Splenomegaly; Amino Acid Metabolism, Inborn Errors; Leukemia; Leukopenia; Thrombocytopenia; Amino Acid Transport System y+L
PubMed: 37528333
DOI: 10.1186/s12887-023-04207-7