Pancytopenia Due to Folate Deficiency.

We found the article on "The Digital Technology in Clinical Medicine: From Calculators to ChatGPT" interesting.1 According to Kulkarni et al., humanity has witnesses four important social system changes, starting with the primitive huntersgatherers and progressing to horticultural, agricultural, industrial, and the current fifth, which is based on digital information technology and has altered the way we present, recognize, and utilize different factors of production. In clinical medicine, digital technology has advanced significantly since the days of computations. According to Kulkarni et al., we have to benefit from these advancements as we all improve the lives of our patients while being cautious not to overturn the doctor-patient relationship. If technology, clinical expertise, and humanistic values are properly balanced, Kulkarni et al. concluded that the future is quite glorious.1 Regulatory organizations are pushing for improvements through clinical trials as a result of recognition of the expanding influence of digital technology in healthcare delivery. The "World Health Organizations Guidelines for Digital Interventions" and the "Food and Drug Administration's Digital Health Center of Excellence" are only two of the projects that are currently being highlighted in the study as efforts to analyze and implement digital health services.

[Two cases of cytopenia associated with multiple malformations]. / 血细胞减少伴多发畸形2例.

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.

Pancytopenia following adjuvant therapy with interferon-gamma in a patient with disseminated nocardiosis.

A patient with disseminated nocardiosis developed pancytopenia after treatment with recombinant interferon-gamma (IFN-γ). While no previous clinical reports link pancytopenia to IFN-γ, our observations align with basic research on myelosuppressive effects of IFN-γ. Adjunctive IFN-γ may improve standard nocardiosis therapy, but vigilant monitoring of its hematologic effects is necessary.

Donor-derived stem cell infusion for sustained pancytopenia after CD19 CAR-T therapy for relapsed patients post allogeneic stem cell transplantation.

OBJECTIVES: To investigate the effectiveness of donor-derived chimeric antigen receptor T (CAR-T) cells in the treatment of relapsed cases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and whether donor-derived peripheral blood stem cells (PBSCs) have a therapeutic effect on pancytopenia after CAR-T cell therapy. METHODS: We analyzed data from five adults with B-cell acute lymphoblastic leukemia (ALL) who had relapse after allo-HSCT and received donor-derived CAR-T cell therapy and donor-derived PBSCs to promote hematopoietic recovery. RESULTS: All patients had negative minimal residual disease after CAR-T therapy, grade 1-2 cytokine release syndrome, and developed grade 4 hematologic toxicity. During the pancytopenia stage after CAR-T cell therapy, donor-derived PBSCs were transfused without graft-versus-host disease (GVHD) prophylaxis. Four patients had grade I-II acute GVHD (aGVHD). After corticosteroid treatment, aGVHD resolved and hematopoiesis was restored. Although steroids in combination with etanercept and ruxolitinib relieved symptoms in one patient with grade IV aGVHD, complete hematopoietic recovery was not achieved, and the patient died due to severe infection. CONCLUSIONS: Donor-derived CAR-T cell therapy is safe and effective in patients with relapsed/refractory ALL after allo-HSCT. Donor-derived PBSCs infusion could achieve hematopoietic recovery with controllable aGVHD in patients with persistent pancytopenia.

Pancytopenia related to acquired sea-blue histiocytosis during chronic parenteral nutrition.

Bone marrow smear showing histiocytes (black arrow) containing sea blue granules stained with May-Grünwald Giemsa.

Massive Splenomegaly with Pancytopenia in an Adult: Gaucher's Disease.

INTRODUCTION: Gaucher's disease (GD) is a rare lysosomal storage disease. It is characterized by the deposition of glucocerebroside in cells of the macrophage-monocyte system. GD presents a broad clinical expression, including hematologic abnormalities (such as pancytopenia), massive hepatosplenomegaly, diffuse infiltrative pulmonary disease, renal involvement in the form of nephropathy and glomerulonephritis, skeletal involvement in the form of bone pain, bony infarct, osteopenia, and pathological fracture. Based on the presence or absence of neurologic involvement, it is differentiated into type 1, type 2, and type 3. Gaucher's disease type 1 is the most common form, having the nonneuropathic form and carrying autosomal recessive traits. Gaucher's disease affects all racial and ethnic groups, while type 1 GD is most prevalent among Ashkenazi Jews. CASE PRESENTATION: A 20-year-old female was admitted to the medicine department with complaints of generalized weakness and easy fatigability, menorrhagia, and a dragging sensation in the abdomen. On clinical evaluation, she had bone marrow failure syndrome features along with massive splenomegaly. Later, she was confirmed with Gaucher disease type 1 disease by clinical and investigation (low ß-glucosidase level) evaluation. CONCLUSION: This case emphasizes keeping a differential diagnosis of glycogen storage disorder while evaluating a case of unexplained pancytopenia with massive splenomegaly in adulthood for an extended period. Currently, enzyme replacement therapy and substrate reduction therapy are the mainstay therapeutic options for GD.

[Pancytopenia associated to acute myeloid leukemia: a case report of aleukemic leukemia]. / Pancitopenia asociada a leucemia mieloide aguda: reporte de un caso de leucemia aleucémica.

Background: Acute myeloid leukemia (AML) is characterized by the presence of ≥ 20% myeloblasts in peripheral blood or bone marrow, as well as specific cytogenetic alterations. It can appear as a de novo disease or be associated with other hematologic diseases, which is why the clinical presentation is heterogeneous. Pancytopenia as a manifestation of aleukemic leukemia is a rare entity. Here, we described a case of AML that presented with pancytopenia as the only manifestation in a secondary care center. Clinical case: 72-year-old man, hospitalized due to pancytopenia, with no history of hematological diseases, asymptomatic, without hepatosplenomegaly or bleeding. Flow cytometry revealed pancytopenia without blasts in peripheral blood. Secondary causes of pancytopenia as infections, splenomegaly and nutritional deficiencies where ruled out. Bone marrow aspirate showed infiltration by 45% of myeloblasts and myelodysplasia. Immunophenotype was compatible with AML. Patient was sent to the Hematology Department at Centro Médico Nacional Siglo XXI (21st Century National Medical Center) to start chemotherapy. Conclusions: AML that is presented as pancytopenia should be considered in the evaluation of marrow failure syndrome. In the context of our hospital, morphological findings remains an essential tool for early diagnosis, since more refined studies such as immunophenotyping and cytogenetic testing are unreachable in a timely manner.

Introducción: La leucemia mieloide aguda (LMA) se caracteriza por presentar ≥ 20% de mieloblastos en sangre periférica o médula ósea, así como alteraciones citogenéticas específicas. Surge como enfermedad de novo o asociada a trastornos hematológicos, por lo que la presentación clínica es heterogénea. La presentación como pancitopenia (leucemia aleucémica) es rara. El objetivo de este trabajo es presentar un caso de LMA que cursó con pancitopenia como única manifestación clínica en un hospital de segundo nivel de atención. Caso clínico: hombre de 72 años, hospitalizado por hallazgo de pancitopenia, sin historial de enfermedades hematológicas, asintomático, sin adenomegalias ni hemorragia. La citometría hemática documentó pancitopenia sin blastos en sangre periférica. Se descartaron causas secundarias como infección, esplenomegalia y deficiencias nutricionales. En el aspirado de médula ósea se observó 45% de mieloblastos y mielodisplasia. El inmunofenotipo fue compatible con LMA. El paciente fue referido a Hematología del Centro Médico Nacional Siglo XXI para iniciar quimioterapia. Conclusiones: la LMA que se presenta como pancitopenia debe ser tomada en cuenta en el protocolo diagnóstico de síndrome de falla medular. En el contexto de nuestro hospital, la morfología hematológica sigue siendo una herramienta indispensable para el diagnóstico temprano de este tipo de enfermedades, ya que estudios más sofisticados, como el inmunofenotipo y la citogenética, no se encuentran disponibles de forma oportuna.

Lysinuric protein intolerance presenting as pancytopenia and splenomegaly mimicking acute leukaemia: a case report.

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.

A novel mutation in MECOM affects MPL regulation in vitro and results in thrombocytopenia and bone marrow failure.

MECOM-associated syndrome (MECOM-AS) is a rare disease characterized by amegakaryocytic thrombocytopenia, progressive bone marrow failure, pancytopenia and radioulnar synostosis with high penetrance. The clinical phenotype may also include finger malformations, cardiac and renal alterations, hearing loss, B-cell deficiency and predisposition to infections. The syndrome, usually diagnosed in the neonatal period because of severe thrombocytopenia, is caused by mutations in the MECOM gene, encoding for the transcription factor EVI1. The mechanism linking the alteration of EVI1 function and thrombocytopenia is poorly understood. In a paediatric patient affected by severe thrombocytopenia, we identified a novel variant of the MECOM gene (p.P634L), whose effect was tested on pAP-1 enhancer element and promoters of targeted genes showing that the mutation impairs the repressive activity of the transcription factor. Moreover, we demonstrated that EVI1 controls the transcriptional regulation of MPL, a gene whose mutations are responsible for congenital amegakaryocytic thrombocytopenia (CAMT), potentially explaining the partial overlap between MECOM-AS and CAMT.

Reversible myelofibrosis secondary to systemic lupus erythematosus.

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.

Persistent Pancytopenia as a Long-COVID Manifestation in a Patient with Adult-Onset Still's Disease: A Case Report.

Background: Adult-onset Still's disease (AOSD) is a rare rheumatic inflammatory condition with an extremely heterogeneous clinical presentation and systemic impairment. Uncommon manifestations may be challenging to manage, especially in patients with previous severe acute SARS-CoV-2 infection. For the first time, we report the case of a patient affected by refractory AOSD presenting with severe pancytopenia as a long-COVID manifestation. The purpose of this case report is to illustrate the clinical presentation, diagnostic and therapeutic management of this unusual manifestation. Moreover, we examine the mechanisms that are potentially responsible for the onset of the pancytopenia observed in our patient. Case presentation: We describe the case of a 40-year-old male who presented with a history of fever for 2 years, arthralgia, maculopapular salmon-pink rash and a previous SARS-CoV-2 infection which required admission to intensive care. The patient's laboratory results revealed elevated inflammatory markers levels (erythrocyte sedimentation rate and C-reactive protein), hyperferritinemia and severe pancytopenia that needed multiple transfusions. A diagnosis of AOSD was made based on clinical and laboratory presentation after excluding neoplastic, infectious and other rheumatic diseases. The previous empirical treatment was not adequate to control the condition; therefore, treatment with high-dose steroids, canakinumab and epoetin alfa was started and led to the resolution of the man's symptoms and a reduction in inflammatory marker levels, whereas blood cell count remained stable without a need for further blood transfusions. The patient is currently under rheumatologic and hematologic follow-up every month. Conclusions: Neither AOSD nor SARS-CoV-2 infection usually manifests with pancytopenia, except in hemophagocytic syndrome or immunodeficient patients, respectively. Identifying the underlying etiology of pancytopenia is mandatory to establish a prompt treatment that generally resolves the disorder. However, in our case, all common causes of pancytopenia were excluded, suggesting a potential manifestation of the long-COVID syndrome. Despite the resolution of the acute infection and the remarkable treatment of AOSD, pancytopenia persists. Herein, we propose for refractory AOSD patients with previous SARS-CoV-2 infection a novel approach to the diagnosis and treatment of pancytopenia.

Genomic and computational analysis of four novel variants of MPL gene in Congenital Amegakaryocytic Thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, genetic, autosomal recessive disorder characterized by severe thrombocytopenia, due to inefficient bone marrow megakaryopoiesis eventually leading to aplasia. Majority of the cases are due to homozygous or compound heterozygous mutations in MPL gene encoding for thrombopoietin (THPO) receptor protein. CAMT can be diagnosed at early phase of life, with major complication of transfusion dependency and hematopoietic transplantation as only curative treatment. We have investigated the sequence variations in MPL gene of 7 bone marrow failure (BMF) subjects, who presented with clinically diverse phenotypes, through next generation sequencing (NGS). Plasma THPO levels were estimated using ELISA. Insilico sequence and structure-based analyses were performed to understand the structural and functional implications of mutations, identified through NGS. We studied 7 CAMT subjects suspected of BMF, who presented with severe thrombocytopenia followed by pancytopenia, bleeding manifestation and physical anomalies. The plasma THPO levels were significantly elevated (p<0.05) in all the cases. Molecular analysis by NGS identified 9 genomic mutations in MPL gene. These included 7 non-synonymous substitution, 1 nonsense substitution and 1 in-del mutations, of which 4 are novel mutations. Insilico analysis predicted damaging effects on THPO-R and its reduced affinity for THPO for all the identified mutations. CAMT is a rare disorder with diverse clinical phenotypes and diagnosis is challenging. The elevated plasma THPO levels should be considered for the primary diagnosis and prognosis of the disease. However, molecular analysis of MPL gene is important for the diagnosis and management of the disease through genetic counselling. Though the cytokines, THPO-R agonist are used for the treatment of CAMT, HSCT is the only curative therapy.

Fever, Pancytopenia, and Tender Erythematous Plaques in a Patient With Multiple Myeloma.

A man in his late 60s who had received the first cycle of a chemotherapeutic regimen of ixazomib, lenalidomide, and dexamethasone for multiple myeloma presented to the dermatologic clinic with a 10-day history of fever and tender lesions on the neck and trunk. What is your diagnosis?

Complex considerations - Fever and pancytopenia after solid organ transplantation.

This case describes a 42-year-old man who underwent kidney transplantation and developed fevers, pancytopenia, and elevated liver function tests starting on post-operative day 9. An extensive microbiologic and molecular workup was performed, ultimately leading to a diagnosis of donor-derived toxoplasmosis with associated hemophagocytic lymphohistiocytosis in the recipient. This case highlights the potential for post-transplant toxoplasmosis in high-risk mismatch (D+/R-) recipients, as well as the role of Toxoplasma-targeted prophylaxis in such patients.