A Curious Case of Autoimmunity, Pancytopenia, and Disseminated Intravascular Coagulation.

HISTORY AND EXAMINATION: A 21-year-old female patient presented to us with severe low back pain for 4 months. On examination, patient was afebrile, with severe pallor, and tenderness in both sacroiliac (SI) joints. Patient was being admitted and evaluated, and during the course of evaluation, developed severe headache, which was severe in intensity and associated with nausea and projectile vomiting. Initial investigations: An X-ray of the bilateral SI joints revealed inflammation, and the antinuclear antibody (ANA) turned out to be 4+ with pancytopenia and raised lactate dehydrogenase (LDH), but the liver function tests were normal. Rest of the rheumatological profile was unremarkable. During the course of the evaluation, she developed a severe headache, which, on imaging, showed presence of cerebral edema with chronic subdural hematoma, and a concomitant coagulopathy workup revealed evidence of disseminated intravascular coagulation (DIC). DISCUSSION: Taking the whole picture into consideration, a malignant process in the body was suspected, and serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) were sent, all of which were raised. Validating the clinical clue was the bone marrow biopsy done for pancytopenia, which revealed malignant epithelial infiltration. A contrast-enhanced computed tomography (CECT) thorax and whole abdomen were done to find out the primary, which showed a neoplastic mass at the gastroesophageal junction along with bony metastases in the vertebrae and left adrenal. Tissue from the primary lesion was taken for histopathological examination (HPE) through upper gastrointestinal endoscopy. Although HPE revealed grade III poorly differentiated stomach adenocarcinoma, the patient had succumbed to the disease process by the time the diagnosis came to light. CONCLUSION: In short, this case perfectly illustrates how solid organ malignancies might be a mimicker of multisystem disorders, thereby delaying diagnosis and worsening the prognosis even further.

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.

Management of granulomatosis with polyangiitis complicated by intestinal perforation and pancytopenia: a case report and literature review.

Granulomatosis with polyangiitis is a systemic vasculitis. While the classic triad typically comprises otorhinolaryngologic, pulmonary, and renal manifestations, it is essential to recognize that granulomatosis with polyangiitis can affect any organ. Furthermore, reports have documented less common sites of involvement, such as the gastrointestinal tract. In this case-based review, we focus on a case of granulomatosis with polyangiitis presenting with intestinal perforation and the added challenge of concurrent pancytopenia.A 25-year-old female was diagnosed with granulomatosis with polyangiitis, with her clinical course progressing from joint pain to severe multi-organ involvement, including gastrointestinal complications. Treatment challenges emerged with the development of pancytopenia. While this may not directly result from granulomatosis with polyangiitis, it introduced an additional layer of complexity and delayed the induction of remission with immunosuppressants. Despite initial stabilization, an unexpected jejunal perforation occurred, requiring surgical intervention and subsequent postoperative care. The case underscores the complex nature of granulomatosis with polyangiitis and its potential complications. A literature search yielded discrete relevant cases in the context of our patient's intricate presentation, which has been summarized.We highlight the complexities in diagnosing and managing granulomatosis with polyangiitis-related complications, especially in uncommon presentations, and emphasize the importance of a personalized approach to patient care in these circumstances.

The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance.

ABSTRACT: Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified patients with CCUS by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs 44.8%, P = .002) but had higher median bone marrow blast percentages. After a median follow-up of 2.2 years, t-CCUS had significantly shorter progression-free survival (PFS, 1.8 vs 6.3 years; hazard ratio [HR], 2.1; P = .007) and median overall survival (OS; 3.6 years vs not reached; HR, 2.3; P = .007) compared with CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

[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.

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.