Incidence of myelosuppression in AML is higher compared with that in ALL.

Acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) are two subtypes of acute leukemia. However, studies investigating the ability of complete blood count (CBC) parameters to distinguish between patients with AML and ALL remain scarce in the literature. The objective of the present study was to compare the parameters of CBC analysis between Chinese patients with AML and ALL and between patients with M3 AML and non-M3 AML. Prognostic factors for overall survival were also estimated, including sex, age, white blood cell count and hemoglobin. The present study included 147 patients, including children and adults, with newly diagnosed acute leukemia. Information on the age, sex, leukemia subtype, initial CBC results and clinical follow-up findings was recorded and compared between the indicated groups using statistical tests of Mann-Whitney U test and χ2 test. Leukopenia (white blood cell count <3.5x109/l), both leukopenia and anemia, both leukopenia and thrombocytopenia and pancytopenia were found to be significantly more frequent among patients with AML compared with that in patients with ALL (P=0.015, 0.016, 0.015 and 0.019, respectively). For patients with ALL, anemia was recognized as a predictor of a favorable outcome (Hazard ratio, 0.185; 95% CI, 0.046-0.747; P=0.018). These findings suggest that normal hematopoiesis is more frequently inhibited in patients with AML compared with that in patients with ALL. Patients with AL with peripheral blood findings indicative of leukopenia, pancytopenia, or both leukopenia and anemia or both leukopenia and thrombocytopenia are more likely to have AML.

Bleeding disorder in a Holstein calf comparable to bovine neonatal pancytopenia.

The clinical findings associated with a bleeding disorder, suspected to be an immune mediated pathogenesis comparable to bovine neonatal pancytopenia (BNP), in a 14-day-old Holstein calf are summarised. The clinical examination, clinical laboratory findings, treatment, postmortem findings and referral laboratory diagnostics are reported and discussed in relation to existing knowledge of bleeding disorders in cattle. Veterinary attention was required for a twin 14-day-old Holstein calf that was lethargic, weak and had pale mucous membranes. On clinical examination the calf was tachycardic had pale mucous membranes with petechial and ecchymotic haemorrhages on the ventral surface of the tongue, petechial haemorrhages on the vulval membranes and scleral haemorrhage. The calf received 1.1 L of whole blood from a donor cow to which the calf initially responded. The calf's health appeared to wax and wane over the following 19 days and despite further intervention, the calf died. A postmortem was carried out and samples were submitted to the state laboratory for cytological, histopathological, parasitological and serological examination. Although no exact aetiology was found, there is evidence to suggest that the bleeding disorder was immune-mediated, with a pathogenesis comparable to BNP. To the author's knowledge, this case report is the first peer-reviewed manuscript to describe the clinical presentation similar to BNP in an Australian Holstein calf.

A Rare Cause of Pancytopenia From Lepromatous Leprosy Diagnosed in Bone Marrow Aspiration: A Bolt From the Blue.

Hansen's disease is caused by Mycobacterium leprae. The clinical presentation of lepromatous leprosy is broad, affecting patients with reduced T-cell immune response and causing anergy. Usually, the patient presents with numerous red to brown nodules over the face and auricles and is diagnosed by skin biopsy. We hereby report an unusual case of a 40-year-old man who presented with altered sensorium and fever. Lepromatous leprosy was diagnosed initially in the bone marrow aspiration without any clinical suspicion or previous skin biopsy confirmation. Bone marrow infiltration by lepra bacilli is very rare, with only a few cases reported in the literature so far.

Clinical characteristics of megaloblastic anemia with pancytopenia.

OBJECTIVES: In this study, we aimed to explore the clinical characteristics of patients with megaloblastic anemia and pancytopenia. METHODS: Data on patient characteristics, laboratory examinations, clinical manifestations, and associated diseases were collected from Changzhou Hospital of Traditional Chinese Medicine. The participants were divided into two groups according to routine blood test results: megaloblastic anemia patients with pancytopenia (Group A) and megaloblastic anemia patients with simple anemia (Group B). RESULTS: The number of patients with fever and bleeding in Group A was much higher than that in Group B. Inpatient days and hospitalization costs in Group A were higher than those in Group B. White blood cell count, red blood cell count, haemoglobin level, and platelet count in Group A were lower than those in Group B. There were no significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and serum levels of lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), vitamin B12, folic acid, and ferritin between the two groups. The incidence of associated diseases, particularly pulmonary infections, was significantly higher in Group A than in Group B. There was no significant difference in the degree of bone marrow hyperplasia between the two groups. CONCLUSION: Patients with pancytopenia and megaloblastic anemia often developed infection and bleeding, which caused more severe anemia, higher hospitalization costs, and longer inpatient days. Early diagnosis and active treatment are required to reduce patient complications and costs.

Hemophagocytic Lymphohistiocytosis in Visceral Leishmaniasis: A Rare yet Treatable Complication.

Hemophagocytic lymphohistiocytosis (HLH) is a rare debilitating condition that can be triggered by an infectious cause, often linked to the Epstein-Barr virus (EBV). In this case, we evaluated a patient with pancytopenia. The bone marrow aspiration revealed the presence of amastigotes and active hemophagocytosis, indicating that the HLH was induced by a Leishmania infection. The patient was treated with lyophilized amphotericin B followed by miltefosine, which effectively resolved the infection and HLH. This case report underscores the presentation and findings of Leishmania-induced HLH, as well as the successful treatment approach that led to improved patient outcomes.

Pancytopenia Related to Splenic Angiosarcoma: A Case Report and Literature Review.

BACKGROUND: Angiosarcomas are highly aggressive malignancies with endothelial differentiation, presenting considerable challenges in oncology, especially when arising in rare locations such as the spleen. These tumors predominantly affect adults and are commonly found in the skin, breast, liver, or soft tissues, with more unusual occurrences in other organs. Angiosarcomas have a high propensity for metastasis, typically spreading to the liver, lungs, lymph nodes, and gastrointestinal tract. Splenic angiosarcoma, with fewer than 300 documented cases, is an especially rare and complex form of this malignancy. CASE PRESENTATION: This report details a case of splenic angiosarcoma in a 45-year-old male, where bone marrow metastases were the first clinical presentation, initially mimicking myelodysplastic syndrome (MDS) due to persistent pancytopenia. CONCLUSIONS: The eventual identification of the splenic origin underscores the diagnostic difficulties and clinical challenges inherent in managing such atypical and rare presentations.

Quantitative detection of macular microvascular abnormalities identified by optical coherence tomography angiography in different hematological diseases.

It is now understood that hematological diseases can have detrimental effects on the retina, reducing retinal capillaries, compromising visual function, and potentially causing irreversible visual impairment. Over the years, there has been limited research on macular microvascular abnormalities, such as changes in vessel density and the foveal avascular zone (FAZ) and variations in the severity of these effects across different types of blood disorders. This study aims to quantitatively assess the impact of various hematological disorders on the retina using optical coherence tomography angiography (OCTA). Compared with healthy eyes, patients with different blood diseases exhibited reductions in linear vessel density (LVD), perfusion vessel density (PVD), FAZ area, and FAZ perimeter. Notably, patients with erythrocyte diseases showed more significant abnormalities in LVD and PVD, while patients with lymphocytic diseases demonstrated more pronounced abnormalities in the FAZ area and perimeter. OCTA imaging could potentially reflect changes of the retinal microvascular of patients with hematological diseases and may serve as a valuable tool for distinguishing abnormalities affecting different blood cell lines. This approach offers a novel avenue for assessing, treating, and monitoring blood disorders.

Etiological spectrum of pancytopenia in adults based on hematological parameters and bone marrow studies.

BACKGROUND: This study aimed to investigate the demographic, clinical, and diagnostic aspects of adult pancytopenia while exploring its etiological spectrum through hematological parameters and bone marrow studies. RESEARCH DESIGN AND METHODS: This observational study involved 117 adult individuals ranging from 13 to 85 years who presented with pancytopenia. A comprehensive examination of demographic features, hematological parameters, clinical presentations, and physical findings, including liver and spleen characteristics, was conducted. Additionally, serological analyses for HBsAg and Anti HCV were performed. The diagnostic spectrum was determined through bone marrow studies. RESULTS: Pancytopenia manifested with varied clinical symptoms, with generalized weakness (72.65%), fever (64.1%), dyspnea (54.70%), bleeding (34.2%), and weight loss (25.6%) being prominent. Physical examination revealed a range of liver and spleen characteristics, with hepatomegaly observed in 32.48% and splenomegaly in 44.4% of cases. Serological findings indicated HBsAg positivity in 8.5% and Anti HCV positivity in 21.37% of cases. The diagnostic distribution encompassed diverse conditions, with aplastic anemia (17.1%), megaloblastic anemia (12.8%), and myelodysplastic syndromes (12.8%) being prevalent. CONCLUSIONS: This study provides a comprehensive overview of the demographic, clinical, and diagnostic aspects of pancytopenia. The observed prevalence of different diagnoses underscores the necessity of a thorough evaluation, including bone marrow studies, for accurate diagnosis and appropriate management.

Postoperative pancytopenia in a patient with giant parathyroid adenoma and brown tumor: a case report.

BACKGROUND: Parathyroid adenoma is the primary cause of primary hyperparathyroidism, commonly presenting with elevated parathyroid hormone (PTH) and blood calcium levels. Chronic primary hyperparathyroidism often results in bone destruction, resulting in the formation of brown tumors. The preferred clinical treatment for parathyroid adenoma is parathyroidectomy. Postoperative pancytopenia, although rare, is a critical complication that warrants further investigation into its mechanisms and management strategies. CASE PRESENTATION: We present a case of a 59-year-old female patient who was admitted due to nausea and vomiting. Positron emission tomography-computed tomography (PET-CT) revealed a mass posterior to the left thyroid lobe and multiple areas of fibrocystic osteitis throughout the body. Hematological tests showed elevated serum calcium and parathyroid hormone (PTH) levels. The patient subsequently underwent parathyroidectomy, and pathological examination confirmed the presence of a parathyroid adenoma. Postoperatively, the patient developed pancytopenia and received symptomatic treatment such as correction of anemia and elevation of white blood. At the two-month follow-up, all indicators had returned to normal. CONCLUSIONS: Pancytopenia is commonly seen in bone marrow diseases, infections and immune-related disorders, nutritional deficiencies, and metabolic diseases. This case confirms that pancytopenia can also occur postoperatively in patients with parathyroid adenoma. Therefore, Clinicians should be aware of the potential for postoperative pancytopenia following parathyroidectomy and the need for prompt management.

A Rare Case of Severe Folate Deficiency-Induced Pancytopenia.

Chronic alcoholism is a well-documented cause of folate deficiency, with past studies revealing high prevalence rates among alcoholics. Despite mandatory folate fortification in the UK from 2021, individuals with chronic alcohol consumption remain susceptible to severe folate deficiencies. This case study explores the hematological impact of severe folate deficiency in a 38-year-old female chronic alcoholic who presented with pancytopenia. The patient's symptoms included cough, shortness of breath, lethargy, reduced appetite, constipation, and rectal bleeding. Her medical history included polycystic ovarian syndrome and fatty liver disease. Blood tests revealed macrocytosis, pancytopenia, elevated bilirubin, and low serum folate levels. Management involved transfusions with packed red blood cells and oral folate supplementation, resulting in rapid hematological improvement. This case underscores the importance of early diagnosis and intervention for folate deficiency, particularly among chronic alcoholics. Folate, or vitamin B9, is essential for DNA synthesis and red blood cell production. Chronic alcohol consumption disrupts folate metabolism and absorption, leading to deficiencies. The patient's improvement with folate supplementation highlights the efficacy of this treatment. This case emphasizes the need for ongoing monitoring and support for chronic alcoholics to prevent recurrent folate deficiency. Further studies are necessary to assess the long-term efficacy of folate-fortification programs and ensure they meet the needs of vulnerable groups, including those with chronic alcohol dependence.

A Case of Autoimmune Myelofibrosis Associated With Autoimmune Hepatitis.

Autoimmune myelofibrosis (AIMF) is a distinct, underrecognized, and rare cause of bone marrow fibrosis. It carries a favorable outcome and responds well to immunosuppression. Systemic lupus erythematosus is the most common association with AIMF, but there are other cases of associated autoimmune disorders defined in the literature. A 44-year-old female presented to hospital with a 1-month history of fatigue, malaise, and jaundice. She was found to be pancytopenic with elevated liver enzymes. Tests for Janus kinase 2, myeloproliferative leukemia, and calreticulin mutations were negative. Extensive investigations for hemolytic anemia including direct antiglobulin test, flow cytometry for paroxysmal nocturnal hemoglobinuria, testing for hereditary hemoglobinopathies, and hereditary red cell membrane disorders were non-contributory. Antinuclear antibody was positive at > 1,280, immunoglobulin G was 17.04 g/L, and anti-smooth muscle antibody (ASMA) was positive at 1:40. Characteristic features of AIMF on bone marrow biopsy led to the diagnosis of AIMF. The patient was started on prednisone 1 mg/kg with prolonged taper. Fibroscan and liver biopsy were consistent with cirrhosis and workups for other causes of liver dysfunction were unremarkable. She met criteria for diagnosis of autoimmune hepatitis (AIH). The pancytopenia and liver enzymes improved with prednisone. After 1 year of clinical stability, the patient had relapse of disease with pancytopenia, elevated liver enzymes, and similar fibrosis on repeat bone marrow biopsy. Prednisone was reinitiated at 1 mg/kg, and she was started on mycophenolate mofetil (MMF). Prednisone was tapered, and she continues to have an excellent response on MMF alone. We report a case of AIMF associated with AIH, complicated by non-immune hemolysis. AIMF is rare, and its association with AIH is described in only four other cases in the English-language literature. Overlapping biochemical features of AIH and non-immune hemolysis, which has not been well described in AIMF, lead to significant diagnostic complexity and delay. Despite this, a rapid response to corticosteroids was observed including reversal of profound transfusion dependence, normalization of hemoglobin, and reversal of biochemical evidence of hepatic inflammation. A shared pathogenesis of autoimmune fibrosis in both the bone marrow and liver is speculative but suggested by the temporal association in this case.

Study of Clinicoetiological Spectrum of Bicytopenia and Pancytopenia in Hospitalized Children.

Background The etiological profile of children with bicytopenia and pancytopenia has a very wide spectrum, ranging from transient causes like infections or nutritional deficiencies to bone marrow failure syndromes. Timely diagnosis and treatment impart favorable prognosis to this entity. There is a paucity of data regarding the etiology of cytopenia in hospitalized children at a tertiary center in India. Additionally, only a few studies have discussed the possible association between the severity of cytopenia at presentation and the possible etiology. Methods This is a cross-sectional observational study analyzing bicytopenia and pancytopenia in hospitalized children. Patient details, along with clinical findings and relevant investigations, were recorded on predesigned pro forma and analyzed statistically. Results Out of 202 children, 174 (86.13%) had bicytopenia, and 28 (13.86%) had pancytopenia, with a male predominance resulting in a male-to-female ratio of 1.65:1. The commonest age group affected was pre-adolescent age group (6-12 years). The causes of bicytopenia and pancytopenia in hospitalized children in the decreasing order of frequency were infections (65.84%), benign hematological disorders (18.81%), systemic illness (10.39%), and malignancies (4.95%). The cytopenia was more severe in children with pancytopenia than bicytopenia. Conclusions Infections outweigh the other causes of bicytopenia and pancytopenia. The severity of the cell line affected can help narrow down a diagnosis of cytopenia etiologies. Most of the children with bicytopenia and pancytopenia had treatable etiology and favorable outcomes.

Methotrexate Toxicity-Induced Pancytopenia and Mucocutaneous Ulcerations in Psoriasis.

Methotrexate (MTX) is a commonly used immunosuppressant and chemotherapeutic agent, widely prescribed for autoimmune diseases such as psoriasis, rheumatoid arthritis, and certain malignancies. It functions by inhibiting dihydrofolate reductase, leading to impaired DNA synthesis and cell proliferation. While generally well-tolerated, MTX has a narrow therapeutic index, and its adverse effects can be severe, including hepatotoxicity, pulmonary toxicity, and hematological complications such as pancytopenia. Pancytopenia involves the reduction of all three blood cell lines and can result in significant morbidity and mortality. The risk of MTX toxicity is notably higher in patients with renal impairment, as the kidneys are the primary route of drug excretion. Renal dysfunction can lead to the accumulation of MTX, enhancing its toxicity. Numerous studies and case reports have highlighted the risks of MTX toxicity, especially in patients with renal impairment. Pancytopenia can present insidiously, with symptoms such as mucosal ulcers, fever, and generalized weakness, making early detection crucial. We report a case of a male patient in his late 40s with a complex medical history, including psoriasis, insulin-dependent type 2 diabetes mellitus, chronic kidney disease (CKD) stage 3b, and coronary artery disease (CAD). The patient presented to the emergency department with a one-week history of fever, generalized weakness, mouth sores, and a five-day history of bilateral lower limb swelling and pain. Vital signs were stable, but physical examination revealed pallor, large ulcerative lesions in the buccal mucosa, and erythematous, scaly lesions on the lower limbs. The patient's medication history included methotrexate, which he had stopped two months prior but was inadvertently resumed at an increased dose two weeks prior to presentation. Laboratory findings revealed pancytopenia with worsening trends, prompting a bone marrow biopsy that showed hypocellular marrow. The patient's CKD likely exacerbated the MTX toxicity due to impaired drug clearance, leading to pancytopenia. Treatment included intravenous leucovorin, blood and platelet transfusions, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite initial critical presentation, the patient showed significant improvement, with recovery of blood counts and resolution of symptoms. He was discharged with stable hemoglobin, platelet, and white blood cell counts.

Clinical and hematological profile of patients with pancytopenia at a tertiary medical center in Ethiopia.

BACKGROUND: Pancytopenia is an important hematological problem encountered in routine clinical practice associated with a multitude of disease states. The possible causes of pancytopenia can be influenced by geography, socioeconomic conditions, and endemic illnesses. Information regarding the underlying clinical conditions and morphologic features of blood cells of pancytopenia is limited and varied across different regions. Thus, this study was designed to assess the peripheral morphologic features of blood cells and the underlying clinical causes of pancytopenia. METHODS: A facility-based cross-sectional study was conducted at the Jimma Medical Center hematology laboratory from June 13 to November 13, 2022. A total of 3 mL of whole blood was collected from each subject for complete blood count analysis and peripheral blood morphology examination. Data on sociodemographic and clinical conditions were collected from medical records using a checklist. The data were analyzed using Statistical Package for the Social Sciences version 26. RESULTS: A total of 163 patients with pancytopenia were identified within the 5 months. Hyper-reactive malarial splenomegaly was the most prevalent cause (29.4%), followed by megaloblastic anemia (20.2%), chronic liver disease (10.4%), and acute leukemia (8.6%). Anisocytosis was the predominant peripheral blood morphology finding (82.2%), along with microcytosis (49.7%), ovalocytosis (31.3%), and macrocytosis (30.7%). Severe anemia was observed in 57% of cases, whereas the majority (92%) exhibited moderate leukopenia. A significant proportion (42.3%) had a platelet count below 50,000/µL. CONCLUSION: Unlike previous studies conducted in other parts of the world, this study showed that hyperreactive malarial splenomegaly was the leading cause of pancytopenia. This emphasizes the necessity of considering this condition as a possible cause for pancytopenia, particularly in malaria-endemic areas. The findings of the hematological profiles and peripheral blood morphology strongly suggest that early identification and prompt management of patients with pancytopenia require collaboration between clinical and laboratory investigations.

Lost and Found: Misdiagnosis of AIDS-Related Bone Marrow Suppression As Neutropenic Fever and Benign Ethnic Neutropenia in a Patient With Congenital HIV.

Neutropenia is a relatively uncommon but notable secondary effect of HIV infection. While the various hematopoietic effects of HIV and AIDS are well-described in the literature, high-quality evidence directly linking neutropenia with mortality in HIV-infected patients remains limited. The multifactorial etiology of neutropenia complicates its diagnosis, particularly when it occurs secondary to HIV. We present the case of a 35-year-old African American male with congenital HIV, who presented with severe neutropenia accompanied by a fever in the context of untreated HIV. The initial differential diagnosis was broad, including benign ethnic neutropenia (given the patient's African American ethnicity), tuberculosis (given the potential for anti-tuberculosis therapy to cause neutropenia and its commonality as a co-infection in HIV patients), sepsis-related neutropenia, and AIDS-related bone marrow suppression. However, through further workup, it became apparent that HIV-related bone marrow suppression ultimately led to pancytopenia. This case highlights how HIV patient non-adherence to antiretroviral therapy (ART) and hematologic abnormalities complicate the diagnosis of hematopoietic abnormalities from HIV. It also discusses how vertical transmission and abrupt ART discontinuation create a new phenotype of HIV patients with delayed presentations of AIDS-related complications. This patient's presentation also provides insight into the consequences of untreated HIV following the self-discontinuation of long-term HIV management therapy due to low healthcare literacy and loss of follow-up. The patient's clinical course, laboratory findings, imaging studies, and treatment outcomes are discussed, emphasizing the need for timely diagnosis and a multidisciplinary approach to care while exploring potential barriers to care in different social contexts.

A Case Report of Hemophagocytic Lymphohistiocytosis Masquerading as Sepsis.

Profound inflammation due to cytokine storm is often the underlying cause of death in patients with hemophagocytic lymphohistiocytosis (HLH). Sepsis, while a precipitant, is also the great masquerader that may hide early signs of HLH. Prompt recognition is important to prevent rapid clinical decline and death. A patient presented with two weeks of unremitting fever of 103°F, dysuria, bilateral flank pain, and confusion. Obstructive uropathy and pyelonephritis were treated with a Foley catheter and antibiotics. There were abnormal developments during his hospitalization including a deep vein thrombus despite prophylactic anticoagulation. Antibiotics and Foley management did not improve fevers or renal injury so he eventually required continuous renal replacement therapy and blood product transfusions. In rapid progression, the patient developed pancytopenia, neutropenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia suspicious for HLH. A bone marrow biopsy was consistent with progressive T-cell lymphoma, the likely cause of secondary HLH. Antineoplastics, corticosteroids, and opportunistic prophylaxis were pursued. Unfortunately, the cytopenias worsened, and the patient developed shock with hypoxemia and hypotension, followed by cardiac arrest and demise.

Investigating the Clinico-Etiological Profile of Pediatric Pancytopenia: A Prospective Study in a Tertiary Care Center.

Background A decrease in red blood cells, white blood cells, and platelets is known as pancytopenia, and it is frequently caused by a variety of illnesses such as bone marrow failure, malnutrition, infections, autoimmune diseases, or blood malignancies. The purpose of this study was to investigate the hematological, clinical, and causative aspects of pancytopenia in children ranging in age from one month to 18 years. Methodology At the Department of Pediatrics, a 12-month prospective observational research involving 70 pediatric patients with pancytopenia was carried out. Documentation included demographic information, clinical manifestations, history of vaccinations, and particular disease features. The study evaluated the frequency of several reasons (autoimmune, neoplastic, nutritional, infectious, and others) that lead to pancytopenia. Results The mean age of the 70 patients was 5.08 ± 3.22 years, comprising 30 males (42.86%) and 40 females (57.14%). Fever (50 cases, 71.43%), arthralgias (39 cases, 55.71%), weight loss (11 cases, 15.71%), and failure to thrive (13 cases, 18.57%) were among the most common symptoms. Examinations of the bone marrow revealed that 29 patients (41.43%) had aplastic alterations, 20 patients (28.57%) had hyperplastic abnormalities, and 21 patients (30%) had normal cellularity. Fourteen patients (20%) had nutritional reasons, mostly megaloblastic anemia, and six patients (8.57%) suffering from neoplastic disorders had acute lymphoblastic leukemia (ALL). Hemolytic anemia, parvovirus B19, miliary tuberculosis (TB), aplastic anemia, and systemic lupus erythematosus were among the other noteworthy etiologies. Conclusion Many cases of pediatric pancytopenia in the region are preventable. Greater awareness and appropriate diagnostic strategies are crucial for the early identification and management of these conditions.

Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients.

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 109/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.

Severe pancytopenia at the presentation of Imerslund-Gräsbeck syndrome in a 23-month-old Italian boy.

BACKGROUND: Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules. CASE PRESENTATION: We describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208-2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported. CONCLUSIONS: Imerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.

Approach to pancytopenia: From blood tests to the bedside.

Pancytopenia is an uncommon abnormality detected on a full blood count. Features of presentation tend to be non-specific, and are due to impaired functions of the cell lines involved. These can include fatigue, infection and bleeding. However, the aetiology of pancytopenia is extensive. This narrative review aims to provide a minimally invasive diagnostic algorithm for generalist clinicians to approach pancytopenia, including investigations into the underlying aetiology, and when a referral to the haematologist is warranted for further investigations such as bone marrow aspiration and trephine biopsy.