A 20-year-old male patient with a history of celiac disease came to medical attention after developing profound fatigue and pancytopenia. Evaluation demonstrated pan-hypogammaglobulinemia. There was no history of significant clinical infections. Bone marrow biopsy confirmed hypocellular marrow consistent with aplastic anemia. Oncologic and hematologic evaluations were unremarkable for iron deficiency, paroxysmal nocturnal hemoglobinuria, myelodysplastic syndromes, T-cell clonality, and leukemia. A next generation genetic sequencing immunodeficiency panel revealed a heterozygous variant of uncertain significance in CTLA4 c.385T >A, p.Cys129Ser (C129S). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is an inhibitory receptor important in maintaining immunologic homeostasis. To determine the functional significance of the C129S variant, additional testing was pursued to assess for diminished protein expression, as described in other pathogenic CTLA4 variants. The results demonstrated severely impaired CTLA-4 expression and CD80 transendocytosis, consistent with other variants causing CTLA-4 haploinsufficiency. He was initially treated with IVIG and cyclosporine, and became transfusion independent for few months, but relapsed. Treatment with CTLA-4-Ig fusion protein (abatacept) was considered, however the patient opted for definitive therapy through reduced-intensity haploidentical hematopoietic stem cell transplant, which was curative.

Olaparib is (ADP-ribose) polymerase inhibitor (PARPi), which stops the repair of single-stranded DNA breaks. This leads to the death of cancer cells with BRCA1/BRCA2 mutations or homologous recombination deficiency. Since being approved by the FDA in 2023 for treating castrate-resistant prostate cancer (CRPC), there have been some reports of myelodysplastic syndrome (MDS) and acute leukemia linked to PARP inhibitor use for ovarian, breast, pancreatic and breast cancers, there have been no reports of aplastic anemia after receiving PARPi therapy. This case report describes a 75-year-old man with BRCA2-positive metastatic castrate-resistant prostate cancer who developed aplastic anemia after taking olaparib.

The use of Bruton\'s tyrosine kinase inhibitors (BTKi) is rapidly increasing for patients with mantle cell lymphoma (MCL). Side effects reported so far are usually manageable. However, here we present two cases of life-threatening aplastic anemia (AA) upon treatment with the BTKi acalabrutinib for MCL. The first patient died of neutropenic infection secondary to AA. The second patient was successfully treated with immunosuppressive treatment but the MCL relapsed shortly thereafter. AA is a potentially fatal complication that should be considered when patients present with pancytopenia during treatment with BTKi.

BACKGROUND: Methimazole is an antithyroid drug known to cause hematological toxicity, including agranulocytosis and, very rarely, pancytopenia. We herein present a case of a patient with Graves\' Disease (GD) who developed methimazole-induced pancytopenia.
METHODS: A 53-year-old Peruvian woman with GD, initially treated with methimazole 20 mg BID, experienced odynophagia, fever, and malaise after 37 days of treatment. The initial diagnosis was agranulocytosis, leading to the discontinuation of methimazole and initiation of antibiotics. Due to persistent neutropenia, a Granulocyte Colony-stimulating Factor (G-CSF) was administered. Eight days later, she developed pancytopenia and was managed with hematopoietic agents and platelet transfusions. The patient recovered with normalization of the blood count, eliminating the need for Bone Marrow (BM) examination. Radioiodine therapy was chosen as the definitive treatment, resulting in hypothyroidism. Currently, the patient is thyroidal and hematologically stable.
CONCLUSIONS: Methimazole-induced pancytopenia is a rare and serious complication; however, with appropriate treatment, complete recovery can be achieved.

Immune check point inhibitors (ICIs) have durable antitumor effects. However, autoimmune toxicities, termed immune-related adverse events, occur in some patients. We report a case of severe immune aplastic anemia (AA) in a patient with non-small cell lung cancer who was receiving atezolizumab with bevacizumab/carboplatin/paclitaxel. Although the cancer has not recurred, his bone marrow is depleted and he did not respond to immunosuppressive therapy. He has survived for 1.5 years with blood transfusions and infection control. Immune AA associated with ICIs is rare, and a treatment has not yet been established. This case report provides information on the management and treatment response of patients with AA caused by ICIs. Further studies should investigate the mechanism and pathogenesis of immune AA caused by ICIs.

Rhupus syndrome is an autoimmune disorder that combines the symptoms of lupus and rheumatoid arthritis. It is a rare condition that affects the connective tissues of the body such as the joints, muscles, and skin. The symptoms of rhupus syndrome can be similar to those of lupus, including joint pain, fatigue, and skin rashes. However, rhupus syndrome can also cause symptoms of rheumatoid arthritis, such as joint stiffness and swelling. Treatment for rhupus syndrome usually involves a combination of medications and lifestyle changes to manage symptoms and improve the overall quality of life. A 24-year-old female patient was referred by a local physician for evaluation of pancytopenia. Her history dates back to six months when she developed progressive fatigue, dyspnea on mild exertion, and polyarthralgia. Initial laboratory investigations revealed pancytopenia, positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Bone marrow examination confirmed the diagnosis of aplastic anemia. She was started on cyclosporine with an aim to maintain a trough level between 200 and 250 ng/mL. She responded well with hematological recovery in three to four months. This case highlighted the excellent response to cyclosporine hematologically and clinically in rhupus syndrome complicated with aplastic anemia. Further studies are required to establish the long-term efficacy of cyclosporine in this patient population.

Aplastic anemia is a hematopoietic deficiency disorder with pancytopenia, and immunosuppressive therapy is effective. We report a case in which plasma cells appeared in the peripheral blood during immunosuppressive therapy for aplastic anemia. Based on the results of morphology and flow cytometry, the plasma cells were considered reactive and disappeared spontaneously after follow-up. Thereafter, the patient had a good hematopoietic recovery. Reactive plasmacytosis has been reported in infectious and autoimmune diseases, but this is the first report of reactive plasmacytosis during immunosuppressive therapy for aplastic anemia, to our knowledge. In this case, reactive plasmacytosis was a sign preceding good hematopoietic recovery.

Aplastic anemia (AA) is a rare, potentially catastrophic hematopoiesis failure manifested by pancytopenia and bone marrow aplasia. AA occurrence in Systemic Lupus Erythematosus (SLE) patients is extremely rare. The diagnosis may be delayed due to other possible pancytopenia etiologies. Confirmation of peripheral cytopenias diagnosis necessitates a bone marrow aspiration. The management of AA is challenging, and the literature reported using glucocorticoids, danazol, plasmapheresis, cyclophosphamide, intravenous immunoglobulin, and cyclosporine. We report two cases of SLE patients who presented with pancytopenia, with bone marrow biopsy confirmed AA. One case was treated with cyclophosphamide but unfortunately succumbed to Acute Respiratory Distress Syndrome (ARDS), while the other case was managed with rituximab with a good response. Interestingly, both patients were on azathioprine before the diagnosis of AA. A comprehensive search for reported cases of AA in PubMed, Scopus, and the Directory of Open Access Journals databases was performed to enhance the understanding of the diagnostic and management challenges associated with AA in SLE, facilitating ongoing exploration and research in this field. The decision to do a BM aspiration and biopsy is recommended for SLE patients with an abrupt decline in blood counts and previously stable blood counts.

BACKGROUND: Immunosuppressive therapy and matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) are the preferred treatments for aplastic anemia (AA).
METHODS: In this report, we describe a 43-year-old male patient with severe AA who carried BRIP1 (also known as FANCJ), TINF2, and TCIRG1 mutations. Screening of the family pedigree revealed the same TINF2 mutation in his mother and older brother, with his older brother also carrying the BRIP1 variant and demonstrating normal telomere length and hematopoietic function. The patient was successfully treated with oral cyclosporine A, eltrombopag, and acetylcysteine, achieving remission 4 years after receiving MSD-HSCT from his older brother.
CONCLUSIONS: This case provides a valuable clinical reference for individuals with suspected pathogenic gene mutations, normal telomere length, and hematopoietic function, highlighting them as potential donors for patients with AA.

BACKGROUND: Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution. In approximately 10%-15% of patients with severe aplastic anemia (SAA), the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy. In some of these patients, myeloid neoplasms appear during or shortly after immunosuppressive therapy. Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.
METHODS: A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria (PNH). With aggravation of systemic inflammatory symptoms, severe pancytopenia developed, and her hemoglobinuria disappeared. Laboratory findings in cytological, immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for \"SAA.\" Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches. Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment, and complete hematological remission was achieved within 4 mo of treatment. Frustratingly, the hematological response lasted for only 3 mo, and pancytopenia reemerged. At this time, cytological findings (increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0% of all nucleated hematopoietic cells), immunological findings (increased percentage of cluster of differentiation 34+ cells that accounted for 12.28% of all nucleated hematopoietic cells) and molecular biological findings (identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes) revealed that \"SAA\" had transformed into acute myeloid leukemia with mutated nucleophosmin-1. The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages, as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo. Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis, and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis. The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.
CONCLUSIONS: Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis, and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.