UNASSIGNED: Hematopoietic stem cell transplantation (HSCT) is an approach that has significantly improved the prognosis and survival of hematological patients. However, ovarian dysfunction and infertility following HSCT have gained increasing attention. Live births have been reported following ovarian tissue cryopreservation prior to HSCT and subsequent retransplantation of these tissues. Still, the feasibility of ovarian tissue cryopreservation (OTC) following graft failure (GF) of HSCT remains unknown. In this study, we report the first case of OTC following a GF of allogenic HSCT (allo-HSCT), as well as the cryopreservation of four MII oocytes via in vitro maturation with informed consent. Despite the lack of clinical outcomes after cryopreserved ovarian tissue retransplantation, we documented an interesting case in a woman after GF of allo-HSCT exhibiting functional ovaries and emphasized a clinical dilemma: whether OTC should be offered to women suffering from GF of HSCT.
UNASSIGNED: A 22-year-old woman with severe aplastic anemia who had suffered GF of allo-HSCT from her sibling brother [HLA allele match (7/10)] with a reduced dose conditioning regimen including fludarabine, cyclophosphamide, and antithymocyte globulin came to our reproductive center for fertility preservation, as she was about to receive the second allo-HSCT. We evaluated the ovarian reserve of this patient. Hormone assessments showed an anti-Müllerian hormone level of 3.921 ng/mL, a follicle-stimulating hormone level of 5.88 IU/L, a luteinizing hormone level of 10.79 IU/L, and an estradiol level of 33.34 pg/mL. Antral follicle counts accessed transvaginally showed 12-15 follicles. All assessments indicated a well-protected ovarian reserve. Due to the urgency of the second allo-HSCT, the patient decided to undergo ovarian cryopreservation. Laparoscopic surgery proceeded. Ovarian tissues were successfully cryopreserved using vitrification technology, and histologic evaluation demonstrated a follicle density of 20 per 2 × 2 mm2 biopsy with good viability. Four MII oocytes were obtained via in vitro maturation technology and cryopreserved. After the second HSCT, the patient relieved from aplastic anemia but suffered iatrogenic premature ovarian failure as predicted.
UNASSIGNED: OTC is applicable to fertility preservation in those undergoing GF of HSCT with benign hematological disorders and especially those who are about to receive the second HSCT.

Severe aplastic anemia (SAA) is a life-threatening disorder with high mortality. The only curative treatment is hematopoietic stem cell transplantation (HSCT), but it is mainly for young patients with suitable donors. The alternative is immunosuppressive therapy (IST), which can improve blood counts in about 58% of patients, but many relapse after discontinuation. Recently, eltrombopag, a thrombopoietic receptor agonist, was tested. As a single drug, it improved blood counts in 40-50% of patients. However, combining eltrombopag and IST proved more effective and safer. A review of 20 randomized controlled trials with 2,469 patients showed that the group receiving eltrombopag and IST had a significantly higher overall response rate (86% vs. 74%) after six months. After two years, 54% of the experimental group had relapsed compared to 39% in the control group. Despite this, eltrombopag tends to increase relapse rates over time. In conclusion, combining eltrombopag with IST is a superior treatment for SAA.

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.

UNASSIGNED: This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.
UNASSIGNED: PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.
UNASSIGNED: This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54-3.12; P < 0.0001) and 6-month OR (OR = 3.66, 95% CI 2.39-5.61, P < 0.001)compared to immunosuppressive therapy for AA patients. In terms of safety, eltrombopag combined with immunosuppressive therapy showed significantly increased pigment deposition and abnormal liver function compared to immunosuppressive therapy alone.
UNASSIGNED: Compared to immunosuppressive therapy alone, eltrombopag combined with immunosuppressive therapy showed significant improvements in 6-month CR and 6-month OR. However, it also resulted in increased pigment deposition and abnormal liver function in terms of safety.

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.

UNASSIGNED: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis.
UNASSIGNED: We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst.
UNASSIGNED: We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT.
UNASSIGNED: Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief.
UNASSIGNED: www.crd.york.ac.uk/PROSPERO/, CRD42023412467.

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.

Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis. Responses ranged from 50 to 70% in inherited BMF, 40-50% in acquired AA and MDS, while very limited evidence emerged for myelofibrosis. In acquired AA, response was associated with presence of non-severe disease; in MDS androgens were more effective on thrombocytopenia or mild to moderate anemia, whilst limited benefit was observed for transfusion dependent anemia. Toxicity profile mainly consisted of virilization and liver enzyme elevation, whilst the risk of leukemic evolution remains controversial.

BACKGROUND: An important but rare adverse effect of vaccines is their association with autoimmune events, including hepatitis and aplastic anemia (AA). In this paper, we report a case of hepatitis followed by AA that occurred after the COVID-19 vaccine was administered.
METHODS: This paper focuses on a 30-year-old female who presented with acute hepatitis three weeks after receiving the second dose of the coronavirus Pfizer/BioNTech vaccine. After an extensive diagnostic evaluation was conducted that did not discover a specific cause, the Pfizer/BioNTech vaccine was suspected and the patient was treated with corticosteroids. One week after the onset of a liver disorder, the patient presented with gum bleeding and pancytopenia, and the diagnosis of AA was established via laboratory testing and bone marrow biopsy. After the diagnosis, the patient received immunosuppressive therapy using anti-lymphocyte serum (ATGAM) and CYCLOSPORINE A with progressive improvements in cytopenia. The important issue is whether AA is related to acute hepatitis or the coronavirus vaccine.
CONCLUSIONS: Clinicians should be aware of the risk of both the possibility of acute hepatitis, AA, or both after receiving the COVID-19 vaccination. It is very hard to distinguish the cause of AA between vaccine- and hepatitis-related AA. Predicting who develops hepatic or myelo-complications after vaccination is difficult.

BACKGROUND: Myelodysplastic syndrome (MDS) is a hematological neoplasm, and an increase in myeloblasts is representative of leukemic hematopoiesis in advanced MDS. Low-risk MDS usually exhibits deranged autoimmunity resembling that of aplastic anemia (AA), whereas advanced MDS is characterized by a phenotype of immune exhaustion. MDS can be normo/hyperplastic or hypoplastic. Generally, bone marrow cellularity and myeloblasts increase with disease progression. Transformation from advanced MDS to AA-like syndrome with leukemic cell regression has not previously been reported.
METHODS: A middle-aged Chinese woman had a 4-year history of leukocytopenia. Six months prior to admission, the patient developed gradually worsening fatigue and performance status. The leukocytopenia further progressed. She was diagnosed with MDS with excess blasts-2 based on increased bone marrow cellularity and an increased percentage of myeloblasts on marrow and blood smears, an increased percentage of cluster of differentiation (CD)34+CD33+ progenitors in immunotyping analysis, a normal karyotype in cytogenetic analysis, and the identification of somatic mutations in CBL, KMT2D and NF1 in molecular analysis. Initially, neutropenia was the predominant hematological abnormality, with mild anemia and thrombocytosis, and the degree of fatigue was far more severe than the degree of anemia. In the following months, the patient experienced several febrile episodes. Intravenous antibiotic treatments were able to control the febrile episodes, but the elevated inflammatory indices persisted. The hematological parameters dramatically fluctuated with the waxing and waning of the inflammatory episodes. With recurrent flares of the inflammatory condition, agranulocytosis and severe anemia developed, with mild thrombocytopenia. During the patient\'s hospitalization, computed tomography (CT) scans revealed the presence of extensive inflammatory lesions involving the lungs, mediastinum, pleura, gastrointestinal tract, peritoneum and urinary tract, with imaging features suggestive of the reactivation of disseminated tuberculosis. Reevaluation of the bone marrow smears revealed that the cellularity became hypoplastic, and the leukemic cells regressed, suggesting that both normal and leukemic hematopoiesis had been heavily suppressed. Immunological analysis of the bone marrow samples revealed a decreased percentage of CD34+ cells and an immunological signature resembling that of severe AA (SAA), confirming the regression of the leukemic cells by autoimmune-mediated attacks. The patient demonstrated resistance to multiple drugs, including antituberculotics, recombinant human granulocyte colony-stimulating factor, broad-spectrum antibiotics, voriconazole, ganciclovir, immune suppressants, eltrombopag and intravenous immunoglobulin, which further worsened the hematological injury and patient\'s performance status. The patient eventually died of overwhelming infection and multidrug resistance.
CONCLUSIONS: Advanced MDS can transform to aplastic cytopenia with leukemic cell regression and an immunological signature of SAA during inflammatory flare-ups.