cell therapies

2026-08-17 | When pancytopenia meets the retina: Bilateral central retinal vein occlusion in idiopathic aplastic anemia

Bilateral central retinal vein occlusion (CRVO) is an uncommon condition that often results from systemic causes, including hematologic neoplasms, hyper viscosity states, and thrombophilia. Bilateral CRVO as a complication of idiopathic aplastic anemia is exceedingly rare. We present a case of a 50-year-old female with acute painless bilateral visual loss occurring over the past five days, with a background history of generalized weakness and intermittent low-grade fever over a period of one month. Ocular examination showed bilateral diffuse flame-shaped hemorrhage with optic disc swelling in both eyes. This finding was suggestive of bilateral CRVO without venous dilatation and tortuosity, which would have been expected in hyper viscosity. In view of the rarity of bilateral CRVO, further systemic workup was conducted, which included pancytopenia with hypocellular bone marrow suggestive of idiopathic aplastic anemia. Testing for hyper viscosity, autoimmune profile, and thrombophilia tests was negative.

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2026-07-30 | Living Donor Liver Transplantation as Salvage Therapy for Steroid-Refractory Chronic Hepatic GVHD Following Allogeneic Hematopoietic Stem Cell Transplantation.

Hepatic graft-versus-host disease (GVHD) is a rare but life-threatening complication following allogeneic hematopoietic stem cell transplantation (HSCT). Steroid-refractory hepatic GVHD carries a high risk of mortality with limited salvage options. Liver transplantation after HSCT poses unique challenges due to dual alloimmunity and is rarely pursued, particularly in pediatric patients. We report a pediatric patient with steroid-refractory chronic hepatic GVHD successfully treated with living donor liver transplantation (LDLT) from a parental donor. A 13-year-old male underwent allogeneic HSCT for idiopathic severe aplastic anemia and developed progressive chronic hepatic GVHD characterized by ductopenia and severe cholestasis. His disease was refractory to corticosteroids and multiple additional therapies, including ruxolitinib, mesenchymal stromal cells, infliximab, sirolimus, anti-thymocyte globulin, alpha-1 antitrypsin, cyclophosphamide, and emapalumab. His course was complicated by Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (PTLD), successfully treated with rituximab. Fifteen months after HSCT, and seven months after clearance of EBV viremia, he underwent LDLT from a parental donor. Donor selection preserved the option for future donor-derived EBV-specific cytotoxic T lymphocyte therapy if needed. Eleven months following LDLT, the patient remains clinically well, with normal liver function, sustained full donor chimerism, and no evidence of recurrent GVHD or PTLD. LDLT may represent a viable option in select pediatric patients with irreversible chronic hepatic GVHD. This case underscores the importance of early multidisciplinary planning and highlights the absence of liver-specific biomarkers or targeted therapies to guide management. Dedicated research into preventive and regenerative strategies is warranted.

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2026-05-01 | C50-26 Epstein-Barr Virus (EBV)-associated Severe Aplastic Anemia Unmasked by a Cytokine Storm: A Distinct and Devastating Presentation

Abstract EBV reactivation can lead to rare instances of severe aplastic anemia (SAA). The virus activates cytotoxic lymphocytes, which invade the bone marrow and subsequently damage the hematopoietic functionality. Early recognition is imperative to prevent these complications and to improve clinical practice.Here, we present a case of reactivated EBV-associated aplastic anemia and cytokine storm. A 65-year-old male with a history of chronic lymphocytic leukemia (CLL) in remission since 2017 presented with four months of severe pancytopenia, recurrent fever, lymphadenopathy, and behavioral disturbances. He had received multiple courses of antimicrobial and antifungal therapy, as well as granulocyte colony-stimulating factor, with minimal improvement.On admission, he was hypotensive and required initiation of vasopressor support. Laboratory evaluation showed profound pancytopenia (WBC 1.3 K/µL, platelets 10 K/µL, Hgb 7.0 g/dL) and elevated transaminases. CT of the chest, abdomen, and pelvis revealed mediastinal and abdominal lymphadenopathy with splenomegaly. Peripheral smear showed no blasts. Bone marrow biopsy demonstrated marked hypocellularity (≈5% hematopoiesis). Flow cytometry was negative for lymphoproliferative disorder. Immunoglobulin G was markedly low.Ferritin was 34,000 ng/mL, triglycerides were elevated, and soluble IL-2 receptor was markedly increased (∼30,000 pg/mL). CD4/CD8 ratio was 0.4, with an absolute CD4 count of 24. EBV PCR was positive (160,308 copies/mL). These findings supported a diagnosis of EBV reactivation with severe aplastic anemia and cytokine storm.Despite aggressive medical therapy including high dose steroids, the patient’s condition continued to worsen and rapidly progressed to multiorgan failure, requiring life-sustaining measures. The patient passed away after 7 days of escalated therapy. Here, we illustrate a case of EBV-associated severe aplastic anemia during reactivation, eventually progressing to cytokine storm, multiorgan failure, and subsequent death. There was a presumptive clinical diagnosis leaning toward recurrent CLL, given the presence of severe pancytopenia and lymphadenopathy, diverting attention from alternative clinical possibilities. However, bone marrow studies ruled this out. There was no testing for EBV prior to the latest Hospitalization, which raises a pivotal question of whether earlier bone marrow evaluation and viral testing could have changed the tragic trajectory of the clinical course in our patient.EBV-associated severe aplastic anemia carries a poor prognosis, with mortality exceeding 50%, particularly in reactivation cases presenting with pancytopenia. The overall outcome remains poor, compounded by the absence of robust clinical practice guidelines. Physicians should maintain a high index of suspicion for EBV-associated aplastic anemia, as early recognition is crucial to initiating timely interventions such as hematopoietic stem cell transplantation. This abstract is funded by: None

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2026-01-01 | Gut Microbiome Alterations in Aplastic Anemia: Mechanistic Insights, Immune-Hematopoietic Crosstalk and Therapeutic Potential

Aplastic anemia (AA) is a rare hematological disorder characterized by peripheral cytopenias and hypocellular bone marrow resulting from failed hematopoiesis. The condition may arise from inherited genetic defects in hematopoietic stem cells (HSCs) or from acquired immune-mediated mechanisms. In acquired AA, immune dysregulation leads to the destruction of hematopoietic stem and progenitor cells (HSPCs), with immunosuppressive therapy remaining the cornerstone of treatment. Emerging evidence highlights the gut microbiome as a critical modulator of immune function and hematopoiesis. Disruptions in gut microbial composition have been linked to autoimmune and inflammatory diseases, yet their specific role in AA pathogenesis is not fully understood. The gut microbiome may influence immune responses, hematopoietic recovery and disease progression. Profiling the gut microbiome could also serve as a non-invasive method for monitoring disease progression, identifying microbial patterns associated with treatment response and assessing individual risk for relapse. Despite these promising insights, clinical trials specifically targeting the gut microbiome in AA remain limited, revealing a significant gap in research. A deeper understanding of the interactions between the gut microbiome, immune system and hematopoiesis is essential for identifying novel biomarkers and therapeutic strategies. These insights could complement existing immunosuppressive therapies and enable more personalized treatment approaches. This review thus synthesizes current evidence on gut microbiome alterations in AA, exploring their potential role in immune regulation, hematopoietic recovery and therapeutic interventions.

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2026-01-01 | Matched Sibling Donor Transplantation in Aplastic Anemia

Abstract Matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT) remains the standard first-line therapy for young patients with severe aplastic anemia (SAA). Advances in conditioning regimens, supportive care, and donor matching have significantly improved outcomes, with survival rates exceeding 90% in children and young adults. Key pretransplant factors influencing success include age, disease severity, transfusion history, and infection status. Cyclophosphamide with anti-thymocyte globulin (Cy-ATG) remains the gold-standard conditioning regimen, while fludarabine-based protocols offer alternatives for older or high-risk patients. Bone marrow (BM) is the preferred stem cell source due to lower graft-versus-host disease (GvHD) risk. Chimerism monitoring, immunosuppression, and management of complications post-transplant are crucial for long-term success. Syngeneic HSCT offers unique advantages with minimal toxicity, though rare. With tailored regimens and early intervention, MSD HSCT offers curative potential for SAA, minimizing the risk of relapse, graft failure (GF), and clonal evolution. Long-term follow-up remains essential to optimize patient outcomes.

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antibodies

2026-07-31 | A Population-Based Study on Childhood Aplastic Anemia-Incidence, Outcomes, and Health-Related Quality of Life.

Childhood aplastic anemia (AA) is a rare disease, and both the disease itself and its treatment cause significant morbidity. We aimed to determine the contemporary incidence of childhood AA in Finland, to compare the clinical characteristics of AA against inherited bone marrow failure syndromes (IBMFS) and refractory cytopenia of childhood (RCC) fulfilling the Camitta criteria for AA, and to describe survival outcomes and health-related quality of life (HRQoL) following childhood bone marrow failure. Our cohort study included all 52 Finnish children fulfilling the classical criteria for AA between 2006 and 2020. The incidence of AA was 2.9/million children/year. Of the 52 patients, 41 (78.9%) had AA, five (9.6%) had IBMFS, and six (11.5%) had RCC. Severe disease was more common among patients with AA than IBMFS or RCC (92.7% vs. 63.6%), whereas a history of hepatitis, 6p copy-number neutral loss of heterozygosity, and paroxysmal nocturnal hemoglobinuria clones were exclusively associated with AA. Immunosuppressive therapy (IST) was given for 27/38 (71.1%) patients with severe AA, with a response rate of 66.7%. Hematopoietic stem cell transplantation (HSCT) was performed for 21/38 (55.3%) patients with severe AA and nine of 11 (81.8%) with IBMFS or RCC. Of the patients with AA receiving IST, 11/27 (41%) subsequently required HSCT. Overall survival was 92.7% for patients with AA, and 81.8% for IBMFS or RCC. Although patients with AA reported generally good long-term HRQoL, especially females experienced problems in several domains. Contemporary treatment facilitates good long-term survival and HRQoL in children with AA.

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2026-04-12 | Successful Spontaneous Twin Pregnancy Following Bone Marrow Transplant and Gastric Cancer Surgery: A Case Report.

BACKGROUND Pregnancy following bone marrow transplantation (BMT) and treatment for gastric cancer is rare because of gonadotoxic conditioning regimens, major abdominal surgery, and the overall burden of chronic illness. Reports of spontaneous twin pregnancy after both allogeneic BMT and gastrectomy are exceptionally uncommon. CASE REPORT We describe the case of a 22-year-old woman with a history of severe aplastic anemia treated with allogeneic BMT (February 2022), who subsequently underwent subtotal gastrectomy for gastric adenocarcinoma (May 2022). She conceived spontaneously with a dichorionic-diamniotic twin pregnancy in 2024, several years after completion of oncologic treatment, without fertility preservation. Early pregnancy was uneventful, with reassuring serial ultrasound scans and normal fetal growth. In the second trimester, she developed extensive lower-limb deep vein thrombosis (superficial femoral vein thrombosis confirmed by compression Doppler ultrasound) requiring therapeutic anticoagulation with enoxaparin 1 mg/kg twice daily, followed by obstructive uropathy due to ureteric compression that necessitated double-J stent insertion. Maternal nutritional status and weight gain were closely monitored with serial laboratory assessment (including hemoglobin, ferritin/iron indices, vitamin B12, folate, and albumin) given her prior gastrectomy. Multidisciplinary care involving maternal-fetal medicine, hematology, oncology, urology, and anesthesia teams guided surveillance and delivery planning. At 35+6 weeks of gestation, an elective cesarean section was performed because of dichorionic twin gestation, prior major abdominal surgery, and ongoing therapeutic anticoagulation requiring coordinated perioperative planning. Two live infants with appropriate birthweights and good Apgar scores were delivered, and the postoperative course was uncomplicated for both mother and neonates. CONCLUSIONS This case illustrates that successful twin pregnancy is possible after BMT and gastric cancer surgery when individualized, multidisciplinary care and careful thromboembolic and urological surveillance are provided. It also supports the need for structured preconception counseling, fertility follow-up, and pragmatic monitoring protocols for high-risk pregnancies in young cancer and transplant survivors.

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2025-11-03 | Efficacy of early single low dose of rituximab in prophylaxis of EBV reactivation and EBV related post-transplant lymphoproliferative disorder after allogeneic hematopoietic cell transplantation

Abstract Introduction: Reactivation of Epstein-Barr virus (EBV) is common in allogeneic hematopoietic cell transplantation(allo-HCT). EBV related post-transplant lymphoproliferative disorder (EBV-PTLD) is a rare but life-threatening complication after allo-HCT. Early clearance of B cells may eliminate the proliferation sites of EBV, reducing the incidence of EBV reactivation and mortality of EBV-PTLD Aims: To explore the efficacy of early single low dose of rituximab after allo-HCT on the incidence of EBV viremia and EBV-related PTLD. Methods: From August 2024 to April 2025, a total of 37 patients with hematological disease underwent allo-HCT at Chengdu BOE Hospital and Shanghai Lu Daopei hematology Hospital. All patients was EBV-specific IgG positive before HCT. All patients received ATG based conditioning, and letermovir for CMV prophylaxis. All patients were treated with rituximab 200mg on the 5th day after stem cell reinfusion (the dose for children was adjusted according to their weight). EBV screening is performed once a week by q-PCR and more frequent if EBV DNA positive. Recurrent EBV viremia is diagnosed by detection of EBV-DNA in plasma. PTLD was screened in patients with EBV viremia by lymph node ultrasound and biopsy if needed. The incidence of EBV viremia and PTLD within 100 days and treatment-related toxicity was retrospectively analyzed, and the incidence of GVHD, CMV reactivation, and the survival status was observed. Results: The median age of the patients was 29 years (range, 8-62). 23 patients were females and 14 were males. Diagnosis was acute myeloid leukemia in 5 patients, acute lymphocytic leukemia/lymphoblastic lymphoma in 30 patients and severe aplastic anemia in 2 pts. The stem cell donors were from matched sibling donors in 5 patients, unrelated donors in 4 patients, cord blood in one patient, and haploidentical donors in 27 patients. The median follow-up was 162 days (101〜285 days). Of the 37 patients, only 3（8%）developed EBV viremia in 100 days, persisting from 1 to 2 weeks, none of the patients developed PTLD. There were no severe adverse effect or aggravated infection events during the medication process. Cumulative incidences (CI) at day +100 of grade II-IV and grade III-IV aGVHD were 10.8% and 2%, respectively. Incidence of CMV reactivation was 10.2%. Till last follow up, all the patients presented with B-cell deficiency and hypoimmunoglobulinemia, requiring immunoglobulin replacement therapy. 36 patients were still alive with disease free and 1 died of acute GVHD. Conclusion: Our study shows that early single low dose of rituximab after allo-HCT can significantly reduce incidence of EBV viremia and the risk of EBV-related PTLD, without severe adverse effect despite delayed humoral immune reestablishment. It will provide an effective prophylactic strategy for patients at high risk of EBV and reduce transplant-related mortality after allo-HCT.

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2025-10-01 | Pigment Nephropathy Mistaken for Complement-Mediated Thrombotic Microangiopathy

Introduction: Complement-mediated thrombotic microangiopathy (CM-TMA) is associated with microangiopathic hemolytic anemia (MAHA) and acute kidney injury. It requires a tissue biopsy for diagnosis. We present a case with aplastic anemia and transfusion related hemolysis (TRH) mistaken for CM-TMA treated with complement inhibitor (CI). Case Description: 78-year-old female with endometrial carcinoma and chronic kidney disease stage 3b presented with weakness, shortness of breath and loose stools after radiation therapy. She had completed carboplatin/paclitaxel/trastuzumab and received trastuzumab 3 weeks ago. Initial laboratory data included hemoglobin 6g/dL, platelets 61K, creatinine 2.5mg/dl, AST 220U/L, ALT 217U/L, total bilirubin 26mg/dL haptoglobin <10mg/dL, rare schistocytes on smear, normal ADAMTS13 and negative Coombs test. Infectious work up was negative and malignancy in remission. TMA from carboplatin was unlikely due to timing. Eculizumab was initiated for CM-TMA while awaiting complement testing. Due to ongoing anemia and thrombocytopenia, bone marrow biopsy was done showing hypoproliferative marrow and no malignancy. A steroid trial was pursued but did not improve the cytopenias. Patient was found to have anti-Jka antibodies likely causing TRH due to multiple transfusions. Renal biopsy showed acute tubular injury, subacute interstitial nephritis and myoglobin casts. Discussion: CIs have provided CM-TMA patients with lifesaving treatments by slowing endothelial dysfunction, hemolysis and organ failure. TMA can occur due to malignancy or antineoplastic agents. Early initiation of eculizumab has promising results, but can lead to hasty diagnosis, which can effect the immune system. This case reflects that laboratory values concerning for MAHA may not indicate TMA and other etiologies along with kidney biopsy must be considered.

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2025-09-20 | Investigating the Pathophysiology and Immunological Mechanisms in Aplastic Anemia: A Focus on Natural Killer (NK) Cell Activity and Immunomodulation

Abstract Aplastic anaemia (AA) refers to a rare and potentially deadly disorder of the blood that is characterized by the disfunction of the bone marrow that combats infections and diseases by producing all types of blood cells to a significant degree, a condition identified as pancytopenia. Whereas the autoimmune obliteration of blood-forming progeny and stem cells (HSPCs) due to self-reactive T cells has been extensively recorded; however, the involvement of natural killing (NK) cells in the onset of aplastic anaemia remains inadequately comprehended.The paper explores the modern understanding of AA emphasizing the quantitative and functional Misfits of NK cells and their potential to be used as a treatment goal. We explore further into immunomodulatory strategies used to restore balance of the immune in individuals affected by Aplastic Anaemia (AA).

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gene therapies

2026-05-12 | Somatic mutations in CSK disrupt immune regulation in a Chinese aplastic anemia cohort.

Aplastic anemia (AA) is a rare hematological disorder characterized by the failure of bone marrow hematopoiesis. Although somatic mutations are known to play pivotal roles in the pathogenesis and clinical progression of AA, their molecular characteristics in Chinese AA patients remain poorly characterized. In this study, we perform whole-exome sequencing on 126 Chinese AA patients to delineate the somatic mutation landscape. Our analysis reveal recurrently mutated genes enriched in immune regulatory pathways. Notably, we identify eight AA cases harboring mutations in the tyrosine kinase motif of C-terminal Src kinase (CSK), a critical regulator of T-cell receptor (TCR) signaling. Functional validation and RNA sequencing in Jurkat T cells demonstrate that these mutations induce aberrant T-cell activation in vitro, suggesting a potential mechanistic link to AA pathogenesis. Furthermore, we detect copy number variations in multiple loci containing immune-related genes, which may additionally contribute to disease development. Collectively, our study provides a comprehensive characterization of somatic mutations in a large Chinese AA cohort and elucidates the functional impact of CSK mutations on AA pathogenesis. These findings deepen our understanding of the disease mechanisms underlying AA and identify potential molecular targets for future therapeutic strategies.

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2023-12-16 | The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry.

The bone marrow failure syndromes (BMFS) are a diverse group of acquired and inherited diseases which may manifest in cytopenias, haematological malignancy and/or syndromic multisystem disease. Patients with BMFS frequently experience poor outcomes, and improved treatment strategies are needed. Collation of clinical characteristics and patient outcomes in a national disease-specific registry represents a powerful tool to identify areas of need and support clinical and research collaboration. Novel treatment strategies such as gene therapy, particularly in rare diseases, will depend on the ability to identify eligible patients alongside the molecular genetic features of their disease that may be amenable to novel therapy. The Australian Aplastic Anaemia and other Bone Marrow Failure Syndromes Registry (AAR) aims to improve outcomes for all paediatric and adult patients with BMFS in Australia by describing the demographics, treatments (including supportive care) and outcomes, and serving as a resource for research and practice improvement.

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2016-08-19 | Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres.

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2005-02-03 | Chemosensitizing tumor cells by targeting the Fanconi anemia pathway with an adenovirus overexpressing dominant-negative FANCA.

Fanconi anemia (FA) is a rare genetic disorder characterized by bone-marrow failure and cellular hypersensitivity to crosslinking agents, including cisplatin. Here, we studied the use of the FA pathway as a possible target for cancer gene therapy with the aim to sensitize tumor cells for cisplatin by interfering with the FA pathway. As proof-of-principle, FA and non-FA lymphoblast-derived tumors were grown subcutaneously in scid mice and treated with two different concentrations of cisplatin. As predicted, the antitumor response was considerably improved in FA tumors. An adenoviral vector encoding a dominant-negative form of FANCA, FANCA600DN, was generated that interfered with endogenous FANCA-FANCG interaction resulting in the disruption of the FA pathway as illustrated by disturbed FANCD2 monoubiquitination. A panel of cell lines, including non-small-cell lung cancer cells, could be sensitized approximately two- to three-fold for cisplatin after Ad.CMV.FANCA600DN infection that may increase upon enhanced infection efficiency. In conclusion, targeting the FA pathway may provide a novel strategy for the sensitization of solid tumors for cisplatin and, in addition, provides a tool for examining the role of the FA pathway in determining chemoresistance in different tumor types.

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small molecules

2026-08-30 | [Aplastic anemia developed after treatment with durvalumab].

A 76-year-old woman with stage IIIB squamous cell lung carcinoma developed pancytopenia following maintenance therapy with durvalumab. She was diagnosed with squamous cell lung carcinoma (T4N2M0, stageIIIB) in December 2023. Following a favorable response to chemoradiotherapy, maintenance therapy with durvalumab was initiated in June 2024. Thrombocytopenia was observed starting in August, and platelet count had decreased to 22,000/µl in October, leading to the discontinuation of durvalumab. However, the condition progressed to pancytopenia. Bone marrow biopsy revealed hypocellular marrow without dysplasia, fibrosis, or hemophagocytosis. Additional findings included paroxysmal nocturnal hemoglobinuria-type blood cells and fatty marrow replacement on spinal MRI. Based on these comprehensive findings, the patient was diagnosed with aplastic anemia (AA) in January 2025. Immunosuppressive therapy combining antithymocyte globulin, cyclosporine A, and eltrombopag was initiated in February 2025, resulting in a favorable response. AA is a relatively rare immune-related adverse event, and reports of AA induced by durvalumab are extremely limited. This case highlights the importance of considering AA in the differential diagnosis of persistent thrombocytopenia or pancytopenia during immune checkpoint inhibitor therapy.

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2026-08-13 | Real-world retrospective analysis of clinical outcomes in pediatric acquired aplastic anemia: a single-center 10-year cohort study

Introduction Pediatric aplastic anemia (AA), a rare and potentially fatal disease, demonstrates significant heterogeneity in pathogenesis, disease severity, therapeutic regimens, and clinical outcomes. Methods In this study, clinical features and outcomes of 70 children with AA, including severe AA (SAA, n = 30), very severe AA (vSAA, n = 21) and nonsevere AA (nSAA, n = 19), were retrospectively analyzed, with a median follow-up of 60.7 months (range, 0.4-136.5 months). Results Patients with nSAA were mainly treated with cyclosporine A, whereas SAA/vSAA patients primarily received allogeneic hematopoietic stem cell transplantation (HSCT) followed by standard immunosuppressive therapy (IST). Ultimate therapy regimens differed significantly between patients with SAA/vSAA and nSAA ( p = 0.001). SAA/vSAA group exhibited a higher overall response rate at the 2-year follow-up (85.5% vs. 55.6%, p = 0.019). The 2-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 97.1% and 48.5%, respectively. In patients with SAA/vSAA, HSCT was associated with higher and faster cumulative complete response (CR) rate ( p &lt; 0.0001) and superior EFS ( p = 0.0297) compared with IST. Two IST-resistant patients were observed to achieved CR with eltrombopag (EPAG) salvage therapy. Discussion pediatric AA carries excellent OS but suboptimal EFS. HSCT tends to yield more favorable EFS compared with IST in SAA/vSAA patients, and EPAG may act as an effective salvage option for appropriately selected IST-resistant individuals. Further multicenter prospective research is warranted prior to implementing these findings in routine clinical practice.

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2026-07-19 | Liver Transplantation in a Patient With Fulminant Failure and Bone Marrow Aplasia Due to Methimazole: A Case Report.

Fulminant hepatitis is a rare but highly lethal complication associated with various drugs, including antithyroid thionamides used for hyperthyroidism. While propylthiouracil (PTU) is more commonly linked to severe hepatotoxicity, methimazole can also cause acute liver failure and, rarely, bone marrow suppression such as aplastic anemia or agranulocytosis. Drug-induced liver injury accounts for a significant proportion of acute liver failure cases requiring transplantation, with antithyroid drugs occasionally implicated. The pathogenesis is thought to be immune-mediated and potentially dose-dependent, with cross-reactivity between thionamides. Simultaneous occurrence of severe hepatotoxicity and aplastic anemia is exceptionally rare, particularly with methimazole. A 37-year-old man with Graves' disease, on methimazole for 4 years without recent follow-up, presented in February 2024 with jaundice, choluria, and acholic stools. Investigations revealed hyperbilirubinemia, elevated transaminases, negative viral/autoimmune serologies, and normal imaging. Liver biopsy confirmed drug-induced injury with ductopenia, portal fibrosis, inflammation, and bilirubinostasis. Methimazole was discontinued. One month later, progressive pancytopenia developed, unresponsive to corticosteroids. Bone marrow biopsy showed hypocellularity consistent with aplastic anemia, requiring transfusions. Liver failure progressed to grade II encephalopathy, bilirubin 30.23 mg/dL (516.93 µmol/L), MELD 29, meeting King's College Criteria. He underwent urgent cadaveric orthotopic liver transplantation on June 13, 2024. Post-transplant, aplastic anemia was managed with erythropoietin, G-CSF, eltrombopag, and transfusions. An opportunistic CMV infection was treated with ganciclovir. Hematopoietic support was eventually discontinued without further transfusions, and the patient was discharged with stable graft and hematological recovery. This case illustrates the rare simultaneous occurrence of methimazole-induced fulminant hepatitis and aplastic anemia necessitating liver transplantation. It underscores the challenges in perioperative management of profound pancytopenia and posttransplant complications in such patients. Multidisciplinary care was key to successful outcome, highlighting the need for vigilant monitoring of antithyroid drug therapy and avoidance of cross-use in cases of severe adverse reactions.

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2026-07-13 | Type B insulin resistance syndrome coexisting with aplastic anemia responsive to early immunosuppressive therapy.

Type B insulin resistance syndrome (IRS) is a rare autoimmune disorder characterized by severe insulin resistance caused by autoantibodies against the insulin receptor. Clinically, it presents with fluctuating hyperglycemia and hypoglycemia and is frequently associated with other autoimmune diseases. We report a case with the rarely reported combination of type B IRS and aplastic anemia. A 77-year-old woman with obesity presented with abrupt deterioration of glycemic control and bilateral lower extremity edema. Despite the administration of up to 300 units/day of insulin after hospitalization, hyperglycemia remained refractory. Markedly elevated insulin receptor autoantibody titers (85.9%) confirmed the diagnosis of type B IRS. Further evaluation for concomitant pancytopenia revealed aplastic anemia on bone marrow examination. Immunosuppressive therapy with cyclosporine and eltrombopag for aplastic anemia improved the hyperglycemia; however, early morning hypoglycemia, renal dysfunction associated with intravascular volume depletion, and persistent lower extremity edema remained unresolved. The addition of glucocorticoid therapy resulted in rapid clinical improvement and marked reduction in the insulin receptor autoantibody titers (8.6%). This case highlights the importance of early and appropriate immunomodulatory therapy to achieve remission in type B IRS, particularly in patients with multiple concomitant autoimmune diseases.

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2026-06-23 | ID #670 A Rare and Severe Complication: Aplastic Anemia After a Single Cycle of Temozolomide in a Child with Recurrent Ependymoma

Abstract Background Temozolomide is an alkylating chemotherapeutic agent commonly used in the management of high-grade central nervous system (CNS) tumors. While myelotoxicity, most commonly manifesting as thrombocytopenia, is a recognized adverse effect, profound myelosuppression in otherwise chemotherapy-naïve patients is rare. Severe aplastic anemia represents an even more uncommon complication of temozolomide therapy, occurring in fewer than 1% of treated patients, reported predominantly in adults (mean age 60.7 years) and associated with substantial morbidity and mortality. Case/Methods A 12-year-old female experienced relapse of PF-A ependymoma approximately two years after initial treatment with gross total resection and focal radiation. At recurrence, only near-total resection was feasible. Given the proximity to prior radiation and location of residual disease, repeat radiation was deemed unsafe. The patient was therefore initiated on oral temozolomide at a standard dose for high-grade CNS tumors (200 mg/m² daily for 5 days). Following a single cycle of therapy, she developed a delayed hypersensitivity reaction characterized by urticaria and emesis three days after completion, which resolved with epinephrine and corticosteroids. Approximately 3.5 weeks after temozolomide administration, she presented with profound pancytopenia, manifesting as acute-onset wet purpura and active mucosal bleeding. Due to the severity of cytopenias and minimal response to transfusion support, a bone marrow biopsy was performed, demonstrating marked aplasia with &lt;5% overall cellularity, nearly absent granulopoiesis and megakaryopoiesis, and markedly decreased erythropoiesis. The patient was treated with prophylactic antibiotics, granulocyte colony-stimulating factor, and romiplostim, resulting in partial hematologic recovery within four weeks. Conclusion Severe aplastic anemia represents a rare but potentially fatal complication of temozolomide therapy in patients with CNS malignancies. To our knowledge, this represents the youngest reported case of temozolomide-induced aplastic anemia, underscoring that this complication can occur in children and highlighting the importance of early recognition and proactive hematologic surveillance, even after a single cycle of treatment. 1. Villano JL, Letarte N, Yu JM, Abdur S, Bressler LR. Hematologic adverse events associated with temozolomide. Cancer Chemother Pharmacol. 2012 Jan;69(1):107-13. doi: 10.1007/s00280-011-1679-8. Epub 2011 May 26. PMID: 21614470. 2. Park AK, Waheed A, Forst DA, Al-Samkari H. Characterization and prognosis of temozolomide-induced aplastic anemia in patients with central nervous system malignancies. Neuro Oncol. 2022 Jun 1;24(6):964-973. doi: 10.1093/neuonc/noab240. PMID: 34647594; PMCID: PMC9159424.

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other

2025-05-07 | Efficiency of Innovative Methods of Treatment of Progressive Facial Neuropathy in Aplastic Anemia

Abstract: Progressive facial neuropathy is a rare but debilitating complication in patients with aplastic anemia, often resistant to standard therapies due to underlying immunosuppression and chronic inflammation. This study aimed to evaluate the clinical efficiency of innovative treatment methods—specifically low-frequency transcutaneous electrical nerve stimulation (TENS) combined with neuropeptide infusion therapy—in comparison with conventional treatment. A total of 34 patients with clinically confirmed progressive facial neuropathy in the setting of aplastic anemia were enrolled and divided into two groups. Group A received standard therapy, while Group B received additional TENS and intravenous plasma-derived neuropeptides. By week 6, Group B showed significantly greater improvement in facial nerve function (House-Brackmann score), pain relief (VAS and NTSS-6), and inflammatory markers (CRP, IL-6), along with better quality of life outcomes. The innovative treatment was welltolerated and led to faster and more complete nerve recovery. These findings support the integration of regenerative and neuromodulatory therapies into neurorehabilitation protocols for hematological patients.

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2024-11-05 | TGF-β Pathway Inhibition Improves Hematopoietic Deficiency and Immune Imbalance By Repairing Endothelial Progenitor Cell Function in Aplastic Anemia

Background: Aplastic anemia(AA), one of bone marrow(BM) failure syndromes, is a rare and life-threatening disease. However, the pathogenesis of AA remains to be elucidated and therapeutic strategies need to be further established. Our recent studies reported the dysfunction of BM endothelial progenitor cells(EPCs), one of critical components in BM microenvironment, are involved in hematopoiesis defect and immune imbalance in hematopietic dysfunction-related diseases, including AA(2016Blood, 2022Haematologica, 2022BMC Med, 2023Sci China Life Sci). Therefore, unveiling the mechanism underlying BM EPC dysfunction may provide a potential target for alleviating AA. Hyperactive TGF-β signaling is reported to inhibit the proliferation of hematopoietic stem cells(HSCs) and lead to BM failure in mice, while TGF-β inhibition promotes hematopoietic recovery. Latest studies indicate one of TGF-β signaling inhibitors, luspatercept, promotes erythroid maturation in patients with myelodysplastic neoplasms and β-thalassaemia. However, whether TGF-β inhibition could restore hematopoiesis and immune status via repairing BM EPCs, and therefore provide a potential therapeutic option for AA patients remain to be elucidated. Aims:To investigate whether TGF-β signaling is activated in BM EPCs of AA patients compared with healthy controls(HCs). Moreover, to explore whether activation of TGF-β signaling in EPCs impairs their biological functions in regulating homeostasis of HSC and T cell differentiation. Finally, to determine whether TGF-β inhibition could restore their multi-lineage hematopoiesis and immune balance via repairing BM EPCs in AA. Methods: A prospective case-control study enrolled AA patients and their age-matched HCs to compare the expression levels of TGF-β1 and TGF-βRI using flow cytometry. BM EPC functions were evaluated by proliferation, apoptosis, migration and tube formation assays. Direct-coculture systems of EPCs and CD34+ or CD3+ cells were used to examine the hematopoiesis-supporting and immune regulation capacity of EPCs, respectively. An impaired EPC model derived from HCs induced by TGF-β1 and a classical AA mice model were established to further validate the role of TGF-β signaling in regulating hematopoiesis and immunological status in vitro and in vivo. Finally, RNA-seq analysis and qRT-PCR were performed to validate previous findings. Results: Compared to HCs, decreased and dysfunctional EPCs with hyperactive TGF-β signaling, which are characterized as decreased double stained cell numbers, reduced angiogenesis and migration capacities, higher apoptosis ratio, impaired HSC-supporting ability and imbalanced T cell differentiation-supporting ability, were observed in AA patients, which could be improved by TGF-β inhibition. Consistently, the same findings were observed in an impaired EPC model triggered by TGF-β1 in vitro. Furthermore, AA mice presented the damage in BM endothelial cells with activated TGF-β signaling, whereas TGF-β inhibition restored hematopoietic defect and rebalanced T cell subsets via repairing endothelial cells, thus contributing to a better performance in peripheral blood including increased erythroid and megakaryocytic lineages. Mechanismly, RNA-seq and qRT-PCR analysis further validated TGF-β signaling is involved in BM EPC dysfunction in AA patients. Summary/Conclusion: We found for the first time that dysfunctional BM EPCs with hyperactive TGF-β signaling are involved in AA, whereas inhibition of TGF-β could promote multi-lineage hematopoiesis recovery and immune balance in AA via repairing dysfunctional EPCs. Our study suggests TGF-β inhibitors, including luspatercept, might be a potential therapeutic strategy for AA patients, which provides a rationale for further clinical trials in AA patients to validate our preliminary findings in the future.

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