• Humans
• Anemia, Aplastic/diagnosis
• Anemia, Aplastic/therapy
• Hematopoietic Stem Cell Transplantation
• Immunosuppressive Agents/therapeutic use
• Cyclosporine/therapeutic use
• Antilymphocyte Serum/therapeutic use
• Benzoates/therapeutic use
• Patient-Centered Care
• Pyrazoles/therapeutic use
• Diagnosis, Differential
• Practice Guidelines as Topic
• Hydrazines/therapeutic use

• Aplastic anemia
• Immune perturbations
• Myeloid-derived suppressor cells (MDSCs)

• Humans
• Anemia, Aplastic/immunology
• Killer Cells, Natural/immunology
• Leukocytes, Mononuclear/immunology
• Leukocytes, Mononuclear/metabolism
• Adult
• Female
• Flow Cytometry/methods
• Myeloid-Derived Suppressor Cells/immunology
• Male
• Middle Aged
• Young Adult
• Aged

• Allo-HSCT
• Anti-HLA Abs
• Severe aplastic anemia

• Humans
• Hematopoietic Stem Cell Transplantation
• Anemia, Aplastic/therapy
• Anemia, Aplastic/mortality
• Anemia, Aplastic/immunology
• Male
• Female
• Adult
• HLA Antigens/immunology
• Adolescent
• Transplantation, Homologous
• Middle Aged
• Retrospective Studies
• Young Adult
• Child
• Child, Preschool

• Biochemical analysis
• Blood serum
• PLS-LDA
• Pancytopenia related diseases
• Surface-enhanced Raman spectroscopy

• Humans
• Spectrum Analysis, Raman/methods
• Pancytopenia/diagnosis
• Pancytopenia/blood
• Diagnosis, Differential
• Discriminant Analysis
• Myelodysplastic Syndromes/diagnosis
• Myelodysplastic Syndromes/blood
• Female
• Least-Squares Analysis
• Middle Aged
• Male
• Early Diagnosis
• Adult
• Anemia, Aplastic/diagnosis
• Anemia, Aplastic/blood
• Aged

• Aplastic anemia
• Olaparib
• Pancytopenia
• Prostate cancer

• Adverse events
• Aplastic anemia
• Case reports
• SARS-CoV-2
• Vaccine

• Humans
• Middle Aged
• Anemia, Aplastic/etiology
• Anemia, Aplastic/therapy
• COVID-19 Vaccines/adverse effects
• SARS-CoV-2
• COVID-19/prevention & control
• Vaccination/adverse effects
• Rare Diseases

• Anemia, Aplastic/therapy
• Graft vs Host Disease/etiology
• Hematopoietic Stem Cell Transplantation/methods
• Humans
• Lymphoma, Follicular
• Retrospective Studies
• Treatment Outcome

In Pakistan, the incidence rate of aplastic anemia is 3.5 cases/million. The associated risk factors are exposure to pesticides, chemicals, and some drugs. The link between aplastic anemia and socio-demographic factors is debatable.

We conducted this study to investigate the role of socio-economic and -demographic factors with aplastic anemia.

A total of 191 lab-confirmed incident cases of aplastic anemia were identified from the tertiary hospital of Karachi-Pakistan in between 2015 and 2018. Age and gender-matched 694 controls were randomly selected from the same institute admitted or visited for other non-neoplastic conditions. Socio-demographic and exposure information was gathered using a data collection form. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed for selected socio-demographic factors.

Among socio-demographic factors, significant associations of aplastic anemia risk emerged for illiteracy (aOR: 2.3; 1.5; 3.5) occupation (any type) (aOR: 2.1; 1.7; 2.5), living in rural environments (aOR: 2.9; 1.9; 4.2). The odds of aplastic anemia increased with the age group 31–50 years (aOR: 1.8; 1.7; 3.5) and >50 years (aOR: 2.5; 2.1; 4.2). We observed no association of income with the risk of aplastic anemia.

This study highlights the importance of socio-demographic factors as a risk factor for the development of aplastic anemia in the population of Pakistan. In order to reduce disease incidence, health education program and use of personal protective equipment and organization of screening camps in high-risk population is warranted.

• Pakistan
• Socio-demographic factors
• aplastic anemia
• case-control study

This study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C).

We retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C.

Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001).

These results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.

• first-line therapy
• hematopoietic stem cell transplantation
• immunosuppressive therapy
• outcome
• severe aplastic anemia

• Aplastic anaemia
• Bone marrow failure syndromes
• Hypoplastic myelodysplastic syndrome
• Large granular lymphocytic leukaemia
• Paroxysmal nocturnal haemoglobinuria

• aplastic anemia
• bone marrow failure
• eltrombopag

• aplastic anemia
• glioblastoma multiforme
• temozolomide

• Acute hepatitis
• Hypertransaminasemia
• Jaundice
• Paroxysmal nocturnal hemoglobinuria

• aplastic anemia
• bone marrow transplant
• matched unrelated donor

ITK (IL-2-inducible tyrosine kinase) belongs to the Tec family kinases and is mainly expressed in T cells. It is involved in TCR signalling events driving processes like T cell development as well as Th2, Th9 and Th17 responses thereby controlling the expression of pro-inflammatory cytokines. Studies have shown that ITK is involved in the pathogenesis of autoimmune diseases as well as in carcinogenesis. The loss of ITK or its activity either by mutation or by the use of inhibitors led to a beneficial outcome in experimental models of asthma, inflammatory bowel disease and multiple sclerosis among others. In humans, biallelic mutations in the ITK gene locus result in a monogenetic disorder leading to T cell dysfunction; in consequence, mainly EBV infections can lead to severe immune dysregulation evident by lymphoproliferation, lymphoma and hemophagocytic lymphohistiocytosis. Furthermore, patients who suffer from angioimmunoblastic T cell lymphoma have been found to express significantly more ITK. These findings put ITK in the strong focus as a target for drug development.

• Autoimmune diseases
• Cancer
• ITK
• Inhibitor

• Animals
• Autoimmune Diseases/etiology
• Autoimmune Diseases/metabolism
• Autoimmune Diseases/pathology
• Biomarkers
• Disease Susceptibility
• Humans
• Inflammation/etiology
• Inflammation/metabolism
• Inflammation/pathology
• Interleukin-2/metabolism
• Neoplasms/etiology
• Neoplasms/metabolism
• Neoplasms/pathology
• Protein Kinase Inhibitors/pharmacology
• Protein-Tyrosine Kinases/antagonists & inhibitors
• Protein-Tyrosine Kinases/genetics
• Protein-Tyrosine Kinases/metabolism

• Deutsche Forschungsgemeinschaft

• AA
• Aplastic anemia
• Defective telomerase function
• HLA-mediated immunity mutations
• Hematopoietic stem cells

• Anemia, Aplastic/pathology
• Clone Cells/pathology
• Exosomes/metabolism
• Hematopoiesis
• Hematopoietic Stem Cells/pathology
• Humans
• Telomerase/metabolism

• University of Zielona Gora

• Aplastic anemia and bone marrow failure
• Red cell disorders
• Transplantation

• Anemia, Aplastic/therapy
• Animals
• Benzoates/therapeutic use
• Combined Modality Therapy
• Hematopoietic Stem Cell Transplantation
• Humans
• Hydrazines/therapeutic use
• Immunosuppression Therapy
• Pyrazoles/therapeutic use
• Transplantation, Homologous

To date, instruments to measure quality of life (QoL) specifically for patients with acquired aplastic anaemia (AA) and paroxysmal nocturnal haemoglobinuria (PNH) are lacking altogether. As a consequence, this issue is either underevaluated or alternatively, instruments originally designed for cancer patients are being used. We therefore started to systematically develop a AA/PNH-specific QoL (QLQ-AA/PNH) instrument in these ultra-rare diseases according to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. While phases I and II of the process have previously been published, we now report on the resulting instrument (phase III of this process). As part of the phase III of the evaluation process, we approached patients through physicians, patient support groups, and patient conferences. After participants completed the preliminary questionnaire and reported socio-demographic data, they were interviewed in person or via phone with a debriefing interview to find out whether the items were relevant, easy to understand, and acceptable to patients and whether there was anything missing in the questionnaire. We hypothesised what items could be combined into a scale and calculated Cronbach’s alpha to define its preliminary internal consistency. After definition of a priori criteria to keep or delete items, a group of six experts met in person, discussed the results, and decided on in- or exclusion. A total of 48 patients were enrolled, 21 of those suffered from AA (44%), 13 from PNH (27%), and 14 from AA/PNH syndrome (29%). The median time to complete the 69 items was 10 min (range 5–20), mean time 11 min. The compliance criterion (> 95% completion) was fulfilled by 57 items. Twenty-three items were mentioned as especially relevant by ≥ 2% of the patients. Cronbach’s alpha of the hypothesised scales ranged from 0.63 (social support) to 0.92 (fear of progression and illness intrusiveness). Finally, 47 items were kept; 16 were deleted, and 5 were changed, while 1 item expanded. This resulted in 54 items in total. As no issues were mentioned to lacking by a minimum of five patients, no items were added to the questionnaire. After completion, the AA/PNH-QoL tool (QLQ-AA/PNH) was translated according to EORTC guidelines into English, French, and Italian. For patients with PNH and AA until now, the standard assessment for QoL was to use the EORTC Quality of Life Questionnaire (QLQ-C30) or the Functional Assessment of Chronic Illness Therapy Fatigue Instrument (FACIT-Fatigue). We herewith present a new instrument aimed to be better tailored to the needs of PNH and AA patients. The anticipated fourth development phase will be performed for psychometric validation; however, we already explored the internal consistency of the hypothesised scales and found the results to be very good. Hence, the new QLQ-AA/PNH with 54 items can be used in trials and clinical studies from now on, according to EORTC strategy even if the scoring algorithm at this point is preliminary and the QLQ-AA/PNH might change slightly after phase IV. This is important, as there are no other disease-specific instruments available for AA/PNH patients right now.

• Aplastic anaemia
• Bone marrow failure syndromes
• Paroxysmal nocturnal haemoglobinuria
• Quality of life

• Aplastic anaemia
• Gene regulation
• T cells
• miR-1202

• Aplastic anemia
• Ethiopia
• Jimma
• Pancytopenia

Fatigue is distressing and affects quality of life (QoL) among patients with myelodysplastic syndrome (MDS), aplastic anemia (AA), and paroxysmal nocturnal hemoglobinuria (PNH). Limited data exist on the impact of fatigue, QoL, and related symptoms in these patients.

Prospectively assess fatigue (functional assessment of cancer therapy‐anemia [FACT‐An]); QoL (FACT‐An subscales); pain (brief pain inventory); and depression, anxiety, and stress (depression anxiety stress scale‐21) and strategies used to manage these symptoms in patients with MDS, AA, and PNH.

Surveys were administered via the AA and MDS International Foundation website and database from October 2014 through April 2015 in a cross‐sectional study. Results were summarized using descriptive statistics.

Of 303 patients, 145 (48%) had MDS, 84 (28%) had AA, and 74 (24%) had PNH; 31 (10%) had >1 diagnosis. The mean age was 57 years, 200 (66%) were female, and 195 (92%) were white. The mean fatigue scores were 25 (range 1‐52) for the whole cohort, 28 for AA, 25 for MDS, and 24 for PNH (P = 0.117); these are all considered severe level. The mean QoL score was 68 (range 10‐104) for the whole cohort, 67 for AA, 69 for MDS, and 67 for PNH (P = 0.821). The ranges for stress were normal; pain and depression, mild; and anxiety, moderate. The most common management strategies perceived as helpful for fatigue in the past month were preserving energy, physical activity, and naps.

Many patients with MDS, AA, and PNH report severe fatigue. The helpfulness of fatigue management strategies may impact patients’ continued use; whether these strategies are beneficial and decrease fatigue levels needs more study.

• aplastic anemia
• fatigue
• myelodysplastic syndrome
• paroxysmal nocturnal hematuria
• quality of life

• Anemia/diagnosis
• Autoantibodies/blood
• Blood Group Incompatibility/diagnosis
• Female
• Humans
• Infant, Newborn
• Infant, Newborn, Diseases/diagnosis
• Male
• Pregnancy
• Pregnancy Complications/blood
• Rh-Hr Blood-Group System/immunology
• Severity of Illness Index

Infection is a major complication in aplastic anemia (AA) patients. Primary objectives of this study were to determine the prevalence of infections and to determine types of pathogens associated with infections in patients with AA. Secondary objectives were to evaluate overall survival after infections as well as risk factors of infections in patients with AA.

The authors retrospectively evaluated the infectious episodes (IEs), type of infections, associated pathogens, and outcomes of infections in patients with AA who were diagnosed and treated at Chiang Mai University between January 2010 and December 2015.

Sixty-seven patients with a median age of 51 years (range, 15–87 years) were enrolled. Forty two patients (62.6%) were severe AA. Median absolute neutrophil count (ANC) was 984 /mm³ (range, 120–5500/mm³). Twenty five patients (37.3%) received antithymocyte globulin plus cyclosporine A, 41 patients (61.1%) received anabolic hormone, and 2 patients (2.9%) underwent allogeneic hematopoietic stem cell transplantation. Overall, 31 IEs were documented in 22 patients (32.8%). The most common microbiologically documented site of infection was bloodstream infection (23.4%) followed by pulmonary infection (14.9%). Culture-negative febrile neutropenia occurred in 12.7%. Common pathogens identified were bacteria (73.9%), mainly gram-negative (52.9%) including Acinetobacter baumannii (23.5%) and Pseudomonas aeruginosa (17.6%). Fungal infections were diagnosed in 21.7% and all were Aspergillus spp. Six patients (9%) died during the study period. All of them died from infection which gram-negative bacteria were most common pathogens (66.7%). Patients with infections had 5-year overall survival of 72% that is significantly less than patients without infection (100%) (p = 0.0002). Only risk factor that correlates with high probability of infection was ANC < 500/mm³. (HR 2.29, 95%CI 1.03–7.72, p = 0.043).

Prevalence of infections in AA patients in Chiang Mai University was 32.8% Bacterial infections especially gram-negative bacteria were the major pathogens. Patients with ANC < 500/mm³ had higher risk of infections. Infection was the most important cause of death in AA.

• Aplastic anemia
• Infections

• Aplastic anemia
• Hematopoiesis
• Hematopoietic stem cell transplantation
• Mesenchymal stem cells
• Stem cells
• Targeted therapies

• TL1 TR001437 NCATS NIH HHS
• UL1 TR001436 NCATS NIH HHS

Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome characterized by partial or total bone marrow (BM) destruction resulting in peripheral blood (PB) pancytopenia, which is the reduction in the number of red blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The first-line treatment option of AA is given by hematopoietic stem cell (HSCs) transplant and/or immunosuppressive (IS) drug administration. Some patients did not respond to the treatment and remain pancytopenic following IS drugs. The studies are in progress to test the efficacy of adoptive cellular therapies as mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable allogeneic transplants in refractory severe aplastic anemia (SAA) cases. Moreover, bone marrow stromal cells (BMSC) constitute an essential component of the hematopoietic niche, responsible for stimulating and enhancing the proliferation of HSCs by secreting regulatory molecules and cytokines, providing stimulus to natural BM microenvironment for hematopoiesis. This review summarizes scientific evidences of the hematopoiesis improvements after MSC transplant, observed in acquired AA/BMF animal models as well as in patients with acquired AA. Additionally, we discuss the direct and indirect contribution of MSCs to the pathogenesis of acquired AA.

• Air Pollutants, Occupational/toxicity
• Amifostine/therapeutic use
• Anemia, Aplastic/chemically induced
• Anemia, Aplastic/pathology
• Anemia, Aplastic/prevention & control
• Animals
• Apoptosis/drug effects
• Benzene/toxicity
• Bone Marrow/drug effects
• Bone Marrow/metabolism
• Bone Marrow/pathology
• Bone Marrow Cells/drug effects
• Bone Marrow Cells/metabolism
• Bone Marrow Cells/pathology
• Chemoprevention
• Disease Models, Animal
• Immunohistochemistry
• In Situ Nick-End Labeling
• Lipid Peroxidation/drug effects
• Male
• Mice
• Mice, Inbred Strains
• Proliferating Cell Nuclear Antigen/metabolism
• Radiation-Protective Agents/therapeutic use
• Reactive Oxygen Species/metabolism
• Spleen/drug effects
• Spleen/pathology

Acquired aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated ultra-rare diseases. Quality of life (QoL) evaluation tools used in studies for AA and PNH are unspecific and designed for cancer patients (e.g., the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, EORTC QLQ-C30). Given the complexity of AA and PNH, variation in symptoms and treatments, younger age of many patients, and the fact that AA and PNH are not classified as malignant diseases, it is likely that cancer-specific questionnaires are inappropriate. We generate an AA/PNH-specific QoL questionnaire (QLQ-AA/PNH), performed according to EORTC guidelines. QoL issues were obtained from the literature and interviews with patients and physicians (phase I), then ranked by patients and physicians. In phase II, items were created. Patients in more than 25 German and Swiss cities were interviewed face to face. In phase I, interviews of 19 patients and 8 physicians specialized in AA/PNH treatment resulted in 649 QoL issues; these were condensed to 175 and graded according to their importance by 30 patients and 14 physicians (phase II). Five physicians took part in phases I and II. Altogether, 97 issues were rated important. Twelve EORTC QLQ-C30 items were not rated important, while several new QoL aspects were brought up. Modifications in wording and phrasing led to two questionnaires with 77 items regarding general QoL aspects and 20 items regarding medical care. Important QoL aspects of PNH/AA patients are inappropriately captured with available QoL tools. Developing a new QoL questionnaire specific for this patient group is warranted.

• Aplastic anemia
• Bone marrow failure syndromes
• Paroxysmal nocturnal hemoglobinuria
• Quality of life

• Adolescent
• Adult
• Aged
• Anemia, Aplastic/diagnosis
• Anemia, Aplastic/epidemiology
• Anemia, Aplastic/psychology
• Female
• Hemoglobinuria, Paroxysmal/diagnosis
• Hemoglobinuria, Paroxysmal/epidemiology
• Hemoglobinuria, Paroxysmal/psychology
• Humans
• Male
• Middle Aged
• Quality of Life/psychology
• Surveys and Questionnaires/standards
• Young Adult

• Aplastic anemia
• Apoptosis
• Cell cycle
• DNA damage response
• Hematopoiesis
• Hematopoietic stem/progenitor cells

• Adult
• Blood Platelets/pathology
• Female
• Humans
• Male
• Middle Aged
• Platelet Count
• Purpura, Thrombocytopenic, Idiopathic/blood
• Purpura, Thrombocytopenic, Idiopathic/diagnosis
• Reference Values
• Thrombocytopenia/blood
• Thrombocytopenia/diagnosis

Aplastic anemia (AA) is a bone marrow failure syndrome that is caused largely by profound quantitative and qualitative defects of hematopoietic stem and progenitor cells. However, the mechanisms underlying these defects remain unclear. Under conditions of stress, autophagy acts as a protective mechanism for cells. We therefore postulated that autophagy in CD34⁺ hematopoietic progenitor cells (HPCs) from AA patients might be impaired and play a role in the pathogenesis of AA. To test this hypothesis, we tested autophagy in CD34⁺ cells from AA samples and healthy controls and investigated the effect of autophagy on the survival of adult human bone marrow CD34⁺ cells. We found that the level of autophagy in CD34⁺ cells from AA patients was significantly lower than in age/sex-matched healthy controls, and lower in cases of severe AA than in those with non-severe AA. Autophagy in CD34⁺ cells improved upon amelioration of AA but, compared to healthy controls, was still significantly reduced even in AA patients who had achieved a complete, long-term response. We also showed that although the basal autophagy in CD34⁺ cells was low, the autophagic response of CD34⁺ cells to “adversity” was rapid. Finally, impaired autophagy resulted in reduced differentiation and proliferation of CD34⁺ cells and sensitized them to death and apoptosis. Thus, our results confirm that autophagy in CD34⁺ cells from AA patients is impaired, that autophagy is required for the survival of CD34⁺ cells, and that impaired autophagy in CD34⁺ HPCs may play an important role in the pathogenesis of AA.

• Adult
• Anemia, Aplastic/pathology
• Antigens, CD34/analysis
• Autophagy
• Bone Marrow Cells/cytology
• Bone Marrow Cells/pathology
• Cell Differentiation
• Cell Proliferation
• Cells, Cultured
• Female
• Humans
• Male
• Middle Aged
• Young Adult