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Objective: The causes of pancytopenia vary in different populations depending on age, gender, nutrition, geographic location, standard of living, and exposure to certain infections and drugs. As the severity of pancytopenia and its underlying etiology determine the management and prognosis, identifying the correct etiology in a given case is crucial and helps in implementing timely and appropriate treatment. The objectives of this study were to study the clinical profile and hematological parameters of pancytopenic adults and to identify different etiologies of pancytopenia. This observational study was conducted in the Medicine department of a tertiary care teaching hospital. Materials and Methods: The study was conducted on 100 adult patients aged 18–65 years presenting with pancytopenia. All the participants were subjected to detailed clinical examination and relevant investigations including bone marrow (BM) examination. Categorical variables were presented in number and percentage (%). Qualitative variables were correlated using the Chi-square test. A P

Screening recommendations for anemia during pregnancy, etiologies of inherited and noninherited forms of anemia, their impact on maternal-fetal outcomes, and the clinical management of pregnant patients presenting with these conditions are reviewed. Anemia during pregnancy can cause adverse perinatal outcomes including preterm labor, premature rupture of membranes, and increased maternal and fetal mortality. Physiologic (dilutional) anemia and iron deficiency anemia are the two most common noninherited forms of anemia, and some cases may be the result of an underlying comorbidity such as diabetes or lupus. Aplastic anemia and autoimmune hemolytic anemia are uncommon forms of noninherited anemias that also merit discussion. Inherited forms of anemia include sickle cell disease, alpha-thalassemia, and beta-thalassemia. Timely diagnosis and treatment of anemia during pregnancy, whether inherited or noninherited, is imperative to protect mother and baby from potential adverse outcomes associated with these conditions.

Key Points TCRαβ/CD19-depleted HLA-haploidentical HSCT is an effective strategy for children with several nonmalignant disorders.Patients given this type of transplant benefit from a low incidence of GVHD and TRM, with graft failure being the main obstacle., Visual Abstract, Several nonmalignant disorders (NMDs), either inherited or acquired, can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). Between January 2012 and April 2020, 70 consecutive children affected by primary immunodeficiencies, inherited/acquired bone marrow failure syndromes, red blood cell disorders, or metabolic diseases, lacking a fully matched donor or requiring urgent transplantation underwent TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative as part of a prospective study. The median age at transplant was 3.5 years (range 0.3-16.1); the median time from diagnosis to transplant was 10.5 months (2.7 for SCID patients). Primary engraftment was obtained in 51 patients, while 19 and 2 patients experienced either primary or secondary graft failure (GF), the overall incidence of this complication being 30.4%. Most GFs were observed in children with disease at risk for this complication (eg, aplastic anemia, thalassemia). All but 5 patients experiencing GF were successfully retransplanted. Six patients died of infectious complications (4 had active/recent infections at the time of HSCT), the cumulative incidence of transplant-related mortality (TRM) being 8.5%. Cumulative incidence of grade 1-2 acute GVHD was 14.4% (no patient developed grade 3-4 acute GVHD). Only one patient at risk developed mild chronic GVHD. With a median follow-up of 3.5 years, the 5-year probability of overall and disease-free survival was 91.4% and 86.8%, respectively. In conclusion, TCRαβ/CD19-depleted haploidentical HSCT from an HLA-partially matched relative is confirmed to be an effective treatment of children with NMDs. Prompt donor availability, low incidence of GVHD, and TRM make this strategy an attractive option in NMDs patients. The study is registered at ClinicalTrial.gov as NCT01810120.

Key Points CXCL9, BAFF, and sC5b-9 are potential biomarkers and therapeutic targets for graft rejection after transplant.Fever monitoring is a widely available and informative predictor of graft rejection after transplant., Visual Abstract, Graft rejection (GR) is a poorly understood complication of hematopoietic cell transplant (HCT). GR risk factors are well published, but there are no reliable biomarkers or therapies known. Fever is the most common symptom of GR, but no study has evaluated fever kinetics as a diagnostic marker of GR. The objectives of this study were to identify mechanisms, biomarkers, and potential therapies for GR after HCT. Chemokine ligand 9 (CXCL9), B-cell activating factor (BAFF), and complement markers (sC5b-9, C3a, and C5a) were measured in 7 patients with GR and compared with 15 HCT controls. All patients had a diagnosis of aplastic anemia, Fanconi anemia, or genetically undefined chromosomal fragility syndrome. All patients with GR were febrile during GR; therefore, control patients who underwent HCT were matched for diagnosis and early fevers after HCT. Patients withh GR had significantly higher CXCL9, BAFF, and sC5b-9 at the time of fever and GR compared with control patients who underwent HCT at the time of fever. The maximum fever was significantly higher and occurred significantly later in the transplant course in patients with GR compared with febrile HCT controls. These data support the use of CXCL9, BAFF, sC5b-9, and fever kinetics as GR markers. Two patients with GR underwent a second HCT that was complicated by high fevers. Both patients received interferon and complement blockers during their second HCT, and both preserved their graft. These laboratory and clinical findings support larger studies to evaluate the safety and efficacy of interferon, complement, and BAFF inhibitors for the prevention and treatment of GR after HCT.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

Graft failure is a major pitfall of unrelated umbilical cord blood transplantation (CBT) in children with rare hematological disorders other than acute leukemia, such as acquired and inherited bone marrow failure, myelodysplastic syndrome, juvenile myelomonocytic leukemia, and chronic myeloid leukemia. We developed a less-toxic conditioning regimen for CBT that achieves a higher rate of complete donor chimerism, and retrospectively compared it against two other conditioning regimens for CBT performed at our single institution. The engraftment rate with complete donor chimerism was 100% and 5-year event-free survival (5y-EFS) was 90.9% in patients using our latest regimen (n = 11) of reduced-intensity conditioning (RIC) containing fludarabine (Flu) 180 mg/m2, melphalan (MEL) 210 mg/m2, and low-dose rabbit anti-thymocyte globulin (LD-rATG) 2.5 mg/kg without irradiation (regimen C). Outcomes were better than in patients (n = 10) treated with previous regimens involving irradiation (5y-EFS 30.0%, p = 0.004): regimen A, consisting of myeloablative conditioning containing cyclophosphamide (CY) and total body irradiation (TBI) with 8-12 Gy, or regimen B, consisting of RIC with Flu, CY, horse ATG, and thoracoabdominal irradiation (TAI) with 6 Gy. In conclusion, Flu/MEL/LD-rATG (regimen C) without TBI/TAI may be preferable as RIC for unrelated CBT in children with rare hematological disorders.

Fanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer. Currently, hematopoietic stem cell transplant (HSCT) is the only curative treatment available for bone marrow failure; however, HSCT increases oral squamous cell carcinoma (OSCC) risk. Here we report the case of a patient diagnosed with Fanconi anemia in childhood who was treated with HSCT and later diagnosed with multiple OSCCs during a 12-year follow-up. Despite multiple surgical interventions and radiotherapy regimens, the patient`s health deteriorated. Management of individuals with Fanconi anemia is challenging and must be provided by a multidisciplinary healthcare team to ensure better staging, treatment planning, and coordination.

Introduction. The use of ionizing radiation as a production factor in the late 1940s - early 1950s. began in the absence of a clear understanding of the permissible radiation doses for workers, as well as knowledge of diagnostic criteria and developed therapeutic measures for developing chronic radiation sickness (CRS). Since then, a great deal of experience has been accumulated in the diagnosis and treatment of CRS. Currently, there are no conditions at the workplace for chronic exposure of workers in doses exceeding the permissible ones. However, taking into account the constant expansion of the scope of using sources of ionizing radiation, it is necessary to remember about the possibility of CRS development due to prolonged exposure in case of violation of their storage or their loss. The study aimed to explore the formation of radiation bone marrow syndrome (RBS) due to chronic exposure in doses that exceed the maximum permissible, accumulated with different dose rates of radiation. Material and methods. We selected the medical records of 27 people (24 men and 3 women) who had RBS as a result of chronic professional gamma radiation exposure. The selection criteria were the diagnosis of grade II-III chronic radiation syndrome (CRS) in the presence of agranulocytosis or anemic syndrome in the period of the disease formation and, especially, in the development of myelodysplastic syndrome (MDS) or aplastic anemia in the period of the CRS consequences. Identified clinical and dosimetric CRS features of 27 patients exposed to chronic irradiation with a dose rate of 0.0002-0,009 Gy/h and the summary dose of 1.7 and 9.6 Gy, accumulated over a period of 6 to 96 months were compared the characteristics of 84 patients CRS exposed a lower dose rates (less than 0,0003 Gy/h) and 26 patients with acute radiation syndrome moderate (II) severity as a result of irradiation the dose rates of 0.14-3,7 Gy/h, total dose of 2 to 4 Gy. Results. The criteria of atypical subacute CRS course are identified: the rate of chronic radiation exposure - not less than 0.001-0.009 Gy/h with a summary dose of 1.7-9.6 Gy accumulated over a period of 6-96 months, the presence of agranulocytosis in the period of CRS formation and anemic syndrome in the periods of CRS formation and outcomes. These signs predict the development MDS in 60% of the patients in the period of the CRS consequences. Conclusion. Retrospective study determined that long-term human exposure to a dose rate of 0.001-0,009 Gy/h (0,005-0,05 Gy/day) and more in the accumulation of a summary dose of 1.7 and 9.6 Gy and duration of contact 6-96 months in 60% of cases can be expected development CRS with a subacute clinical course RBS. The main factor determining this feature of the course of RBS is the dose rate exceeding 0.001 Gy / h (2 Gy/year). In the subacute course of CRS, the early outcome in MDS is essentially deterministic. The development of agranulocytosis and anemic syndrome are typical signs of the subacute course of CRS.

The timely identification of germline genetic causes of pediatric bone marrow failure (BMF) impacts medical screening practices, family counseling, therapeutic decision-making, and risk of progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). At diagnosis, treatment decisions need to be made quickly to mitigate risks associated with profound cytopenias. As genetic testing options are rapidly evolving, an efficient multi-disciplinary approach and algorithm, including early involvement of a genetics team, is needed to expedite diagnosis and therapeutic decision-making. This process aids in the identification of appropriate candidates for molecular genetic testing. We present our single center experience reviewing the implementation of genetic counseling and a diagnostic and therapeutic algorithm used to guide genetic evaluation of pediatric BMF. Disease-specific next-generation sequencing (NGS) panels were most often pursued in patients who presented with a clinical phenotype consistent with a known inherited BMF syndrome and when trying to reduce incidental or uninformative results. Broader BMF NGS panels were most often utilized when unable to narrow the suspected etiology to a single disorder. Whole exome sequencing helped with optimizing treatment decision-making in higher risk children with BMF who required expedited hematopoietic stem cell transplantation. The experience has led to improvements to our process for evaluating patients with BMF.

Thus far, there have been no large cohort studies on total body irradiation (TBI)-containing conditioning regimens without antithymocyte globulin (ATG) in adults with aplastic anemia (AA) undergoing umbilical cord blood (UCB) transplantation (UCBT). We retrospectively analyzed 115 adults with idiopathic AA undergoing UCBT using TBI-containing reduced-intensity conditioning (RIC) regimens without ATG between 2000 and 2018 on behalf of the Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation. We then compared transplantation outcomes between a fludarabine (Flu)- and melphalan (Mel)-based regimen (FM) and a Flu- and cyclophosphamide (Cy)-based regimen (FC). The median patient age at UCBT was 41 years. The median total nucleated cell and total CD34+ cell doses in a UCB unit at cryopreservation were 2.5 × 107/kg and 0.7 × 105/kg, respectively. The median follow-up period for survivors was 47 months. The cumulative incidence rate of neutrophil engraftment was 76.5%, and the 4-year overall survival (OS) rate was 64.3%. In multivariate analysis, the covariates that were significantly associated with a higher neutrophil engraftment were total CD34+ cell dose in an UCB unit (≥ 0.7 × 105/kg; hazard ratio, 0.57, P = 0.01) and total dose of TBI (4 Gy of TBI; hazard ratio, 0.32, P = 0.01). There was no significant difference in the cumulative incidence of neutrophil engraftment and the 4-year OS between the FM and FC groups. In conclusion, TBI-containing RIC regimens without ATG are suitable for adults with AA undergoing UCBT. There were no significant differences in transplantation outcomes between the FM and FC groups.

Background: Immunosuppressive therapy is the Initial therapy for children with severe Aplastic anemia (SAA) and lacking a matched related donor. Cyclosporine A (Cy A) alone has been tried as single agent in resource poor Countries. Patients and Methods: This retrospective study was done to assess the outcome of immunosuppressive therapy (IST) in SAA children. It included 23 patients treated at Ain Shams University Pediatrics Hospitals between 2011- 2019 with IST, they received rabbit anti-thymocyte globulin (r ATG) plus (Cy A) (Group I, 8 patients) or Cy A alone (Group II, 15 patients). The median follow- up duration was 59 months. Results: one patient (4.3%) developed AML clone. another patient (4.3%) developed PNH clone. There was no significant difference in response between the two groups, Complete response was 34.7%, 43.5%, and 47.8% and partial response was 34.7%, 26.1%, 21.7% at 3, 6, and 12 months, respectively in the whole cohort. NR was present in 30.4% at 3, 6, and 12 months. Hypertension in 62.5% and higher levels of ALT, total and direct bilirubin were observed in group I as compared to group II. HAAA was clinically evident in 7 patients; 4 of them were hepatitis A, 1 was EBV, and 2 were seronegative for all viruses. At presentation they had significantly higher level of ALT, total bilirubin, and direct bilirubin. Conclusion: IST is an effective therapy in patients with SAA with overall response of 70%. Cy A alone can be an effective therapy in developing countries.

Background: Pancytopenia is a hematological entity which is relatively common. Its evaluation is important for arriving at an early and correct diagnosis, to aid in appropriate management. Materials and Methods: It was an observational study conducted in the Department of General Medicine and Clinical Hematology of our institute from June 2019 to May 2020. Clinical, hematological and biochemical parameters of 100 pancytopenic patients were evaluated and descriptive statistics was used. Results: The age ranged from 18-75 years. The commonest presentation was easy fatigability and fever. Besides pallor, splenomegaly and hepatomegaly were the presenting signs. Megaloblastic anaemia was detected in 64% followed by aplastic anaemia in 12% and acute leukemia in 6% patients. Among infective etiologies, two cases of malaria (P. falciparum). And each case of HIV, tuberculosis and dengue were seen. Lowest Hb% of 1.8 gm/dl, lowest total leucocyte count (TLC) of 500cells/cmm and lowest total platelet count (TPC) of 4000 cells/cmm was noted in a case of aplastic anemia. Macrocytic anemia was predominant blood picture. Hypercellular marrow was noted in 70(70%) cases and common cause was megaloblastic anemia, followed by leukaemia. Hypocellular marrow was noted in 12(12%) patients with aplastic anemia being commonest cause. Conclusion: In our study diagnosis of pancytopenia and its causes were ascertained by hematological investigations. An early and prompt treatment was given according to the cause and severity. Most of the cases had good prognosis due to a treatable cause. Keywords: Pancytopenia, Megaloblastic anaemia, Aplastic anaemia.

Background: TORCH infection has a role in aplastic anemia (AA). Fetal hemoglobin may be high in certain acquired hematological conditions such as aplastic anemia. We conducted this study to evaluate the correlation between certain congenital infections and severity of aplastic anemia and to study fetal Hb as a follow up marker during treatment of aplastic anemia. The aim of study was to correlation between certain congenital infection and severity of aplastic anemia and to study of hemoglobin F (HbF) as a follow up marker during treatment of aplastic anemia. Methods: Our prospective study was conducted on 20 children aged up to 18 years diagnosed with aplastic anemia following either bone marrow aspiration or biopsy that proves bone marrow hypocellularity with absence infiltrative BM disease or inherited BM disease recruited from Pediatric Hematology-Oncology Unit of Tanta University Hospital. Patients were classified according to level of HbF in to high HbF group and normal HbF group. Results: TORCH infections were detected in certain numbers of patients . HbF decreased in high HbF group after treatment. There was significant increase in CBC parameters in high HbF group than normal HbF group after treatment. There was insignificant decrease in mortality in high HbF group than normal HbF group. Mild to moderate cases were significantly higher with TORCH IgM +ve cases Conclusions: Acquired AA is associated with TORCH infection. In treated cases of AA, improvement of hematological parameters is associated with high HbF and from these results, it can be used as a prognostic marker to monitor the successful response of these cases to the used line of treatment.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were 10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed. Copyright r 2021 Wolters Kluwer Health, Inc. 34669357

Muhammad Asif Syed,1 Aneela Atta Ur Rahman,2 Muhammad Nadeem Shah Syed,3 Naveed Masood Memon4 1Field Epidemiology & Laboratory Training Program (FELTP), Karachi, Pakistan; 2Department of Community Medicine & Public Health Sciences, Liaquat University of Medical and Health Sciences, Jamshoro, Sindh, Pakistan; 3Federal NSTOP Officer, National Emergency Operation Center, Islamabad, Pakistan; 4Provincial Disease Surveillance and Response Unit, Hyderabad-Sindh, Field Epidemiology & Laboratory Training Program (FELTP), Karachi, PakistanCorrespondence: Muhammad Asif SyedField Epidemiology Laboratory Training Program (FELTP) Pakistan, Karachi, Sindh, PakistanTel +0092-286-34-77Email asif.mph@gmail.ccomIntroduction: Drug-induced aplastic anemia has long been a menacing outcome of modern pharmacotherapy. The incidence of idiosyncratic, drug-induced aplastic anemia varies depending on the genetic susceptibility and the associated drug. Only scarce studies have explained the epidemiology and actual incidence of this reaction.Purpose: The aim of the study was to establish the association between drugs and aplastic anemia.Methods: A case-control study was conducted with 191 cases and 696 controls at a tertiary hospital for blood diseases in Karachi-Pakistan. Cases were patients of aplastic anemia diagnosed through bone marrow biopsy. The controls did not have either AA or chronic diseases. Each case was paired with four sex and age group match controls. Cases and controls were compared with respect to the drugs used. Univariate and multivariate analysis were performed in order to delineate the association.Results: Median age of the study-participants was 27 years (04– 69 years). The majority 84 (44%) were from age group 16 to 30 years. The male-to-female ratio was 2:1. Among study participants, various drugs were significantly associated with aplastic anemia. Treatment of epilepsy with carbamazepine showed a positive association (OR=2.7, 95% C.I, 1.0– 6.8). An increased risk of aplastic anemia was noted with exposure to thiazide (OR=3.1, 95% C.I, 1.3– 7.4) and mebendazole (OR=3.7, 95% C.I, 1.5– 9.2). However, risks were not increased with chloramphenicol, trimethoprim/sulfamethoxazole, benzodiazepines, antihistamines, oral contraceptives, and herbal medicine.Conclusion: This large-scale case–control study provide association of aplastic anemia with exposure to carbamazepine, thiazides and mebendazole in population of Pakistan. Patients should be monitored with complete blood indices for early detection of drug toxicity.Keywords: drug induced aplastic anemia, case–control study, Karachi, Pakistan

Objective: Aplastic anemia (AA) is characterized by pancytopenia and hypocellular bone marrow. Several factors like infections, toxins, chemotherapeutics and radiations are known causes for the suppression of hematopoietic cells which results in bone marrow failure but the exact etiology is unknown. The current study was conducted to assess the baseline demographics, laboratory and clinical characteristics of patients presenting with aplastic anemia and evaluate their cytogenetic profile. Materials and Methods: A retrospective cohort study conducted at National Institute of Blood Diseases and Bone Marrow Transplantation after approval by Institutional Ethics Committee. In this study, AA patients were enrolled from January 2010 to December 2018. Data collection included demographic, laboratory and clinical characteristics including age, gender, symptoms, treatment, and blood counts. Cytogenetic analysis was performed on bone marrow samples. Data analysis was done by using SPSS version 23. Results: Based on camitta classification, a total of 362 aplastic anemia patients were enrolled in the study. The frequency of severe aplastic anemia was most common 199(55%). Median and interquartile range (IQR) age of overall patients was 17(11-26) years, for children and adult population it was 12(9-14) years and 28 (21-43) years respectively. Male predominance was observed i.e.251(69%). The most common presenting complaint was fever 202(55.8%). The median and IQR of hemoglobin (Hb) was 7.8(5.8-9.4)g/dl, MCV 90(83-91)fl, total leucocyte count (TLC) 2.6 (1.9-3.6) × 109/l, absolute neutrophil count (ANC) 0.64 (0.27-1.2)×109/l and platelet count 13 (5-27) ×109/l. Bone marrow cytogenetics was done and 76 (67%) patients were found to have normal karyotype. CMV was positive in 24(6.6%). Majority of patients were treated with blood transfusion and supportive care only 230(64%) and the survival rate was 84%. Conclusion: In conclusion, the study represents a large cohort of aplastic anemia in the country. Majority of cases were acquired aplastic anemia predominantly being severe aplastic. Limited numbers of patients opted for standard treatment options probably due to financial reservations to afford standard treatments like immune suppression therapy and hematopoietic stem cell transplant. Further, local studies with larger number of sample size and provision of standard treatment options are needed to explore the treatment response, etiological factors, prognosis and outcomes. Keywords: Aplastic anemia, Cytogenetics, Clinicohematological characteristics, Laboratory analysis, Survival outcome, Pakistan.

This article illustrates the development of a rare case of spontaneous subdural hematoma (SDH) secondary to aplastic anemia and conservative treatment of SDH. Clinical Presentation: a 43-year-old male complained of severe progressive headaches that starting from one month ago. His laboratory values showed pancytopenia and his peripheral blood smear showed no abnormalities except for the lack of number of erythrocytes, leukocyte, and thrombocyte. We could not find any malignancy in the smear. The patient experienced progressive headache, disorder of balance, and decrease of consciousness. CT imaging of the head showed a 7.0 cm (2 cm thickness) left frontal-parietal subdural hematoma. Patient were managed conservatively. This is a rare case of aplastic anemia with subdural hematoma and the patient was discharged in good condition.

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II-IV aGvHD, including two with grade III-IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

Establishing a diagnosis of aplastic anemia (AA) can be challenging, but it is absolutely critical to appropriate management, especially differentiating between acquired and inherited forms of the disease. The hematology field requires updated diagnostic guidelines to ensure that appropriate clinical pathways are pursued for patients and their safety. There are increasing clinical options for patients with immunosuppressive therapy and transplant once the diagnosis is made. In a case-based format, this review emphasizes the newer data on molecular (somatic and germline) findings in AA and how they are (or are not) helpful during diagnosis. There are key details on somatic mutation profiles and stated evidence where available for prognostic and treatment indications. Germline details of newer syndromes are also outlined, which make this review modern and reflect areas of uncertainty for clinicians.

Introduction The use of TKIs in CML has dramatically altered the natural course of the disease and improved outcomes for patients. TKIs overall have a very favorable safety profile. Dasatinib, a second generation TKI, is commonly used as a first-line treatment option in CML. Case report We describe the first two reported cases of first-line dasatinib induced aplastic anemia in CML. In both patients, pancytopenia occurred within one year of diagnosis/starting dasatinib. Both bone marrow biopsies showed hypocellularity with mild fibrosis and persistent BCR-Abl1 positivity. Management & outcome Dose reduction was attempted without success in both patients. In one patient, multiple TKIs were trialed, while in the other, growth factor support was attempted; neither regimen was effective. Ultimately, the cytopenias associated with dasatinib were only resolved after immunosuppression in one patient and allogeneic stem cell transplant in the other patient. Discussion Prior reports have shown that aplasia/aplastic anemia can rarely be associated with imatinib and nilotinib. Here we show that dasatinib can lead to this phenomenon as well. This diagnosis should be considered in patients with CML who unexpectedly develop cytopenias.

This study aims to determine the comparison of hemoglobin levels in patients with aplastic anemia who are transfused using fresh blood and save blood in H. Adam Malik General Hospital Medan. This study was conducted descriptively by comparing the results of the increase in post-transfusion hemoglobin levels using fresh blood and save blood in patients with aplastic anemia. The results showed that the average value of hemoglobin in patients with aplastic anemia before being transfused with fresh donor blood was 6.4 gr/dL, increasing to 8.9 gr/dL, while the average value of hemoglobin levels in patients with aplastic anameia before transfusion of save blood is 6.8 gr/dL increased after transfusion to 7.9 gr/dL. It can be concluded that blood transfusion using fresh blood is better than storing blood transfusion in increasing hemoglobin levels in patients with aplastic anemia, with an average percentage increase in fresh blood of 38.0% and donor save blood an average of 17.4%.

BACKGROUND Bone marrow of patients with aplastic anemia (AA) is different from that of patients with myelodysplastic syndrome (MDS) and is difficult to identify by blood examination. IDEAL-IQ (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) imaging might be able to quantify fat fraction (FF) and iron content in bone tissues. PURPOSE To determine if IDEAL-IQ measurements of bone marrow FF and iron content can distinguish between patients with AA and MDS. STUDY TYPE Retrospective. POPULATION Fifty-seven patients with AA, 21 patients with MDS, and 24 healthy controls. FIELD STRENGTH/SEQUENCE 3.0 T, IDEAL-IQ sequence. ASSESSMENT Three independent observers evaluated the IDEAL-IQ images and measured FF and R2* in the left posterior superior iliac spine. STATISTICAL TESTS Kruskal-Wallis test, linear correlations, and Bland-Altman analysis were used. A P-value of

This review focuses on the impact of bone marrow adipocytes on hematopoiesis and the development of hematological diseases. Bone marrow fat is a metabolically active organ capable of accumulating energy required for active hematopoiesis as well as of performing endocrine functions and participating in bone formation. Adipocytes can interact with the surrounding cells both directly and indirectly via cytokines and chemokines. Apart from their active involvement in the normal hematopoiesis, BMA have also been shown to play an important role in such diseases as leukemia, multiple myeloma and aplastic anemia. The role of fat cells in hematopoiesis is still unclear and not well studied, yet it is undoubtedly important, as demonstrated by the ever increasing number of publications supporting this conclusion.

Objectives Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response. Methods From May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. A 1:1 block randomization was employed for 2.5 and 3.5 mg/kg doses of r-ATG. Results No significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups (63% vs. 58%, P = .894). Median r-ATG concentrations on days 14 and 28 after IST were 15.2 (0.0-97.7) and 1.8 (0.0-74.9 µg/mL), respectively. According to r-ATG concentration, response rates were significantly higher in the group with higher r-ATG concentration than in those with lower r-ATG concentration (day 14, 88% vs. 52%; P = .006 and day 28, 79% vs. 46%; P = .005). In multivariate analysis, higher r-ATG concentrations at day 28 were independent predictors of favorable response to IST at 6 months (odds ratio, 0.29; 95% confidence interval, 0.09-0.93; P = .037). Conclusions The present data indicate that higher r-ATG concentration at day 28 resulted in improved IST response.

Introduction Aplastic anemia is a rare and potentially life-threatening hematological disorder with incidence of 1.4 to 14 cases/million. It is associated with exposures to certain environmental chemicals, drugs and infections. The objective was to investigate the association of illness with family history of aplastic anemia, exposure to pesticides and chemicals. Methodology A hospital-based case–control study (191 cases, 696 controls) was conducted from 1st January 2015 to 31st December 2018 in Karachi, Sindh. Cases were patients with diagnosis of aplastic anemia confirmed with bone marrow biopsy. Controls neither had aplastic anemia nor other hematological chronic diseases. An in-person interview was conducted to collect demographic information, family history of aplastic anemia, and history of pesticide and chemical exposure. The adjusted odds ratios (aOR) with 95% confidence intervals (CI) were estimated via SPSS v22. Results A total of 191 confirmed aplastic anemia cases were selected. Mean age was 29 years (range: 4–69) and predominantly there were males 129 (67.5%). The majority, 84 (44.0%), of the cases were aged 16–30 years. In multivariate analysis models, the significant associations were observed between aplastic anemia with family history of aplastic anemia (aOR=13.3, 95% C.I 3.66–48.50), exposure to pesticides (aOR=2.1, 95% C.I 1.23–3.61) and chemicals (aOR=3.6, 95% C.I 2.06–6.34). Conclusion This study observed a significant association of aplastic anemia with family history of aplastic anemia, exposure to pesticide and insecticide exposure. However, to establish this connection, further longitudinal studies are warranted., Video Abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/qPDeSjfZPbo

Introduction Celiac disease typically presents with symptoms of malabsorption, but extraintestinal manifestations are increasingly reported. Aplastic anemia as the mode of celiac disease presentation is extremely rare in children. Case presentation We report a 2‐year‐old boy who presented with loose stools, loss of appetite, and bicytopenia with severe aregenerative normocytic anemia. Investigations, including bone marrow aspirate and biopsy, revealed aplastic anemia. Screening for malabsorption showed increased plasma concentrations of anti‐transglutaminase and anti‐gliadin antibodies. A duodenal biopsy confirmed the histologic features of celiac disease. The child received a packed red cell transfusion and was started on a gluten‐free diet, with a very good prognosis and normalization of both his blood and histological parameters. To the best of our knowledge, our report is the sixth pediatric case in the literature. Conclusion Screening for celiac disease should be performed in children with unexplained hematological abnormalities such as aplastic anemia with or without gastrointestinal symptoms.

Aplastic anemia or medullary aplasia is a medical condition characterized by pancytopenia and is associated with a high prevalence of morbidity and mortality. In patients in whom bone marrow transplantation cannot be attempted, an immunosuppressive regimen is considered to be the first-line therapy. Also, the addition of eltrombopag from the first day of immunosuppressive treatment seems to significantly increase response rate. Unfortunately, there are a small number of patients who remain unresponsive to all these therapies. Here we present the case of a young woman who was referred by the family doctor complaining of marked physical asthenia, new onset dyspnea, and dizziness. Apart from a severe pancytopenia, no further changes have been brought to light by paraclinical investigations. After multiple secondary causes were excluded, the patient was diagnosed with idiopathic aplastic anemia. Even if bone marrow transplant was the first-line therapy in this case, because of the severe leukopenia, it was not possible to determine the HLA type. Therefore, the patient was prescribed immunosuppressive treatment. Despite the three drug-associated therapy (horse anti-thymocyte globulin, cyclosporin A, and eltrombopag), the response was unsatisfactory, with the persistence of severe pancytopenia.

Thrombosis is a leading cause of morbidity and mortality in paroxysmal nocturnal hemoglobinuria (PNH). Multiple factors are responsible for the thrombotic tendency in these patients. Endothelial progenitorcells (EPCs) originate from primitive hematopoietic stem cells. The EPC count is considered indicative of potential damage and restoration capacity in vascular disease; lower EPC counts are deemed as a risk factor in cardiovascular diseases. We aimed to investigate the count of circulating EPCs in PNH and aplastic anemia (AA) patients receiving eculizumab treatment or not receiving treatment and their relationship with thrombosis. Seventeen PNH patients, 18 AA patients, and 10 healthy volunteers were included in the study. The CD309, CD133, and CD34 antibodies were used to determine counts of circulating EPCs using flowcytometry. EPC levels were compared between the PNH, AA, and healthy control groups. Kolmogorov–Smirnov test. ANOVA, Kruskal–Wallis, and Mann–Whitney U testswereperformedto analyze the quantitative data, while χ2 testing was performed to analyze the qualitative data. Therewasnosignificantdifference in EPC levelsbetweenpatientswithandwithout a history of thrombosis (P > 0.05). Further, therewasnosignificantdifference in thelevels of EPCsbetweenthe AA and PNH groups (P > 0.05). However, there was a significant positive correlation between levels of EPCs and lactate dehydrogenase (LDH) in multivariate analysis (P

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

Thrombocytopenia results from a variety of conditions, including radiation, chemotherapy, autoimmune disease, bone marrow disorders, pathologic conditions associated with surgical procedures, hematopoietic stem cell transplant (HSCT), and hematologic disorders associated with severe aplastic anemia. Immune thrombocytopenia (ITP) is caused by immune reactions that accelerate destruction and reduce production of platelets. Thrombopoietin (TPO) is a critical component of platelet production pathways, and TPO receptor agonists (TPO-RAs) are important for the management of ITP by increasing platelet production and reducing the need for other treatments. Romiplostim is a TPO-RA approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia, as well as for use in patients with refractory aplastic anemia in Japan and Korea. Romiplostim binds to and activates the TPO receptor on megakaryocyte precursors, thus promoting cell proliferation and viability, resulting in increased platelet production. Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. In addition to its efficacy in ITP, studies have shown that romiplostim is effective in improving platelet counts in various settings, thereby highlighting the versatility of romiplostim. The efficacy of romiplostim in such disorders is currently under investigation. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease.

The article presents two cases of hepatitis-associated aplastic anemia in the last year. The literature data on the new nosology are presented. The clinical picture, diagnosis and treatment are discussed. The questions of diagnosis and treatment that affect the prognosis are raised. Treatment preference should be given to allogeneic bone marrow transplantation, as it has better results than aggressive immunosuppressive therapy that is difficult for patients to tolerate.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial injury syndrome that complicates hematopoietic stem cell transplant (HSCT). Morbidity and mortality from TA-TMA remain high, making prevention critical. We describe our retrospective single-center experience of TA-TMA after pediatric allogeneic HSCT and present a novel pre-HSCT risk-stratification system and prophylaxis regimen. From January 2012 through October 2019, 257 patients underwent 292 allogeneic HSCTs. Prospective risk stratification was introduced in December 2016. High-risk (HR) patients were treated with combination prophylaxis with eicosapentaenoic acid and N-acetylcysteine. The 1-year cumulative incidence of TA-TMA was 6.3% (95% confidence interval [CI], 3.2-9.4). Age ≥10 years, myeloablative conditioning with total body irradiation, HLA mismatch, diagnosis of severe aplastic anemia or malignancy, prior calcineurin inhibitor exposure, and recipient cytomegalovirus seropositivity were found to be pre-HSCT risk factors for development of TA-TMA. Before routine prophylaxis, TA-TMA rates were significantly different between the HR and standard-risk groups, at 28.2% (95% CI, 0-12.7) vs 3.2% (0.1-6.3), respectively (P < .001). After introduction of prophylaxis, the 1-year cumulative incidence of TA-TMA in the HR group decreased to 4.5% (95% CI, 0-13.1; P = .062, compared with the incidence before prophylaxis). Multicenter pediatric studies are needed to validate these risk criteria and to confirm the efficacy of the prophylactic regimen.

To evaluate the efficacy and safety of Pai-Neng-Da Capsule (派能达胶囊, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P

Eltrombopag is being investigated for the treatment of aplastic anemia (AA) by stimulating hematopoietic stem cell (HSC) proliferation. To evaluate the efficacy and safety of eltrombopag in the first-line therapy of pediatric AA. The present retrospective study assessed pediatric patients with newly diagnosed AA administered immunosuppressive therapy (IST) (rabbit ATG combined with CSA) with eltrombopag at a single center from March to September 2017. All patients were followed up for2 years. A total of 14 patients (8 males), averagely aged 86 months, were enrolled in this study. Eltrombopag was administered with a median time to initiation of 19.5 days after IST; the median course of treatment was 253 days. Complete and overall response rates at 6 months were 64.3% (9/14 case) and 78.6% (11/14 cases), respectively. The survival rate was 100%, and no relapse occurred in responders. Eltrombopag was well-tolerated; however, the most common adverse events included indirect bilirubin elevation, jaundice, and transient liver-enzyme elevation. By the end of follow-up, bone marrow chromosomes were normal, and no abnormal myelodysplastic syndrome (MDS)-related clones appeared. Addition of eltrombopag to IST is associated with markedly increased complete response with respect to hematology in pediatric patients with SAA compared with a historical cohort, without intolerable side effects.

For cord blood transplantation (CBT), appropriate patient and conditioning regimen selection is necessary to achieve long-term disease-free survival. This review aims to provide comprehensive guidelines on these issues using evidence from the literature and experience at dedicated CBT centers. Topics include patient and disease characteristics that make CBT a good or poor choice and a review of outcomes in commonly used conditioning regimens in CBT. This is accompanied with recommendations on regimen intensity based on disease, organ function, and patient performance status and age. In addition, the use of antithymocyte globulin in CBT is discussed, as is the choice of conditioning in aplastic anemia patients who have access to acceptable CB units.

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.

Immune thrombocytopenia is an immune condition where antibodies are produced against platelets. Eltrombopag is a thrombopoietin receptor agonist that stimulates and promotes platelet production approved for treating thrombocytopenia in patients with chronic immune thrombocytopenia, where other treatments such as corticosteroids, splenectomy or immunoglobulins are inadequate. The aim of this meta-analysis was to evaluate the efficacy and safety of the eltrombopag in adults and children with immune thrombocytopenia. We included 7 studies with a total of 765 patients (606 adults and 159 children). We evaluated the number of patients that achieved a post-treatment platelet count equal or above 50x109/L (primary result-target) without the need of rescue treatment for at least 4 weeks. Our data showed that patients who received eltrombopag were almost 4 times more probable in achieving the primary target when compared to patients who received placebo (RR 3.84, 95% CI 2.39 to 6.14; I2 = 46%). The number of patients needed rescue treatment and the number of bleeding incidents were reduced in the group that received eltrombopag when compared to those who received placebo (RR 0.40, 95% CI 0.25 to 0.62; I2 = 40%) (RR 0.74, 95% CI 0.62 to 0.89; I2 = 68%). The total number of side effects did not statistically differ between the two groups (RR 0.99, 95% CI 0.90 to 1.08; I2 = 14%). Our findings were similar to previously published studies and confirm that eltrombopag is safe and efficient in immune thrombocytopenia. However, more clinical trials are needed in order to enhance our findings.

Severe aplastic anemia and congenital amegakaryocytic thrombocytopenia are rare bone marrow failure syndromes. Treatment for aplastic anemia consists of hematopoietic stem cell transplantation (HSCT) from a matched sibling donor or immunosuppressant drugs if there is no donor available. Congenital amegakaryocytic thrombocytopenia is a rare autosomal recessive disease that causes bone marrow failure and has limited treatment options, except for transfusion support and HSCT. In the absence of a suitable matched sibling donor, matched-unrelated, haploidentical, or mismatched donors may be considered. A 2-step partial T-cell-depletion strategy can remove CD45RA+ naïve T cells responsible for graft-versus-host disease (GvHD) while preserving memory T cells. Five patients underwent transplantation using this strategy with rapid neutrophil and platelet recovery. Acute and chronic GvHD ≥ grade 2 appeared in two and one patient, respectively. No severe infections were observed before day + 100. A high (60%) incidence of transplant-associated microangiopathy was observed. Three patients (60%) remain alive, with a median follow-up of 881 (range 323-1248) days. CD45RA-depleted HSCT is a novel approach for patients lacking a suitable matched donor; however, further improvements are needed.

Primary immune thrombocytopenia (ITP) in children is a diagnosis of exclusion, but cases of secondary ITP and nonimmune thrombocytopenia (non-IT) are generally difficult to recognize in a timely fashion. We describe a pediatric population with a revised diagnosis of secondary ITP or non-IT within 24 months of follow-up. Data were extracted from the Pediatric and Adult Registry on Chronic ITP, an international multicenter registry collecting data prospectively in patients with newly diagnosed primary ITP. Between 2004 and 2019, a total of 3974 children aged 3 months to 16 years were included. Secondary ITP and non-IT were reported in 113 patients (63 female subjects). Infectious (n = 53) and autoimmune (n = 42) diseases were identified as the main causes, with median ages at diagnosis of 3.2 years (interquartile range: 1.2; 6.7 years) and 12.4 years (interquartile range: 7.6; 13.7 years), respectively. Other causes included malignancies, aplastic anemia, immunodeficiency, and drug use. Patients with malignancy and aplastic anemia had significantly higher initial platelet counts (37 and 52 × 109/L) than did those with infection or autoimmune diseases (12 and 13 × 109/L). Characteristics of patients with secondary ITP due to infection were similar to those of children with primary ITP at first presentation, indicating similar mechanisms. Significant differences were found for age, sex, comorbidities, initial bleeding, sustained need for treatment, and disease persistence for the remaining noninfectious group compared with primary ITP. Based on our findings, we propose a diagnostic algorithm that may serve as a basis for further discussion and prospective trials.

In this large single-centre study, we report high prevalence (25%) of, small (p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH−, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH− for HSCT; in AA: 78 vs. 50% for IST, p p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival [73% (95% CI 68–77) vs. 51% (48–54), p p

Background Invasive fungal infections (IFIs) are a leading cause of morbidity and death in immunocompromised patients. Data on efficacy and pharmacokinetics of posaconazole in pediatric patients are rare (1 to 5). Herein, we retrospectively analyzed adolescent patients who had received posaconazole as antifungal prophylaxis. Methods We retrospectively analyzed patients who received posaconazole as primary or secondary antifungal prophylaxis. Results A total of 34 adolescent patients, 19 men (55.9%) and 15 women (44.1%) with a mean age of 15.8±2.1 years were included. Twenty-five of 34 (73.5%) patients were on primary and nine of 34 (26.5%) patients were on secondary antifungal prophylaxis. Diagnosis of the patients receiving posaconazole as primary antifungal prophylaxis were acute myeloid leukemia (n=12, 48%), hematopoietic stem cell transplantation (n=7, 28%), acute lymphoblastic leukemia (n=5, 20%), and Fanconi aplastic anemia (n=1, 4%). Five patients (55.6%) with hematopoietic stem cell transplantation, 1 patient with acute myeloid leukemia (11.1%), 1 patient with Fanconi aplastic anemia (11.1%), and 2 (22.2%) patients with chronic granulomatous disease received posaconazole as secondary antifungal prophylaxis. Twelve of 25 (48%) patients receiving posaconazole as primary antifungal prophylaxis were complicated by IFI; 4 of them were proven, 6 probable, and 2 with possible IFI. Three of 9 patients (33.3%) receiving posaconazole as secondary antifungal prophylaxis was complicated by IFI (P=0.29), 2 of them were probable and 1 was possible IFI. Five of 25 patients (20%) receiving posaconazole as primary prophylaxis died because of IFI. Conclusion Improvement of antifungal prophylaxis in patients with high risk of invasive infections seems clearly necessary, and analyzing serum posaconazole levels and individualizing dosing may be 1 approach to improve outcomes.

Introduction: Pregnancy-associated aplastic anemia (pAA) occurs when aplastic anemia (AA) is diagnosed for the first time during pregnancy and it is a rare but serious condition leading to severe maternal and fetal complications. It is unknown whether pregnancy triggers bone marrow failure or if this state is unrelated to the pathogenesis of pAA.Areas covered: In this review, three new cases of pAA are presented and its controversial etiologic relationship with pregnancy, its atypical presentation, and management are also discussed. Furthermore, a literature review of pAA cases between 1975 and 2020 was performed in PubMed, accessed via the National Library of Medicine PubMed interface. Keywords included 'aplastic anemia' AND 'pregnancy'. We found 54 cases reported in the literature with a clear diagnosis of pAA.Expert opinion: The diagnosis of pAA is challenging since pregnancy is associated with physiologic hematological changes in the complete blood count which can mask the disease. Meticulous monitoring and adequate support therapy given by a trained multidisciplinary team have the potential to improve outcomes for women and their neonates. All women should receive frequent assessments to optimize their care during pregnancy and after delivery, definitive treatment should be offered.

Platelet transfusion refractoriness results in adverse outcomes and increased health care costs. Managing refractoriness resulting from HLA alloimmunization necessitates the use of HLA antigen–matched platelets but requires a large platelet donor pool and does not guarantee full matching. We report the first randomized, double-blind, noninferiority, crossover trial comparing HLA epitope–matched (HEM) platelets with HLA standard antigen–matched (HSM) platelet transfusions. Alloimmunized, platelet-refractory, thrombocytopenic patients with aplastic anemia, myelodysplastic syndrome, or acute myeloid leukemia were eligible. HEM platelets were selected using HLAMatchMaker epitope (specifically eplet) matching. Patients received up to 8 prophylactic HEM and HSM transfusions provided in random order. The primary outcome was 1-hour posttransfusion platelet count increment (PCI). Forty-nine patients were randomized at 14 UK hospitals. For intention to treat, numbers of evaluable transfusions were 107 and 112 for HEM and HSM methods, respectively. Unadjusted mean PCIs for HEM and HSM methods were 23.9 (standard deviation [SD], 15) and 23.5 (SD, 14.1), respectively (adjusted mean difference, −0.1; 95% confidence interval [CI], −2.9 to 2.8). Because the lower limit of the 95% CI was not greater than the predefined noninferiority limit, the HEM approach was declared noninferior to the HSM approach. There were no differences in secondary outcomes of platelet counts, transfusion requirements, and bleeding events. Adequate 1-hour PCI was more frequently observed, with a mean number of 3.2 epitope mismatches, compared with 5.5 epitope mismatches for inadequate 1-hour increments. For every additional epitope mismatch, the likelihood of an adequate PCI decreased by 15%. Epitope-matched platelets should be considered to support HLA alloimmunized patients. This trial was registered at www.isrctn.com as #ISRCTN23996532.

Introduction Aplastic anemia (AA) is characterized by diminished hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. In Pakistan, AA is not uncommon, and allogeneic hematopoietic stem cell transplant remains the only curative option for these patients. Objective The objective of this study was to determine the transplant outcome of combined granulocyte colony-stimulating factor (G-CSF) primed blood and bone marrow grafts in adult and pediatric patients with AA. Methods We retrospectively collected the data of all transplant procedures performed from 2004 to 2019 at Aga Khan University in Karachi, Pakistan. Variables analyzed included age, sex, type of stem cells used, conditioning regimens, and overall survival for patients undergoing transplant in AA. Results A total of 351 transplants were performed during the study period. Out of these, 239 were allogeneic transplants, whereas 112 were autologous procedures. We performed 70 transplants for AA during the study period, of which 52 were male patients and 18 were female patients. The median age ± standard deviation (SD) was 17.5 ± 9.4 years (range, 2-43 years). Cyclophosphamide/antithymocyte globulin (ATG) was used as a conditioning regimen in 65 patients, while ATG/cyclophosphamide/fludarabine was used in 5 patients. In 60 patients, a combination of G-CSF primed blood and bone marrow stem cells were used. The mean CD34 count was 5.2 × 106/kg. Graft-vs-host disease (GVHD) prophylaxis was done with cyclosporine and methotrexate. All patients received standard infection prophylaxis. Engraftment was achieved in 86% of patients. The median day of myeloid engraftment was 15 (range, 10-22 days). Chronic GVHD was present in 3 patients while 4 had acute GVHD. The overall survival was 71.2% (median duration of 80 months). The main cause of mortality was gram-negative sepsis. Conclusion A combination of blood and bone marrow stem cells results in early engraftment with decreased frequency of GVHD in AA. The overall survival was comparable to international literature.

Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naive and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan.

Background: Pancytopenia is a triage of anemia, leukopenia, and thrombocytopenia. The etiology causing pancytopenia varies depending upon factors such as age, sex, occupation, and geographical distribution. Unfortunately, the major treatises of hematology have not given emphasis on the hemorrhagic manifestation of different etiologies causing pancytopenia. Objective: This observational study was carried out with the aim to identify hemorrhagic manifestation in patients with pancytopenia in eastern India. Design: This study was conducted over a period of two years at the Department of Medicine of a tertiary care teaching institute in eastern India. All the patients with features of anemia, thrombocytopenia, or leukopenia were screened for pancytopenia and a total of 214 cases were selected. Patients were divided into two groups as patients with age more than 14 years constitute group one and the patients less than 14 years constitute the second group. A detailed physical examination, hematological, and biochemical investigation was done to ascertain the hemorrhagic manifestations in pancytopenia patients. Results: In the groups, the most common cause of hemorrhagic manifestation in patients with pancytopenia was aplastic anemic, leukemia, myelodysplastic syndrome, and myelofibrosis. No bleeding manifestation was seen in patients with megaloblastic anemia, kala-azar, hypersplenism, and other causes of pancytopenia. Conclusions: Patients with pancytopenia caused by aplastic anemia, acute leukemia, and myelodysplastic syndrome have more chances of bleeding manifestation as compared with pancytopenia caused by megaloblastic anemia, kala-azar, or hypersplenism.