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Aplastic anemia

What's new

Updated 2024 ASTCT guidelines for allogeneic hematopoietic cell transplantation in aplastic anemia .

Background

Overview

Definition
AA is a rare hematopoietic stem cell disorder that results in pancytopenia and hypocellular bone marrow.
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Pathophysiology
The pathophysiology of AA is largely immune-mediated, with autoreactive lymphocytes mediating the destruction of hematopoietic stem cells. This immune dysregulation leads to bone marrow failure and the cessation of new blood cell production.
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Epidemiology
The incidence of AA is estimated at 0.2-0.3 per 100,000 person-years in Europe.
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Risk factors
Risk factors for AA include exposure to specific medications, pesticides, and certain chemicals, as well as genetic predisposition and low socioeconomic status.
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Disease course
Clinically, patients may present with symptoms related to anemia, such as fatigue and pallor, bleeding tendencies due to thrombocytopenia, and increased susceptibility to infections due to neutropenia. A significant complication of AA is the risk of progression to myelodysplastic syndromes or acute myeloid leukemia.
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Prognosis and risk of recurrence
The prognosis of AA can vary widely. Some patients may have mild symptoms that require little or no therapy, while others may present with life-threatening pancytopenia.
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Guidelines

Key sources

The following summarized guidelines for the evaluation and management of aplastic anemia are prepared by our editorial team based on guidelines from the American Society for Transplantation and Cellular Therapy & Cell Therapy Transplant Canada (ASTCT 2024), the British Society for Haematology (BSH 2024,2018), the North American Pediatric Aplastic Anemia Consortium (NAPAAC 2021), and the Kidney Disease: Improving Global Outcomes ...
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Classification and risk stratification

Severity assessment: as per BSH 2024 guidelines, assess the severity of AA according to the Camitta criteria.
B
Modified Camitta criteria for aplastic anemia severity
Marrow cellularity
< 25% or 25-50% with < 30% residual hematopoietic cells
Neutrophils
≥ 0.5×10⁹/L
< 0.5×10⁹/L
< 0.2×10⁹/L
Platelets
≥ 20×10⁹/L
< 20×10⁹/L
Reticulocytes
≥ 20×10⁹/L
< 20×10⁹/L
Non-severe aplastic anemia
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Diagnostic investigations

Initial assessment: as per ASTCT 2024 guidelines, obtain testing to confirm the diagnosis and look for underlying causes of bone marrow failure in all patients with AA. Assess all newly diagnosed patients with AA for indications for hematopoietic cell transplantation and initiation of donor search.
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  • Evaluation for inherited AA

  • Medication history

  • Screening for paroxysmal nocturnal hemoglobinuria

Diagnostic procedures

Bone marrow biopsy
As per BSH 2024 guidelines:
Perform bone marrow aspiration of an adequate sample and trephine biopsy of good length (> 1.5 cm) for the diagnosis of AA and exclusion of other causes of pancytopenia with a hypocellular marrow.
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Differentiate AA from hypoplastic myelodysplastic syndrome by integrating cytohistological and genetic features.
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Medical management

General principles: as per BSH 2024 guidelines, ensure a multidisciplinary team meeting approach to collate relevant results and develop a treatment plan. Consider seeking expert advice on the diagnosis and management where there is uncertainty or when an inherited bone marrow failure syndrome is being considered.
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  • Antithymocyte globulin

  • Cyclophosphamide

  • Eltrombopag

  • Iron chelation therapy

  • Antimicrobial prophylaxis

Therapeutic procedures

Blood transfusion
As per BSH 2024 guidelines:
Insufficient evidence to recommend RBC transfusion support in patients with AA.
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Consider using a restrictive transfusion strategy (hemoglobin 70-80 g/L; 80 g/L for patients with CVD) in stable hospitalized patients. Consider adopting individual transfusion plans in outpatients depending on symptoms and comorbidities in line with the limited data in myelodysplastic syndrome.
C
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  • Platelet transfusion

  • Hemopoietic stem cell transplantation (indications)

  • Hemopoietic stem cell transplantation (conditioning regimens)

  • Hemopoietic stem cell transplantation (GvHD prophylaxis)

  • Hemopoietic stem cell transplantation (management of poor graft function)

  • Hemopoietic stem cell transplantation (management of donor-specific anti-HLA antibodies, prevention)

  • Hemopoietic stem cell transplantation (management of donor-specific anti-HLA antibodies, testing)

  • Hemopoietic stem cell transplantation (management of donor-specific anti-HLA antibodies, desensitization therapy)

  • Hemopoietic stem cell transplantation (management of donor-specific anti-HLA antibodies, follow-up)

  • Hemopoietic stem cell transplantation (management of non-donor-specific anti-HLA antibodies)

Specific circumstances

Pediatric patients, evaluation: as per NAPAAC 2021 guidelines, obtain the following evaluations in all patients:
Situation
Guidance
Baseline laboratory tests
CBC with differential
Absolute reticulocyte count
Peripheral smear
Serum electrolytes, liver transaminases, total and direct bilirubin
BUN, creatinine
LDH, uric acid
Direct/indirect antiglobulin test (Coombs)
PT, PTT, fibrinogen
Bone marrow aspiration
Morphology
Evaluation for leukemic blasts (flow cytometry unless insufficient cells, with or without appropriate immunostaining)
Iron stain
Cytogenetics
Fluorescent in situ hybridization, including evaluation for 7/del (7q), -5/del (5q), +8, del (20q)
Bone marrow biopsy
Cellularity
Morphology (including immunohistochemical staining for CD34 to evaluate for blasts and CD61 to evaluate for micromegakaryocytes)
Reticulin stain
Infectious diseases
Hepatitis serology (serology for hepatitis A, B, C, and E)
EBV (serology, PCR)
CMV (serology, PCR)
Parvovirus (serology, PCR)
Human herpes virus 6 (PCR)
HIV-1 (antigen/antibody screen)
HSV 1 and 2 (serology)
Varicella (IgG, baseline before treatment)
Immunologic
Immunoglobulins (IgG, IgM, IgA)
Lymphocyte subset immunophenotyping (CD3, CD4, CD8, CD19, CD56)
Rheumatologic
ANA
Complement 3 and 4
Fetal hemoglobin
Hemoglobin F level (hemoglobin electrophoresis or high-performance liquid chromatography)
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria screening panel of RBCs and WBCs (high sensitivity multi-parameter flow cytometry on peripheral blood)
Fanconi anemia
Chromosomal fragility testing (diepoxybutane assay, or mitomycin C as an alternative assay
Dyskeratosis congenita
Telomere evaluation by flow-fluorescent in situ hybridization (6-cell panel, or 2-cell panel if 6-cell panel not readily available)
HLA typing
High-resolution typing in patients, including class I (A, B, C) and class II (DR, DQ, DP)
High-resolution typing on all full siblings (consider obtaining low-resolution typing if high-resolution cannot be obtained or per institutional guidelines)
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  • Pediatric patients (management)

  • Elderly patients

  • Pregnant patients

  • Patients with antibody-mediated pure red cell aplasia (evaluation)

  • Patients with antibody-mediated pure red cell aplasia (cessation of ESA therapy)

  • Patients with antibody-mediated pure red cell aplasia (peginesatide)