1.Camitta criteria divide reocclusion into heavy and light.
(1) Diagnostic criteria for heavy reoccurrence
1) Bone marrow cell hyperplasia <25% of normal; if <50% of normal, then hematopoietic cells should be <30%.
2) Blood picture: two of the following three must be present: neutrophils <0.5×109/L; reticulocytes <1% or absolute value <4×109/L; platelets <20×109/L. If neutrophils <0.2×109/L is very heavy.
(2) Diagnostic criteria for mild reocclusion
1)Myeloproliferative hypoplasia.
2)Decreased whole blood cell.
2. The pathophysiology of aplastic anemia includes.
(1)immune-mediated bone marrow destruction
(2) Loss of hematopoietic stem cells in aplastic anemia: stem cell reserve is probably the ultimate important factor affecting the prognosis of non-transplant treatment. Stem cell-stimulating small molecules can improve complete blood counts in some patients with chronic refractory aplastic anemia and accelerate blood recovery in untreated patients, implying that stem cells are sensitive to value-added signals in their hypoproliferative bone marrow.
(3) Genetics of bone marrow failure in acquired aplastic anemia: TERT or TERC gene mutations are considered risk factors but not genetic factors for bone marrow failure, there are no systematic data on transplantation outcomes in patients with TERT and TERC gene mutations, but genetic determination of potential family members is essential to avoid selection of donors with the same gene mutation and stem cell reserve insufficiency.
3. Treatment concepts
(1) Immunosuppressive therapy: The combination of equine anti-thymocyte globulin and cyclosporine remains the first-line standard of immunosuppressive therapy.
(2) Stem cell stimulation therapy: The improvement of eltrombopar in patients with refractory severe aplastic anemia was completely unanticipated. Eltrombopar is a thrombopoietin mimetic, a small molecule designed to trigger mpl surface antibodies and signal transduction pathways for avoiding intact thrombopoietin protein antibody formation and medical-derived idiopathic thrombocytopenia problems. Eltrombopta is now used in combination with standard equine ATG and cyclosporine for the treatment of severe reoccurrence, and initial results are encouraging, with efficacy at least as high as immunosuppressive therapy alone and rapid growth in blood cell counts.
(3) Supportive therapy: Although the patient’s initial treatment concentration at an experienced higher center is consistent with the study protocol, long-term therapy should also be left to the local physician’s management. The dramatic improvement in general survival of patients with aplastic anemia may be explained by physician education and the introduction of effective, easily administered antifungal drugs that were greatly improved.
(4) Bone marrow transplantation therapy
1) HLA-matched sibling donor transplantation
For patients younger than 40 years of age, allogeneic hematopoietic stem cell transplantation (HSCT) is a pre-treatment option for younger patients with severe aplastic anemia (SAA). Cyclophosphamide (CY) in combination with anti-thymocyte globulin (ATG) as a pretreatment regimen and cyclosporine A (CsA) and methotrexate (MTX) is an effective treatment.
The gold standard for patients with acquired aplastic anemia receiving transplantation from an HLA-matched sibling donor is: CY + ATG treatment of the bone marrow source and CsA + MTX for prevention of graft-versus-host disease (GVHD). Increasing the total amount of anti-thymocyte globulin (ATG) and cyclophosphamide (CY) up to 200 mg/kg has been shown to have a good implantation-promoting effect and long-term results that will ensure a low incidence of graft-versus-host disease (GVHD). Post-transplant prophylaxis of graft-versus-host disease (GVHD) with cyclosporine A (CsA) in combination with methotrexate (MTX). Adequate post-transplant immunosuppressive therapy is important to prevent graft-versus-host disease and to ensure adequate suppression of the host’s immune system and to prevent graft rejection.
For patients older than 40 years, immunosuppressive therapy is usually chosen first, and transplantation is chosen after 1 to 2 courses of immunosuppressive therapy (IST) have failed.
2) Unrelated donor (UD) transplantation
Unrelated donor transplantation is now often considered after a course of immunosuppressive therapy. Unrelated donor bone marrow transplantation is even considered as a first-line treatment option for some pediatric patients with severe remittent disease. Fludarabine (Flu) + cyclophosphamide (CY) in combination with ATG (FCA) is the most commonly used regimen for acquired aplastic anemia and unrelated donor hematopoietic stem cell transplant pretreatment. The European Blood Bone Marrow Transplant Consortium (EBMT) working group for severe aplastic anemia (SAA) currently recommends fludarabine (Flu) 30 mg/O x 4, cyclophosphamide (CY) 30 mg/kg x 4, and ATG. radiotherapy can be added for patients older than 14 years of age (2 GY)