|
|
Line 82: |
Line 82: |
| ===Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone=== | | ===Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone=== |
|
| |
|
| * The presence of an abnormal cytogenetic clone in the presence of an otherwise typical aplastic anaemia does not necessarily equate with a diagnosis of [[myelodysplastic syndromes]] (MDS) or [[acute myeloid leukaemia]] (AML), as abnormal cytogenetic clones occur in up to 12% of patients with [[aplastic anaemia]].
| | Management of Patients with Aplastic Anaemia Who Have a Significant PNH Clone, Resulting in Clinical and/or Laboratory Evidence of Haemolysis |
| * The presence of monosomy 7 is more often sinister with a high risk of transformation to MDS or AML.
| | |
| | Small PNH clones, in the absence of evidence of haemolysis, occur in up to 50% of patients with aplastic anaemia. |
| | ATG is not recommended if there is a history of PNH-associated thrombosis. |
| | All patients who are not transplanted should be screened for PNH by flow cytometry every 12 months. |
|
| |
|
| }} | | }} |
Revision as of 15:50, 23 September 2012
Editor-In-Chief: Aric Hall, M.D., Beth Israel Deaconess Medical Center, Boston, MA [1]
Overview
Medical therapy of aplastic anemia often includes a short course of anti-thymocyte globulin (ATG or anti-lymphocyte globulin) and several months of treatment with cyclosporin to modulate the immune system. Mild chemotherapy with agents such as cyclophosphamide and vincristine may also be effective. Antibodies therapy, such as ATG, targets T-cells, which are believed to attack the bone marrow. Steroids are generally ineffective.
Medical Therapy
Supportive Care in treatment of aplastic anemia [1] (DONOT EDIT)
“
|
Supportive Care
- Prophylactic platelet transfusions should be given when the platelet count is <10 x 109/L (or <20 x 109/L in the presence of fever).
- Irradiated blood products should be given routinely to all patients having antithymocyte globulin (ATG) treatment.
- Transfusion of irradiated granulocyte transfusions may be considered in patients with life-threatening neutropenic sepsis.
- The routine use of recombinant human erythropoietin (rHuEPO) in aplastic anaemia is not recommended.
- A short course of granulocyte colony-stimulating factor (G-CSF) may be considered for severe systemic infection that is not responding to intravenous antibiotics and anti-fungal drugs, but should be discontinued after 1 week if there is no increase in the neutrophil count.
- Prophylactic antibiotic and antifungal drugs should be given to patients with neutrophil count <0.2 x 109/L.
- Systemic antifungal therapy should be introduced into the febrile neutropenia regimen early if fevers persist.
- Iron chelation therapy should be considered when the serum ferritin is >1000 µg/L.
|
”
|
“
|
- Infection or uncontrolled bleeding should be treated first before giving immunosuppressive therapy.
- This also applies to patients scheduled for bone marrow transplant (BMT), although it may sometimes be necessary to proceed straight to BMT in the presence of severe infection as a BMT may offer the best chance of early neutrophil recovery.
- Haemopoietic growth factors, such as rHuEPO or G-CSF, should not be used on their own in newly diagnosed patients in an attempt to 'treat' the aplastic anaemia.
- Prednisolone should not be used to treat patients with aplastic anaemia because it is ineffective and encourages bacterial and fungal infection.
|
”
|
Specific Treatment of Aplastic Anaemia: Human Leucocyte Antigen (HLA)-identical Sibling Donor Transplantation [1] (DONOT EDIT)
“
|
Human Leucocyte Antigen (HLA)-identical Sibling Donor Transplantation
- Allogeneic BMT from an HLA-identical sibling donor is the initial treatment of choice for newly diagnosed patients if they have severe or very severe aplastic anaemia, are <40 years old, and have an HLA-compatible sibling donor.
- Patients with Fanconi anaemia and other types of inherited aplastic anaemia need special consideration and should not follow recommendations made in this guideline.
- There is no indication for using irradiation-based conditioning regimens for patients undergoing HLA-identical sibling BMT for aplastic anaemia.
- The recommended source of stem cells for transplantation in aplastic anaemia is bone marrow.
- Fertility is well preserved after high dose cyclophosphamide conditioning in BMT for aplastic anaemia, and patients should be given appropriate contraceptive advice to prevent unwanted pregnancy. Until longer term data is available in patients receiving fludarabine-based regimens, cryopreservation of sperm and oocytes should be planned.
|
”
|
Specific Treatment of Aplastic Anaemia: Immunosuppressive Therapy: ATG and Ciclosporin [1] (DONOT EDIT)
“
|
Immunosuppressive Therapy: ATG and Ciclosporin
- Immunosuppressive therapy is recommended for:
- patients with non-severe aplastic anaemia who are transfusion dependent
- patients with severe or very severe disease who are >40 years old, and
- younger patients with severe or very severe disease who do not have an HLA-identical sibling donor.
- ATG is a powerful immunosuppressive drug and its use in severely neutropenic patients requires very careful monitoring, prophylaxis and treatment of fevers, and adequate (and sometimes intensive) platelet transfusional support.
- ATG must only be given as an in-patient:
- Ciclosporin should be continued for at least 12 months after achieving maximal haematological response, followed by a very slow tapering, to reduce the risk of relapse.
|
”
|
Specific Treatment of Aplastic Anaemia: Matched Unrelated Donor Bone Marrow Transplantation (MUD BMT): ATG and Ciclosporin [1] (DONOT EDIT)
“
|
Matched Unrelated Donor Bone Marrow Transplantation (MUD BMT)
- MUD BMT may be considered when a patient has a fully matched donor, is <50 years old (or 50–60 years old with good performance status), has failed at least one course of ATG and ciclosporin, and has severe aplastic anaemia.
- There is currently insufficient data on outcome for patients >60 years of age.
- The optimal conditioning regimen for MUD BMT is uncertain, but currently a fludarabine, non–irradiation-based regimen is favoured for younger patients.
|
”
|
Specific Treatment of Aplastic Anaemia: Trial Therapy or Clinical Research Protocols [1] (DONOT EDIT)
“
|
Trial Therapy or Clinical Research Protocols
- The use of high dose cyclophosphamide without stem cell support is not recommended in the treatment of aplastic anaemia.
- Mycophenolate mofetil (MMF) does not appear to be effective in the treatment of aplastic anaemia.
- The routine use of long term G-CSF, or other haemopoietic growth factors, after ATG and ciclosporin is not recommended outside the setting of prospective clinical trials.
|
”
|
Specific Treatment of Aplastic Anaemia: Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone [1] (DONOT EDIT)
“
|
Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone
- The presence of an abnormal cytogenetic clone in the presence of an otherwise typical aplastic anaemia does not necessarily equate with a diagnosis of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML), as abnormal cytogenetic clones occur in up to 12% of patients with aplastic anaemia.
- The presence of monosomy 7 is more often sinister with a high risk of transformation to MDS or AML.
|
”
|
Specific Treatment of Aplastic Anaemia: Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone [1] (DONOT EDIT)
“
|
Management of Aplastic Anaemia in the Presence of an Abnormal Cytogenetic Clone
Management of Patients with Aplastic Anaemia Who Have a Significant PNH Clone, Resulting in Clinical and/or Laboratory Evidence of Haemolysis
Small PNH clones, in the absence of evidence of haemolysis, occur in up to 50% of patients with aplastic anaemia.
ATG is not recommended if there is a history of PNH-associated thrombosis.
All patients who are not transplanted should be screened for PNH by flow cytometry every 12 months.
|
”
|
References