I型戈谢病的干预目标

Short-term management goals for Gaucher disease type 1 – ERT/SRT related

Anaemia related symptoms

Eliminate blood transfusion dependency (Source: Pastores et al. 2004)

Increase haemoglobin levels within 12 to 24 months to N 11.0 g/dL for women and children and N 12.0 g/dL for men (Source: Pastores et al., 2004)

Bleeding tendency

Increase platelet counts during the first year of treatment sufficiently to prevent surgical, obstetrical, and spontaneous bleeding (Source: Pastores et al.,2004)
In patients with splenectomy: normalization of platelet count by 1 year of treatment (Source: Pastores et al., 2004)
In patients with an intact spleen: achieve platelet count of ≥100,000/mm3 by 3 years of treatment (Adapted from: Pastores et al., 2004)

Mobility

Lessen bone pain that is not related to irreversible bone disease within 1 to 2 years (Adapted from: Pastores et al., 2004)
Decrease bone marrow involvement, as measured by a locally used scoring system (e.g. Bone Marrow Burden (BMB) score or Düsseldorf Gaucher Score (DGS)) in patients without severe irreversible bone disease at baseline (Source: literature search)
Increase bone mineral density (BMD) by 2 years in adults for patients with a T-score below −2.5 at baseline (Adapted from: Pastores et al0., 2004)
Attain normal or ideal peak skeletal mass in children (Source: Pastores et al. 2004)
Normalize growth such that the height of the patient is in line with target height, based upon population standards and parental height, within 2 years of treatment (Adapted from: Pastores et al., 2004)

Visceral complications
Avoid splenectomy (may be necessary during life threatening haemorrhagic events) (Source: Pastores et al., 2004)
Alleviate symptoms due to splenomegaly: abdominal distension, early satiety, new splenic infarction (Source: Pastores et al., 2004)
Eliminate hypersplenism (Source: Pastores et al., 2004)
Reduce spleen volume to b2 to 8 times normal (or in absence of volume measurement tools reduce spleen size) by year 1–2, depending on baseline spleen volume (Adapted from: Pastores et al., 2004)
Reduce the liver volume to 1.0 to 1.5 times normal (or in absence of volume measurement tools aim for normal liver size) by year 1–2, depending on baseline liver volume (Adapted from: Pastores et al., 2004)

General well-being

Improve scores from baseline of a validated quality-of-life instrument within 2 to 3 years or less depending on disease burden (Source: Pastores et al.,2004)
Reduce fatigue (not anaemia related) as measured by a validated fatigue scoring system (Sources: input from patients, literature search)
Improve or restore physical function for carrying out normal daily activities and fulfilling functional roles (Source: Pastores et al., 2004)

Long-term management goals for Gaucher disease type 1 – ERT/SRT related.

Anaemia related symptoms
Maintain improved haemoglobin values achieved after the first 12 to 24 months of therapy (Source: Pastores et al., 2004)

Bleeding tendency

Maintain platelet count of ≥100,000/mm3 (Adapted from: Pastores et al., 2004)
Reduce increased bleeding tendency, whether caused by low platelet numbers, platelet defects or coagulation abnormalities
(Sources: input from patients, national guidelines, literature search)

Mobility

Prevent bone complications: avascular necrosis, bone crises, bone infarcts and pathological fractures (Sources:Pastores et al., 2004, input from patients, national guidelines, literature search)
Prevent osteopenia and osteoporosis (i.e. maintain BMD T-scores (DEXA) of N−1) (Source: literature search)
Prevent chronic use of analgesic medication for bone pain (Source: literature search)
Maintain normal mobility or, if impaired at diagnosis, improve mobility (Source: literature search)
Increase physical activity (Source: literature search)

Visceral complications

Maintain spleen volume of b2 to 8 times normal after year 1–2 (Source: Pastores et al. 2004)
Maintain (near) normal liver volume after year 1–2 (Sources: Pastores et al., 2004, literature search)
Prevent liver fibrosis, cirrhosis and portal hypertension (Sources: input from patients, national guidelines, literature search)

Pulmonary complications
Prevent or improve pulmonary disease, such as pulmonary hypertension and hepatopulmonary syndrome (Adapted from: Pastores et al., 2004)

General well-being

Maintain good quality of life as measured by a validated instrument (Sources: input from patients, national guidelines, literature search)
Maintain normal participation in school and work activities (Source: literature search)
Minimize psychosocial burdens of life-long treatment (Source: literature search)
Achieve normal onset of puberty (Source: Pastores et al., 2004)
Normalize life expectancy (Source: consensus panel)

Pregnancy and delivery

Prevent GD related complications during pregnancy and delivery (Source: consensus panel)

Management goals for Gaucher disease type 1 – related to general disease management

Long-term complications

Early detection of haematological malignancies, including multiple myeloma, lymphoma and amyloidosis (Sources: input from patients, national guidelines, literature search)
Early detection of solid tumours, including hepatocellular carcinoma and renal cell carcinoma (Sources: input from patients, national guidelines,literature search)
Early detection of parkinsonism/Parkinson disease (Sources: input from patients, national guidelines, literature search)
Early detection of insulin resistance and type 2 diabetes mellitus (Source: literature search)

General

Proper education of the patient and his family about the disease and therapy (Source: consensus panel)
Early detection of signs and symptoms indicative of GD3, such as eye movement abnormalities (Source: consensus panel)