Fanconi anemia medical therapy

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Overview

• Treatments for fanconi anemia include red blood cell transfusions, and marrow stem cell transplants, and medicines.
• The Allogenic HSCT is curative therapy in Bone marrow failure.
• Androgen and G-CSF and RBC transfusion are useful to increase blood count.
• People who have mild or moderate bone marrow failure may need supportive treatment as symptoms will resolve.
• Fanconi anemia management is challenging because SCT is curative for bone marrow failure and haematological neoplasms but not for non haematological features.
• Patient also need increased surveillance for both hematologic and non hematologic features and reduced intensity therapy is typically used for HCT and cancer treatment.
• Blood transfusions and medicine help relieve the symptoms of fancon ianemia, but they're not curative treatment

Management of patients with FA is challenging because hematopoietic stem cell transplantation (HCT) is curative for bone marrow failure and hematologic neoplasms but not for the non-hematologic features.   

Patients also require increased surveillance for both hematologic and non-hematologic malignancies, and reduced-intensity therapy is typically used for HCT and cancer treatment.

Androgen therapy may be a reasonable option to improve blood counts for some patients including those with moderate bone marrow failure for whom no donor is available, those who do not meet medical eligibility criteria for HCT due to pre-existing organ dysfunction or ongoing infection, and those who decline HCT

Bone Marrow Failure:

Allogenic HSCT is the only curative therapy for bone marrow failure and hematological malignancies (myelodysplastic syndrome (MDS) and acute leukaemia) in falcon anaemia patients.

Outcome of HCT in FA improved drastically in 2000, when a trend has started by development of FA-specific reduced intensity approaches to conditioning and improvement in the understanding and supportive care for these patients.

All patients who have evidence of bone marrow failure with FA we refer to specialised HCT centre to discuss the risk and benefits of HCT and evaluation of HCT donor.

It is also applicable to refer individuals of FA without bona more failure to HCT centre to discuss these issues.

However, We do not recommend individuals performing HCT who have adequate bone marrow function, with rationale of aplastic anemia, those with mild cytopenia, will not develop bone marrow failure.

Furthermore, HCT earlier to the onset of bone marrow failure may require increased conditioning intensity and thus carries risk of increased toxicity.

Monitoring bone marrow function:

Initial approach of monitoring bone marrow function is classified according to the severity of bone marrow failure and the presence or absence of clonal hematopoietic neoplasms.

● For those with mild bone marrow failure: described as absolute neutrophil count (ANC) between 1000 and 1500/microL, platelet count between 50,000 and 150,000/microL, and hemoglobin ≥10 g/dL, and we should monitor CBC with differential every 3-4 months as the blood count remain stable, and we also perform a bone marrow examination with cytogenetics annually.

If there are any changes in blood count without an apparent cause (e.g: infection) we should increase the frequency of CBC monitoring and the bone marrow studies repeated regardless of the date of last study.

● For those with moderate bone marrow failure (ANC between 500 and 1000/microL, platelet count between 30,000 and 50,000/microL, hemoglobin between 8 and 10 g/dL) whose counts continue to decrease, we initiate HCT planning with an HLA-matched related donor (first choice) or closely matched unrelated donor.

Androgen therapy may be an alternate option to improve blood counts for some patients including those with moderate bone marrow failure for whom no donor is available, those who do not meet medical eligibility criteria for HCT due to pre-existing organ dysfunction or ongoing infection, and those who decline HCT.

Alternatively, If the individual is asymptomatic with stable cell counts and no clonal abnormality, it may be reasonable to monitor the CBC every three to four months and perform a bone marrow examination annually as done for mild bone marrow failure.

If cytogenetic abnormality is associated with poor risk-MDS in absence of other MDS defining feature, CBC and bone marrow should be monitored more frequently (eg, CBC every 1-2months, Bone marrow every 1-6months), and should be proceed with the best available donor.

• For severe bone marrow failure (ANC ≤500/microL, platelet count ≤30,000/microL, hemoglobin <8 g/dL), and/or transfusion dependence, We pursue HCT  with the best available donor, An HLA_matched sibling/family member who has been determined not to have FA would be preferable, second choice should be closely matched unrelated donor. If neither of above options available then we should start trial of androgen therapy while pursuing other alternative donor such as cord blood or haploidentical HCT, with attempt to avoid transfusion exposure and opportunistic infection during the androgen trial. For individuals who do not have access to HCT for whatever reason (eg, medically ineligible, lack of donor, cost), androgen therapy or investigational approaches such as gene therapy may be good options.
• This monitoring T schedule and management approach is consistent with the 2014 Fanconi Anemia Guidelines for Diagnosis and Managementfrom the Fanconi Anemia Research Fund [1].

Medical Therapy[edit | edit source]

Androgen therapy is helpful in moderate bone marrow failure cases if no donor is available for HCT, or whom do not meet eligibility criteria for HCT due to pre existing organ dysfunction or ongoing infection, and those who decline HCT.

• Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
• Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
• Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
• Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].

Disease Name[edit | edit source]

• 1 Stage 1 - Name of stage
  • 1.1 Specific Organ system involved 1
    • 1.1.1 Adult
      • Preferred regimen (1): drug name 100 mg PO q12h for 10-21 days (Contraindications/specific instructions)
      • Preferred regimen (2): drug name 500 mg PO q8h for 14-21 days
      • Preferred regimen (3): drug name 500 mg q12h for 14-21 days
      • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
      • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
      • Alternative regimen (3): drug name 500 mg PO q6h for 14–21 days
    • 1.1.2 Pediatric
      • 1.1.2.1 (Specific population e.g. children < 8 years of age)
        • Preferred regimen (1): drug KKJ 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
      • 1.1.2.2 (Specific population e.g. 'children < 8 years of age')
        • Preferred regimen (1): drug name 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
        • Alternative regimen (1): drug name 10 mg/kg PO q6h (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
  • 1.2 Specific Organ system involved 2
    • 1.2.1 Adult
      • Preferred regimen (1): drug name 500 mg PO q8h
    • 1.2.2 Pediatric
      • Preferred regimen (1): drug name 50 mg/kg/day PO q8h (maximum, 500 mg per dose)

• 2 Stage 2 - Name of stage
  • 2.1 Specific Organ system involved 1

    Note (1):

    Note (2):

    Note (3):

    • 2.1.1 Adult
      • Parenteral regimen
        • Preferred regimen (1): drug name 2 g IV q24h for 14 (14–21) days
        • Alternative regimen (1): drug name 2 g IV q8h for 14 (14–21) days
        • Alternative regimen (2): drug name 18–24 MU/day IV q4h for 14 (14–21) days
      • Oral regimen
        • Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
        • Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
        • Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
    • 2.1.2 Pediatric
      • Parenteral regimen
        • Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
        • Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
        • Alternative regimen (2):  drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '(Contraindications/specific instructions)'
      • Oral regimen
        • Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
        • Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
  • 2.2 'Other Organ system involved 2'

    Note (1):

    Note (2):

    Note (3):

    • 2.2.1 Adult
      • Parenteral regimen
        • Preferred regimen (1): drug name 2 g IV q24h for 14 (14–21) days
        • Alternative regimen (1): drug name 2 g IV q8h for 14 (14–21) days
        • Alternative regimen (2): drug name 18–24 MU/day IV q4h for 14 (14–21) days
      • Oral regimen
        • Preferred regimen (1): drug name 500 mg PO q8h for 14 (14–21) days
        • Preferred regimen (2): drug name 100 mg PO q12h for 14 (14–21) days
        • Preferred regimen (3): drug name 500 mg PO q12h for 14 (14–21) days
        • Alternative regimen (1): drug name 500 mg PO q6h for 7–10 days
        • Alternative regimen (2): drug name 500 mg PO q12h for 14–21 days
        • Alternative regimen (3):drug name 500 mg PO q6h for 14–21 days
    • 2.2.2 Pediatric
      • Parenteral regimen
        • Preferred regimen (1): drug name 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
        • Alternative regimen (1): drug name 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
        • Alternative regimen (2):  drug name 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
      • Oral regimen
        • Preferred regimen (1): drug name 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
        • Preferred regimen (2): drug name 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
        • Preferred regimen (3): drug name 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
        • Alternative regimen (1): drug name 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
        • Alternative regimen (2): drug name 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
        • Alternative regimen (3): drug name 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)