What is the role of Leukovarin (folinic acid) in treating pancytopenia?

Role of Leucovorin (Folinic Acid) in Treating Pancytopenia

Leucovorin (folinic acid) is indicated for the treatment of pancytopenia when it is caused by folate deficiency or as a rescue therapy for methotrexate-induced pancytopenia, with dosages of 1-5 mg/day recommended for folate deficiency and potentially higher doses for drug toxicity. 1, 2

Causes of Pancytopenia Where Leucovorin is Beneficial

• Folate deficiency can cause megaloblastic anemia and pancytopenia, with symptoms including glossitis, angular stomatitis, oral ulcers, and neuropsychiatric manifestations 1
• Methotrexate toxicity is a common iatrogenic cause of pancytopenia that responds well to leucovorin rescue therapy 3, 4, 5
• Congenital toxoplasmosis treatment with pyrimethamine requires leucovorin supplementation to prevent bone marrow suppression 1
• Nutritional deficiencies of folate can lead to severe pancytopenia, which responds rapidly to folate supplementation 6, 7, 8

Diagnostic Approach

• In patients with macrocytic anemia or at risk of malnutrition, folate status should be measured at first assessment 1
• Serum folate levels should be ≥10 nmol/L and red blood cell folate ≥340 nmol/L 1
• Always evaluate for concomitant vitamin B12 deficiency when folate deficiency is suspected, as symptoms overlap and treating folate deficiency alone can worsen neurological manifestations of B12 deficiency 1, 9
• Bone marrow examination may be necessary to differentiate from hematologic malignancies and aplastic anemia 8

Treatment Recommendations

For Folate Deficiency-Induced Pancytopenia:

• Oral administration of folic acid at 1-5 mg/day is recommended for dietary deficiency 1
• Treatment should continue for four months or until the underlying cause is corrected 1
• After clinical symptoms subside and blood counts normalize, maintenance therapy should be continued at 330 μg DFE (dietary folate equivalents) daily for adults 1

For Methotrexate-Induced Pancytopenia:

• Leucovorin rescue therapy significantly shortens recovery time compared to regimens without folinic acid (5.47 ± 2.9 days vs. 10 ± 3.77 days) 5
• Leucovorin can be used as monotherapy or in combination with G-CSF for faster recovery 5
• Dosing may need to be higher than for nutritional deficiency, with some protocols using 10 mg twice daily 3

For Pancytopenia During Chemotherapy:

• Leucovorin is effective in reversing bone marrow suppression during maintenance therapy for leukemia with methotrexate and 6-mercaptopurine 4
• Regular monitoring of complete blood counts is essential during treatment 3

Monitoring and Safety Considerations

• Follow-up measurement of folate status should be performed within 3 months after supplementation to verify normalization 1
• When leucovorin is used with pyrimethamine, weekly complete blood count monitoring is recommended 1, 10
• Leucovorin should be continued for 1 week after pyrimethamine discontinuation due to the long half-life of pyrimethamine 1, 10
• Excess folic acid is generally considered non-toxic and is excreted in the urine, but upper limit is set at 1 mg/day to avoid masking vitamin B12 deficiency 1

Clinical Pearls and Pitfalls

• Rapid diagnosis and treatment of folate deficiency is important since body stores are low 7
• Pancytopenia from methotrexate toxicity may occur suddenly and unpredictably, even after years of therapy 3
• Patients with renal insufficiency are at higher risk for methotrexate toxicity and may require dose adjustments of both methotrexate and leucovorin 3
• Folic acid should not be prescribed until pernicious anemia (B12 deficiency) has been ruled out, as it can mask hematologic manifestations while allowing neurological damage to continue 9