Platelet response, administration, and monitoring of treatments in children with ITP
| Therapy . | Platelet response‡ . | Typical dosing/administration . | Recommended screening/monitoring . | Notable potential side effects . | Populations for consideration . |
|---|---|---|---|---|---|
| Initial/rescue therapies | |||||
| Corticosteroids*,† | 70-80% initial response within 1-7 d72-76 | Prednisone 4 mg/kg/d orally (maximum 120 mg/d) × 4-7 d16 Dexamethasone 0.6 mg/kg/d orally (maximum 40 mg/d) × 4 d | Screening: CBC/differential, initial review of peripheral blood film | Risk of side effects increases with longer courses (short courses < 7 d are recommended). Psychiatric/behavioral effects, appetite changes, weight gain, Cushingoid features, effect on growth/bone health, adrenal suppression, GI effects, hyperglycemia, hypertension, cataracts | Prior to surgery or rescue treatment of bleeding Try to avoid in patients with medical contraindications (eg, obesity, diabetes, mood disorders) Avoid courses > 7 d and/or recurrent courses due to short- and long-term side effects |
| IVIG† | 70-80% initial response within 1-7 d60,77,78 | 0.8-1 g/kg IV | Screening: CBC/differential, initial review of peripheral blood film, immunoglobulin levels (IgG, IgA, IgM, and IgE), direct antiglobulin test, any indicated antibody-based testing | Serum sickness, aseptic meningitis, infusion reactions, severe headache, hemolysis, hypersensitivity reaction (IgA deficiency) FDA black box warning: renal failure, thrombosis | Prior to surgery or rescue treatment of bleeding Regular interval infusions may be effective maintenance therapy in some patients (eg, while awaiting effect of immunosuppression or failure of rituximab) |
| Anti-D immune globulin† | 70-80% initial response73,79,80 | 50-75 μg/kg IV | Screening: CBC/differential, reticulocyte count, initial review of peripheral blood film, direct antiglobulin test, urinalysis Monitoring: after infusion, monitor for 8 h for signs of hemolysis | Renal failure, hypersensitivity reaction (IgA deficiency), thrombosis FDA black box warning: intravascular hemolysis | Rh+, nonsplenectomized nonanemic patients Prior to surgery or rescue treatment |
| Second-line/maintenance therapies | |||||
| Romiplostim† | Platelet count > 50 × 109/L for 2 consecutive weeks: 88% romiplostim vs 0% placebo81, Platelet counts > 50 × 109/L maintained for a median of 7 wk vs 0 wk for placebo81 Platelet count > 50 × 109/L for ≥6 of 8 wk: 52% romiplostim vs 10% placebo82 | Weekly subcutaneous injection (dose ranges: 1-10 µg/kg, median starting dose in clinical practice 3-5 µg/kg)83 | Monitoring: initial weekly platelet counts; monthly monitoring once on stable dose Review of peripheral blood film every 6-12 mo | Headache, marrow fibrosis, thrombosis, thrombocytosis | Children who have failed initial first-line therapy16 Bridge therapy prior to surgery or remission |
| Eltrombopag† | Platelet count > 50 × 109/L: 62-75% eltrombopag vs 21-32% placebo84,85 Platelet count > 50 × 109/L once: 86%86 52% of patients have a continuous response ≥ 25 wk86 | Oral medication 12.5-75 mg daily, decreased efficacy if taken with supplements or foods with polyvalent cations (eg, calcium) | Monitoring: monthly CBC and LFTs Review of peripheral blood film every 6-12 mo | Headache, marrow fibrosis, thrombosis, thrombocytosis FDA black box warning: hepatoxicity | Children who have failed first-line therapy16,87 Bridge therapy prior to surgery or remission |
| Rituximab | Platelet count > 50 × 109/L 6 mo postinfusion: 40-60%88 | IV infusion in the physician office setting. Optimal dosing regimen in ITP is uncertain and multiple dosing regimens are reported (375 mg/m2 IV weekly for 4 wk) | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing), HIV, hepatitis B/C, and tuberculosis evaluation Consider vaccinations prior to treatment Monitoring: consider IgG monitoring postinfusion | Lower immunization response, neutropenia, hypogammaglobulinemia FDA black box warning: infusion-related reactions, severe mucocutaneous reactions, infectious risk (including progressive multifocal leukoencephalopathy) | Primary or secondary ITP (may be higher risk for infection and/or persistent hypogammaglobulinemia with secondary ITP) Immunized children with chronic ITP |
| Mycophenolate mofetil | 52-69%69,89,90 | Oral medication, 400 mg/m2 twice daily, maximum 1 g twice daily | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing) before starting Monitoring: monthly CBC/differential, LFTs, creatinine, avoid live virus vaccines | Headache, gastrointestinal disorders, diarrhea, neutropenia/anemia FDA black box warning: infections, malignancy risk with long-term use (possibly in specific subpopulations), pregnancy loss | Immune cytopenias associated with immune deficiency Patients with a likelihood of remission Patients with primary ITP who fail other agents |
| Sirolimus | 25-58%91-94 | 1-2 mg daily maintenance, adjust to target trough levels (5-15 ng/mL) | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing) Monitoring: regular trough levels; monthly CBC, LFTs, cholesterol, triglycerides, creatinine, urinary protein; monitor blood pressure | Aphthous ulcers, hypertriglyceridemia, hyperlipidemia, angioedema, lymphedema, renal failure, poor wound healing FDA black box warning: infections, malignancy risk with long-term use (possibly in specific subpopulations) | Immune cytopenias associated with immune deficiency Patients with primary ITP who fail other agents |
| Splenectomy | Early response: 66-92%95-97 Durable response: 60-70%96,97 | Laparoscopic or open total splenectomy | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, genetic testing) Also consider genetic evaluation for IPD Vaccinations presplenectomy | Perisurgical risks, lifelong risk for serious infections (eg, encapsulated organism sepsis), thrombosis | Primary ITP Life-threatening bleeding (intracranial hemorrhage) Fully immunized children age ≥ 5 y with chronic ITP refractory to medical therapy and with unrevealing evaluation for genetic causes for thrombocytopenia (immune and IPDs) |
| Therapy . | Platelet response‡ . | Typical dosing/administration . | Recommended screening/monitoring . | Notable potential side effects . | Populations for consideration . |
|---|---|---|---|---|---|
| Initial/rescue therapies | |||||
| Corticosteroids*,† | 70-80% initial response within 1-7 d72-76 | Prednisone 4 mg/kg/d orally (maximum 120 mg/d) × 4-7 d16 Dexamethasone 0.6 mg/kg/d orally (maximum 40 mg/d) × 4 d | Screening: CBC/differential, initial review of peripheral blood film | Risk of side effects increases with longer courses (short courses < 7 d are recommended). Psychiatric/behavioral effects, appetite changes, weight gain, Cushingoid features, effect on growth/bone health, adrenal suppression, GI effects, hyperglycemia, hypertension, cataracts | Prior to surgery or rescue treatment of bleeding Try to avoid in patients with medical contraindications (eg, obesity, diabetes, mood disorders) Avoid courses > 7 d and/or recurrent courses due to short- and long-term side effects |
| IVIG† | 70-80% initial response within 1-7 d60,77,78 | 0.8-1 g/kg IV | Screening: CBC/differential, initial review of peripheral blood film, immunoglobulin levels (IgG, IgA, IgM, and IgE), direct antiglobulin test, any indicated antibody-based testing | Serum sickness, aseptic meningitis, infusion reactions, severe headache, hemolysis, hypersensitivity reaction (IgA deficiency) FDA black box warning: renal failure, thrombosis | Prior to surgery or rescue treatment of bleeding Regular interval infusions may be effective maintenance therapy in some patients (eg, while awaiting effect of immunosuppression or failure of rituximab) |
| Anti-D immune globulin† | 70-80% initial response73,79,80 | 50-75 μg/kg IV | Screening: CBC/differential, reticulocyte count, initial review of peripheral blood film, direct antiglobulin test, urinalysis Monitoring: after infusion, monitor for 8 h for signs of hemolysis | Renal failure, hypersensitivity reaction (IgA deficiency), thrombosis FDA black box warning: intravascular hemolysis | Rh+, nonsplenectomized nonanemic patients Prior to surgery or rescue treatment |
| Second-line/maintenance therapies | |||||
| Romiplostim† | Platelet count > 50 × 109/L for 2 consecutive weeks: 88% romiplostim vs 0% placebo81, Platelet counts > 50 × 109/L maintained for a median of 7 wk vs 0 wk for placebo81 Platelet count > 50 × 109/L for ≥6 of 8 wk: 52% romiplostim vs 10% placebo82 | Weekly subcutaneous injection (dose ranges: 1-10 µg/kg, median starting dose in clinical practice 3-5 µg/kg)83 | Monitoring: initial weekly platelet counts; monthly monitoring once on stable dose Review of peripheral blood film every 6-12 mo | Headache, marrow fibrosis, thrombosis, thrombocytosis | Children who have failed initial first-line therapy16 Bridge therapy prior to surgery or remission |
| Eltrombopag† | Platelet count > 50 × 109/L: 62-75% eltrombopag vs 21-32% placebo84,85 Platelet count > 50 × 109/L once: 86%86 52% of patients have a continuous response ≥ 25 wk86 | Oral medication 12.5-75 mg daily, decreased efficacy if taken with supplements or foods with polyvalent cations (eg, calcium) | Monitoring: monthly CBC and LFTs Review of peripheral blood film every 6-12 mo | Headache, marrow fibrosis, thrombosis, thrombocytosis FDA black box warning: hepatoxicity | Children who have failed first-line therapy16,87 Bridge therapy prior to surgery or remission |
| Rituximab | Platelet count > 50 × 109/L 6 mo postinfusion: 40-60%88 | IV infusion in the physician office setting. Optimal dosing regimen in ITP is uncertain and multiple dosing regimens are reported (375 mg/m2 IV weekly for 4 wk) | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing), HIV, hepatitis B/C, and tuberculosis evaluation Consider vaccinations prior to treatment Monitoring: consider IgG monitoring postinfusion | Lower immunization response, neutropenia, hypogammaglobulinemia FDA black box warning: infusion-related reactions, severe mucocutaneous reactions, infectious risk (including progressive multifocal leukoencephalopathy) | Primary or secondary ITP (may be higher risk for infection and/or persistent hypogammaglobulinemia with secondary ITP) Immunized children with chronic ITP |
| Mycophenolate mofetil | 52-69%69,89,90 | Oral medication, 400 mg/m2 twice daily, maximum 1 g twice daily | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing) before starting Monitoring: monthly CBC/differential, LFTs, creatinine, avoid live virus vaccines | Headache, gastrointestinal disorders, diarrhea, neutropenia/anemia FDA black box warning: infections, malignancy risk with long-term use (possibly in specific subpopulations), pregnancy loss | Immune cytopenias associated with immune deficiency Patients with a likelihood of remission Patients with primary ITP who fail other agents |
| Sirolimus | 25-58%91-94 | 1-2 mg daily maintenance, adjust to target trough levels (5-15 ng/mL) | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, consider genetic testing) Monitoring: regular trough levels; monthly CBC, LFTs, cholesterol, triglycerides, creatinine, urinary protein; monitor blood pressure | Aphthous ulcers, hypertriglyceridemia, hyperlipidemia, angioedema, lymphedema, renal failure, poor wound healing FDA black box warning: infections, malignancy risk with long-term use (possibly in specific subpopulations) | Immune cytopenias associated with immune deficiency Patients with primary ITP who fail other agents |
| Splenectomy | Early response: 66-92%95-97 Durable response: 60-70%96,97 | Laparoscopic or open total splenectomy | Screening: immune evaluation (immunoglobulin levels, lymphocyte subsets, soluble markers, genetic testing) Also consider genetic evaluation for IPD Vaccinations presplenectomy | Perisurgical risks, lifelong risk for serious infections (eg, encapsulated organism sepsis), thrombosis | Primary ITP Life-threatening bleeding (intracranial hemorrhage) Fully immunized children age ≥ 5 y with chronic ITP refractory to medical therapy and with unrevealing evaluation for genetic causes for thrombocytopenia (immune and IPDs) |
Most commonly used second-line treatments are included, but the treatment list does not include all treatments used for pediatric ITP.
CBC, complete blood count; GI, gastrointestinal; LFTs, liver function tests.
ASH 2019 guidelines suggest prednisone rather than dexamethasone.
Approved by the FDA for treatment of childhood ITP.
Measure of platelet count response by platelet count is not consistent or comparable among studies.