Treatment options for severe immune cytopeniasa
| Treatmenta . | AIHA,b ES . | Immune thrombocytopenia . |
|---|---|---|
| Goal: remission . | Goals: no risk of hemorrhage, quality of life . | |
| First-line options | • Prednisolone 2–5 mg/kg/day days 1–3, then 1–2 mg/kg/day, wean off after 4 wk > 8 wk | • IVIG 0.5–0.8 g/kg according to local standards |
| • If Rh+: anti-D (25) 50–75 µg/kg s.c. or i.v. | ||
| • Dexamethasone 5–10 (20) mg/m2/day >3–5 d | ||
| Second-line optionsc | • Prednisolone + MMF 1,200 mg/m2/day | • MMF 1,200 mg/m2/day ± prednisolone |
| • If DNT ↑: prednisolone + sirolimus 1–2.8 mg/m2/day Trough level 5(-15) ng/mL (if successful, keep as low as possible) | • If DNT ↑: sirolimus instead of MMF | |
| • If signs of CID, consider targeted therapy,d HSCT | ||
| • If signs of CID, consider targeted therapy,d HSCT | ∘ Wean off MMF after 6–12 mo > 3–6 mo | |
| ∘ Wean off prednisolone after 4 wk | • TPOR agonists: eltrombopag 25–50 (–75) mg/day (0.8–1.2 mg/kg <6 y) orally or romiplostim 100–250 µg/m2/week s.c. | |
| ∘ Wean off MMF after 6–12 mo > 3–6 mo | ||
| • Rituximab 375 mg/m2 once per week, 4 times (consider prior vaccination against pneumococci, haemophilus influenzae type b, meningococci) | ||
| • Methylprednisolone 10–30 mg/kg/d > 4 d | ||
| • Dexamethasone 5–10 mg/m2 > 4 d | ||
| Third-line optionsc | • AZT, VCR, bortezomib,e danazol,f carfilzomib,e eculizumabd (CAD, PNH), CY, CSA, ibrutinib,e daratumumabe | • Rituximab, danazol,f AZT, VCR, dapson, (retinoidse) |
| • Splenectomy | • Adults: splenectomy (vaccinate before; consider OPSI prophylaxis) | |
| • HSCT | ||
| Targeted treatment optionsc,d | • If underlying disease is identified or suspected on the basis of specific clinical and laboratory immune phenotypic abnormalities and typical history: | |
| • In CID or PIRD: consider indication for allogeneic HSCT (eg, additional severe immunodeficiency, refractoriness of cytopenia to medical treatment, risk of malignancy) | ||
| • For patients with predominantly antibody deficiencies and IgG replacement therapy: consider B cell-depleting or other B- or plasma cell-directed therapy | ||
| • In ALPS or conditions with increased DNT cells: sirolimus or MMF | ||
| • In LRBA or DEF6 deficiency and CTLA4 haploinsufficiency: abatacept, sirolimus | ||
| • In APDS: PI3K∂/p110 inhibition | ||
| • In ADA2 deficiency: anti-TNFa therapy for vasculitis, HSCT for refractory cytopenias | ||
| • In overactivated JAK/STAT signaling: ruxolitinib or other JAK1/2 inhibitors | ||
| • In PNH, TMA, or TTP: eculizumab and other complement-blocking drugs | ||
| Treatmenta . | AIHA,b ES . | Immune thrombocytopenia . |
|---|---|---|
| Goal: remission . | Goals: no risk of hemorrhage, quality of life . | |
| First-line options | • Prednisolone 2–5 mg/kg/day days 1–3, then 1–2 mg/kg/day, wean off after 4 wk > 8 wk | • IVIG 0.5–0.8 g/kg according to local standards |
| • If Rh+: anti-D (25) 50–75 µg/kg s.c. or i.v. | ||
| • Dexamethasone 5–10 (20) mg/m2/day >3–5 d | ||
| Second-line optionsc | • Prednisolone + MMF 1,200 mg/m2/day | • MMF 1,200 mg/m2/day ± prednisolone |
| • If DNT ↑: prednisolone + sirolimus 1–2.8 mg/m2/day Trough level 5(-15) ng/mL (if successful, keep as low as possible) | • If DNT ↑: sirolimus instead of MMF | |
| • If signs of CID, consider targeted therapy,d HSCT | ||
| • If signs of CID, consider targeted therapy,d HSCT | ∘ Wean off MMF after 6–12 mo > 3–6 mo | |
| ∘ Wean off prednisolone after 4 wk | • TPOR agonists: eltrombopag 25–50 (–75) mg/day (0.8–1.2 mg/kg <6 y) orally or romiplostim 100–250 µg/m2/week s.c. | |
| ∘ Wean off MMF after 6–12 mo > 3–6 mo | ||
| • Rituximab 375 mg/m2 once per week, 4 times (consider prior vaccination against pneumococci, haemophilus influenzae type b, meningococci) | ||
| • Methylprednisolone 10–30 mg/kg/d > 4 d | ||
| • Dexamethasone 5–10 mg/m2 > 4 d | ||
| Third-line optionsc | • AZT, VCR, bortezomib,e danazol,f carfilzomib,e eculizumabd (CAD, PNH), CY, CSA, ibrutinib,e daratumumabe | • Rituximab, danazol,f AZT, VCR, dapson, (retinoidse) |
| • Splenectomy | • Adults: splenectomy (vaccinate before; consider OPSI prophylaxis) | |
| • HSCT | ||
| Targeted treatment optionsc,d | • If underlying disease is identified or suspected on the basis of specific clinical and laboratory immune phenotypic abnormalities and typical history: | |
| • In CID or PIRD: consider indication for allogeneic HSCT (eg, additional severe immunodeficiency, refractoriness of cytopenia to medical treatment, risk of malignancy) | ||
| • For patients with predominantly antibody deficiencies and IgG replacement therapy: consider B cell-depleting or other B- or plasma cell-directed therapy | ||
| • In ALPS or conditions with increased DNT cells: sirolimus or MMF | ||
| • In LRBA or DEF6 deficiency and CTLA4 haploinsufficiency: abatacept, sirolimus | ||
| • In APDS: PI3K∂/p110 inhibition | ||
| • In ADA2 deficiency: anti-TNFa therapy for vasculitis, HSCT for refractory cytopenias | ||
| • In overactivated JAK/STAT signaling: ruxolitinib or other JAK1/2 inhibitors | ||
| • In PNH, TMA, or TTP: eculizumab and other complement-blocking drugs | ||
ADA2, adenosine deaminase 2; ALPS, autoimmune lymphoproliferative syndrome; APDS, activated phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K) δ syndrome; AZT, azathioprine; CAD, cold agglutinin disease; CSA, cyclosporin A; CTLA4, cytotoxic T lymphocyte antigen 4; CY, cyclophosphamide; DNT ↑, increased proportion of T cell receptor α-β positive CD4- and CD8-negative (double negative) T cells (ie, >2.5% of CD3+ T cells or >1.5% of total lymphocytes in the background of normal or increased lymphocyte counts); ES, Evans syndrome (defined as at least 2-lineage autoimmune cytopenia); i.v., intravenously; IVIG, intravenous immunoglobulin; JAK/STAT pathway, Janus kinase/signal transducer and activator of transcription signaling pathway; LRBA, lipopolysaccharide-responsive beige-like anchor protein; OPSI, overwhelming post-splenectomy infection; PNH, paroxysmal nocturnal hemoglobinuria; Rh+, Rhesus factor positive; s.c., subcutaneously; TMA, thrombotic microangiopathy; TPOR agonists, thrombopoietin receptor agonists; TTP, thrombotic thrombocytopenic purpura; VCR, vincristine.
These treatment options and lines were collected from various international guidelines and reviews as referenced1-4,7,8,25,33-37 ; they include generic names of off-label drugs and are to be considered as selections that are somewhat biased from the perspective of treating IEIs. This table does not include treatment recommendations for malignancy-associated or post-transplant autoimmune cytopenias.
In this review, AIHA refers to warm autoimmune hemolytic anemia only and does not include cold agglutinin disease or paroxysmal cold hemolytic anemia.
The order depends on the immune or phenotypical abnormality; dosing rules cannot be generally provided for third-line and targeted treatment options, ideally given within clinical studies only; see also Figure 3.
Selection.
This is based on largely anecdotal evidence, ideally given in clinical studies only.
This is used especially in bone marrow failure syndromes, eg, Fanconi anemia or telomere biology disorders but historically also in other conditions (eg, “primary” ES).