Evidence‑Based Management of Pancytopenia

Diagnostic Recommendations

Cytogenetic analysis is essential for diagnosing myelodysplastic syndromes (MDS) and for risk stratification using the Revised International Prognostic Scoring System (IPSS‑R). 1, 2

Erythropoiesis‑stimulating agents (ESAs) are recommended as first‑line therapy for patients whose serum erythropoietin level is ≤ 500 mU/mL. (International consensus) 2
For del(5q) MDS with anemia, the NCCN classifies lenalidomide as a Category 1 preferred treatment. 3
When anemia persists after ESA failure in MDS with ring sideroblasts, luspatercept is recommended. (International consensus) 2
Granulocyte‑colony stimulating factor (G‑CSF) improves neutropenia in 60–75 % of lower‑risk MDS patients but does not affect overall survival. (International consensus) 1
Thrombopoietin‑receptor agonists (romiplostim or eltrombopag) demonstrate efficacy for thrombocytopenia in patients with < 5 % marrow blasts; however, they are not approved in Europe. (International consensus; NCCN) 1, 4, 3

Hypomethylating agents (azacitidine or decitabine) improve survival and are recommended as first‑line therapy for higher‑risk MDS. (International consensus; NCCN) 2, 3
Allogeneic hematopoietic stem‑cell transplantation is the only curative option for eligible higher‑risk MDS patients. (International consensus) 2
Immunosuppressive therapy (e.g., antithymocyte globulin ± cyclosporine) may be considered for patients < 60 years with < 5 % blasts, hypocellular marrow, or a PNH clone. (NCCN) 3

Equine antithymocyte globulin (ATG) with or without cyclosporine A is recommended for younger patients with severe aplastic anemia. (NCCN) 3
Early allogeneic stem‑cell transplantation should be considered for younger patients who have a matched donor. (International consensus) 2

Maintain hemoglobin ≥ 8 g/dL (or 9–10 g/dL in patients with comorbidities) through red‑cell transfusion. (International consensus) 4
Prophylactic platelet transfusions are not routinely recommended except for active bleeding or invasive procedures. (International consensus) 4

Iron chelation therapy is strongly recommended for transplant candidates with iron overload. (International consensus) 2
Consider chelation after 20–60 red‑cell units transfused or ferritin > 1 000–2 500 µg/L in lower‑risk MDS with favorable prognosis. (International consensus) 4
Cardiac magnetic resonance T2* imaging should be performed in patients heavily transfused (> 70–80 units) to monitor cardiac iron. (International consensus) 4

Prompt broad‑spectrum antibiotics are required for febrile neutropenia; routine prophylactic antibiotics are not recommended. (International consensus) 4
Short‑course G‑CSF can be used during severe infections in neutropenic patients. (International consensus) 4

Immediate referral is indicated when a malignancy such as MDS, leukemia, or lymphoma is suspected. (International consensus) 1
Patients with aplastic anemia who require immunosuppressive therapy or transplant evaluation should be referred promptly. (NCCN) 3
Refractory pancytopenia despite treatment of reversible causes warrants hematology referral. (International consensus) 1
Referral is needed for patients requiring advanced therapies (hypomethylating agents, targeted agents, or cellular therapy). (NCCN) 3

Inadequate cytogenetic analysis can lead to missed or incorrect MDS diagnosis and risk stratification. (International consensus) 1, 2
Use of thrombopoietin‑receptor agonists in MDS with > 5 % blasts increases the risk of blast proliferation and transformation to acute myeloid leukemia. (International consensus; NCCN) 1, 4
Under‑transfusion (maintaining hemoglobin below recommended thresholds) compromises quality of life and should be avoided. (International consensus) 4