Therapy for Hereditary Sideroblastic Anemia

A trial of pyridoxine (100 to 200 mg/day taken orally) is indicated for 3 months for all patients with hereditary sideroblastic anemia. Response is variable and ranges from complete correction of hemoglobin levels to no effect. Even when pyridoxine completely corrects the anemia, the increase in mean corpuscular volume (MCV) may not reach normal values, and a population of hypochromic, microcytic cells remains.

About 25% to 50% of patients with hereditary sideroblastic anemia show a full or partial response to pyridoxine, and this vitamin should be continued on a lifelong basis in the responders. A lower maintenance dose should be determined for each responding patient by progressive dose reduction, because long-term therapy with pyridoxine at 100 to 200 mg/day has been associated with peripheral neuropathy.¹ The adult nutritional requirement for pyridoxine is 1 to 2 mg/day; some patients have been maintained on as little as 4 mg/day as a supplement.² Folic acid supplements should also be administered because the erythroid hyperplasia increases demand for this vitamin.

There is one report of successful allogeneic peripheral blood stem cell transplantation in a 19-year-old man with transfusion-dependent hereditary sideroblastic anemia.³ Transfusions are the mainstay of treatment for severe anemia unresponsive to pyridoxine. Regular administration of packed red cells using white blood cell filters are given to relieve symptoms and permit normal childhood development. Iron overload and secondary hemosiderosis rapidly progress after transfusions begin; chelation therapy with desferrioxamine or oral deferasirox should be initiated from the onset.

Iron removal may be of great benefit for patients who have mild or moderate anemia and evidence of iron overload.^4,5 These patients can often tolerate intermittent phlebotomy, which is preferable to chelation therapy for iron removal, and should be continued to reduce ferritin levels to less than 300 ng/mL. All patients with iron overload should avoid ingestion of ascorbic acid supplements, which enhance iron absorption and increase the tissue toxicity of elemental iron. Alcohol should also be avoided. Splenectomy is contraindicated in this disease.

Therapy for Acquired Sideroblastic Anemia

Transfusions are indicated for relief of symptomatic anemia. A trial of pyridoxine at 100 to 200 mg/day for 3 months is worthwhile in patients who have anemia but who do not display neutropenia or thrombocytopenia. However, few patients with acquired idiopathic sideroblastic anemia respond to this vitamin. If any response is achieved, maintenance therapy with pyridoxine at lower dosage is indicated. Cyclosporin (5 to 6 mg/kg/day) has been reported to benefit the anemia of the closely related myelodysplastic condition of refractory anemia, although the response appeared limited to those with hypoplastic bone marrows.¹⁴

Clinical and Laboratory Evaluation of Sideroblastic Anemia

Typically, sideroblastic anemia develops insidiously in a middle-aged or elderly patient with normal or increased mean corpuscular volume (MCV) and a blood smear showing a population of hypochromic red cells. Hepatosplenomegaly may be present. Leukocyte and platelet counts are usually normal, but some patients have thrombocytosis that occasionally exceeds 1000 × 10⁹/L.⁶ If leukopenia or thrombocytopenia is present, a careful search should be made for myelodysplastic features, which lead to the more descriptive term of refractory cytopenia for the condition.^7,8 An iron stain of the bone marrow aspirate shows ring sideroblasts, which should total more than 15% of all erythroblasts to make the diagnosis of acquired sideroblastic anemia.^8–10 Iron cannot be assessed in the marrow trephine biopsy core because it may leach out during decalcification.

The bone marrow also shows erythroid hyperplasia. Although mild dyserythropoiesis (e.g., multinuclearity, nuclear budding) and megaloblastoid changes are present, myelopoiesis and megakaryopoiesis are usually normal. When changes are confined to dyserythropoiesis, the condition has been called pure sideroblastic anemia.^8,11 However, dysplasia of myelopoietic and megakaryopoietic elements may be present (i.e., trilineage dysplasia) with the following features: Pelger-Huët–like anomaly, hypersegmentation or hypogranularity of neutrophils, micromegakaryocytes, large mononuclear megakaryocytes, and megakaryocytes with multiple small nuclei (see Chapter 24).⁸ Dysmegakaryopoiesis is more easily detected in trephine biopsies than in marrow smears, although the trephine may also show unsuspected islands of myeloblasts characteristic of myelodysplasia.¹² The overall blast count in marrow smears is, by definition, less than 5%, and the peripheral blood monocyte count is less than 1.0 × 10⁹/L. Cytogenetic analysis of marrow aspirates provides important information, because a normal karyotype predicts long survival in any type of acquired sideroblastic anemia.¹³

Figure 11-3 THIS 70-YEAR-OLD MAN WAS BEING TREATED WITH ZINC SUPPLEMENTATION AND WAS FOUND TO HAVE ANEMIA AND NEUTROPENIA (HEMOGLOBIN, 8.3 G/DL; HEMATOCRIT, 23.9%; AND WHITE BLOOD CELL COUNT, 1200/µL).

His peripheral smear (A) showed a biphasic erythroid population with some small slightly hypochromic cells and increased anisocytosis (red blood cell distribution width [RDW], 23.9%). The bone marrow aspirate showed a left shift in granulopoiesis with vacuolization of immature granulocytic and erythroid precursors (B and C). A Prussian blue–stained aspirate revealed ring sideroblasts (D). The patient’s copper level was less than 0.1 mcg/mL (normal reference range, 0.75 to 1.45 mcg/mL).