Successful eltrombopag treatment of severe refractory thrombocytopenia in chronic myelomonocytic leukemia: Two cases reports: A CARE-compliant article

Abstract

Rationale: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually attributed to impaired marrow production resulting from cytotoxic drug use or CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP"). However, treatment of severe thrombocytopenia in patients with CMML is still a challenge.

Patient concerns: Case 1 was a 61-year-old female patient admitted to our hospital because of skin petechiae and purpura for 6 days. She had increased monocyte cell count (1.82 × 10/L), markedly decreased platelet count (2 × 10/L), hypercellularity of the megakaryocyte lineage with many immature megakaryocytes, and ZRSR2(zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2) mutation. She failed to the treatment of corticosteroids, intravenous immunoglobulin (IVIg), TPO (thrombopoietin), and cyclosporin A (CsA). Case 2 was a 72-year-old female patient with thrombocytosis and monocytosis for 4 years, and thrombocytopenia for 6 months. After 10 courses of decitabine therapy, she had a persistent severe thrombocytopenia and decreased number of megakaryocytes, TET2 (tet methylcytosine dioxygenase 2) and SRSF2 (serine and arginine rich splicing factor 2) mutations were detected. She was dependent on platelet transfusion.

Diagnoses: Case 1 was diagnosed as CMML-associated ITP, and case 2 as CMML with decitabine therapy-induced thrombocytopenia.

Interventions: Both patients were treated with eltrombopag.

Outcomes: In both patients, the platelet counts returned to the normal within 1 week after eltrombopag therapy. The platelet count in case 1 patient remained stable at 141-200 × 10/L for 20 months with stopping therapy for 3 months. In case 2 patient, eltrombopag was stopped 1 month later. Her platelet count decreased to 41 × 10/L, but was stable at ∼30 × 10/L for 3 months with platelet transfusion independency for 12 months. Both patients had no adverse effects with eltrombopag.

Lessons: CMML-associated ITP is very rare and easily misdiagnosed. To the best of our knowledge, case 1 is the first reported case of the successful treatment of CMML-associated ITP with eltrombopag. Both CMML-associated ITP and decitabine therapy-induced thrombocytopenia in these 2 patients were highly sensitive and safe to eltrombopag therapy.

Figure 1

Morphology of bone marrow aspirate (A) and histopathology and immunohistochemistry of bone marrow biopsy (B–F) in case 1 patient (CMML-associated ITP). A. Megakaryocytes were markedly hypercellular (Wrights × 10). B. Megakaryocytic hyperplasia (HE × 400). C. CD61 immunohistochemistry: hypercellularity and dysplasia of megakaryocytes with micromegakaryocytes, naked nucleus, and hypolobated megakaryocytes (IHC × 400). D. CD34 immunohistochemistry: a few myeloid blasts positive (IHC × 400). E. CD68 immunohistochemistry: monocytes and macrophages positive (IHC × 400). F. AgNOR stain: +(×200). CMML = chronic myelomonocytic leukemia, ITP = immune thrombocytopenia.

Figure 3

Case 1: MD-CMML-associated ITP. The patient was initially treated with intravenous immunoglobulin (IVIg), dexamethasone (Dx), prednisone, thrombopoietin (TPO), cyclosprin A (CsA), and platelet transfusion which were not effective, however, the white blood cells (WBC), monocytes (MONO), and serum creatinine (CR) were increased. Then eltrombopag was initiated. The platelet count was increased to 78 × 10⁹/L 2 days later, 170 × 10⁹/L 5 days later, and was remained stable at ∼200 × 10⁹/L. The eltrombopag dose was decreased to 25 mg/d 2 weeks later. And 2 months later, eltrombopag was decreased to 12.5 mg/d, 3 months later was further decreased to 8.3 mg/d (1/6 tablet) and then was stopped 18 months later. The platelet count has been stable at 140–200 × 10⁹/L and monocyte count has been 1.04–1.95 × 10⁹/L for nearly 20 months. CR = serum creatinine, CsA = cyclosprin A, Dx = dexamethasone, ITP = immune thrombocytopenia, IVIg = intravenous immunoglobulin, MD-CMML = myelodysplastic-chronic myelomonocytic leukemia, MONO = monocytes, PLT = platelets, Pred = prednisone, TPO = thrombopoietin, WBC = white blood cells.

Figure 4

Morphology of bone marrow aspirate (A and B) and histopathology and immunohistochemistry of bone marrow biopsy (C–H) in case 2 patient (CMML with decitabine-induced thrombocytopenia). A. Megaloblastoid change of myelocyte, and increased monocytes (Wrights × 100). B. Micromegakaryocytes and monolobar megakaryocytes (Wrights × 100). C. Cluster of myeloid blasts (HE × 400). D. CD34 immunohistochemistry: cluster of myeloid blasts (IHC × 400). E. Hypolobated megakaryocytic (HE × 400). F. CD61 immunohistochemistry: megakaryocytes hyperplasia, micromegakaryocytes, hypolobated and monolobar megakaryocytes (IHC × 400). G. CD68 immunohistochemistry: monocytes and macrophages positive (IHC × 400). H. AgNOR stain: + (×200). CMML = chronic myelomonocytic leukemia

Figure 6

Case 2: Decitabine therapy-induced thrombocytopenia in MP-CMML. During the first 9 courses of decitabine therapy, transient thrombocytopenia appeared and could be restored. After 10 courses of decitabine therapy, persistent thrombocytopenia appeared, therefore, eltrombopag initiated. The platelet count was increased to 30 × 10⁹/L 3 days later, and to 140 × 10⁹/L 1 week later. Eltrombopag was decreased gradually and finally stopped after 1 month, then the platelet count was decreased to 41 × 10⁹/L, but was stable at ∼30 × 10⁹/L for 3 months. DAC = decitabine, MONO = monocytes, MP-CMML = myeloproliferative-chronic myelomonocytic leukemia, PLT = platelets, WBC = white blood cells.