Dasatinib and Azacitidine Followed by Haploidentical Stem Cell Transplant for Chronic Myeloid Leukemia with Evolving Myelodysplasia: A Case Report and Review of Treatment Options

Fabian Lang, Lydia Wunderle, Heike Pfeifer, Susanne Schnittger, Gesine Bug, Oliver G Ottmann, Fabian Lang, Lydia Wunderle, Heike Pfeifer, Susanne Schnittger, Gesine Bug, Oliver G Ottmann

Abstract

BACKGROUND CML presenting with a variant Philadelphia translocation, atypical BCR-ABL transcript, additional chromosomal aberrations, and evolving MDS is uncommon and therapeutically challenging. The prognostic significance of these genetic findings is uncertain, even as singular aberrations, with nearly no data on management and outcome when they coexist. MDS evolving during the course of CML may be either treatment-associated or an independently coexisting disease, and is generally considered to have an inferior prognosis. Tyrosine kinase inhibitors (TKI) directed against BCR-ABL are the mainstay of treatment for CML, whereas treatment modalities that may be utilized for MDS and CML include allogeneic stem cell transplant and - at least conceptually - hypomethylating agents. CASE REPORT Here, we describe the clinical course of such a patient, demonstrating that long-term combined treatment with dasatinib and azacitidine for coexisting CML and MDS is feasible and well tolerated, and may be capable of slowing disease progression. This combination therapy had no deleterious effect on subsequent potentially curative haploidentical bone marrow transplantation. CONCLUSIONS The different prognostic implications of this unusual case and new therapeutic options in CML are discussed, together with a review of the current literature on CML presenting with different types of genomic aberrations and the coincident development of MDS. Additionally, this case gives an example of long-term combined treatment of tyrosine kinase inhibitors and hypomethylating agents, which could be pioneering in CML treatment.

Conflict of interest statement

Conflict of interest: None declared

Conflict of interest

None.

Figures

Figure 1.
Figure 1.
Blood count. (A) Hemoglobin levels. The hemoglobin levels over time represent the course of the disease showing a transfusion-independent anemia (grade 1–2). Hb levels are presented in g/dl. (B) Thrombocyte count. Thrombocyte count also over time reflects disease progression with mild thrombocytopenia (grade 1–2), not resulting in any bleeding complications. Thrombocyte counts are shown in thrombocytes/nl. (C) Absolute neutrophil count. The absolute neutrophil count is the most sensitive parameter in the course of the disease of this patient. The progression results in a severe grade 4 granulocytopenia requiring antibiotic prophylaxis. ANC is shown in neutrophils/nl. Severe granulocytopenia did not change under dasatinib/azacitidine treatment.
Figure 2.
Figure 2.
Disease and treatment history. The emergence of different clones and molecular aberrations correlates with the development of MDS and the loss of cytogenetic response. Notably, appearance of monosomy 7 predates manifestation of MDS by 2 years. The corresponding therapeutic regimens are shown (HU – hydroxyurea, IM – imatinib), demonstrating prolonged disease stabilization by combined dasatinib and azacitidine treatment for 4 years. The atypical BCR-ABL transcript was detectable continuously prior to SCT. Worsening of red blood count (RBC) and platelet count (Plts) are indicated by * and #, respectively.

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