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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.
Maintenance therapy after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is conceptually attractive to prevent relapse, but has been hampered by the limited number of suitable anti-leukemic agents. The deacetylase inhibitor (DACi) panobinostat demonstrated moderate anti-leukemic activity in a small subset of patients with advanced AML and high-risk MDS in phase I/II trials.1, 2 It also displays immunomodulatory activity3 that may enhance leukemia-specific cytotoxicity4 and mitigate graft versus host disease (GvHD), but conversely could impair T- and NK cell function.5, 6 We conducted this open-label, multi-center phase I/II trial (NCT01451268) to assess the feasibility and preliminary efficacy of prolonged prophylactic administration of panobinostat after HSCT for AML or MDS. The study protocol was approved by an independent ethics committee and conducted in compliance with the Declaration of Helsinki. All patients provided written informed consent. ...