Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy after major molecular response was achieved

Abstract

Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.

Myodesopsia is a symptom of central nervous system blast crisis in chronic myeloid leukemia

“…Our patient complained of myodesopsia at diagnosis, and in retrospect, CML cells might have been present in the CNS at this early stage, although we did not examine the CFS at diagnosis and MRI of the head revealed no abnormality. In a previous report of a patient with CML BC having CML cells in the CSF at diagnosis [6], dura thickening was identified by MRI of the head, leading to the discovery of CNS invasion. However, the patient in this case was in the blast phase, in which infiltration of CML cells into the CNS can be expected, whereas our case was in the chronic phase.…”

Sudden Blast Crisis After Excellent Initial Response in Chronic Myeloid Leukemia

“…In the era of TKIs, the development of blast crisis after an optimal response is an uncommon feature but nevertheless a probability. Reports of blast crisis transformation following therapy with imatinib [ 17 , 18 ], dasatinib [ 20 ], nilotinib [ 21 , 22 ] show us that there are underlying hidden clinical and biological factors that influence this unfavorable outcome. Ph-positive/Ph-negative mosaicism [ 17 ], clonal evolution [ 18 ], mutations such as T315l [ 22 ] among others are some of the findings observed when the patients transformed into blast phase.…”

Measurable residual disease in chronic myeloid leukemia

“…Progression to advanced phase after the establishment of a durable MMR is unusual but has been described. 86 , 87 Although the achievement of MMR has been termed a ‘safe haven’, Claudiani and colleagues showed that attainment of DMR, sustained for at least 12 months, was associated with a remarkably low probability of losing MMR in the absence of other events such as a trial of treatment discontinuation, lack of compliance, or reduced drug dosing. 88 The mechanism of treatment failure in Patient 1 is unknown.…”