Promyelocytic Blast Crisis of Chronic Myeloid Leukemia in a Patient Undergoing Therapy with a Tyrosine Kinase Inhibitor

Abstract

A 58-year-old male with the chronic phase of chronic myeloid leukemia (CML), treated with a tyrosine kinase inhibitor (TKI), bosutinib, since the past two years, presented with bright red bleeding per rectum and disseminated intravascular coagulation. A bone marrow biopsy reverse transcription-polymerase chain reaction revealed a promyelocytic blast crisis, with leukemic cells displaying both BCR/ABL and PML/RARα chimeric genes. Cytogenetic studies revealed translocations of both t(15;17) and t(9;22). With the initiation of all-trans retinoic acid, arsenic trioxide and gemtuzumab, the patient achieved remission, with absent PML/RARα by fluorescence in situ hybridization analysis. This case highlights the importance of long-term monitoring of patients with CML, especially those on TKIs, for the development of secondary leukemias in the future.

Tyrosine kinase inhibitor independent gene expression signature in CML offers new targets for LSPC eradication therapy

“…On the other hand, we have shown that GO is effective at reducing the number of CML CD34 + cells. Previous studies have shown that GO is effective against CML chronic phase mononuclear cells in vitro [36] and it has been used with partial success when treating patients with TKI resistant CML blast crisis [41-43]. Here we show that GO could be used for the treatment of CML-CP as it seems to push CML CD34 + cells into cell cycle (Figure 3e) and drives CML LSC into differentiation, as suggested by the sequencing results (Figure 5e).…”

Tyrosine Kinase Inhibitor Independent Gene Expression Signature in CML Offers New Targets for LSPC Eradication Therapy

“…On the other hand, we have shown that GO is effective at reducing the number of CML CD34 + cells. Previous studies have shown that GO is effective against CML chronic phase (CML-CP) mononuclear cells in vitro [ 36 ], and it has been used with partial success when treating patients with TKI-resistant CML blast crisis [ 41 , 42 , 43 ]. Here, we show that GO could be used for the treatment of CML-CP as it seems to push CML CD34 + cells into the cell cycle ( Figure 3 e) and drives CML LSC into differentiation, as suggested by the sequencing results ( Figure 5 e).…”

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

“…One early trial showed responses in 2/9 patients with BP-CML when combined with fludarabine and cytarabine, 93 but subsequent to this, only isolated cases have been reported. 71,94 A recent single-centre, retrospective study of venetoclax with TKI-based regimens has shown some promising results in BP-CML (n = 9), 95 with a median OS of 10.9 months, and further studies are warranted. The aurora kinase inhibitor danusertib has demonstrated responses in a Phase 1 trial in patients with the T315I mutation, 96 including BP-CML, but further clinical development was halted due to practicalities of the drug infusion frequency.…”

“…Despite the success of the anti‐CD33 drug–antibody conjugate gemtuzumab ozogamicin in AML, 92 this has not been extensively assessed in myeloid BP‐CML. One early trial showed responses in 2/9 patients with BP‐CML when combined with fludarabine and cytarabine, 93 but subsequent to this, only isolated cases have been reported 71,94 . A recent single‐centre, retrospective study of venetoclax with TKI‐based regimens has shown some promising results in BP‐CML ( n = 9), 95 with a median OS of 10.9 months, and further studies are warranted.…”