Myelomastocytic Blast Cell Crisis in Resistant Tyrosine Kinase Inhibitor Chronic Myelogenous Leukemia: Case Report and Review of Literature

Abstract

We present the clinical case of a 29-year-old male with a diagnosis of chronic myeloid leukemia (CML) in high-risk chronic phase since February 2010. He started treatment with imatinib at a dose of 400 mg obtaining a hematologic response early but without reaching a cytogenetic response in month 18. Then, dasatinib was prescribed. The BCR-ABL transcription level of 58% was documented. It was decided to start treatment with nilotinib but in March 2017 we diagnosed a progression to blast crisis (BC) of myeloid origin with a bone marrow study that documented 72% of blasts with normal karyotype, also very striking, the concomitant skin infiltration, bone lesions of lytic type and hypercalcemia that required the use of zoledronic acid as an emergency. At the end of chemotherapy induction with 7 + 3 (seven days of cytarabine and three days of idarubicin) chemotherapy associated with bosutinib for 14 days and after several infectious complications, we documented a percentage of blasts by flow cytometry of 29% in the bone marrow and the existence of 46% of cells with basophilic characteristics versus mast cells. A basophilic transformation was suspected versus aggressive systemic mastocytosis with a clonal, nonmastocytic hematological disorder. Levels of serum tryptase and mutation D816V C KIT were requested, which were not possible to perform. Treatment with CLAG-M was proposed, however, the patient died early with hyperleukocytosis and severe thrombocytopenia with central nervous system bleeding.

A case report and case review: Chronic myeloid leukemia (CML) blast phase with myelomastocytic differentiation

“…Martinez-Cordero et al. [3] reported a CML patient in blast phase with 29% myeloblasts and 46% of immature cells with basophilic or mast cell characteristics (CD117 + , CD25 + , CD123 + , CD34 partial + , myeloperoxidase − , and tryptase not reported). Serum tryptase and Kit mutations were not tested.…”

“…In the blast phase, blasts are myeloblasts in 70% of cases and lymphoblasts in 20% to 30% of cases. They are rarely megakaryoblasts, basophilic blasts, monoblasts, or eosinophilic blasts [ 2 , 3 ]. It has been found that patients treated with TKIs are more likely to show unusual blasts (43.5%) than patients who do not undergo TKI treatment (11.4%) [4] .…”

“…It has been found that patients treated with TKIs are more likely to show unusual blasts (43.5%) than patients who do not undergo TKI treatment (11.4%) [4] . Blast phase CML with blasts of mast cell phenotype (myelomastocytic blasts) has rarely been reported and could pose a diagnostic challenge and cause treatment confusion [ 3 , 5 , 6 ]. The term myelomastocytic leukemia has previously been described for advanced myeloid neoplasms with blasts showing metachromatic granules in the cytoplasm and mast cell or basophilic phenotypes [7] .…”

Cerebrospinal fluid infiltration by chronic myeloid leukaemia: Evaluation of cytomorphological features

“…2,8 Other uncommon blast lineages are megakaryocytic, erythroid, basophilic, monocytic, myelomonocytic, eosinophilic and mastocytic. 14 Furthermore, lymphoid blasts are reported to infiltrate the CNS more than myeloid and bilineage blasts. 10 The index study also had a higher number of cases of lymphoid CML-BC showing CSF infiltration.…”

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

“…There is some evidence that dasatinib crosses the blood–brain barrier 50 ; it has demonstrated improved survival in a murine model of BCR‐ABL1‐positive CNS leukaemia, and clinical responses in patients with BCR‐ABL1‐positive leukaemia and CNS disease. There are isolated case reports for the use of nilotinib and bosutinib in BCR‐ABL1‐positive CNS leukaemia 80,83 . He et al 84 report a series of nine cases of Ph + leukaemia with CNS disease and T315I mutation (five Ph + ALL and four BP‐CML), post alloHSCT who were treated with ponatinib.…”