Blast Phase in Chronic Myelogenous Leukemia Is Skewed Toward Unusual Blast Types in Patients Treated With Tyrosine Kinase Inhibitors

Abstract

Blast phase CML in TKI- and non-TKI-treated patients differs in the morphology and immunophenotype of blasts, cytogenetic findings, and associated findings in the peripheral blood and bone marrow.

PML-RARA Fusion Transcripts Detectable 8 Months prior to Promyelocytic Blast Crisis in Chronic Myeloid Leukemia

“…The interval of time between initial CML diagnosis and promyelocytic blast crisis was less than 1 year in 33% of cases, including two patients who presented with promyelocytic blast crisis at CML diagnosis, 1–5 years in 52% of cases, and greater than 5 years in 14% of cases (average 30 months). This interval of time to promyelocytic blast crisis is similar to the reported time of development of nonpromyelocytic blast crisis (3 years) [ 4 ].…”

“…Therapies that target the BCR-ABL1 fusion tyrosine kinase have dramatically improved survival in CML; however, transformation to blast crisis remains a significant cause of mortality. Though fewer patients now develop blast crisis, the prognosis after blast transformation is still poor, with death generally 7–11 months after diagnosis with TKI therapy as compared to 3-4 months in the pre-TKI era [ 4 , 6 ]. Herein, we describe an unusual variant of blast crisis in which the PML-RARA fusion characteristic of acute promyelocytic leukemia (APL) is acquired during progression of the disease and summarize a review of 21 cases of promyelocytic blast crisis of CML in the literature [ 9 – 28 ].…”

“…Small molecule tyrosine kinase inhibitors (TKIs) that selectively inhibit the BCR-ABL1 fusion protein have dramatically prolonged survival of CML patients from an average of 3 years to greater than 8 years and decreased the annual rate of progression to blast crisis from 20% to less than 1% per year [ 1 , 3 – 5 ]. While fewer patients continue on to develop blast crisis, the prognosis in blast crisis remains poor, with death generally 3-4 months after diagnosis in pre-TKI era and 7–11 months with TKI therapy [ 4 , 6 ].…”

“…Blast crisis in CML derives from the myeloid lineage in 70% of cases, with the majority of the remaining cases having a lymphoid origin [ 4 ]. Rare forms of blast crisis have been described including megakaryocytic, erythroid, monoblastic, eosinophilic, basophilic, and biphenotypic [ 4 ]. Promyelocytic blast crisis is a rare variant with <25 cases reported in the literature.…”

Improved detection of diffuse large B‐cell lymphoma by flow cytometric immunophenotyping—Effect of tissue disaggregation method

“…FCI was performed after staining aliquots of cell suspension with either pre‐mixed 4‐fluorochrome‐conjugated antibodies (fluorescein isothiocyanate, phycoerythrin, peridinin chlorophyll protein, and allophycocyanin) or pre‐mixed 8‐fluorochrome‐conjugated antibodies (fluorescein isothiocyanate, phycoerythrin, phycoerythrin‐cyanine 7, peridinin chlorophyll protein, allophycocyanin (APC), APCH7, V450, and V500) using the “stain/lyse/fix” wash protocol routinely used in our flow cytometry laboratory and described previously . The antibodies included in the panel consisted of the following: leukocyte common antigen (CD45), B‐cell antigens (CD19, CD20, CD22, κ, and λ light chains), T‐cell antigens (CD3, CD4, CD5, CD7, and CD8), myeloid antigens (CD11c, CD14, and CD33), stem cell antigens (CD123), and CD1a, CD10, CD23, CD25, CD26, CD38, CD52, CD56, CD71, and CD103 (Becton Dickinson Biosciences, San Diego, CA).…”