Persistent Basophilia May Suggest an “Accelerated Phase” in the Evolution of CALR-Positive Primary Myelofibrosis Toward Acute Myeloid Leukemia

Abstract

Basophils are white blood cells that play an important role in the human immune system. These cells physiologically increase in number in immune response to certain allergies, chronic inflammation, and parasitic infections. Basophils are also a significant indicator for the presence of certain malignancies such as chronic myeloproliferative neoplasms and acute myeloid leukemia. In the current manuscript we present a statistically significant correlation between persistent basophilia in primary myelofibrosis (PMF) and the risk for the subsequent development of acute myeloid leukemia. We have retrospectively identified in the files of the Department of Hematology, Ion Chiricuta Clinical Cancer Center in Cluj Napoca, Romania 623 consecutive patients diagnosed with AML over a period spanning from 2008 to 2018. We afterwards identified 32 patients with AML diagnosis following a previous diagnosis of myelofibrosis (either post-PV, post-ET, or post-PMF). All the patients were diagnosed according to the WHO criteria. We subsequently established a control group consisting of 32 patients with underlying BCR–ABL-negative MPN who did not develop AML (AML-negative group). Following this, we assessed whether the AML-negative patients from our control group also had a persistent (>3 months) absolute basophilia. When comparing both groups of patients with myelofibrosis, the group with subsequent AML development and the one without AML, the follow-up did not present statistically significant differences between the two groups. In the univariate analysis, patients who progressed to AML had more frequently basophilia, longer basophilia duration, higher pre-therapy absolute, and relative basophil count and presented more frequently calreticulin (CALR) mutations. In the current study, we emphasize the need for a closer clinical monitoring for chronic MPNs with marked basophilia, with an important potential clinical impact.

Development and Validation of a Novel Prognostic Model for Acute Myeloid Leukemia Based on Immune-Related Genes

“…The presence of this gene is included in the current diagnostic criteria of Ph (−) MPN ( 24 ). The AML patients converted from MPN had more CALR mutation rate frequency ( 25 ). Moreover, there are reports that the expression of CALR is remarkably higher than other hematologic malignancies, such as ambiguous lineage, ALL, MPN, MDS/MPN ( 26 ).…”

Accelerated Phase of Myeloproliferative Neoplasms

“…Dobrowolski and colleagues [59] demonstrated that correlation of leukemic transformation risk and persistent basophilia in PMF in the fibrotic stage was statistically significant. Other groups showed that monocytosis was a strong adverse indicator of progression to the accelerated phase and inferior survival in patients with PMF [60-62].…”

Progression in Ph-Chromosome-Negative Myeloproliferative Neoplasms: An Overview on Pathologic Issues and Molecular Determinants

“…Monocytosis has also been reported as a strong indicator of AP and inferior survival in patients with PMF [ 84 , 85 ]: in a large case series, the presence of an absolute monocytosis (≥1 × 10 9 /L and >3 × 10 9 /L) increased the hazard risk of leukemic transformation by 2- and 4-fold, respectively [ 85 ]. Dobrowolski and colleagues reported persistent basophilia in advanced-stage PMF patients as a risk for leukaemic transformation [ 86 ].…”