Characteristics and outcome of patients with Philadelphia chromosome negative,bcr/ablnegative chronic myelogenous leukemia

Abstract

BACKGROUNDUp to 5% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia (Ph) translocation t(9;22)(q34;q11) or a bcr/abl molecular rearrangement. Although the diagnostic criteria of this entity are still under debate, there is general agreement that patients with Ph negative, bcr/abl negative CML have a severe clinical course that is not affected significantly by current treatment options.METHODSA population of 76 patients with bcr/abl negative CML who had received minimal or no previous therapy was characterized carefully with the intent of investigating clinical and hematologic variables and their association with survival by univariate, correlation, and multivariate analyses. A group of 73 patients with Ph negative CML who were not tested for the bcr/abl rearrangement (bcr/abl unknown) was analyzed separately and used for extension of the analysis.RESULTSIn the bcr/abl negative patient population, the median overall survival was 24 months. At the time of the analysis, 38 patients (50%) had died, and blastic transformation preceded death in 31%. Chromosomal abnormalities were found in 30% of the 76 patients, with trisomy 8 the most common abnormality. Complex chromosomal abnormalities were rare, and monosomy 7 was not observed. Survival was not affected significantly by treatment. Multivariate analysis identified older age (> 65 years), anemia (hemoglobin < 10 g/dL), and severe leukocytosis (white blood cells > 50 × 109/L) as variables with independent prognostic significance for poor survival. A prognostic scoring system stratified patients into a low‐risk group (53%) and a high‐risk group (47%), with median survivals of 38 months and 9 months, respectively.CONCLUSIONSBcr/abl negative CML is a distinct clinical entity associated with very poor prognosis. Two risk categories are identifiable using a simple scoring system based on age, hemoglobin level, and leukocyte number. Cancer 2002;95:1673–84. © 2002 American Cancer Society.DOI 10.1002/cncr.10832

JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome–negative CML, and megakaryocytic leukemia

“…Individual characteristics of the non-PV/ET/MF patients carrying the 1849GϾT JAK2 mutation are summarized in Table 1. 17,18 In 4 patients, the proportion of mutant allele was lower than 20%, suggesting the presence of minor populations of cells carrying the mutation. We confirmed the presence of the mutant allele in all these patients by cloning PCR products in a plasmid vector and pyrosequencing 50 clones for each patient.…”

The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features

“…[21][22][23][24][25]44,45 Progression to acute leukemia occurs in approximately 15-30% of cases. A number of clinical and hematological parameters, including splenomegaly, severity of anemia and degree of leukocytosis, have been reported to be important factors in predicting the course of the disease.…”

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

“…97 BCR-ABL-negative CML is associated with a very poor prognosis. 98 Translocation t(9;22) is also found in 4-7% of childhood ALL and in 25-45% of adult precursor-B-ALL and correlates with a poor prognosis. 30,97,99,100 The Ph translocation results in the joining of the 3' end of the ABL gene (9q34) to the 5' part of the BCR gene (22q11), creating the BCR-ABL fusion gene.…”