Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML

Plas, D van der; Grosveld, Gerard; Hagemeijer, Anne

doi:10.1016/0165-4608(91)90457-6

Cited by 71 publications

(13 citation statements)

References 58 publications

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“…This distribution is consistent with the reported incidence of bcr/ abl positive disease among patients with Ph negative CML. 9,12,15,19,23,24,33,51 Our findings in a large and strictly defined study group confirmed the results of our previous report 23 and the results of other authors, 1,3,[5][6][7]52,53 namely, that patients with Ph negative CML have a poor prognosis. The median survival was 24 months, with only 7% of patients surviving beyond 5 years.…”

Section: Discussionsupporting

confidence: 81%

“…50,64 The causes of death among patients with bcr/abl negative CML are controversial. One study 26 suggested that increased tumor load and bone marrow failure is a more frequent cause of death compared with evolution into a blastic phase, which is very common in patients with bcr/abl positive CML, whereas another study 19 reported frequent transformation into the blastic phase. In our cohort of patients with bcr/abl negative CML, progression to the blastic phase was documented in 31% of patients for whom the cause of death was known.…”

Section: Discussionmentioning

confidence: 99%

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

Onida

Ball

Kantarjian

et al. 2002

Cancer

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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

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

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

Onida

Ball

Kantarjian

et al. 2002

Cancer

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“…Cases of atypical CML display a high incidence of complex karyotypes involving both chromosome 5 or 7, similar to myelodysplastic syndromes and secondary acute myeloid leukemia. 1,24 In contrast to chronic myelogenous leukemia and a large proportion of the other subtypes of chronic myeloproliferative disorders, the molecular pathogenesis of CMML is still only minimally understood. Mutations of RAS are detected in approximately one-third of CMML cases.…”

Section: Cytogenetic Resultsmentioning

confidence: 99%

Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology

et al. 2006

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The World Health Organization criteria for diagnosing chronic myelomonocytic leukemia (CMML) are largely based on findings observed in the peripheral blood and bone marrow aspirate. A specific diagnostic role for the bone marrow biopsy has not been adequately explored. We examined whether bone marrow biopsy supplemented by immunohistochemistry may be helpful in distinguishing CMML from cases of chronic myelogenous leukemia and atypical chronic myeloid leukemia (aCML). We immunostained 25 cases of CMML with paraffin reactive antibodies which included CD68 (KP1), CD68R (PG-M1), and CD163, and compared the results with those observed in six cases of chronic myelogenous leukemia and in three cases of atypical CML. In addition, we examined whether CD34 immunohistochemistry could be useful in separating cases of CMML with less than 10% blasts (type-1) from cases of CMML with blasts accounting for 10-19% (type-2), and cases of CMML in acute transformation to acute myeloid leukemia (blastsZ20%). The presence of nodules of plasmacytoid monocytes was investigated by CD123 staining. CD42b was used to highlight abnormal megakaryocytes. Our results demonstrate significant differences between the groups. CD34 analysis allowed separating CMML type-1 from type-2 and the former from CMML in acute transformation. CD123-positive plasmacytoid monocyte nodules were found only in CMML and not in the other two disease groups. Overlap between CMML and the other two groups were observed with CD68 immunostaining. CD68R was more restricted to bone marrow macrophages and monocytes than CD68, but the differences between CMML and chronic myelogenous leukemia or atypical CML were still not significant. Although CD42b immunostaining facilitated the detection of dwarf megakaryocytes often present in CMML, the distinction between those and the small forms seen in chronic myelogenous leukemia was still problematic.

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“…Thus, Ph chromosome or the bcr/abl fusion gene serves as the hallmark of CML and also as a prognostic marker during the treatment of CML with interferon or bone marrow transplantation (BMT). [2][3][4][5][6][7] Until recently, detection of Ph chromosome has been primarily done by karyotype analysis of freshly obtained bone marrow cells. The major limitation of the karyotypic technique is an absolute need for metaphases in testing cells.…”

Section: Introductionmentioning

confidence: 99%