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Clinical and prognostic features of Philadelphia chromosome-negative chronic myelogenous leukemia
Insights
Philadelphia chromosome-negative chronic myelogenous leukemia (Ph-negative CML) is a distinct disease with a poor prognosis. Key factors like low platelets, low hemoglobin, and older age predict survival in Ph-negative CML patients.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Philadelphia chromosome-negative chronic myelogenous leukemia (Ph-negative CML) is a rare myeloproliferative neoplasm.
- Distinct clinical and laboratory features differentiate Ph-negative CML from Philadelphia chromosome-positive CML.
Purpose of the Study:
- To characterize the clinical and laboratory features of Ph-negative CML.
- To identify prognostic factors and develop a risk stratification model for Ph-negative CML.
Main Methods:
- Retrospective analysis of 105 patients with Ph-negative CML diagnosed between 1965 and 1982.
- Multivariate analysis to identify independent prognostic factors.
- Development of a risk model based on pretreatment characteristics.
Main Results:
- Median survival was 14 months, with only 10% surviving beyond 5 years.
- Common chromosomal abnormalities included trisomy 8 and abnormalities in chromosomes #5 and #7.
- Independent prognostic factors for poor survival were severe thrombocytopenia, hemoglobin <10 g/dl, increased peripheral blasts/promyelocytes, and age ≥60 years.
- A risk model stratified patients into low, intermediate, and high-risk groups with median survivals of 36, 16, and 3 months, respectively.
Conclusions:
- Ph-negative CML is a distinct entity with a poor prognosis.
- Established prognostic factors and a risk model can aid in patient management.
- Further research into novel therapeutic strategies for Ph-negative CML is warranted.
Abstract:
Between 1965 and 1982, 105 patients with a diagnosis of Philadelphia chromosome-negative chronic myelogenous leukemia were referred to our institution with minimal or no prior therapy. The median age was 63 years and 64% were males. The overall median survival from time of referral was 14 months; 53% of patients survived 1 year and only 10% survived beyond 5 years. At the time of analysis, 92 patients (88%) were dead, 56% of deaths being preceded by a blastic crisis. Compared with Philadelphia chromosome-positive disease, patients with Philadelphia chromosome-negative chronic myelogenous leukemia were older and had a significantly higher incidence of anemia, thrombocytopenia, monocytosis, marrow blasts, decreased marrow megakaryocytes and a lower incidence of basophilia and thrombocytosis. Chromosomal abnormalities occurred in 33% of patients and consisted most frequently of trisomy 8, or an additional chromosome C, loss of the Y chromosome, or abnormalities in chromosomes #5 and #7. Of nine pretreatment characteristics significantly associated with poor survival, a multivariate analysis identified four to have independent additive prognostic significance: severe thrombocytopenia, hemoglobin levels less than 10 g/dl, increasing peripheral blasts and promyelocytes, and age 60 years or older. Monocytosis was not of prognostic significance. The derived prognostic model divided patients into three risk groups, low, intermediate, and high, with median survivals of 36, 16, and 3 months, respectively. The authors conclude that Philadelphia chromosome-negative chronic myelogenous leukemia is a distinct entity among the myeloproliferative syndromes with characteristic clinical and laboratory features and a poor prognosis. Prognostic factors and related risk categories were demonstrated within this disease entity.