Clinical and prognostic features of philadelphia chromosome-negative chronic myelogenous leukemia

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. Chro-mosomal 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.

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

“…As a consequence, the percentage of cases of Ph negative CML has been reduced from 10%-15% [2][3][4] to less than 5%, mainly by elimination of cases fulfilling tbe presently established criteria for CMMoL, jCML, MDS, and ANLL. Discrimination hetween Ph-positive and Ph-negative CML is not possible using clinical or helnatologic characteristics only.…”

“…Each patient is assessed for the diagnostic criteria of XLP: One or more of the phenotypes (Table 1) has to occur in two or more maternally related males [2][3][4]. A morphological evaluation is made of slides of peripheral blood smears, surgical biopsy specimens, bone marrow, and tissues obtained at autopsy.To document the involvement of EBV, we perform a battery of tests depending on the availability of samples.…”

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

“…Except for a difference in the cut-off value for the peripheral white blood cell (WBC) count (WBC Ͼ 10 ϫ 10 9 /L in this study compared with WBC Ͼ 20 ϫ 10 9 / L 22,23,33 ), the criteria used to establish a diagnosis of Ph negative CML were identical to the criteria we used in our 1986 report: 22 1) absence of Ph on analysis of at least 20 bone marrow mitoses; 2) hypercellular bone marrow with granulocytic hyperplasia, leftward shift in myeloid maturation, bone marrow blasts Ͻ 30%, and absence of significant dysplasia; 3) persistent, unexplained peripheral granulocytic leukocytosis (WBC count Ͼ 10 ϫ 10 9 /L); 4) peripheral blast cells Ͻ 30%; 5) monocyte percentage Ͻ 10% in the peripheral blood cells and absolute monocyte count Ͻ 1 ϫ 10 9 /L in patients with WBC counts Ͻ 20 ϫ 10 9 /L 12,33 ); and 6) absence of substantial bone marrow myelofibrosis. An absence of molecular evidence for the bcr/abl fusion gene was the final and necessary criterion used to define the bcr/abl negative subpopulation of patients.…”

“…Various cut- off values, including those that demonstrated significance in our previously published reports, 22,23,33 were analyzed individually. Older age (Ͼ 65 years) was associated with shorter survival.…”

“…32 Thus, reliable information on the natural history of bcr/abl negative CML and survival-associated covariates is needed. Herein, we expand our experience 22,23,33 with patients who have Ph negative CML, giving particular attention to the subset of patients with bcr/abl negative CML. The objectives of this study were 1) to analyze patient and disease characteristics of Ph negative, bcr/abl negative CML; 2) to identify independent covariates associated with survival; and 3) to design a simple and clinically useful scoring system capable of identifying different risk groups that would help to assign patients to riskoriented therapeutic strategies.…”