Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long term follow-up results

Abstract

Background. Five to 10% of patients with chronic myelogenous leukemia (CML) do not have the Philadelphia chromosome (Ph), but one‐third of them have rearrangements of the breakpoint cluster region (BCR‐positive). Methods. The authors analyzed the characteristics, treatment response, and prognosis of 23 patients with BCR‐positive, Ph‐negative CML, and compared them with patients with Ph‐positive CML, Ph‐negative BCR‐negative CML and chronic myelomonocytic leukemia (CMML) treated during the same period. Results. Seventeen patients had early chronic phase CML, 3 had late chronic phase, 2 had accelerated phase, and 1 had blastic phase. The median age was 44 years (range, 14‐71 years), median platelet count was 402 × 109/l, and median leukocyte count was 86 × 109/l. Fourteen of the 17 patients with early chronic phase CML received alpha‐interferon; 12 (86%) achieved complete hematologic remission. Median survival in chronic phase CML was 60 months (range, 3‐90+ months). Patients with Ph‐negative BCR‐positive CML and those with Ph‐positive CML had similar characteristics and outcome. Compared with patients with Ph‐negative BCR‐negative CML and CMML, patients with Ph‐negative BCR‐positive CML and Ph‐positive CML were significantly younger, had a significantly higher incidence of leukocytosis, thrombocytosis, and peripheral and marrow basophilia, and a significantly lower incidence of anemia, thrombocytopenia, marrow blast percent, and peripheral and marrow monocytosis. The median survival was 60 months for Ph‐negative BCR‐positive CML, 73 months for Ph‐positive CML, 25 months for Ph‐negative BCR‐negative CML, and 9 months for CMML (P < 0.001). When analyzed adjusting for their stage, patients classified with Ph‐negative BCR‐positive CML Stage I disease had a significantly better survival than did patients with Ph‐negative BCR‐negative CML (P < 0.02). Conclusions. Patients with Ph‐negative BCR‐positive CML are similar to those with Ph‐positive CML and should be treated with the same approaches. Cancer 1995;75:464‐70.

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

“…Although several studies compared patients who had bcr/abl negative CML with patients who had bcr/abl positive CML (for reviews, see Costello et al, 12 Kurzrock et al, 26 and Aurich et al 62 ), the two largest series of patients with bcr/abl negative CML, which included 23 patients 24 and 35 patients 63 , could not identify significant prognostic factors in patients with bcr/abl negative CML. In this larger study group, by multivariate analysis, we identified older age, anemia, and severe leukocytosis as variables that were associated independently with poorer prognosis.…”

Chronic myeloid leukemia from basics to bedside

“…The Ph−/bcr+ cases showed the same clinical behavior as the Ph+/bcr+ patients. 118 Moreover, both groups showed a very comparable response to interferon-alfa. These results indicate that Ph− but bcr+ leukemias behave very similarly to classic CML.…”

“…118 However, Morris et al 119 demonstrated that in two out of five Ph-negative patients the same bcr-abl gene rearrangements could be observed as in the Phpositive samples. These Ph-negative but bcr-abl-positive cells are often the result of variant translocations and can be detected using fluorescence in situ hybridization (FISH), genomic Southern blotting and RT-PCR techniques.…”

Chronic Myelogenous Leukemia

“…56 Therefore, further evaluation for other diseases is warranted for patients with BCR-ABL-negative disease. Patients whose cells are BCR-ABL-positive (according to karyotype analysis, FISH, or molecular techniques) are the focus of these NCCN guidelines.…”