Philadelphia Chromosome Positive Acute Myeloid Leukemia: An Aggressive Acute Leukemia with Clinicopathologic Features Distinct from Chronic Myeloid Leukemia in Blast Crisis.

Philadelphia chromosome positive acute myeloid leukemia (Ph+ AML) is a rare entity reported to comprise 1% of tumors bearing the Philadelphia chromosome. Controversy exists over whether this represents a distinct entity or is merely presentation of patients in the blastic phase of chronic myeloid leukemia (CML). Our study sought to determine the clinicopathologic characteristics of Ph+ AML in comparison to CML in blast crisis. We searched the archival files of Massachusetts General Hospital, Brigham and Women’s Hospital, Dana Farber Cancer Institute, and MD Anderson Cancer Center from 1995 to 2005 for cases of apparent de novo Ph+ AML. After excluding biphenotypic leukemias and cases with any evidence of prior CML or other myeloid neoplasia, we retrieved 18 Ph+ AML cases. 20 cases of documented CML in myeloid blast crisis (CML-MBC) who had not received prior imatinib mesylate therapy or bone marrow transplant were used as a control group. The clinical and laboratory features, bone marrow morphology, immunophenotype, cytogenetics, and type of BCR/ABL transcript were analyzed. The Ph+ AML patients included 13 males and 5 females with a median age of 55 years, which was not significantly different from CML-MBC patients. The median WBC at presentation was 15.7 x 109/L. Compared to CML-MBC patients, the Ph+ AML patients were less likely to have splenomegaly (22% vs. 68%, p=0.008) or peripheral basophilia (median absolute basophil count 0.16 vs. 1.24 x 109/L, p=0.003). The bone marrow in Ph+ AML patients was less cellular (median cellularity 80% vs. 98%, p=0.002) with a lower myeloid:erythroid ratio (1.3 vs. 4.8, p=0.01), but more prominent erythroid and myeloid lineage dysplasia (p=0.04) than that of CML-MBC patients. While cytogenetic abnormalities in addition to t(9;22) occurred in 67% of Ph+ AML cases, the typical additional cytogenetic changes of CML-MBC (+8, +19, iso17q, and +Ph+) were uncommon (22% vs. 87% for CML-MBC, p=0.0004). In 5/6 Ph+ AML cases with multiple clones, the Ph+ was present in all clones, suggesting that this represents an early event in the evolution of these leukemias. RT-PCR revealed a predicted BCR/ABL product of p210 (10/13 cases), p190 (2/13 cases) or p230 (1/13 cases). 6/7 Ph+ AML patients treated with imatinib showed at least a partial hematologic response, but this was of a short duration (median 2.5 months, range 1–6 months) in comparison to the reported median response duration of 10 months in imatinib-responsive CML-MBC. The median survival of the Ph+ AML patients was 10.5 months, similar to that of CML-MBC and AML with adverse cytogenetics. In summary, Ph+ AML is a rare entity distinct from CML-MBC, with an aggressive clinical course and only transient response to imatinib.