Blastic Phase Blast Crisis

A diagnosis of blastic phase is made when more than or equal to 30% blasts are present in the blood or bone marrow. Immunophenotyping is mandatory to determine whether the blasts have myeloid (60-70% of cases) or lymphoid differentiation (20-30% of cases), since this has major implications for optimal management. In the case of myeloid blast crisis, the blasts may fulfill the diagnostic criteria for any of the French-American-British (FAB) subgroups, but myelomonocytic differentiation is most frequent. Immunophenotypic analysis reveals pos-itivity for myeloperoxidase and myeloid markers (CD13, CD14, and CD33). Lymphoid blast crisis usually has a pre-B-cell phenotype, with positivity for B-cell markers (CD19 and CD20), CD10, and TdT.1213 T-lymphoid blast crisis is extremely rare. Approximately 10% of cases are undifferentiated or biphenotypic. Regardless of the phe-notype, the blasts almost invariably express the CD34 antigen. A diagnosis of blastic phase is also established in the case of extramedullary disease, with the exception of liver or spleen involvement.

of patients with a diagnosis of CML based on clinical and morphologic criteria. The Ph chromosome, originally thought to be a shortened chromosome 22 and thus referred to as 22~3 is the result of a reciprocal translocation between the long arms of chromosomes 9 and 22 [t(9;22)(q34;q11)].14 As a consequence, genetic sequences from the BCR gene on 22q34 are fused 5' of the ABL* gene on 9q11, and vice versa, generating a BCR-ABL fusion gene on the derivative chromosome 22 and an ABL-BCR fusion gene on the derivative chromosome 9 [Figure 17.1(a) and 17.1(b)].15'16 Approximately 10% of patients with typical CML are negative for the t(9;22)(q34;q11) by conventional G- or R-banding techniques. In approximately half of these patients, the BCR-ABL translocation is detectable by fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR), a situation referred to as cryptic or silent Ph translocation. The clinical course of these individuals is not different from classical Ph-chromosome-positive CML, while the remaining 5% of patients have truly BCR-ABL-nega-tive disease. According to the World Health Organization, CML is defined by presence of the BCR-ABL translocation, and thus the term Ph-negative or BCR-ABL-negative CML should not be used any longer. Depending on specific features, it may be possible to classify such patients as having chronic myelomonocytic leukemia if there is persistent monocytosis of more than 109/L, or atypical CML if there is prominent dysgranulopoiesis. Otherwise, the disease should be referred to as chronic myeloprolif-erative disease, unclassifiable. The exclusive definition of CML as the BCR-ABL-positive disease has become even more important with the advent of ima-tinib as a specific targeted therapy for this disorder.17

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