Page 1498 - Williams Hematology ( PDFDrive )

1472 Part X: Malignant Myeloid Diseases Chapter 89: Chronic Myelogenous Leukemia and Related Disorders 1473

CMML, 903,927,1014–1016 some cases are indistinguishable from classic CML Laboratory Features The LDH is often elevated. The marrow
but without the BCR-ABL1 after exhaustive molecular diagnostic evalu- is hypercellular with variable evidence of dysmorphic granulopoiesis
ation. 1017–1021 In a report of 76 such patients, the median age was 66 years and dysmorphic megakaryocytopoiesis. Mild marrow reticular fibrosis
(range: 24 to 88), splenomegaly was present in 50 percent of cases, the may be evident. Clonal cytogenetic abnormalities may occur but do not
median white cell count was 38,000 cells/μL (38 × 10 cells/L; range: include translocations characteristic of classical chronic myeloid neo-
9
11 to 296), and the median hemoglobin was 11 g/dL (range: 7 to 16), plasms, such as a BCR-ABL1 or translocations involving PDGFR-α,
with classical morphologic features in blood and marrow. 1021 As the dis- PDGFR-β, or FGFR1 seen in chronic eosinophilic leukemia with or
ease progressed, patients developed severe cytopenias. 1018 Median sur- without mastocytosis. Common myeloid-related cytogenetic abnormal-
vival was 24 months and only 7 percent survived for more than 5 years. ities may occur, such as trisomy 8, del(20q), and others.
Myeloid blast phase occurred in one-third of those followed until their Therapy This type of neoplasm has no specific treatment and is
death. Occasional patients had extended complete remissions with IFN- usually treated “symptomatically” with red cell or platelet transfusion
γ therapy. 1020 Hydroxyurea can be useful as palliative therapy. and an agent to reduce the white cell count, if that is a problem (e.g.,
Some patients have transposition of ABL1 to chromosome hydroxyurea, 5-azacytidine, low-dose cytarabine, numerous others). 1031
22 but not the classic translocation. In such cases, including TEL- Appropriate patients may be considered for allogeneic hematopoi-
ABL1 translocations, transient responses to imatinib have been etic stem cell transplantation, if a suitable donor is available, but this
observed. 1022 approach is problematic in an older population because they would be
Uncommon cases of coexisting BCR-negative and BCR-positive transplanted during active disease and with a higher-risk of GVHD.
clones have been described, and the basis for such cases is in dispute. 1023 Nonmyeloablative allogeneic stem cell transplantation has also been
One proposed explanation is that this case is an example of “field car- used.
cinogenesis” in which multiple clones coexist. 1023 An alternative expla- Course and Prognosis This patient population has a median sur-
nation is that these cases represent the dual progeny of a single unstable vival of approximately 18 months, but the upper range is approximately
clone. 1024 The long-term survival of patients with CML may permit the 5 years. The disease may undergo clonal evolution to AML.
emergence of a drug-induced or spontaneous second malignancy, and
in the former it may be notably associated with imatinib (see “Secondary
Chromosomal Changes with Tyrosine Kinase Inhibitors above). 1025–1027 REFERENCES
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