Deletion 5q in Acute Myeloid Leukemia (AML): a Clinicopathological Description of 79 Cases From a Single Institution
Rafael Santana-Davila, Shernan G. Holtan, Rhett P. Ketterling, Ryan A. Knudson, David P. Steensma, Dong Chen, James D. Hoyer, Curtis A. Hanson, Ayalew Tefferi.
Background: Deletion 5q (del(5q)) is a lenalidomide-sensitive cytogenetic abnormality commonly seen in patients with myeloid disorders. In this study we analyze the clinicopathological characteristics of patients with AML and del(5q).
Methods: Patients with del(5q) and AML were identified through a database query of our institutional cytogenetic database from May, 1992 through December, 2005. Both peripheral blood and bone marrow specimens from each patient were morphologically examined by a hematopathologist (DC, JDH and/or CAH). A morphologic diagnosis was given based on current WHO criteria. A critical review of the patient history was performed for each patient.
Results: A total 79 patients were identified. Median age was 71 (range 39–87) years, 56% (n=43)were female. The most common subtype according to the FAB classification was M2 (n=23, 29%). In 35 (44%) patients AML developed a median of 9.4 (range 1–294) months since the diagnosis of a pre-existing myeloid malignancy, of which myelodysplastic syndrome accounted for 24 (9 cases of MDS NOS, 6 of RA, 6 of RAEB1, 2 of RAEB-2, and a single RARS), a myeloproliferative neoplasm in 10 (4 cases of a CMPD NOS, 4 cases of PV and a single case of ET and PMF each) and 1 case of a prior history of AML with a t(8;21). The del(5q) was documented in 7 of this 24 patients in the antecedent hematologic disorder. Neither a history of prior exposure to cytotoxic agents nor a prior myeloid disorder was found in 44% (n=35) of the patients. Del(5q) was commonly associated with a complex karyotype (n=67), however in 9 patients it was found to be the sole abnormality. The most frequent breakpoint was q13q33 (n=47) followed by q15q33 (n=12). Initial pathological description did not identify any morphological abnormalities in 6 cases, in contrast myelodysplasia involving at least two cell lines was appreciated in 58% (n=46) of the patients. The median survival was 2.8 months. The majority of the subjects (n=51, 65%) received palliative treatment, 7 patients were lost to follow up and no treatment information was available for review and the remaining 21 received induction chemotherapy with a curative intent, in this group median survival was 8.8 months with 52% (n=11) of patients achieving a complete response. Surprisingly the only factor that appeared to alter survival in the whole group was the presence of the breakpoint in chromosome 5 being distal to q15 (median 2.8 vs 4.1 months, p=0.025)
Conclusions: This study constitutes the largest review of del(5q) in AML, its presence is currently associated with advanced age and a poor survival. Close to half of the patients in our series were classified as de novo AML. Although more commonly encountered as part of a complex karyotype it can also be present as a single abnormality. The different cytogenetic characteristics of the del(5q) may impact survival and this deserves further investigation.
Disclosures: No relevant conflicts of interest to declare.