The clinical significance of negative flow cytometry immunophenotypic results in a morphologically scored positive bone marrow in patients following treatment for acute myeloid leukemia.
In a patient with acute myeloid leukemia (AML) following therapy, finding ≥5% bone marrow (BM) blasts is highly concerning for residual/relapsed disease. Over an 18-month period, we performed multicolor flow cytometry immunophenotyping (MFC) for AML minimal residual disease on >4,000 BM samples, and identified 41 patients who had ≥5% myeloblasts by morphology but negative by MFC. At the time of a negative MFC study, an abnormal cytogenetic study converted to negative in 14 patients and remained positive at a low level (2.5-9.5%) by fluorescence in situ hybridization in 3 (14%), of the latter, abnormalities subsequently disappeared in the repeated BM in 2 patients. Positive pretreatment mutations, including FLT3, NPM1, IDH1, CEBPA, became negative in all 10 patients tested. Of the seven patients with favorable cytogenetics, PML/RARA, CBFB-MYH11 or RUNX1-RUNX1T1 fusion transcripts were detected at various levels in six patients but all patients remained in complete remission. With no additional chemotherapy given, 39 patients had BM repeated (median 2 weeks, range <1-21), and all cases showed <5% BM blasts and a continuously negative MFC. In the end of follow-up (median 10 months, range 1-22), 13 patients experienced relapse, 12/13 showing clonal cytogenetic evolution/switch and 11 demonstrating major immunophenotypic shifts. We conclude that MFC is useful in identifying a regenerating BM sample with ≥5% BM blasts that would otherwise be scored as positive using standard morphologic examination. We believe this conclusion is supported by the changes in molecular cytogenetic status and the patient clinical follow-up data.
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
Juan
J
Ouyang
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Maitrayee
M
Goswami
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Guilin
G
Tang
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.|Department of Hematology Oncology, the First Affiliated Hospital of Xiangya Medical School Central South University, Changsha, Hunan, China.
Jie
J
Peng
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Farhad
F
Ravandi
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Naval
N
Daver
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Mark
M
Routbort
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Sergej
S
Konoplev
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Pei
P
Lin
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
L Jeffrey
LJ
Medeiros
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Jeffrey L
JL
Jorgensen
Department of Hematopathology, the University of Texas MD Anderson Cancer Center, Houston, Texas.
Sa A
SA
Wang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018365:Neoplasm, Residual / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000090243:Nucleophosmin
C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; D000090243:Nucleophosmin