TY - JOUR
T1 - The clinical significance of negative flow cytometry immunophenotypic results in a morphologically scored positive bone marrow in patients following treatment for acute myeloid leukemia
AU - Ouyang, Juan
AU - Goswami, Maitrayee
AU - Tang, Guilin
AU - Peng, Jie
AU - Ravandi, Farhad
AU - Daver, Naval
AU - Routbort, Mark
AU - Konoplev, Sergej
AU - Lin, Pei
AU - Medeiros, L. Jeffrey
AU - Jorgensen, Jeffrey L.
AU - Wang, Sa A.
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.23988
DO - 10.1002/ajh.23988
M3 - Article
C2 - 25732229
AN - SCOPUS:84929503272
SN - 0361-8609
VL - 90
SP - 504
EP - 510
JO - American journal of hematology
JF - American journal of hematology
IS - 6
ER -