The utility of flow cytometric immunophenotyping in cytopenic patients with a non-diagnostic bone marrow: A prospective study

Truong, Francoise; Smith, Brian R.; Stachurski, Dariusz; Černý, Jan; Medeiros, L. Jeffery; Woda, Bruce A.; Wang, Sa A.

doi:10.1016/j.leukres.2009.01.012

Cited by 49 publications

(32 citation statements)

References 31 publications

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“…This scenario further supports the need for clinical validation of the diagnostic use of MFC in MDS, which should be evaluated together with patient outcomes. 36 It is also clear, however, that, in the current series, 129 patients who had MDS clearly proven by CM did not have dysplastic features identified by MFC. Thus, the results of this crude analysis are suggestive of a combined use of CM and MFC in the diagnostic evaluation of patients with suspected MDS.…”

Section: Discussionmentioning

confidence: 46%

Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome

Kern¹,

Haferlach²,

Schnittger³

et al. 2010

Cancer

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BACKGROUND:The diagnosis and classification of myelodysplastic syndromes (MDS) is based on cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) may add important diagnostic information. METHODS: To evaluate the potential role of MFC in the diagnostic setting of MDS, the authors analyzed the results from 1013 patients with suspected MDS by using CM, CG, and MFC in parallel. RESULTS: Concordance between CM and MFC was 82% for diagnostic results in 788 patients who had unequivocal CM results. An additional 225 patients had only minor dysplastic features identified by CM, including 51 patients (22.7%) who had clear evidence of MDS by MFC. Twelve patients who had no indication of MDS identified by CM had MDS-typical CG aberrations; in 6 of those patients (50%), MFC revealed MDS characteristics. In another 11 of 23 patients (47.8%) who had minor dysplastic features identified by CM and MDS-typical CG aberrations, MFC revealed MDS characteristics. The percentages of blasts determined by CM and by MFC were strongly correlated (P < .001). The frequency of aberrantly expressed antigens differed significantly between patients rated by CM as MDS (highest frequencies), suspected MDS, and no MDS (lowest frequencies). In various patients, MFC identified MDS-typical aberrant antigen expression in cell compartments that were not rated dysplastic by CM. The numbers of aberrantly expressed antigens were correlated with International Prognostic Scoring System scores and overall survival. CONCLUSIONS: The current analysis clearly demonstrated an increased diagnostic yield with MFC when added to CM and CG in patients with suspected MDS. Cancer

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Section: Discussionmentioning

confidence: 46%

Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome

Kern¹,

Haferlach²,

Schnittger³

et al. 2010

Cancer

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“…However, recognition of the potential contracted effect contributed to designation of some findings as equivocal-aberrant rather than aberrant because confident identification of subtle, but possibly more significant alterations was difficult. This conservative approach may account, at least in part, for the lower incidence of aberrant alterations in neutrophil maturation patterns seen in MDS in this study compared to that reported previously as asynchronous or abnormal by others (9,10,17,18). …”

Section: Discussionmentioning

confidence: 51%

“…In addition, this study reported abnormalities in patients without MDS: CD11b vs. CD16 in 3.2% and of CD13 vs. CD16 in 9% of 277 patients. Altered patterns have also been reported by others occasionally in association with aplastic anemia, Hodgkin lymphoma, cytopenias secondary to various medical causes, therapy with granulocyte colony-stimulating factor and in marrow regeneration after transplantation (9,10,14,21).…”

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confidence: 57%

“…Several studies have confirmed the utility of evaluating CD11b, CD13, and CD16 among maturing neutrophils for the identification of MDS, but many report a lower frequency of abnormalities in MDS than initially described and some found abnormalities in patients without MDS (9)(10)(11)14,(18)(19)(20)(21). In the largest study to date of comprehensive FC evaluation in MDS, Kern et al reported abnormal patterns of CD11b vs. CD16 in only 28% and CD13 vs. CD16 in only 42.9% of 511 MDS patients (18).…”

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confidence: 98%

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Altered neutrophil maturation patterns that limit identification of myelodysplastic syndromes

Monaghan

Surti

Doty

et al. 2012

Cytometry Part B Clinical

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Background:Altered neutrophil maturation patterns have been reported useful for identification of myelodysplastic syndromes (MDS).Methods:Neutrophil maturation patterns based on CD11b, CD13, and CD16 were visually and numerically evaluated in 19 control, 23 MDS, 37 nondiagnostic for MDS (NDM) specimens, and 19 also processed 1 and 2 days subsequently.Results:In contrast to maturation patterns illustrated previously by others as “normal,” 84% of controls displayed diminished acquisition of CD16, imparting a contracted appearance. Such divergence from published “normal” patterns was usually mild‐moderate, considered nonspecific, and associated with delayed processing: longer intervals between collection and processing (median 20.5 vs. 5.2 h), and following 1 and 2 days delay. Findings restricted to nonspecific contraction were found in 56% MDS and 78% NDM specimens. Evaluation for aberrant patterns was still performed with mild‐moderate contraction present, but concern for over interpretation led to use of an equivocal‐aberrant category. Nine cases had aberrant or equivocal‐aberrant patterns (seven MDS, two NDM) with distinct visual alterations that differed from nonspecific contraction and had numerical evidence for a left shift: myeloblasts increased (67%) and least mature neutrophils (CD11b‐/low, CD16‐/low) increased (78%). Although evidence for a left shift was associated with MDS, it was also seen in NDM specimens with a synchronous left shift.Conclusions:Neutrophil maturation patterns that diverge from previously illustrated “normal” patterns, not specific for MDS, may be common in some settings. Laboratories seeking to implement FC evaluation for MDS must determine which findings have sufficient specificity for MDS within their own practice and patient population. © 2012 International Clinical Cytometry Society

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“…Because the FINE algorithm uses single high-dimensional datasets, we selected cases for analysis based on availability of data from a single tube that contained markers previously reported as useful in the analysis of dysgranulopoiesis in MDS (3,4,(10)(11)(12): CD11b, CD16, CD45, and CD56. When available for a given case, we also separately analyzed a single tube that contained CD13, CD16, HLA-DR, and CD45, a combination also previously reported as useful in the analysis of the myeloid compartment in MDS (2)(3)(4)12).…”

Section: Materials and Methods Data Retrieval And Preparationmentioning

confidence: 99%

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

Finn

Harrington

Carter

et al. 2011

Cytometry Part B Clinical

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Background: The role of flow cytometry (FCM) in diagnosing myelodysplastic syndromes (MDS)remains controversial, because analysis of myeloid maturation may involve subjective interpretation of sometimes subtle patterns on multiparameter FCM.Methods: Using six-parameter marker combinations known to be useful in evaluating the myeloid compartment in MDS, we measured objective immunophenotypic differences between non-neoplastic (n 5 25) and dysplastic (n 5 17) granulopoiesis using a novel method, called Fisher information nonparametric embedding (FINE), that measures information distances among FCM datasets modeled as individual high-dimensional probability density functions, rather than as sets of two-dimensional histograms. Information-preserving component analysis (IPCA) was used to create information-optimized ''rotated'' twodimensional histograms for visualizing myelopoietic immunophenotypes for each individual sample.Results: There was a consistent trend of segregation of higher-grade MDS (RAEB and RCMD) from benign by FINE analysis. This difference was accentuated in cases with morphologic dysgranulopoiesis and in cases with clonal cytogenetic abnormalities. However, lower grades of MDS or cases that lacked morphologic dysgranulopoiesis showed much greater overlap with non-neoplastic cases. Two cases of reactive left shift were consistently embedded within the higher-grade MDS group. IPCA yielded twodimensional histogram projections for each individual case by relative weighting of measured cellular characteristics, optimized for preserving information distances derived through FINE.Conclusions: Objective analysis by information geometry supports the conclusions of previous studies that there are immunophenotypic differences in the maturation patterns of benign granulopoiesis and high grade MDS, but also reinforces the known pitfalls of overlap between low-grade MDS and benign granulopoiesis and overlap between reactive granulocytic left shifts and dysplastic granulopoiesis.

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The utility of flow cytometric immunophenotyping in cytopenic patients with a non-diagnostic bone marrow: A prospective study

Cited by 49 publications

References 31 publications

Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome

Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome

Altered neutrophil maturation patterns that limit identification of myelodysplastic syndromes

Immunophenotypic signatures of benign and dysplastic granulopoiesis by cytomic profiling

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