Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia

Kern, Wolfgang; Voskova, Daniela; Schoch, Claudia; Hiddemann, Wolfgang; Schnittger, Susanne; Haferlach, Torsten

doi:10.1182/blood-2004-03-1036

Cited by 240 publications

(171 citation statements)

References 35 publications

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“…In CML monitoring of the BCR-ABL transcript levels is included in routine strategies in the post transplantation period to identify the need for adoptive immunotherapy or TKI treatment, 34,128 but in all other myeloid malignancies, AML, MDS and the BCR-ABL-negative CMPD, comparable approaches still have to be developed with regard to quantitative PCR, 18,20,147 multiparameter flow cytometry, [53][54][55] and interphase FISH. 45 Studies that analyze these methods for their predictive value within the post transplantation period are still limited.…”

Section: Discussionmentioning

confidence: 99%

“…80 The decrease of cells with a specific LAIP when compared at diagnosis and shortly after initial therapy correlates significantly with the achievement of CR and with survival, [53][54][55][56] and the reduction of aberrant cells to a threshold of 0.1% after chemotherapy was assessed as predictor for long-time survival in another study. 105 However, in the post transplantation setting the use of multiparameter flow cytometry still has to be validated as changes of the immunophenotype might be more frequent in relapse following SCT than after standard therapy where complete loss of the previous LAIP is seen in B25%.…”

Section: Multiparameter Flow Cytometrymentioning

confidence: 99%

“…Thus, immunophenotyping by multiparameter flow cytometry with sensitivities up to 1:10 2 -1:10 4 provides an additional suitable method for the post transplant period. The definition of leukemia-associated immunophenotypes (LAIPs) of the blasts is possible in 495% of patients [53][54][55][56] and should be performed in AML and advanced MDS at diagnosis and before SCT as basis for MRD diagnostics within the post transplant period.…”

Section: Molecular Techniques and Immunophenotypingmentioning

confidence: 99%

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Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Bacher

Zander

Haferlach

et al. 2008

Bone Marrow Transplant

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Allogeneic SCT is important in myelodysplastic syndrome, the BCR-ABL-negative chronic myeloproliferative diseases (CMPDs) and in poor-risk AML. Techniques to monitor the minimal residual disease, for example, by PCR or immunophenotyping gain increasing importance in the post transplantation period as basis for improved and earlier therapeutic interventions in impending relapse. Recent markers such as the NPM1 mutations in AML or the JAK2V617F mutation in the CMPD can be exactly quantified by real-time PCR and were evaluated for their prognostic value in the post transplantation phase and for their utility to plan adoptive immunotherapy in case of molecular relapse. With respect to chimerism, new and very sensitive methods were introduced, for example, quantitative assessment of genetic polymorphisms by realtime PCR, but also methods here are still highly individualized. Only in CML, where SCT focuses now on poor-risk cases or cases of tyrosine kinase inhibitor failure, follow-up schedules are standardized. Standardization of the different diagnostic techniques and of the intervals in the post transplantation period is urgently needed also in other myeloid malignancies and should be focus of future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Multiparameter Flow Cytometrymentioning

confidence: 99%

Section: Molecular Techniques and Immunophenotypingmentioning

confidence: 99%

See 1 more Smart Citation

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Bacher

Zander

Haferlach

et al. 2008

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…However, increasing evidence suggests that leukemia relapse may be related to minimal residual disease (MRD), a small fraction (below the threshold of morphological detection) of leukemic cells persisting within leukemia patients after achieving CR. Since high levels of MRD are significantly associated with a high frequency of relapse and a short duration of survival, MRD has been considered an important risk factor for leukemia relapse [29,30]. It has been postulated that MRD cells adopt a drug-resistant phenotype during the course of chemotherapy and have the potential to form a regrowing leukemic population, thereby leading to leukemia relapse [31].…”

Section: Discussionmentioning

confidence: 99%

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

et al. 2008

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“…The prognostic impact of flow cytometry was independent of cytogenetics or other prognostically relevant parameters in multivariate analysis. 48 In addition, numerous studies demonstrated an increase of LAIP-positive cells before the occurrence of morphological relapse. In a study on 252 pediatric patients with AML, a proportion of 40.5% cells with the aberrant blast phenotype was associated with a threefold increased relapse risk when compared to patients below this threshold.…”

Section: Immunophenotypingmentioning

confidence: 99%

Interactive diagnostics in the indication to allogeneic SCT in AML

Bacher

Haferlach

Schnittger

et al. 2009

Bone Marrow Transplant

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Owing to the heterogeneity of AML, the indication for allogeneic SCT (allo-SCT) requires an exact definition of the individual subentity and risk category. A comprehensive diagnostic approach is needed, which combines cytomorphology, cytogenetics, FISH, molecular genetics and immunophenotyping. Whereas the categorization in three prognostic karyotype groups is well established, rare recurrent aberrations as the unfavorable t(8;16)(p11;p13), inv(3)(q21q26) and t(6;9)(p23;q34) must also be considered. In normal karyotype, PCR analyses reveal prognostically relevant mutations in 485% of cases, and a molecular data set composed of the FLT3-ITD, MLL-PTD, NPM1 and CEBPA mutations was found able to guide the selection of patients for allo-SCT. Some novel markers as the WT1 mutations might further contribute to risk stratification in normal karyotype. The panel of minimal residual disease parameters is being expanded at this time, for example, by quantitative PCR for the NPM1 mutations. Immunophenotyping allows the definition of leukemia-associated phenotypes in nearly all cases, but its position in the indication to allo-SCT has to be validated. Thus, the optimization of the indication to allo-SCT is an ongoing process that should remain in continuous interaction with the increasing panel of known genetic markers and diagnostic methods.

show abstract

Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia

Cited by 240 publications

References 35 publications

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Minimal residual disease diagnostics in myeloid malignancies in the post transplant period

Preferential loss of mismatch repair function in refractory and relapsed acute myeloid leukemia: potential contribution to AML progression

Interactive diagnostics in the indication to allogeneic SCT in AML

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