Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia

Oelschlägel, Uta; Nowak, Ralf; Schaub, A; Köppel, C; Herbst, Regina; Mohr, Brigitte; Löffler, Claudia; Range, Ursula; Günther, H.; Aßmann, Michael; Siegert, E.; Wendt, Elizabeth; Huhn, Renate; Bräutigam, Edeltraut; Ehninger, Gerhard

doi:10.1002/1097-0320(20000815)42:4<247::aid-cyto5>3.0.co;2-v

Cited by 38 publications

(28 citation statements)

References 29 publications

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“…However, the diagnosis of CSF abnormalities by FC is not devoid of drawbacks such as the presence of normal or reactive lymphocytes, low cell count and shifting of aberrant antigen expression at relapse. 14 In addition, lymphoma or leukemia can shed only few abnormal cells into the CSF. 15 Several reports have compared cytology with FC showing a broad range of concordant results.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Waterhouse

Bartsch

Bertz

et al. 2015

Bone Marrow Transplant

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Central nervous system (CNS) complications have been described in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal fluid (CSF) analysis is included in the diagnostic workup in patients with neurological symptoms after alloHCT. CSF donor-recipient chimerism analysis usually is not used to evaluate patients with neurological complications after alloHCT. To assess the potential contribution of CSF donor-recipient chimerism in patients with neurological complications, we analyzed 85 CSF samples from 50 patients with neurological complications after alloHCT. After alloHCT, 21 patients showed the presence of recipient-derived DNA. In 13 of these patients, recurrence of the underlying disease was detected in CSF. There was a moderate correlation between the recipient DNA percentage as detected by short tandem repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66 P = 0.004). The percentage of cells with immunophenotypic abnormalities from patients relapsing in the CNS detected by flow cytometry showed a strong correlation with the percentage of recipient-derived DNA in CSF assessed by STR analysis (Spearmann r: 0.83 P = 0.0008). Donor-recipient chimerism analysis in CSF in patients with neurological symptoms after alloHCT is a practical, feasible and useful complementary method to the already established methodologies included in the diagnostic workup.Bone Marrow Transplantation (2016) 51, 127-131; doi:10.1038/bmt.2015; published online 5 October 2015 INTRODUCTIONNeurological complications after allogeneic hematopoietic cell transplantation (alloHCT) have been reported with a varying incidence between 8% and 42% in bone marrow recipients. 1 Among this type of complication, the incidence of central nervous system (CNS) relapse of the underlying disease ranged from 2.9% to 11% in patients undergoing alloHCT. 2 To begin a proper treatment as early as possible, an accurate and prompt diagnosis is mandatory. However, because of the several etiologies of neurological symptoms and the lack of optimal diagnostic methods, diagnosis could be challenging. In addition to neurological evaluation, several methods can be used to establish an accurate diagnosis.Cerebrospinal fluid (CSF) examination constitutes a part of the diagnostic work-up of patients with neurological symptoms after alloHCT. Cytological analysis is considered to be the gold standard for the detection of malignant cells in CSF. 3 However, cytology exhibits limitations regarding sensitivity and positive predictive value in the identification of malignant cells. Characterization of CSF cells using flow cytometry (FC) improved the detection of malignant and non-malignant cells and constitutes a useful diagnostic complement. 4 The reported use of molecular biology techniques in CSF cells in patients undergoing alloHCT is scarce, and these reports mostly refer to the pediatric population involving small patient cohorts. 5,6 Donor-recipient chimerism routinely used to evaluate hematopoietic chimerism foll...

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Waterhouse

Bartsch

Bertz

et al. 2015

Bone Marrow Transplant

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“…Two major pitfalls have the potential to reduce the value of flow-cytometry immunophenotypic detection of MRD: the absence of leukemia-specific antigens and the existence of phenotypic changes at relapse that could induce false-negative results [4][5][6][7][8][32][33][34][35]. However, immunophenotypic detection of MRD is possible in acute leukemia because the neoplastic cells frequently express aberrant or unusual phenotypes.…”

Section: Methodologic Approachesmentioning

confidence: 99%

Immunologic monitoring in adults with acute lymphoblastic leukemia

Vidriales

Órfão²,

Miguel³

2003

Curr Oncol Rep

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Investigation of minimal residual disease (MRD) by immunophenotyping and molecular techniques has proven to be a powerful approach for disease monitoring in patients with acute leukemia. Multiparameter flow cytometry, through the use of triple or quadruple marker combinations, identifies aberrant or uncommon phenotypic profiles in more than 90% of adult patients with acute lymphoblastic leukemia (ALL) at diagnosis. These profiles allow identification of residual leukemic cells in bone marrow or peripheral blood once morphologic complete remission is achieved. Until now, most immunophenotypic MRD studies in ALL have focused on children. In contrast, information on the value of MRD in adults with ALL is scanty and usually restricted to polymerase chain reaction studies. In this review, we focus on technical aspects of MRD detection by flow cytometry and on the clinical data concerning the value of immunologic MRD studies as a tool for relapse prediction in adult ALL. Although prospective studies are needed, we assert that immunophenotypic MRD studies are clinically useful. Such studies should be incorporated into the routine management of adult ALL patients for identification of those at high risk of relapse, who could benefit from new alternative therapeutic approaches, and to distinguish these patients from others who could be cured with more conventional approaches.

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“…It should, however, be noted that in some cases, these features may be lost over time. [130][131][132] The subset of leukemic cells which persists will nevertheless retain a clonal quality, i.e. continue to present homogeneous features.…”

Section: T O R T I F O U N D a T I O Nmentioning

confidence: 99%

“…Several authors then reported on two-then three-color approaches, using aberrant antigen expression on ALL blast cells. 130,139 In 1998, a large study from Dario Campana's group 140 described data that correlated well with other reported predictive features associated with either good or poor prognosis. 141 The techniques used at this time were quite cumbersome yet began to consistently reach a sensitivity of 1×10 -4 .…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

Béné

Kaeda²

2009

Haematologica

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Resistance to therapeutic agents is a major factor in the failure of cancer treatments. In leukemia, the resistant cells remaining in the bone marrow and/or peripheral blood constitute minimal residual disease and are detectable by highly sensitive assays when the patient appears to be in complete remission. Early detection of the expansion of residual cells permits clinical intervention with the aim of reversing the proliferation of resistant leukemic cells. Therefore, accurate and precise measurement of minimal residual disease can greatly enhance optimization of oncology patients' clinical management. This notion is supported by a large body of data among chronic myeloid leukemia patients, but minimal residual disease detection and monitoring is increasingly applied to other types of leukemia, and is starting to be a factor in decision-making for some therapeutic trials in childhood acute lymphoblastic leukemia. Here, from the solid ground of minimal residual disease detection in chronic myeloid leukemia, the current state of the art and development of molecular techniques in other leukemias and the growing field of multiparameter flow cytometry are reviewed in two separate parts reporting on the respective advances, advantages and pitfalls of these emerging methods.Key words: minimal residual disease, leukemia, flow cytometry, standardization, monitoring. LeukaemiaNet. Haematologica 2009;94:1135-1150. doi:10.3324/haematol.2008 Citation: Béné MC and Kaeda JS. How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European

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Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia

Cited by 38 publications

References 29 publications

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Immunologic monitoring in adults with acute lymphoblastic leukemia

How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

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