scholarly journals Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia

Leukemia ◽  
2003 ◽  
Vol 17 (1) ◽  
pp. 138-148 ◽  
Author(s):  
E Björklund ◽  
J Mazur ◽  
S Söderhäll ◽  
A Porwit-MacDonald
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Information ◽  
Flow Cytometric ◽  
Minimal Residual

scholarly journals Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie L. Rellick ◽  
Gangqing Hu ◽  
Debra Piktel ◽  
Karen H. Martin ◽  
Werner J. Geldenhuys ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Tumor Cells ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adherent Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.

scholarly journals Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 2984-2990 ◽  
Author(s):  
Stella M. Davies ◽  
Michael J. Borowitz ◽  
Gary L. Rosner ◽  
Kristin Ritz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Response To Therapy ◽  
Oncology Group ◽  
Risk Status ◽  
Prognostic Features ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis.

1989 ◽  
Vol 7 (3) ◽  
pp. 338-343 ◽  
Author(s):  
M Bregni ◽  
S Siena ◽  
A Neri ◽  
R Bassan ◽  
T Barbui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Gene Rearrangement ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Immune Selection ◽  
Gene Rearrangement Analysis ◽  
Minimal Residual

We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease.

Comparison of minimal residual disease levels in bone marrow and peripheral blood in adult acute lymphoblastic leukemia

Leukemia ◽  
2019 ◽  
Vol 34 (4) ◽  
pp. 1154-1157 ◽  
Author(s):  
Michaela Kotrova ◽  
Antonia Volland ◽  
Britta Kehden ◽  
Heiko Trautmann ◽  
Matthias Ritgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Minimal Residual

Status of Minimal Residual Disease Determines Outcome of Autologous HSCT in Adults with High-Risk Acute Lymphoblastic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2321-2321
Author(s):  
Sebastian Giebel ◽  
Beata Stella-Holowiecka ◽  
Malgorzata Krawczyk-Kulis ◽  
Nicola Goekbuget ◽  
Dieter Hoelzer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Minimal Residual

Abstract Abstract 2321 Poster Board II-298 The role of autologous hematopoietic stem cell transplantation (autoHSCT) in the treatment of adult acute lymphoblastic leukemia (ALL) is a subject of controversies as several prospective studies failed to prove its advantage over maintenance chemotherapy. Those studies, however, did not take into account the status of minimal residual disease (MRD), which is now recognized a potent predictor for relapse among patients treated with conventional-dose chemotherapy. The goal of this analysis was to determine the impact of MRD on outcome of autoHSCT. Data on 123 autoHSCT recipients collected from 6 study groups cooperating in the European Leukemia Net were analyzed. Median age of 77 B-lineage and 46 T-lineage high-risk ALL patients was 31 (16-59) years. Ph+ ALL was recognized in 20 cases. All patients were in first complete remission (CR) lasting 6 (1.5-22) months. Peripheral blood was used as a source of stem cells in 67 patients whereas bone marrow, in 56 cases. Conditioning was based on chemotherapy alone (n=76) or total body irradiation (n=47). MRD was evaluated in bone marrow with the use of either multiparametric flow cytometry (n=79) or molecular techniques (n=44). MRD level of 0.1% bone marrow cells was used as a cut-off point for the purpose of this study. At the time of autoHSCT MRD was &0.1% in 93 patients and ≧0.1% in 30 cases. With the median follow up of 5 years, the probability of leukemia-free survival (LFS) at 5 years for the whole group equaled 48% (+/-5). Three patients died of transplantation-related complications. The LFS rate was significantly higher for patients with the MRD level at transplantation &0.1% compared to those with MRD ≧0.1% (57% vs. 19%, p=0.0002). The difference was particularly pronounced for peripheral blood HSCT (66% vs. 20%, p=0.0006) and for T-lineage ALL (62% vs. 8%, p=0.001). In a multivariate analysis adjusted for other potential prognostic factors (age, CR duration, Ph+ ALL, immunophenotype, source of stem cells, type of conditioning), the MRD status &0.1% remained the only independent factor associated with increased LFS (HR=2.5, p=0.0009). CONCLUSIONS: MRD status is the most important predictor for LFS after autoHSCT in adults with ALL. More than half of patients with high risk disease and low MRD level at the time of transplantation may be cured. This observation may contribute to re-evaluation of the role of autoHSCT in the therapy of adult ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Interphase cytogenetic analysis detects minimal residual disease in a case of acute lymphoblastic leukemia and resolves the question of origin of relapse after allogeneic bone marrow transplantation

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1087-1091
Author(s):  
J Anastasi ◽  
M Thangavelu ◽  
JW Vardiman ◽  
AL Hooberman ◽  
ML Bian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Cytogenetic Analysis ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Trisomy X ◽  
Donor Cells ◽  
Interphase Cells ◽  
Minimal Residual

We used in situ hybridization with a probe for the X chromosome to study interphase cells of bone marrow and peripheral blood specimens from a male patient with acute lymphoblastic leukemia characterized by hyperdiploidy, including trisomy X. In a posttreatment bone marrow specimen, which was interpreted as a regenerating bone marrow morphologically and which demonstrated a normal karyotype cytogenetically, trisomy X was found in 16 of 1,000 interphase cells. This finding indicated the presence of leukemic cells that were undetected by conventional morphologic and cytogenetic techniques (ie, minimal residual disease). Cytogenetic studies of a relapse specimen obtained after a sex-mismatched bone marrow transplant showed only a normal female karyotype in each of 40 metaphase cells, suggesting that the relapse occurred in donor cells. However, interphase analysis demonstrated trisomy X in more than 80% of interphase cells and indicated that the relapse was of the original clone and was not a transformation of donor cells. This case illustrates that interphase analysis can be useful as an adjunct to conventional cytogenetic analysis in the detection of minimal residual disease and in the analysis of interphase cells that are not accessible to routine cytogenetic methods. It also illustrates that previously reported instances of relapse of leukemia in donor cells could have been incorrect if supported by cytogenetic data alone.

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