Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) on Peripheral Blood (PB) and Bone Marrow (BM) Samples for Monitoring Minimal Residual Disease (MRD) in Patients (pts) With Acute Promyelocytic Leukemia (APL) Treated With All-Trans-Retinoic Acid (ATRA) and Arsenic Trioxide (ATO)

PURPOSE Patients with neuroblastoma in molecular remission remain at considerable risk for disease recurrence. Studies have found that neuroblastoma tissue contains adrenergic (ADRN) and mesenchymal (MES) cells; the latter express low levels of commonly used markers for minimal residual disease (MRD). We identified MES-specific MRD markers and studied the dynamics of these markers during treatment. PATIENTS AND METHODS Microarray data were used to identify genes differentially expressed between ADRN and MES cell lines. Candidate genes were then studied using real-time quantitative polymerase chain reaction in cell lines and control bone marrow and peripheral blood samples. After selecting a panel of markers, serial bone marrow, peripheral blood, and peripheral blood stem cell samples were obtained from patients with high-risk neuroblastoma and tested for marker expression; survival analyses were also performed. RESULTS PRRX1, POSTN, and FMO3 mRNAs were used as a panel for specifically detecting MES mRNA in patient samples. MES mRNA was detected only rarely in peripheral blood; moreover, the presence of MES mRNA in peripheral blood stem cell samples was associated with low event-free survival and overall survival. Of note, during treatment, serial bone marrow samples obtained from 29 patients revealed a difference in dynamics between MES mRNA markers and ADRN mRNA markers. Furthermore, MES mRNA was detected in a higher percentage of patients with recurrent disease than in those who remained disease free (53% v 32%, respectively; P = .03). CONCLUSION We propose that the markers POSTN and PRRX1, in combination with FMO3, be used for real-time quantitative polymerase chain reaction–based detection of MES neuroblastoma mRNA in patient samples because these markers have a unique pattern during treatment and are more prevalent in patients with poor outcome. Together with existing markers of MRD, these new markers should be investigated further in large prospective studies.

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Comparison of bone marrow high mitotic index metaphase fluorescence in situ hybridization to peripheral blood and bone marrow real time quantitative polymerase chain reaction on the International Scale for detecting residual disease in chronic myeloid leukemia

Haematologica ◽

10.3324/haematol.11910 ◽

2008 ◽

Vol 93 (2) ◽

pp. 178-185 ◽

Cited By ~ 8

Author(s):

T. Lundan ◽

V. Juvonen ◽

M. C. Mueller ◽

S. Mustjoki ◽

T. Lakkala ◽

...

Keyword(s):

Bone Marrow ◽

Polymerase Chain Reaction ◽

In Situ Hybridization ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Quantitative Polymerase Chain Reaction ◽

Chain Reaction ◽

Polymerase Chain

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Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow

Blood ◽

10.1182/blood.v83.12.3800.3800 ◽

1994 ◽

Vol 83 (12) ◽

pp. 3800-3807 ◽

Cited By ~ 109

Author(s):

JG Gribben ◽

D Neuberg ◽

M Barber ◽

J Moore ◽

KW Pesek ◽

...

Keyword(s):

Bone Marrow ◽

Polymerase Chain Reaction ◽

Peripheral Blood ◽

Residual Disease ◽

Pcr Amplification ◽

Chain Reaction ◽

Lymphoma Cells ◽

Polymerase Chain ◽

Residual Lymphoma ◽

Minimal Residual

Abstract Polymerase chain reaction (PCR) amplification of the t(14;18) has been shown to be a highly sensitive method to detect minimal residual disease in patients with non-Hodgkin's lymphoma (NHL) whose tumors bear this translocation. The ideal tissue source to detect residual lymphoma would be from a previously involved lymph node. However, lymphoid tissue is rarely available once patients achieve complete remission. Although PCR amplification has been used to detect residual lymphoma cells in both bone marrow (BM) and peripheral blood (PB) of patients in complete remission, it is presently unknown whether BM and PB are equivalent tissue sources to detect residual disease. In the present study, we compared the clinical utility of the detection of residual lymphoma in both the BM and the PB of patients with advanced-stage non- Hodgkin's lymphoma before, at the time of, and after high-dose therapy and autologous BM transplantation (ABMT). The detection of residual lymphoma in either the BM or PB was associated with decreased disease- free survival. However, in the present study, 44% of patients who relapsed had no evidence of circulating lymphoma cells in their PB. At the time of BM harvest, PCR-detectable residual lymphoma cells were detected in 211 of 212 patients; although, in a subset of these patients analyzed, lymphoma cells were detected in the peripheral blood of only 49% of patients. When residual lymphoma cells within the autologous BM are infused into the patient these cells are rapidly detectable circulating in the PB in the patient. These cells continue to circulate during the immediate posttransplant period and be detectable in the PB in the majority of patients who are infused with marrow containing residual lymphoma. We conclude that BM is a more informative tissue source than PB in detecting minimal residual disease at the time of and after ABMT, and that contamination of PB early after ABMT appears to be the consequence of reinfusion of lymphoma cells within autologous marrow.

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