Evaluation of Minimal Residual Disease Based on NPM1 Mutations in AML with Intermediate Risk Cytogenetics: A Prospective Study of 36 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2847-2847
Author(s):  
Aline Renneville ◽  
Florence Pasquier ◽  
Selim Corm ◽  
Nathalie Philippe ◽  
Charikleia Kelaidi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Genomic Dna ◽  
Residual Disease ◽  
Normal Karyotype ◽  
Intermediate Risk ◽  
Npm1 Mutation ◽  
Log Reduction ◽  
Minimal Residual

Abstract Mutations in exon 12 of the nucleophosmin (NPM1) gene occur in approximately 50% of adult acute myeloid leukemia (AML) with normal karyotype. More than 40 mutant variants have been identified. Most of these mutations consist of a 4-bp insertion, which can be used as a target for minimal residual disease (MRD) monitoring. We previously checked the stability of NPM1 mutations at relapse in 21 NPM1-mutated patients at initial diagnosis. In this prospective study, we evaluated MRD by real-time quantitative PCR (RQ-PCR) in 36 NPM1-mutated AML patients corresponding to 33 adult and 3 pediatric cases, treated according to the French ALFA9801 or ALFA9802 and ELAM02 protocols, respectively. Out of these patients, 31/34 (91%) had normal karyotype, 13/33 (39%) had a high initial white blood cell count, and 10/36 (28%) were FLT3-Intern Tandem Duplication (FLT3-ITD) positive. 28 (78%) patients carry NPM mutation A, 3 (8%) mutation B and 5 (14%) other rare variants. RQ-PCR assays using a mutation-specific primer were performed on cDNA for mutation A and B and on genomic DNA for other NPM1 mutants. In our experiments, the maximal reproductible sensitivity of NPM1-based MRD detection is about 10−4 on genomic DNA and 10−5 to 10−6 on cDNA. The median follow-up was 260 days [40–791]. 2 to 9 follow-up samples from bone marrow and/or peripheral blood were analysed per patient. No correlation was found between leukocytosis at diagnosis and initial expression ratio of NPM1 mutation. The study of MRD log reduction after induction therapy shows that molecular responses are very heterogeneous (from 4.10−2 to more than 1.10−5), but 50% of patients reach at least a 4 log reduction in NPM1 levels. Patients with FLT3-ITD tend to have lower log reduction after induction than patients without FLT3-ITD, although not statistically significant (P=0.07). The analysis of NPM1-MRD in bone marrow and in peripheral blood at the same follow-up time-points shows that NPM1 levels can be until 1 log higher in bone marrow. This indicates that the evaluation of NPM1-MRD in bone marrow is more informative than in peripheral blood. We found all relapses had NPM1-MRD levels comparable to those observed at diagnosis. Among the 5 patients who relapsed so far, 2 were predictable by increasing MRD levels 1 to 4 months before hematological relapse. In 29 out of 36 cases, we could monitor MRD by both NPM1 mutation and WT1 gene expression. The comparison of the MRD profiles obtained by these two approaches reveals some discordant results, which can be, at least in part, explained by difference in the sensitivity of the RQ-PCR techniques, since the sensitivity of WT1 expression as MRD target is generally not higher than 10−3. In conclusion, NPM1 mutations are very specific and sensitive markers for MRD monitoring in AML. Further studies are required to determine if NPM1-MRD provides an independent prognostic factor and may be useful for therapeutic stratification in AML patients with intermediate risk cytogenetics.

Monitoring of Minimal Residual Disease in NPM1 Mutated Acute Myeloid Leukemia (AML) – a Single Center Experience in 27 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4672-4672
Author(s):  
Dana Dvorakova ◽  
Zdenek Racil ◽  
Ivo Palasek ◽  
Marketa Protivankova ◽  
Ivana Jeziskova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Quantitative Polymerase Chain Reaction ◽  
Npm1 Mutation ◽  
Mgb Probe ◽  
Minimal Residual

Abstract Abstract 4672 Background Mutations within NPM1 gene occurs in about 60% of adult cytogenetic normal AML (CN-AML) and represent the single most frequent molecular aberration in this subgroups of patients. These mutations usually occur at exon 12 and induce most frequently a net insertion of four base pairs. Aims To examine the applicability and sensitivity of DNA-based real-time quantitative polymerase chain reaction (RQ-PCR) with mutation-specific reverse primers and common minor groove binding (MGB) probe and to evaluate whether minimal residual disease levels are of prognostic relevance in CN-AML patients with NPM1 mutations. Methods Patients were treated within different AML trials and follow-up samples of peripheral blood or bone marrow were referred to perform an RQ-PCR. Samples were analysed at diagnosis, during, and after therapy. The NPM1 mutations were A (17 pts), B (1 pt), D (2 pts) and 7 patients with individual rare types. For all cases, levels of minimal residual disease were determined by DNA-based RQ-PCR with mutation-specific reverse primer, one common forward primer and one common MGB probe. The NPM1 mutation value was normalized on the number of albumin gene copies and expressed as the number of NPM1 mutations every 106 genomic equivalents. This assay is highly specific as no wildtype NPM1 could be detected. Maximal reproducible sensitivity was 10 plasmide molecules per reaction. Results A total of 950 samples of bone marrow and/or peripheral blood from 27 patients have been analyzed. Twenty of 27 patients (74%) achieved molecular remission (MR), twenty-six of 27 patients (96%) achieved hematological remission (HR). 6 of 27 (22%) patients achieved HR without MR and one patient failed therapy. 8 of 20 patients (40%) with MR after treatment relapsed at molecular level and except one in all these patients hematological relaps occured (one patient is still in HR with bone marrow blast present, but < 5%). Considering relapsed patients, time from molecular to hematological relapse was 1 to 5 months (median: 3 months). Considering all 14 patients with HR without MR (6 pts) or with molecular relapse (8 pts), in 11 of them hematological relaps occured (79%) and molecular positivity anticipating hematological relaps with median of 3,5 month (1-7 months). 3 of these 14 patients are still in HR. Conclusions Mutations within NPM1 gene are a sensitive marker for monitoring minimal residual disease in CN-AML patients. RQ-PCR using a MGB probe is an efficient approach to long-term follow-up of residual leukemia cells and frequent quantitative monitoring is useful for reliably predicting hematological relapse. Achievement of negativity appears to predict favorable clinical outcome. This work was partially supported by research grant No. MSM0021622430 Disclosures: No relevant conflicts of interest to declare.

Quantification of Minimal Residual Disease (MRD) in MLL-PTD Positive AML Can Be Used for Prognostication in AML with Normal Karyotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2026-2026
Author(s):  
Martin Weisser ◽  
Claudia Schoch ◽  
Wolfgang Kern ◽  
Wolfgang Hiddemann ◽  
Torsten Haferlach ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Early Detection ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Normal Karyotype ◽  
Significant Prognostic Factor ◽  
Expression Levels ◽  
Log Reduction ◽  
Minimal Residual

Abstract Partial tandem duplications of the MLL gene (MLL-PTD) occur with the same frequency of approximately 6% as PML-RARA, AML1-ETO, and CBFB-MYH11 that have previously been shown to be relevant markers for detection of minimal residual disease (MRD). MLL-PTD has a frequency of 11% in the normal karyotype and here it is associated with an unfavourable prognosis. In the normal karyotype AML PCR-based MRD detection was not applicable so far, and thus MLL-PTD may be a promising MRD marker for this large intermediate AML subtype. So far, the clinical significance of the expression level of MLL-PTD at diagnosis or MRD during the course of therapy have not been investigated. Using real time RT-PCR MLL-PTD expression levels were quantified relative to the control gene ABL. Quantitative data were available from 143 patients at diagnosis. The range of the MLL-PTD/ABL ratios at diagnosis was 9.6–1255 (median: 149). The levels of MLL-PTD expression in 50 healthy control samples were between 0 and 0.08 (median 0.02). In total 47 of these patients with a median follow up sample number of 4 per patient (range 2–17) were evaluated for MRD during and after therapy. Twenty-one patients were evaluable for MRD analysis after 2 months after start of therapy. Thirty-one patients were evaluable for MRD analysis after 4 and 6 months after start of therapy. A 2-log reduction of MLL-PTD expression after 2 months, 4 months and 6 months was a significant prognostic factor for overall survival (OS: p=0.0179, p=0.035, p=0.048, respectively) as well as for event free survival (EFS: p=0.0047, p=0.037, p=0.020, respectively). There is no evidence that a 3-log reduction after 2 and 4 months improves OS significantly (p=0.62 and 0.24 respectively). This was mainly due to the low number of patients that achieved a 3 log decrease (6/21 and 10/31 respectively). In contrast, at 6 months a 3-log decrease had a significant impact on OS and EFS (p=0.049 and p=0.030, respectively). Neither the expression levels at diagnosis nor fusion type (involved MLL exons) showed prognostic significance. However, age above 60 years and leukocytosis above 50 G/l were associated with a worse prognosis (p=0.028 and p=0.0035, respectively). Overall, the MLL-PTD expression levels correlated well to the course of the disease and a molecular relapse was detected before clinical manifestation in 2 patients based on increasing expression ratios. Another 15 cases were assessed at clinical relapse when expression levels were again in the range of the diagnostic sample. Here the median interval between the last follow up and relapse was too long (9.2 months) for early detection of relapse. Thus, more frequent follow up analyses at least every three months should improve the early detection rate. In conclusion, this analysis confirms the significance of MRD levels as a prognostic factor in this AML subtype. 1) MLL-PTD can be applied in 11% of intermediate risk group AML. 2) Patients with an apriori high risk for relapse can be identified on the basis of a 2 log reduction. 3) Relapses can be early detected based on increasing expression ratios.

scholarly journals The Presence of Minimal Residual Disease, As Determined By Highly Sensitive Quantitation of NPM1-Mutatation, Provided Powerful Prognostic Information in Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5097-5097
Author(s):  
Atsushi Marumo ◽  
Hiroki Yamaguchi ◽  
Yuho Najima ◽  
Kensuke Usuki ◽  
Shinichi Kako ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Bone Marrow Cells ◽  
Residual Disease ◽  
Normal Karyotype ◽  
Npm1 Mutation ◽  
Minimal Residual ◽  
Hematological Remission ◽  
Acute Myeloid

Background: As recurrence of acute myeloid leukemia (AML) is difficult to predict, it is important to detect it by measuring minimal residual disease (MRD). PML-RARA, RUNX-RUNX1T1, CBFB-MYH11 are regarded as the reliable MRD markers. However, in AML with normal karyotype and many other forms, no MRD markers have been established. NPM1 mutations, occurring in approximately 30% of adult AML cases, and 50-60% of AML cases with normal karyotype, represent one of the most frequent mutations in AML. Recently, NPM1 mutation is reported to be useful in assessing MRD. We undertook a retrospective and prospective investigation of the usefulness of NPM1 mutation as an MRD marker in Japanese patients with AML. Methods: The subjects were 38 NPM1-mutated AML patients with first hematological remission at several hospitals related to our institution between 2001 and 2018. This study was approved by the ethics committee of Nippon Medical School and the informed consents were obtained from all patients, according to the Declaration of Helsinki. We analyzed peripheral blood cells or bone marrow cells at diagnoses, and evaluated only bone marrow cells after diagnoses. Detection of NPM1 mutation was carried out using allele-specific real time PCR following creation of a complementary primer. After dilution of the samples, sensitivity to TCTG, CATG, and CCTG was found to be 0.001%. The NPM1 mutant copies were qualified only at successful amplification of internal control. Results: The median age of the patients was 58 years (18-79 years). There were 32 cases with intermediate cytogenetic prognosis and 6 cases with unclear chromosomal profile. Of the 38 cases, 14 cases (37%) were FLT3-ITD-positive and allogeneic hematopoietic stem cell transplantation was carried out in 14 cases (37%). The base sequence was TCTG in 36 cases and CCTG in 2 cases. Persistence of NPM1-mutatation was present in 25 patients with first hematological remission (66%). Compared with patients with MRD negative, patients with MRD positive were associated with DNMT3A mutation (MRD positive 12/25 vs MRD negative 0/13, p=0.003). The rate of relapse in patients with MRD positive was significantly higher than those of in patients with MRD negative (MRD positive 76% vs MRD negative 23%, p=0.004). The rates of relapse free survival (RFS) and overall survival (OS) in patients with MRD positive were significantly lower than those in patients with MRD negative (RFS at 2 years: MRD positive 14% vs MRD negative 86% p=0.003; Figure 1, OS at 2 years: MRD positive 25% vs MRD negative 93%, p<0.001). In FLT3-ITD negative group, the rates of RFS in patients with MRD positive were significantly lower than those in patients with MRD negative. (RFS at 2 years: MRD positive 21% vs MRD negative 92% p=0.001; Figure 1). Conclusion: The presence of MRD with NPM1 mutation is significantly associated with relapse and it is useful to decide their treatment strategy. Especially, there is the usefulness of NPM1 mutation as an MRD marker in NPM1 positive Flt3-ITD negative AML patients who are generally classified as favorable risk. According to previous reports, it is known that NPM1-mutated AML sometimes relapse with losing NPM1 mutations. However, in this study, all NPM1-mutated AML relapse without losing NPM1 mutations. We need to collect more patients and are going to confirm whether there are patients who relapse with losing NPM1 mutations or not. We plan to analyze the genetic background of MRD positive and negative patients with next-generation sequencing. We are going to announce the genetic characteristics in addition to this result at ASH. Disclosures Usuki: Astellas Pharma Inc: Research Funding, Speakers Bureau; Daiichi Sankyo Co., Ltd.: Research Funding, Speakers Bureau. Kako:Bristol-Myers Squibb: Honoraria; Pfizer Japan Inc.: Honoraria. Inokuchi:Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria; Pfizer: Honoraria.

Bone Marrow May Be More Informative Than Peripheral Blood To Evaluate Minimal Residual Disease During 1st and 2nd Year Follow Up After First-Line Fludarabine, Cyclophosphamide, and Rituximab For Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1621-1621
Author(s):  
Paolo Strati ◽  
Michael J. Keating ◽  
Susan O'Brien ◽  
Jan A. Burger ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Response Assessment ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Final Response ◽  
Minimal Residual

Abstract Background Minimal Residual Disease (MRD) status at end of first-line chemoimmunotherapy is an independent prognostic factor for patients (pts) with chronic lymphocytic leukemia (CLL). In the CLL8 trial of the German CLL Study Group, peripheral blood (PB) was monitored for MRD during follow up. Because the microenvironment is important for CLL cell growth and survival and typically it is the last site to eliminate residual disease with chemoimmunotherapy, bone marrow (BM) might be a more reliable site to monitor MRD. Methods Two-hundred thirty-seven pts with CLL and an indication for therapy (IWCLL-WG 2008) received first-line fludarabine, cyclophosphamide, and rituximab (FCR) on protocol between 09/2008 and 09/2012. MRD was prospectively assessed in BM and/or PB by flow cytometry using the highly sensitive international standardized approach, 2 months after the last course of treatment (final response assessment) and every 3-6 months thereafter. Kaplan-Meier estimates were compared using the log-rank test. Results Sixty-one percent of pts were male, 21% were >65 years old, 40% had Rai stage III-IV, 41% had beta2-microglobulin (B2M) ≥4 mg/L, 61% had unmutated IGHV, and 21% had FISH analysis positive for deletion 11q and 7% for deletion 17p. Seventy-five percent of pts received ≥3 total courses of FCR. The complete remission (CR) and overall response (OR) rates were 65 and 97%, respectively. BM MRD negativity was achieved in 59% of pts at final response assessment. For monitoring, BM MRD was assessed in 121 pts during the 1st year and in 30 pts during the 2nd year after completion of treatment with FCR; all samples were serial. PB MRD was assessed in 106 pts during the 1st year and in 57 during the 2nd year of follow up; again all samples were serial. BM MRD negativity was observed in 63 (52%) pts during the 1st year of follow up and in 15 (50%) pts during the 2nd year. PB MRD negativity was observed at the same staging times in 81 (76%) and 29 (51%) pts, respectively. Concurrent BM and PB samples were taken during the 1st year in 51 pts, and in 6 pts during the 2nd year of follow up. We evaluated the association between MRD negativity during the 1st and 2nd year of follow-up and progression-free survival (PFS). BM MRD positive status was associated with shorter PFS when assessed during both the 1st and 2nd year of follow up (p<0.001 and p=0.001, respectively; Figure). In contrast, PB MRD positive status did not correlate with PFS for either time (p=0.15 and p=0.79, respectively; Figure). Conclusions After first-line FCR for pts with CLL, positive BM MRD may identify pts at higher risk for progression. Based on this finding, BM may be preferred to assess MRD status and pts with positive BM MRD could be considered for maintenance or consolidation strategies. Additional studies confirming these findings are warranted. Disclosures: No relevant conflicts of interest to declare.

Using MALDI-TOF mass spectrometry for tracking of minimal residual disease in peripheral blood from patients with multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Marion Eveillard ◽  
Even Rustad ◽  
Mikhail Roshal ◽  
Yanming Zhang ◽  
Amanda Ciardiello ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Maldi Tof ◽  
Minimal Residual ◽  
Active Disease

e19525 Background: Minimal residual disease (MRD) negativity after completed therapy is associated with longer progression-free survival (PFS) in patients with multiple myeloma (MM). Current standard of care for MRD testing use flow cytometry and/or next generation sequencing (NGS)-based assays applied on bone marrow (BM) aspirate samples. To develop a strategy for MRD tracking in peripheral blood (PB), we were motivated to evaluate MALDI-TOF head-to-head with established bone marrow-based MRD assays. Methods: We used MALDI-TOF mass spectrometry to detect M-proteins in PB. Our cohort included patients who had serum samples available at 2 timepoints including during active disease and within 60 days of MRD results as determined by flow cytometry of BM aspirates. The cohort enrolled 71 patients (26 females, 45 males) with a median age of 61 years (37-78 years). Twenty-seven patients had high-risk cytogenetics at baseline. Patients were classified at diagnosis as ISS1 (n = 38), ISS2 (n = 18) or ISS3 (n = 6). The flow cytometry based MRD assay was performed using MSKCCs 10-color, single-tube method. MALDI-TOF analysis was performed as described by Mills et al. Samples taken during active disease were used to identify the mass/charge ratio of the M-protein at baseline and in follow-up samples. MALDI-TOF results were compared to flow cytometry bone marrow-based MRD results. Results: The median time between diagnosis and the MRD timepoint was 13.4 months (3.4-91 months). MALDI-TOF in PB and flow cytometry BM-based MRD results were concordant for 44/71 (62%) patients (8+/+, 36 -/- respectively) while 27 were discordant (10 +/-, 17-/+). Fifty-four of 71 patients were in complete response (CR) (45/54 in sCR) at the time of MRD. MALDI-TOF was still positive in 13 of these 54 CR patients. In this cohort, the median PFS since MRD assessment was not reached in the 2 subgroups of double negative patients (n = 31) or in patients with a positive result in at least one technique (n = 23) with a median follow-up of 11.2 months (0-34.6 months). Conclusions: In 44/71 (62%) samples, MALDI-TOF of PB results and flow cytometry BM-based MRD results were concordant. MALDI-TOF of PB may be useful for detecting measurable residual disease and for the monitoring of MM patients during maintenance therapy with the future goal to rule out early recurrent disease.

Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8010-8010
Author(s):  
Noemi Puig ◽  
Bruno Paiva ◽  
Teresa Contreras ◽  
M. Teresa Cedena ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Prognostic Value ◽  
Residual Disease ◽  
Newly Diagnosed ◽  
Time Points ◽  
Minimal Residual

8010 Background: Analysis of minimal residual disease (MRD) in the bone marrow (BM) of patients with multiple myeloma (MM) is accepted by the IMWG to evaluate treatment efficacy and is a well-established prognostic factor. However, there is an unmet need to explore the clinical value of MRD in peripheral blood (PB). Methods: Newly diagnosed MM patients enrolled in the GEM2012MENOS65 trial received six induction (Ind) cycles of bortezomib, lenalidomide, and dexamethasone (VRD) followed by autologous stem cell transplantation (ASCT) and 2 further cycles of consolidation (Cons) with VRD. MRD was analyzed in BM using Next Generation Flow (NGF) and in serum by Mass Spectrometry (MS) using IgG/A/M, κ, λ, free κ and free λ specific beads, both after Ind, at day 100 after ASCT, and after Cons. Sequential samples from the first 184 patients were analyzed. Results: Results of both methods were in agreement (NGF+/MS+ and NGF-/MS-) in 83% of cases post-Ind (152/184), 80% post-ASCT (139/174) and 76% post-Cons (128/169). Stratifying by the log range of MRD by NGF, discordances (NGF+/MS- and NGF-/MS+) seemed to increase at the lower MRD ranges, being 22%, 21% and 19% from ≥10−5 to <10−4 and 21%, 21%, 23% at ≥x10−6(post-Ind, ASCT and Cons, respectively). Analysis of discordances showed that they could be partly explained by the higher percentages of cases found to be positive by MS as compared by NGF at part of the time-points analyzed and at each log range of MRD. From ≥10−5 to <10−4, MRD was detected by NGF in 36%, 28%, 20% of cases post-Ind, ASCT and Cons, respectively vs MS in 37%, 29%, 21% of them; at ≥x10−6, NGF was positive in 11%, 14%, 19% of cases vs MS in 23%, 19% and 16% of them. Considering NGF as a reference, the negative predictive value (NPV) of MS per MRD range (≥10−5 to <10−4 and ≥x10−6, respectively) was: post-Ind: 83% (p<0,0001), 94% (p=0,034); post-ASCT 86% (p<0,0001), 90% (p=0,022); post-Cons 89% (p<0,0001), 85% (p=0,0469). Despite these discordances, the prognostic value of each technique in terms of undetectable MRD and progression-free survival (PFS) was consistent at all time-points (Table) and further, discordant cases (NGF+/MS- and NGF-/MS+) did not display a significantly different PFS as compared to NGF-/MS- cases. Conclusions: The results of MRD assessed by NGF in BM and by MS in PB show a significant concordance and are associated with a similar prognostic value analyzed in terms of PFS. Given its high NPV, MRD in peripheral blood by MS provides a gateway for BM aspiration/biopsy and MRD assessment by NGF.[Table: see text]

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

scholarly journals Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1556-1560 ◽  
Author(s):  
S Wheaton ◽  
MS Tallman ◽  
D Hakimian ◽  
L Peterson
Keyword(s):  
Bone Marrow ◽  
Minimal Residual Disease ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Hematoxylin And Eosin ◽  
Anti Cd20 ◽  
Minimal Residual

Minimal residual disease (MRD) can be detected in bone marrow core biopsies of patients with hairy cell leukemia (HCL) after treatment with 2-chlorodeoxyadenosine (2-CdA) using immunohistochemical (IHC) techniques. The purpose of this study was to determine whether the presence of MRD predicts bone marrow relapse. We studied paraffin- embedded bone marrow core biopsies from 39 patients with HCL in complete remission (CR) 3 months after a single cycle of 2-CdA. Biopsies performed 3 months posttherapy and annually thereafter were examined by routine hematoxylin and eosin (H&E) staining and IHC using the monoclonal antibodies (MoAbs) anti-CD45RO, anti-CD20, and DBA.44. At 3 months after therapy, 5 of 39 (13%) patients had MRD detectable by IHC that was not evident by routine H&E staining. Two of the five patients (40%) with MRD at 3 months have relapsed, whereas only 2 of 27 (7%) patients with no MRD and at least 1 year of follow up relapsed (P = .11). Over the 3-year follow-up period, two additional patients developed MRD. Overall, three of six (50%) patients with MRD detected at any time after therapy have relapsed, whereas only 1 of 25 (4%) patients without MRD has relapsed (P = .016). These data suggest that the presence of MRD after treatment with 2-CdA may predict relapse.

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

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3800-3807 ◽  
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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