scholarly journals Prognostic significance of receptor for hyaluronan acid-mediated motility (CD168) in acute pediatric leukemias – assessment of clinical outcome, post induction, end of treatment and minimal residual disease

2018 ◽  
Vol 40 (4) ◽  
pp. 310-316 ◽  
Author(s):  
Chinnathambi Narayanan Sai Shalini ◽  
Febe Renjitha Suman ◽  
Jerusha Samuela Jacob ◽  
Rithika Rajendran ◽  
Julius Xavier Scott ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Post Induction ◽  
End Of Treatment ◽  
Minimal Residual

Minimal Residual Disease In Adult AML

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4969-4969
Author(s):  
Ihab A. Eldessouki ◽  
Ola Khorshid ◽  
Eman Kandeel ◽  
Nasr Lahloubi
Keyword(s):  
Treatment Response ◽  
Minimal Residual Disease ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Burden ◽  
Multiparametric Flow Cytometry ◽  
Post Induction ◽  
Minimal Residual

Abstract Background The achievement of complete hematologic remission (CR) is used as predictor for treatment response in patients with myeloid leukemia (AML).However <5% blasts in the bone marrow does not reflect the presence of tumor burden precisely. Minimal residual disease (MRD) in the first complete remission (CR1) may play a critical rule in assessment of treatment response and prediction of subsequent relapse. Patients and Methods Leukemia associated immunophenotyping (LAIP) for 73 patients with denovo AML monitored at diagnosis , day 14 and day28 post-induction by multiparametric flow cytometry (MFC). Results CR achieved in 60(82%) patients and 13(18%) patients did not. Among the 60(80%) patients who achieved CR 9 (15%) were MRD negative and 51(85%) were MRD positive at day14. Significant association between MRD detection and disease free survival (DFS) using 0.01% cut off value (P=.015). Day 28 post induction show highly significant association between MRD and DFS using 0.01% cut off value (P=0.001) as 38(63%) patients were MRD negative and (27%) were positive. Significant association between MRD detection and overall survival (50 month) at day 14 and day 28 (P=0.02, P=0.001) respectively using cut off value 0.01%. MRD was positive in 63(86%) at day 14 and (37%) at day 28. Conclusion MRD detection at day28 and d14 at the end of induction in patients in CR may have a prognostic significance on clinical outcome and may thus be a useful marker for risk stratification. Disclosures: No relevant conflicts of interest to declare.

Minimal Residual Disease Assessed by WT1 Expression and NPM1 Mutations Specific RQ-PCR Assays Identifies Patients with Distinct Outcomes in the ALFA 0701 Trial and Is Decreased by Treatment with Gemtuzumab Ozogamicin

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 659-659 ◽  
Author(s):  
Juliette Lambert ◽  
Jerome Lambert ◽  
Olivier Nibourel ◽  
Cécile Pautas ◽  
Sandrine Hayette ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Gemtuzumab Ozogamicin ◽  
Poor Responders ◽  
Prognostic Impact ◽  
Transcript Levels ◽  
Post Induction ◽  
Minimal Residual

Abstract Abstract 659 Background: NPM1 mutations and WT1 expression are frequently identified in acute myeloid leukemia (AML). Both markers have been reported as suitable molecular target for minimal residual disease (MRD) monitoring. Recently, Gemtuzumab Ozogamicin (GO) has been shown to improve event free survival and overall survival in adult AML. Aims: To follow MRD in AML patients with NPM1 mutations (NPM1mut) and/or WT1 expression (WT1+) and treated in the randomized ALFA 0701 GO trial conducted by the Acute Leukemia French Association (Castaigne et al, Lancet 2012), in order to validate their prognostic significance and to evaluate the effect of GO on MRD response. Methods: The ALFA 0701 trial included 278 patients aged 50–70 years with newly-diagnosed de novo AML, randomized to receive or not five doses of 3 mg/m2 GO, on day 1, 4 and 7 of standard induction chemotherapy and on day 1 of two consolidation chemotherapy courses, respectively. A total of 77 NPM1mut (35 in control arm, 42 in GO arm) and 178 WT1+ (87 in control arm, 91 in GO arm) AML patients were studied. WT1 + at diagnosis was defined as a ratio WT1/ABL transcript above 25% in bone marrow (BM) or 5% in peripheral blood (PB) samples. PB and BM samples were collected at diagnosis, after induction and after each consolidation course. MRD levels were assessed using cDNA-based real-time quantitative PCR (RQ-PCR) and reported as the ratio NPM1mut or WT1 transcript/100 ABL transcript. Occurrence of a MRD level below the threshold (NPM1mut <0.1% and WT1 transcript < 0.5% in PB) was defined here as a good MRD response. The prognostic value of MRD was assessed by comparing the outcome of good versus poor MRD responders after induction in terms of cumulative incidence of relapse (CIR) at 18 months. Effect of GO was then evaluated by comparing MRD response in both treatment arms. Results: 178 patients (favorable cytogenetics: 4%, intermediate: 69%, unfavorable: 27%) were WT1+. WT1 transcript levels at diagnosis had no prognostic impact on complete remission (CR) rate or CIR. In the 104 patients who achieved CR, post-induction WT1 MRD level was predictive of relapse: 18-month CIR was 70% (95%CI: [49% - 84%]) in poor responders (n=31) versus 38% [26% - 50%] in good responders (n=73) (p=0.0001). When adjusted on cytogenetics, randomization arm and FLT3-ITD status, WT1 MRD remained independently associated with relapse (HR: 2.43, [1.25 – 4.75], p=0.009). Similarly, NPM1mut transcript levels at diagnosis had no prognostic impact on CR rate or CIR. Among the 67 NPM1mut patients who achieved CR, post-induction NPM1mut MRD level was predictive of relapse: 18-month CIR was 64% [45% – 70%] in poor responders (n=50) versus 25% [10% – 42%] in good responders (n=17) (p=0.0007). When adjusted on randomization arm and FLT3-ITD status, NPM1 MRD remained independently associated with relapse (HR: 4.2, [1.2 – 14.3], p=0.02). We were able to evaluate both MRD markers in 53 patients after induction (NPM1+/WT1+ n=16, NPM1+/WT1- n=24, NPM1-/WT1- n= 13). 18-month CIR was significantly different in the 3 groups (respectively 69% [38% - 87%], 40% [19% - 60%] and 25% [5% - 51%], p=0.008). In patients with poor MRD response assessed by NPM1mut, the presence of a positive WT1 MRD level was associated with a higher CIR. NPM1 MRD good response was more frequently observed in GO arm as compared to control arm (OR: 4.38 [2.12 – 9.03], p<0.0001). The rate of good NPM1 MRD response was 41% versus 7% after induction, 76% versus 35% and 93% versus 62% after first and second consolidation in GO and control arms respectively. WT1 MRD good response was more frequently observed in GO arm, although not reaching statistical significance (OR: 1.84 [0.89 – 3.77] p=0.098). The rate of good WT1 MRD response was 76% versus 65% after induction, 87% versus 66% and 87% versus 80% after first and second consolidation, respectively in GO and in control arms (figure 1). Conclusion: Our study confirms the predictive value of MRD based on NPM1 mutations and WT1 expression in patients treated in the ALFA 0701 randomized trial. In multivariate analysis, WT1 and NPM1 MRD levels remained independent prognostic factors for relapse. We showed that treatment with GO significantly improved MRD response in adult AML. Disclosures: Castaigne: Wyeth: Consultancy.

scholarly journals Impact of Minimal Residual Disease in Transplant Ineligible Myeloma Patients: Results from the UK NCRI Myeloma XI Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 245-245 ◽  
Author(s):  
Ruth Mary de Tute ◽  
Andy C Rawstron ◽  
David A Cairns ◽  
Charlotte Pawlyn ◽  
Faith E Davies ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Research Funding ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Continuous Variable ◽  
Powerful Predictor ◽  
Qualitative Variable ◽  
The Impact ◽  
Minimal Residual ◽  
Support Research

Abstract Introduction. Minimal residual disease (MRD) is a powerful predictor of outcome in multiple myeloma (MM). We have previously demonstrated, in transplant eligible patients, that the level of MRD as a continuous variable independently predicts both PFS and OS, with approximately a one year median OS benefit per log depletion (J Clin Oncol 2013; 31:2540-7 and Blood 2015; 125:1932-5). The impact of MRD also appears to be independent of therapy received. There is more limited data on the applicability of MRD assessment in transplant ineligible patients, largely as a consequence of low rates of CR historically within this patient cohort. Patients and Methods. In this analysis we have assessed the impact of MRD on PFS amongst patients treated within the non-intensive arm of the NCRI Myeloma XI trial. Patients were randomised between thalidomide (CTDa) and lenalidomide (RCDa) based induction therapies with responding patients being subsequently randomised to maintenance with lenalidomide monotherapy, or no further therapy. Bone marrow aspirates were obtained at the end of induction and this analysis represents a subset of 297 patients (median age 74 years). MRD was assessed using flow cytometry (sensitivity 10-4) with a minimum of 500,000 cells evaluated with six-colour antibody combinations including CD138/CD38/CD45/CD19 with CD56/CD27 in all cases and CD81/CD117 in additional cases as required. Results. Overall MRD-negativity was demonstrated in 41/297 (13.8%). When considered according to induction therapy received 25/154 (16.0%) of patients randomized to RCDa were MRD-negative compared to 16/143 (10.8%) of those randomized to CTDa (p=0.24; Fisher's exact test). MRD-negativity was associated with a significant outcome advantage as the median PFS was 34 months versus 18 months for MRD-positive patients (p<0.0001, HR 0.44 [95% confidence interval (CI 0.29-0.67)]). This effect was noted in both RCDa (median PFS 17m v 32m; p=0.001, HR 0.41 [95%CI 0.23-0.69]) and CTDa (median PFS 19m v 34m; p=0.03, HR 0.49 [95%CI 0.26-0.95]). When the impact of MRD was assessed according to induction regimen the outcome of MRD-negative and MRD-positive patients was similar with both regimens (see figure). The impact of MRD was also assessed as a continuous variable across 5 logs of residual disease. Sequential improvements in outcome with each log reduction were demonstrable. Median PFS for the following disease levels; <0.01%, 0.01 - <0.1%, 0.1% - <1%, 1% - <10% and >/=10% were 34, 26, 16, 14 and 9 months respectively (p<0.0001). This pattern was demonstrable in both RCDa and CTDa treated patients (p<0.0001 for both). Multivariate analysis confirmed the independent predictive value of MRD both as a qualitative and continuous quantitative variable (p<0.0001 for both). In both instances achieving an immunofixation-negative CR was not a significant prognostic variable when included in the model with MRD. Conclusions. We would conclude that MRD is a powerful predictor of outcome in transplant ineligible patients and is a meaningful therapeutic goal in this patient group. In contrast to conventional CR it retains independent prognostic significance both as a quantitative and qualitative variable. This data further supports the role of MRD as a primary endpoint and surrogate marker for survival in future clinical trials. Figure. Figure. Disclosures Rawstron: Janssen: Research Funding; BD Biosciences: Other: Remuneration; Gilead: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Honoraria; Genzyme: Honoraria; AbbVie: Honoraria; Roche: Honoraria; Celegene: Honoraria. Pawlyn:Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy. Davies:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kaiser:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support; Chugai: Consultancy. Jones:Celgene: Honoraria, Research Funding. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Jenner:Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel support; Takeda: Consultancy, Honoraria, Other: Travel support. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jackson:MSD: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment. Owen:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Other: Travel support; Janssen: Consultancy, Other: Travel support.

TMOD-15. CHARACTERIZATION OF THE MINIMAL RESIDUAL DISEASE STATE REVEALS DISTINCT EVOLUTIONARY TRAJECTORIES OF HUMAN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi218-vi218
Author(s):  
Maleeha Qazi ◽  
Sabra Salim ◽  
Kevin R Brown ◽  
Neil Savage ◽  
Nicholas Mickolajewicz ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
A Priori ◽  
Prognostic Significance ◽  
Disease State ◽  
Cell Populations ◽  
Human Glioblastoma ◽  
Transcriptomic Level ◽  
Minimal Residual

Abstract Recurrence of solid tumors renders patients vulnerable to a distinctly advanced, highly treatment-refractory disease state that has an increased mutational burden and novel oncogenic drivers not detected at initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding of cancer cell populations that expand from the post-therapy, minimal residual disease (MRD) state. We profiled barcoded tumor cell populations through therapy at tumor initiation/engraftment, MRD and recurrence in our therapy-adapted, patient-derived xenograft models of glioblastoma (GBM). Tumors showed distinct patterns of recurrence in which clonal populations exhibited either a priori, pre-existing fitness, or equipotent fitness acquired through therapy. Characterization of the MRD state by single-cell and bulk RNA sequencing revealed a tumor-intrinsic immunomodulatory signature with strong prognostic significance at the transcriptomic level and in proteomic analysis of cerebrospinal fluid (CSF) collected from GBM patients at all stages of disease. Our results provide insight into the innate and therapy-driven dynamics of human glioblastoma, and the prognostic value of the interrogating of the MRD state in solid cancers.

scholarly journals PROGNOSTIC SIGNIFICANCE AND TREATMENT IMPLICATIONS OF MINIMAL RESIDUAL DISEASE STUDIES IN PHILADELPHIA-NEGATIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014062 ◽  
Author(s):  
Orietta Spinelli ◽  
Manuela Tosi ◽  
Barbara Peruta ◽  
Marie Lorena Guinea Montalvo ◽  
Elena Maino ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Cure Rates ◽  
Sensitive Individual ◽  
Minimal Residual ◽  
Risk Of Relapse

Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. 

Importance of Minimal Residual Disease Testing During the Second Year of Therapy for Children With Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (4) ◽  
pp. 704-709 ◽  
Author(s):  
Glenn M. Marshall ◽  
Michelle Haber ◽  
Edward Kwan ◽  
Ling Zhu ◽  
Daniella Ferrara ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Maintenance Chemotherapy ◽  
Childhood All ◽  
Second Year ◽  
Minimal Residual

Purpose: A high level of minimal residual disease (MRD) after induction chemotherapy in children with acute lymphoblastic leukemia (ALL) is an indicator of relative chemotherapy resistance and a risk factor for relapse. However, the significance of MRD in the second year of therapy is unclear. Moreover, it is unknown whether treatment intervention can alter outcome in patients with detectable MRD. Patients and Methods: We assessed the prognostic value of MRD testing in bone marrow samples from 85 children at 1, 12, and 24 months from diagnosis using clone-specific polymerase chain reaction primers designed to detect clonal antigen receptor gene rearrangements. These children were part of a multicenter, randomized clinical trial, which, in the second year of treatment, compared a 2-month reinduction-reintensification followed by maintenance chemotherapy with standard maintenance chemotherapy alone. Results: MRD was detected in 69% of patients at 1 month, 25% at 12 months, and 28% at 24 months from diagnosis. By univariate analysis, high levels of MRD at 1 month, or the presence of any detectable MRD at 12 or 24 months from diagnosis, were highly predictive of relapse. Multivariate analysis showed that MRD testing at 1 and 24 months each had independent prognostic significance. Intensified therapy at 12 months from diagnosis did not improve prognosis in those patients who were MRD positive at 12 months from diagnosis. Conclusion: Clinical outcome in childhood ALL can be predicted with high accuracy by combining the results of MRD testing at 1 and 24 months from diagnosis.

Co-Existence of Various Sub-Clones in TEL-AML1 Positive Acute Lymphoblastic Leukemia in Association with Sub-Microscopic Deletion of AML1.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1096-1096
Author(s):  
Amos Toren ◽  
Rachel Rothman ◽  
Bella Bielorai ◽  
Malka Reichart ◽  
Ninette Amariglio ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Gene Rearrangement ◽  
Chromosomal Abnormalities ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Submicroscopic Deletion ◽  
Minimal Residual

Abstract The TEL/AML1 fusion gene is the most common gene rearrangement in pediatric acute lymphoblastic leukemia (ALL). Although considered to be a low risk leukemia it has a 20% risk of late relapse. The coexistence of different sub clones at diagnosis, based on polymerase chain reaction (PCR) studies of Ig/TCR gene rearrangement, was recently reported in this subtype of ALL. Their different response to chemotherapy may explain the emergence of certain sub clones at relapse, and may serve as a marker for minimal residual disease follow-up. Several chromosomal rearrangements such as t(9;22), t(8;21), inv(16) and rearrangements of the MLL gene are frequently associated with submicroscopic deletions and some of them have prognostic significance. Such deletions were not reported in t(12;21) positive ALL. Bone marrow cells from 76 pediatric patients with ALL at diagnosis were analyzed for the presence of the TEL/AML1 fusion gene by interphase fluorescence in situ hybridization (FISH). We used a new system of combined analysis enabling a very large-scale study of the cells of interest with regard to morphology, FISH and immunophenotyping. Fourteen patients were positive for the translocation. Four of them had several sub clones associated with various combinations of additional chromosomal abnormalities. The most striking was an atypical and unexpected hybridization pattern consistent with a submicroscopic deletion of the 5′ region of the AML1 breakpoint (intron2) not previously reported. We describe the use of a larger probe for AML1 (AML1/ETO) to exclude the possibility of insertion of TEL into the AML1 region without breakage and to reduce the false positivity due to optical fusion. This may enable a better monitoring of minimal residual disease in cases with submicroscopic deletion. All patients had some sub-clones with TEL deletion. Other abnormalities included trisomy and tetrasomy 21 as well as double TEL-AML1 fusion. The analysis of numerous sub-clones at presentation in these patients suggests clonal evolution at an early stage of the disease. These sub-clones may have different sensitivities to chemotherapy, and some of them may reappear at relapse. The frequency of AML1 deletion in t(12;21) in addition to other chromosomal abnormalities, is unknown. The involvement of these findings in the generation of leukemic sub clones, their prognostic significance and role in minimal residual disease follow-up deserves further studies in a large number of patients and a longer follow-up.

Minimal Residual Disease Status Is the Most Important Preditive Factor in Adults with Acute Lymphoblastic Leukemia. Prospective, Multicenter PALG 4-2002 MRD Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2821-2821 ◽  
Author(s):  
Jerzy Holowiecki ◽  
Malgorzata Krawczyk-Kulis ◽  
Sebastian Giebel ◽  
Krystyna Jagoda ◽  
Beata Stella-Holowiecka ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Disease Status ◽  
High Dose ◽  
Risk Criteria ◽  
Minimal Residual

Abstract Current therapeutic protocols for adult acute lymphoblastic leukemia (ALL) take into account the risk of relapse, in order adjust the treatment intensity to individual patient needs. It is postulated that in addition to “classical” risk criteria the status of minimal residual disease (MRD) should be considered for treatment decisions. The aim of this study was to prospectively evaluate the feasibility and prognostic significance of MRD detected with the use of immunophenotyping for outcome of ALL patients treated according to 4-2002 protocol of the Polish Adult Leukemia Group (PALG). Induction therapy included PDN, Asp and 4x epirubicin+VCR. Consolidation consisted of 2x high-dose AraC+Cy, 2x Mtx+Vep, 6MP, and CNS prophylaxis. Patients stratified to high risk (HR) group according to “classical” criteria based on those formerly developed by GMALL (bcr/abl(+), WBC>30 G/L, prepreB, early or mature T phenotype, age>35y, or prolonged time to achieve CR) were further referred for hematopoietic cell transplantation (HCT), whereas those assigned to standard risk (SR) group were treated with maintenance for 2 years. MRD was tested at the level of 0.1% after completion of induction and consolidation therapy in patients achieving CR, employing multicolor flow-cytometry, including a new “empty spaces” method taking into account an individual pattern of antigen expression on blast cells. 165 ALL pts (B-lineage 79%, T-lineage 21%), aged 29 y (17–60) were included. CR rate equaled 85,5%. 23% of CR pts were assigned to SR, 77%- to HR according to classical criteria. MRD evaluation was possible in all but 8 pts. After induction 37% of CR pts were found MRD(+). Among those who remained in CR, MRD after consolidation was detected in 26% of cases. 64% of patients were MRD(−) at both time-points, whereas in the remaining 36% of cases MRD was detected at least once. MRD status affected both relapse incidence (RI) and leukemia-free survival (LFS). After 3 years the RI was higher for pts with MRD(+) vs. MRD(−) if assessed after induction (82%vs.29%,p=0.00007) and after consolidation (62%vs.41%,p=0.05). For pts with MRD(−) at both study end-points the probability of LFS was 65% whereas for those with MRD(+) after either induction and/or consolidation − 26% (p=0.008). In the respective subgroups RI equaled 28% and 73% (p=0.004). The difference was observed for patients assigned to SR group (20%vs.92%,p=0.01) as well as to HR group (33%vs.70%,p=0.05). In a multivariate analysis including classical risk criteria the MRD status remained the only significant factor predictive for RI (HR: 2.5(1.3–4.8),p=0.006) and LFS (HR: 2.1(1.2–3.9),p=0.01). We conclude that immunophenotyping employing “empty spaces” method is feasible for MRD evaluation in adults with ALL. MRD stzatus after induction and consolidation is the most important predictive factor for RI and LFS. Based on our findings patients with MRD detected after induction and/or consolidation should be offered intensified treatment with the use of HCT irrespective of the absence of other risk factors.

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