Predictable Recurrence by Regular Monitoring Minimal Residual Disease with Flowcytometry In the Patients with Both AML and ALL: A Single-Center Study of 158 Cases.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1661-1661 ◽  
Author(s):  
Chunrong Tong ◽  
Junfang Yang ◽  
Yuehui Lin ◽  
Xinhong Fei ◽  
Jie Zhao ◽  
...  
Keyword(s):  
High Risk ◽  
Minimal Residual Disease ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Newly Diagnosed ◽  
Aberrant Expression ◽  
Hematopoietic Stem ◽  
The Difference ◽  
Almost All ◽  
Minimal Residual

Abstract Abstract 1661 Minimal residual disease (MRD) is the most important factor to predict the prognosis after chemotherapy in the patients with acute leukemia(AL). Among the techniques for MRD detection, flowcytometry (FCM) is both sensitive and feasible tool, which can be used in almost all patients no matter with or without cytogenetic or molecular marker. It has been widely recognized that the MRD by FCM can predict the prognosis of the patients with ALL after several cycles of chemotherapy, but there are few reports on the value of MRD by FCM in AML. To investigate the clinical prognostic value of monitoring MRD regularly with FCM, the correlation of MRD and leukemia-free survival (LFS) in patients with AL without initial high risk factors was studied. From April 2005 to July 2009, 119 newly diagnosed patients (AML 85, ALL 34) and 39 treated cases (AML 19, ALL 20) were included. Those treated patients had attained the first complete remission (CR1) for more than 1 year after chemotherapy in other hospital and then were transferred to our hospital and detected MRD by FCM regularly since then. MRD in bone marrow (BM) was detected every 1 to 3 months in the first year after CR1, and every 2 to 6 months thereafter until hematological or extramedullary relapse or by July 2010. The special antibody combinations were employed for each patient according to aberrant expression of leukemia cells detected by the primary immune phenotype, or antigen drift in the follow-up. MRD was analyzed by the same doctor and assessed according to some abnormal characteristics, including antigen over-expression, antigen low-expression or even loss, co-expression of different lineages or different stage antigens on a single cell, and abnormal patterns in light scatters. MRD+ was defined as the aberrant cells more than 0.01% in BM at the twelfth month for AML and the fifth month for ALL. Among 85 newly diagnosed AML, 33 cases were MRD+ with the median ages 29(4-73)years old, 52 cases were MRD- with the median ages 35(9-68)years old. A total of 2/33 patients in MRD+ group and 40/52 patients in MRD- group remained in LFS. The probability of LFS at 12 months and 24 months was 56% and 16% in MRD+ group, 100% and 84% in MRD- group, respectively (see Figure 1), the difference between MRD+ and MRD- groups was significant statistically (p<0.001). Among 34 newly diagnosed ALL, 13 cases were MRD+ with the median ages 20(12-45)years old, 21 cases were MRD- with the median ages 17(6-35)years old . A total of 1/13 patients in MRD+ and 19/21 patients in MRD- remained in LFS. The probability of LFS at 12 months and 24 months was 46% and 38% in MRD+ group, 95% and 95% in MRD- group(see Figure 2), the difference between MRD+ and MRD- groups was significant statistically (p<0.001). Similar pattern was seen in treated patients. Among 19 treated AML, 0/6 in MRD+ group and 11/13 in MRD- group remained in LFS. Among 20 treated B-ALL, 0/5 in MRD+ group and 14/15 in MRD- group remained LFS. In conclusion, our data indicate that MRD monitored by FCM in both AML and B-ALL correlates to LFS very well. It is important to monitor MRD regularly with FCM in the patients with AL after remission in order to earlier identify high-risk patients for relapse who need intensified treatment, such as allogeneic hematopoietic stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

Minimal residual disease at end of induction and consolidation remain important prognostic indicators for newly diagnosed children and young adults with very high-risk (VHR) B-lymphoblastic leukemia (B-ALL): Children’s Oncology Group AALL1131.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10004-10004
Author(s):  
Wanda L. Salzer ◽  
Michael James Burke ◽  
Meenakshi Devidas ◽  
Yunfeng Dai ◽  
Nyla A. Heerema ◽  
...  
Keyword(s):  
Young Adults ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Post Induction ◽  
Children And Young Adults ◽  
Very High ◽  
Minimal Residual

10004 Background: Children and young adults with very high risk (VHR) B-acute lymphoblastic leukemia (B-ALL) [13-30 years of age with any features or 1-30 years of age with adverse prognostic features including KMT2A rearrangements, iAMP21, hypodiploidy (<44 chromosomes/DNA index < 0.81), central nervous system disease, end of induction (EOI) minimal residual disease (MRD) >0.01%, or induction failure] collectively have a predicted 4-year disease free survival (DFS) of approximately 70%. Whether patients with VHR B-ALL who are MRD positive at EOI and become MRD negative at the end of consolidation (EOC) will have improved survival versus patients remaining MRD positive at EOC is unknown. Methods: Patients with newly diagnosed NCI high risk B-ALL enrolled on AALL1131 or NCI standard risk B-ALL enrolled on AALL0932 and classified as VHR at EOI were treated on the VHR stratum of AALL1131 which sought to improve DFS with intensive post-Induction therapy using fractionated cyclophosphamide (CPM), etoposide (ETOP) and clofarabine (CLOF).Patients were randomly assigned post-Induction to Control Arm (CA) with modified augmented BFM CPM + fractionated cytarabine + mercaptopurine, Experimental Arm 1 (Exp1) with CPM + ETOP, or Experimental Arm 2 (Exp2) with CLOF + CPM + ETOP during Part 2 of Consolidation and Delayed Intensification. Doses of vincristine and pegaspargase were identical on all arms. Exp2 was permanently closed September 2014 due to excessive toxicities, and these patients are excluded from this report. MRD was measured by 6-color flow cytometry at EOI and for those who consented at the EOC. Results: 4-yr DFS for all patients (n=823) with VHR B-ALL was 76.8 ± 2.0%. As we reported previously, 4-year DFS was not significantly different between CA and Exp 1 (85.5 ± 6.8% versus 72.3 ± 6.3%; p=0.76; Burke, Haematologica 2019). 4-yr DFS for patients who were EOI MRD <0.01%, (n=325) versus >0.01 (n=498) was 83.3% ± 2.6% vs 72.0% ± 2.8%, p=0.0013. 4-Year DFS of Patients EOI MRD > 0.01%. Conclusions: MRD is a powerful prognostic indicator in VHR B-ALL with inferior outcomes in patients who are EOI MRD positive. Among patients who were EOI MRD positive treated on Exp1, outcomes were similar for EOC MRD negative and EOC MRD positive, though numbers were small. In contrast, patients who were EOI MRD positive treated on CA that were EOC MRD negative had significantly improved DFS compared to those that were EOC MRD positive. The CA remains the standard of care for COG ALL trials. With this therapy, patients with VHR B-ALL that are EOI MRD positive and EOC MRD negative have significantly improved DFS compared to those that remain MRD positive at EOC. Clinical trial information: NCT02883049. [Table: see text]

Impact of Minimal Residual Disease (MRD) on Prognosis in Children with Philadelphia Positive Acute Lymphoblastic Leukemia (ALL) Treated in the AIEOP-BFM ALL 2000 Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1511-1511
Author(s):  
Andrea Biondi ◽  
André Schrauder ◽  
Maria Grazia Valsecchi ◽  
Claus R Bartram ◽  
Georg Mann ◽  
...  
Keyword(s):  
High Risk ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Patient Specific ◽  
Poor Responders ◽  
Induction Phase ◽  
Hematopoietic Stem ◽  
Group I ◽  
Minimal Residual

Abstract Introduction: The International “Berlin-Frankfurt-Münster” Study Group (I-BFM-SG) pioneered the evaluation of minimal residual disease (MRD) based on Immunoglobulin and T-cell Receptor gene rearrangements as PCR targets. The prospective AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica)-BFM ALL 2000 study is the largest in which standardized quantitative assessment of PCR-MRD at two time points (TP) was used for stratification in 127 centers. Objective: To assess whether PCR-MRD levels discriminate outcome in patients with childhood Philadelphia positive (Ph+) ALL treated with intensive chemotherapy. Material and Methods: Between 07–2000 and 07–2006, 79 Ph+ patients were enrolled in the AIEOP-BFM ALL 2000 study. They were eligible for the high risk (HR) treatment arm and treated with Induction (protocol IA + IB), poly-chemotherapy blocks, reinduction (by one or more Protocols II or III), followed by maintenance therapy. BM samples obtained at day 33 (Time Point 1, TP1) and 78 (TP2) of induction therapy were used for MRD analysis by patient specific PCR targets. At least one or two sensitive markers (≥ 1 × 10−4) could be determined in 62 (78.5%) and 54 (68.4%) patients, respectively. MRD-Standard Risk (SR) was defined by MRD-negative at both TP1 and TP2; MRD-HR by MRD ≥1×10−3 at TP2; MRD-Intermediate Risk (IR): all others. Median follow-up was 3 years; 5-year survival and event-free survival (EFS) (SE) estimates are given. Results: Out of 79 registered patients, 3 (3.7%) died during Induction phase, 15 (19.2%) were Prednisone-poor responders (PPR), 12 (19.2%) were resistant to phase IA and 75 (94.9%) achieved CR. Forty-six patients (58.2%) underwent hematopoietic stem cell transplantation (HSCT). Overall, EFS and Survival (SE) were 44.3%(6.5) and 61.5%(6.2), respectively. Sixty-two patients were stratified by MRD (i.e. they were alive and valuable at day 78 and had at least one sensitive PCR marker). Eleven patients (17.7%) were at MRD-SR: 8 remained in CCR (4 after BMT), 1 died in CCR and 2 relapsed at 2.7 and 5.7 years from diagnosis; 28 (45.2%) were at MRD-IR: 18 remained in CCR (14 after BMT), 1 died in CCR and two for TRM after HSCT; 7 relapsed after 0.6 to 5.1 years; 23 (37.1%) were at MRD-HR and only 4 remained in CCR (all after BMT). The relapse rate was 18% in MRD-SR, 25% in MRD-IR and 61% in MRD-HR. Of note, within the Prednisone good-response subgroup (n=61), the evaluation of MRD identified those patients (MRD-HR, n=12 out of 51 PGR, MRD stratifiable) at very high risk of relapse (6/12: 50%). Conclusions: PCR-MRD is a strong predictor for outcome in Ph+ ALL patients treated with BFM therapy. MRD response detected by PCR can tailor the selection of the best treatment (Imatinib or other tyrosine kinase inhibitors and chemotherapy with or without transplant). The prognosis in the subgroup of Ph+ALL as defined HR according to PCR-MRD detection is still very poor even after HSCT and accordingly new therapeutic strategies are needed.

Treatment of High-Risk Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia in Adolescents and Adults According to Early Cytologic Response and Minimal Residual Disease After Consolidation Assessed by Flow Cytometry: Final Results of the PETHEMA ALL-AR-03 Trial

2014 ◽  
Vol 32 (15) ◽  
pp. 1595-1604 ◽  
Author(s):  
Josep-Maria Ribera ◽  
Albert Oriol ◽  
Mireia Morgades ◽  
Pau Montesinos ◽  
Josep Sarrà ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Prognostic Factor ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Low Flow ◽  
Hematopoietic Stem ◽  
Adolescents And Adults ◽  
Minimal Residual

Purpose Minimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Español de Tratamientos en Hematología (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation. Patients and Methods Patients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 × 10−4 at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level ≥ 5 × 10−4. Results Complete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (≥ 1 × 10−3 after induction and ≥ 5 × 10−4 after early consolidation) as the only prognostic factor for DFS and OS. Conclusion Prognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS.

Depth of response and minimal residual disease status in ultra high-risk multiple myeloma and plasma cell leukemia treated with daratumumab, bortezomib, lenalidomide, cyclophosphamide and dexamethasone (Dara-CVRd): Results of the UK optimum/MUKnine trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Martin F. Kaiser ◽  
Andrew Hall ◽  
Katrina Walker ◽  
Ruth De Tute ◽  
Sadie Roberts ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Plasma Cell ◽  
Residual Disease ◽  
Cell Leukemia ◽  
Ultra High Risk ◽  
Grade 3 ◽  
Minimal Residual

8001 Background: Patients with ultra high-risk (UHiR) newly diagnosed multiple myeloma (NDMM) and patients with plasma cell leukemia (PCL) continue to have dismal outcomes and are underrepresented in clinical trials. Recently, improved responses with anti-CD38 monoclonal antibody combination therapy have been reported for NDMM patients. We report here outcomes for NDMM UHiR and PCL patients treated in the OPTIMUM/MUKnine (NCT03188172) trial with daratumumab, cyclophosphamide, bortezomib, lenalidomide, dexamethasone (Dara-CVRd) induction, augmented high-dose melphalan (HDMEL) and ASCT. With final analysis follow-up surpassed in Feb 2021, we report here early protocol defined endpoints from induction to day 100 post ASCT. Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM by central trial genetic (≥2 high risk lesions: t(4;14), t(14;16), t(14;20), gain(1q), del(1p), del(17p)) or gene expression SKY92 (SkylineDx) profiling, or with PCL (circulating plasmablasts > 20%) were included in OPTIMUM across 39 UK hospitals. Patients received up to 6 cycles of Dara-CVRd induction, HDMEL and ASCT augmented with bortezomib, followed by Dara-VR(d) consolidation for 18 cycles and Dara-R maintenance. Primary trial endpoints are minimal residual disease (MRD) status post ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. Data is complete but subject to further data cleaning prior to conference. Results: Median follow-up for the 107 patients in the safety population was 22.2 months (95% CI: 20.6 – 23.9). Two patients died during induction due to infection. Bone marrow aspirates suitable for MRD assessment by flow cytometry (10-5 sensitivity) were available for 81% of patients at end of induction and 78% at D100 post ASCT. Responses in the intention to treat population at end of induction were 94% ORR with 22% CR, 58% VGPR, 15% PR, 1% PD, 5% timepoint not reached (TNR; withdrew, became ineligible or died) and at D100 post ASCT 83% ORR with 47% CR, 32% VGPR, 5% PR, 7% PD, 10% TNR. MRD status was 41% MRDneg, 40% MRDpos and 19% not evaluable post induction and 64% MRDneg, 14% MRDpos and 22% not evaluable at D100 post ASCT. Responses at D100 post ASCT were lower in PCL with 22% CR, 22% VGPR, 22% PR, 22% PD, 12% TNR. Most frequent grade 3/4 AEs during induction were neutropenia (21%), thrombocytopenia (12%) and infection (12%). Grade 3 neuropathy rate was 3.7%. Conclusions: This is to our knowledge the first report on a trial for UHiR NDMM and PCL investigating Dara-CVRd induction and augmented ASCT. Response rates were high in this difficult-to-treat patient population, with toxicity comparable to other induction regimens. However, some early progressions highlight the need for innovative approaches to UHiR NDMM. Clinical trial information: NCT03188172.

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