scholarly journals Pre-Allogeneic Hematopoietic Cell Transplant Minimal Residual Disease Predicts Post-Transplant Relapse in Pediatric Acute Myeloblastic Leukemia

2011 ◽  
Vol 17 (2) ◽  
pp. S263
Author(s):  
K. Ammon ◽  
M.J. Cowan ◽  
B. Horn ◽  
C.C. Dvorak
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Hematopoietic Cell ◽  
Acute Myeloblastic Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Post Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Minimal Residual

Pre-transplant molecular minimal residual disease (MMRD) is associated with inferior outcomes in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7547-7547
Author(s):  
Muhammad Husnain ◽  
Krishna Komanduri ◽  
Jeremy Ramdial ◽  
Lazaros J. Lekakis ◽  
Trent Peng Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Molecular Data ◽  
Cell Transplant ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Risk Patients ◽  
The Impact ◽  
Minimal Residual

7547 Background: Allogeneic Stem Cell Transplant (alloSCT) continues to be the optimal consolidation strategy for many patients with AML; cytogenetic and molecular abnormalities are known predictors of post-transplant outcomes. There is increasing evidence that Molecular Minimal Residual Disease (MMRD) following induction has important prognostic implications and its value in the prediction of post-transplant relapse continues to be elucidated. We aim to evaluate the impact of genetics and pre-transplant MMRD on clinical outcomes following alloSCT. Methods: We retrospectively evaluated eighty-nine patients, ≥18 years with a diagnosis of AML in complete morphologic remission (i.e. < 5% BM blasts by morphologic assessment) who received alloSCT between 01/2012-05/2018 at the University of Miami and for whom cytogenetic and comprehensive molecular data was available prior to transplantation. Patients were stratified into favorable, intermediate and poor-risk categories based on 2017 ELN criteria. MMRD was defined as persistent leukemia-specific mutations prior to transplantation (i.e. NPM1, FLT3, CEBPA, IDH1-2, RUNX1 and TP53). Persistence of DTA mutations (DNMT3A, TET2 and ASXL1) was not considered MMRD, patients with unavailable cytogenetic/molecular data at diagnosis were excluded. Results: Seventy-four (83%) patients were transplanted in CR1, myeloablative conditioning was used in 72% of patients. Two-year OS and LFS were 69.4% and 78.2%, respectively. Stratification by ELN criteria resulted in prognostic separation for patients transplanted in CR1: 2-year OS for favorable (87%), intermediate (68%) and adverse risk (51%) patients (p = 0.0417). The presence of MMRD was the strongest predictor of post-transplant outcomes for the whole cohort with 2-year OS and LFS of 29.4% and 37.1% (HR 5.45 [95%CI 2.43-12.3] p = 0.0001; HR 12.4 [95%CI: 3.76 to 39.8] p = 0.0001); respectively. Subgroup analysis confirmed that MMRD was associated with significantly inferior LFS for IM/favorable and adverse risk patients (HR: 6.76 [95% CI 1.12 to 40.9], p = 0.038). Conclusions: Pre-transplant MMRD was the most important prognostic factor for relapse and survival in our cohort of AML patients undergoing alloSCT. Correlation of MMRD with other transplant variables such as conditioning intensity, MRD status by MFC and the impact of pre-emptive/therapeutic strategies in high-risk patients continues to be explored.

Relapse Prediction Post Allogeneic Hematopoietic Cell Transplant for Myelodysplastic Syndromes Is Not Improved with Use of the More Stringent Blast Percentage Categories in the Revised International Prognostic Scoring System

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2011-2011
Author(s):  
Leyla Shune ◽  
Zohar Sachs ◽  
Todd E. Defor ◽  
Michelle Dolan ◽  
Daniel J. Weisdorf ◽  
...  
Keyword(s):  
Scoring System ◽  
Disease Burden ◽  
Residual Disease ◽  
Hematopoietic Cell ◽  
International Prognostic Scoring System ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Myeloablative Conditioning ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Relapse Prediction

Abstract Abstract 2011 Residual disease at the time of allogeneic hematopoietic cell transplant (HCT) has been shown to adversely affect outcomes in patients with acute myelogenous leukemia (AML). Assessment of the impact of MDS disease burden at HCT on post-transplant outcomes is less well defined. While blast percentage is easily quantified on morphology and flow cytometry, the blast percentage captures only a fraction of the true MDS clone. Consequently, improved measures of residual disease in MDS patients are needed to improve post HCT outcome prediction. We hypothesized that a more stringent blast percentage cutoff as well as an assessment of recognizable residual cytogenetic disease burden would better predict outcome post HCT. Disease burden at HCT was characterized as reported in the Revised International Prognostic Scoring System (IPSS-R) (<2%, >2-<5%, 5–10% and >10%) and by assessment of cytogenetic residual disease by calculating the percent of metaphases with ongoing cytogenetic abnormalities immediately prior to transplant (% positive metaphases <25%, 25–50%, and > 50%). Metaphase data was unavailable in n=7. Those patients with normal cytogenetics (n=26) were classified in the <25% category. One hundred consecutive patients with MDS undergoing allogeneic HCT at the University of Minnesota between 1995 –2011 were studied. Their median age was 52 (18–69). At diagnosis, the majority of patients had either refractory cytopenia of multilineage dysplasia (RCMD) (25%) or refractory anemia with excess blasts (RAEB) 1 or 2 (49%) and were INT-1 (37%) or INT-2/High risk (60%). Donor type was related donor (52%), matched unrelated (13%) and umbilical cord blood (35%). Half received myeloablative conditioning and Karnofsky Performance Status (KPS) > 80 in 95%. Results: (Table) Both higher blast percentage at HCT and high percentage of residual cytogenetically positive cells correlated with inferior overall survival as well as more frequent NRM. Relapse incidence was similar in those with blasts up to 10%. Percentage of abnormal metaphases was not predictive of relapse. Conditioning intensity was the only factor that impacted the 2 year relapse rate with decreased relapse seen with myeloablative conditioning. Conclusion: These data suggest that survival and relapse prediction are not improved by using the more stringent IPSS-R blast cutoff of < 2% versus <5% at HCT. Additionally, our data suggest that use of a disease burden measure as represented by % residual positive metaphases at HCT may serve as another predictor of outcome. Survival and NRM were worse with >10% blasts or > 50% residual positive metaphases. These patients require additional therapy or new strategies to improve post HCT outcomes. A refined measure of disease burden at HCT using both blast count and % residual abnormal metaphases may allow for more comprehensive prediction of post HCT outcomes in MDS. Disclosures: No relevant conflicts of interest to declare.

Assessment of Minimal Residual Disease in Multiple Myeloma patients undergoing Autologous Stem Cell Transplant using Multiparameter Flow Cytometry

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
NN Mostafa ◽  
WA El-Salakawy ◽  
HM Abdelbary ◽  
RA Radwan ◽  
RK Fathy ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Multiparameter Flow Cytometry ◽  
P Value ◽  
Cell Transplant ◽  
Post Transplant ◽  
Minimal Residual

Abstract BACKGROUND Multiple Myeloma (MM) is still considered an incurable relapsing disease, despite major advances in multidrug combinations, incorporation of autologous transplant and achieving higher rates of CR. This suggests persistent presence of residual disease, not detected by current techniques. Minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) is a powerful tool to quantitatively measure residual disease and allow tailoring of the management plan on individual basis. AIM To assess the value of MRD by MFC in determining the efficacy of treatment, monitoring depth of remission and predicting impending relapse. PATIENTS AND METHODS We included 33MM patients, who were candidates for ASCT in this prospective study. MFC (with a 0.01% limit of detection) on a BM aspirate obtained before transplant and at day 100 post-transplant, was used to measure MRD for all patients. Patients were then later assessed for progression 1-year post-transplant. RESULTS MRD status at 100 days post-transplant was strongly related to the risk of 1-year post-transplant progression (p-value 0.001), and by using a ROC curve, we found that MRD (%) at 100 days post-transplant can predict progression after 1 year with a best cutoff value ≥ 0.04 achieving a 75% sensitivity and 81.2% specificity. On dividing the patients according to their MRD status before and after transplant, group 3 who were MRD positive pre- and post-transplant, had a high risk of progression 1year post-transplant (p-value 0.003). The use of bortezomib-based regimens resulted in a deeper response and a more negative MRD pre-transplant (p-value 0.01), that was maintained post-transplant. Also, ASCT resulted in the development of deeper remission (p-value 0.004) and more MRD negativity (p-value 0.02). CONCLUSION we recommend the use of MRD by MFC as a powerful prognostic tool that should be incorporated in routine myeloma workup.

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