P49.01 Drug Holiday Based on Minimal Residual Disease Status After Local Therapy Following EGFR-TKI Treatment for Patients With Advanced NSCLC

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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Early lymphocyte recovery (ELR) impact on disease outcome following autologous hematopoietic stem cell transplantation (HDT/ASCT) for multiple myeloma (MM) in the era of novel agents.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e19539 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e19539-e19539

Author(s):

Jeremy Scott McDuffie ◽

Bipin N. Savani ◽

Wichai Chinratanalab ◽

Stacey Goodman ◽

John P. Greer ◽

...

Keyword(s):

Minimal Residual Disease ◽

Residual Disease ◽

Disease Status ◽

Novel Agents ◽

Disease Outcome ◽

Disease Stage ◽

Response Criteria ◽

Hematopoietic Stem ◽

Significant Difference ◽

Minimal Residual

e19539 Background: Absolute lymphocyte count (ALC) > 500 cells/ µL on day 15 (ELR+) after HDT/ASCT, has been reported to be an independent prognostic indicator, for improved OS and PFS in patients with MM. Novel agents (immunomodulatory drugs (IMiDs) and proteasome inhibitors), mediate there effect through T-cell stimulation, NK cell activation, anti-proliferation, and are now main stay of therapy for MM. We sought to determine their effects on ELR, and correlated to disease outcome. Methods: A retrospective review of all MM patients seen at our institution undergoing HDT/ASCT from January 2008 to December 2012 was performed. Patients were identified from our CIBMTR database. ALC was determined pre-HDT/ASCT (T1), on day15 (T2) and d30 (T3) post-HDC/ASCT. No restrictions on inclusion were made based upon the International Myeloma Working Group response criteria. All had novel agents as part of their initial induction regimen. Disease response was determined by standard clinical and laboratory CIBMTR response criteria, and minimal residual disease status (MRD) by multiparameter flow cytometry. Results: In our study (n= 184), 52/184 patients had ELR+ while 132/184 had ALC < 500 cells/mL (ELR-) at T2. 21% received IMiDs, 33% proteasome inhibitor and 46% combination therapies. 52% of the ELR+ patients were MRD negative (-) at T1, and improved to 74% and 89% at D100, and 1 year post-HDC/ASCT respectively. Similarly 63%, 70%, and 80% of the ELR- patients, were MRD (-) at similar time-points. Chi squared analysis showed no significant difference in rates of MRD (-) based on ELR. ELR also had no impact on disease status as determined by CIBMTR response criteria, or 1 year PFS and OS (p = 0.383), (p = 0.577) respectively. Multivariate analyses, using cox-regression showed no impact of ALC at T1, T2, T3, age, sex, race, cytogenetic risk, or disease stage on disease outcome. Conclusions: Novel agents improve disease control independent of ELR following HDC/ASCT. Understanding their biologic effect on immune-reconstitution will provide a platform for adoptive immunotherapy to better target minimal residual disease.

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Minimal residual disease status in pre-B acute lymphoblastic leukemia patients after chemotherapy and bone marrow transplantation: Assessment of the anti-leukemic effects of chemotherapy and BMT

Leukemia Research ◽

10.1016/0145-2126(93)90073-t ◽

1993 ◽

Vol 17 (8) ◽

pp. 677-684 ◽

Cited By ~ 4

Author(s):

Hitoshi Kiyoi ◽

Tomoki Naoe ◽

Tatsuya Yamauchi ◽

Hisashi Fukatani ◽

Kazuaki Kubo ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Bone Marrow Transplantation ◽

Minimal Residual Disease ◽

Marrow Transplantation ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Disease Status ◽

Minimal Residual

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Prognostic value of minimal residual disease before allogeneic hematopoietic stem cell transplantation in patients with acute leukemia

Hematology and Transfusiology ◽

10.35754/0234-5730-2021-66-4-539-555 ◽

2021 ◽

Vol 66 (4) ◽

pp. 539-555

Author(s):

Z. V. Konova ◽

E. N. Parovichnikova ◽

I. V. Galtseva ◽

M. Yu. Drokov ◽

Yu. O. Davydova ◽

...

Keyword(s):

Acute Leukemia ◽

Minimal Residual Disease ◽

Prognostic Value ◽

Residual Disease ◽

Disease Status ◽

Long Term Results ◽

Disease Relapse ◽

Hematopoietic Stem ◽

Post Transplant ◽

Minimal Residual

Introduction. One of the main causes of treatment failure after allogeneic hematopoietic stem cells transplantation (alloHSCT) for acute leukemia (AL) is disease relapse. In recent years, multiparameter fl ow cytometry (MPC) has been widely used to detect minimal residual disease (MRD) because of its capacity to identify patients with a high risk of relapse due to availability and the ability to obtain results in a timely manner.Aim — to evaluate the prognostic value of MRD status before allo-HSCT and the effect of donor type and conditioning intensity on long-term results of allo-HSCT of MOB-positive patients.Patients and methods. The analysis included 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL) who underwent allo-HSCT between September 2015 and June 2020. All patients were in complete morphological remission before allo-HSCT. At the time of allo-HSCT 91 patients with AML and 37 patients with ALL were in the first complete remission (CR), in their second and more than two CRs were 16 and 26 patients, respectively. The median follow-up was 18 (1.5–48) months for AML and 14 (1.8–60.1) months for ALL. Immunophenotypic study was performed before allo-HSCT. MRD was detected using a combination of the “different from normal” method and the search for cells with a leukemia-associated immunophenotype.Results. The disease status at the time of transplantation and the presence of MRD before allo-HSCT were independent factors infl uencing the probability of relapse (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304) and post-transplant mortality (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304). In univariate analysis, the relapse-free survival of MRD+ patients with AL in the first CR was significantly worse than in MRD– (AML: 23 % versus 57 %, p < 0.0001, ALL: 34 % versus 61.7 %, p = 0.0484), and the probability of relapse in MRD+ patients was significantly higher (AML: 75 % versus 12 %, p < 0.0001, ALL: 57 % versus 7 %, p = 0.0072). Pre-transplant MRD status was not prognostically significant for AL-patients in the second and third remission. The development of chronic GVHD reduces post-transplant mortality if it does not require systemic therapy with glucocorticosteroids (HR = 0.006, 95% CI: 0.008–0.446).Conclusion. Testing for MRD of patients with AL in the first CR before allo-HSCT is necessary for risk stratification and identification of patients who will need preventive post-transplant therapy in order to prevent disease relapse.

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