scholarly journals AML: Negative Prognostic Impact of Early Blast Persistence Can be Overcome By Subsequent Remission Induction

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1324-1324
Author(s):  
Jana Ihlow ◽  
Sophia Gross ◽  
Leonie Busack ◽  
Alma Herneth ◽  
Igor-Wolfgang Blau ◽  
...  
Keyword(s):  
Decision Making ◽  
Bone Marrow ◽  
Induction Therapy ◽  
Remission Induction ◽  
Prognostic Impact ◽  
First Line ◽  
Allogeneic Hsct ◽  
Entire Cohort ◽  
Remission Status

Introduction: In acute myeloid leukemia [AML] intensive treatment usually includes an interim bone marrow assessment in the context of the first induction chemotherapy cycle. Early blast clearance has been shown to predict for achievement of a complete remission [CR], which makes the interim bone marrow result a widely used additive for further therapy decision making. However, there is an ongoing debate on the prognostic role of early blast clearance (day 14 - 21) and consistent clarification of this issue is still lacking. Here, we provide monocentric data from a large intensively treated AML cohort addressing the prognostic impact of early remission status on long-term survival. Methods: Data of 1008 intensively treated AML patients who were diagnosed between 2000 and 2017 and aged between 18 and 86 years were retrieved from our local AML database. Evaluation of bone marrow aspirates and / or biopsies was conducted by cytologic, flow cytometric and histopathological methods. Remission status was determined in accordance with the European-Leukemia Net [ELN] criteria of 2017. Patients were grouped according to their remission status after induction 1 (day 14 - 21) and prior to further therapy (chemotherapy and / or allogeneic hematopoietic stem cell transplantation [HSCT]). Baseline characteristics of the two groups such as age, cytogenetic / molecular risk according to ELN 2010, performance score according to Eastern Cooperative Oncology Group [ECOG] and Charlson Comorbidity Index [CCI] were compared using chi-square test and Kruskal-Wallis H test followed by post-hoc testing. Overall- and relapse-free-survival [OS, RFS] were analyzed using Kaplan-Meier- and Cox regression models. Results: In 57 % (n = 572) of the entire cohort, complete / incomplete remission [CR / CRi] or at least morphologic leukemia free state [MLFS] were observed after the first cycle of induction therapy. Partial response [PR] was found in 19 % (n = 196) and persistent disease [PD] in 24 % (n = 240) of all patients. The three different groups (CR / CRi / MLFS vs. PR vs. PD) did not significantly differ in age, ECOG-score or CCI, but - as expected - substantially with regard to ELN risk classification. Of the entire cohort, 62 % (n = 626) received a double induction, 61 % (n = 617) consolidation chemotherapy and 47 % (n = 477) allogeneic HSCT as a part of first-line therapy. Prior to HSCT, 85 % (n = 406) of the patients were in first CR / CRi / MLFS. Amongst these 406 patients, 51 % (n = 243) had only achieved PR / PD in early bone marrow puncture on day 14 - 21 of induction therapy. 71 % of these patients (n = 173) were converted into CR / CRi / MLFS prior to HSCT by additional chemotherapy. Within the non-transplanted group, 58 of 130 patients (44 % with initial PR / PD) achieved CR / CRi / MLFS after an additional cycle of induction chemotherapy. Early blast persistence and refractory disease were generally associated with inferior OS as compared with blast clearance (p < 0.001). Interestingly, early PR lost its negative prognostic impact on survival after conversion into CR / CRi / MLFS by additional therapy prior to post-induction therapy. This could particularly be observed in patients undergoing HSCT, but also in non-transplanted patients receiving a second cycle of induction therapy. In patients without allogeneic HSCT, early PR with blast clearance beyond induction 1 resulted in impaired RFS (p = 0.045) but not OS, possibly due to the influence of subsequent salvage therapy. Early PD remained prognostically unfavorable for OS and RFS in both transplanted and non-transplanted patients even after subsequent conversion into CR / CRi / MLFS (p = 0.002 and p = 0.021). Conclusion: Our results show that the achievement of CR / CRi / MLFS prior to post-remission therapy overrides the negative impact of an early partial response on OS, irrespective of the favorable prognostic impact that early blast clearance generally has on OS. With regard to OS, our results suggest a predominant role of the final remission quality after induction therapy. However, the adverse impact of achieving no response at interim bone marrow assessment can apparently not be attenuated by a later remission induction. On the assumption that the final depth of remission after induction therapy is predictive for OS, MRD-guided decision making prior to consolidation treatment might further improve first-line AML therapy, particularly in the intermediate ELN risk group. Disclosures Bullinger: Abbvie: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Menarini: Honoraria; Janssen: Honoraria; Hexal: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Astellas: Honoraria; Amgen: Honoraria; Bayer: Other: Financing of scientific research; Seattle Genetics: Honoraria; Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria.

Prognostic Factors for Outcome of Patients Undergoing Allogeneic HSCT from Unrelated and Related Donors for AML and MDS: A Retrospective Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1147-1147
Author(s):  
Thorsten Graef ◽  
Matthias Vaupel ◽  
Roland Fenk ◽  
Leilani Ruf ◽  
Fabian Zohren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Prognostic Impact ◽  
Allogeneic Hsct ◽  
Remission Status ◽  
Unrelated Donors ◽  
One Year

Abstract PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for many patients with myeloid leukemia, especially in refractory or relapsed disease. To determine prognostic factors that correlate with outcomes after HSCT in adults with AML and MDS we analysed several clinical and haematological parameters. PATIENTS AND METHODS: In this unicenter retrospective study, we studied 120 adults who received allogeneic HSCT for AML (n=88) or MDS (n=32) between 1993 and 2003. The median age was 44 years (range 21–72), included were 59 male and 61 female patients. 42% of the patients were transplanted in first complete remission (CR1), 17% were transplanted in CR after salvage therapy and 41% were in relapse or refractory to induction or salvage therapy. The grafts consisted in 88 cases (73%) of PBSCT and in 32 cases of bone marrow, in 34% unrelated donors were used. The medium number of infused CD34+ cells was 5.51x106/kg. As conditioning regimen standard myeloablative therapies without (53%) or with (25%) TBI, or a non-myeloablative regimen including TBI (22%) were used. The prognostic impact for several groups with different clinical and hematological parameters were assessed by univariate and multivariate analyses using the Cox regression model. RESULTS: One-year and three-year probabilities of overall survival (OS) were 52% (48% to 57%) and 38% (36% to 43%). In univariate analysis, remission status and cGvHD were significantly associated with OS (CR vs. non-CR p=0.00001; cGvHD vs. non-cGvHD p=0.00001). Median OS for patients who underwent transplantation in CR were 2374 vs 180 days and for chronic GvHD 2374 vs 294 days. One-year and three-year probabilities of relapse were 30% (31% to 17%) and 31% (34% to 24%). CR, cGvHD and ablative regimens resulted in a lower relapse rate (p=0.00001; p=0.0002, p=0.028). One-year and three-year probabilities of transplant-related mortality (TRM) were 27% (28% to 30%) and 34% (32% to 40%). Extensive cGvHD, transplantion before 1997 and unrelated donor were significantly associated with higher TRM (p=0.03; p=0.04; p=0.03). Multivariate analysis was performed to test for the prognostic role of those factors that had achived a p-value of 0.25 or less in the Log-Rank test. For OS, sex, donor, tbi, remission status, and cGvHD and time from diagnosis to transplantation were included. For a better OS and lower RR especially the remission status and the occurrence of cGvHD were significant prognostic factors for the outcome after allogeneic transplantation (OS: p=0.0001, p=0.001; RR: p=0.0001, p= 0.001); sex and time from diagnosis to transplantation were also predictive for a better OS (p=0.007, p= 0.045) and the use of non-tbi based regimens resulted in a lower RR (p=0.006); for TRM, transplantions before 1997 and unrelated donors were detect as significant prognostic factors (p=0.027, p=0.033). CONCLUSION: Remission status at transplantation and the occurrence of cGvHD are the major prognostic factors for the outcome after allogeneic HSCT in AML and MDS. We therefore conclude that allogeneic stem cell transplantation should be performed early in haematological remission in patients with high-risk AML and MDS, if a suitable donor is available.

Study of Sequential Treatment of Newly Diagnosed De Novo AML Patients with DA and CAG Regimens as Remission Induction Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4630-4630
Author(s):  
Hui ping Sun ◽  
Wei Hong Liu ◽  
Jun min Li ◽  
Qiu sheng Chen ◽  
Yu Chen
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Peripheral Blood ◽  
De Novo ◽  
Classification Criteria ◽  
Sequential Treatment ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Fab Classification ◽  
De Novo Aml

Abstract Objectives To evaluate the efficacy and safety of sequential treatment of newly diagnosed de novo AML patients with DA and CAG regimens as induction therapy. Methods Those who were newly diagnosed as de novo AML (FAB classification criteria) were enrolled and DA regimen chemotherapy were administered. Bone marrow aspirates were performed and BM smears were examined at 48 hours since the end of chemotherapy. If severe hypocellularities were not achieved, the percentage of blasts in BM was between 20%–60% and peripheral WBC was in the range of (0.5–10) x109/L, the patients would receive CAG regimen therapy since 72 hours. Patients’ general status and the important parameters, such as peripheral blood count, liver function, renal function, thrombosis and hemostasis parameters were monitored throughout the course of the treatment and thereafter. When the clinical symptoms were relieved and peripheral blood counts returned to normal, or it was the end of the second or third week since the end of the CAG regimen, Bone marrow were examined again to evaluate the efficacy of the sequential therapy. Results 14 patients consisted of 9 male and 5 female patients were enrolled. Out of them, 2 were M1, 5 M2, 4 M4 and 3 M5 according to FAB classification criteria. Median of blasts in BM were 38.5%(20%–60%) before CAG regimen. Of the 14 patients, 10 reached CR, 2 PR and 2 NR. CR rate was 71.4% (10/14) and total response rate was 85.7%(12/14). Time to achieve CR was on 15th(14th–29th)day medianly since the end of the treatment. During the CAG therapy courses, the nadir of peripheral blood cell counts and the time when it occurred were as follows: WBC 1.0(0.2–3.5)(x109/L),10(1–23)(d); Hb 57.5(44–69) (g/L), 10(1–27)(d)and PLT 11.5(10–65)(x109/L), 12(3–23)(d), respectively. Neutropenia (WBC<1.0x109/L) and thrombocytopenia (PLT<20.0x109/L) were lasted for 0(0–24) and 11(0–21)days, respectively. Median units of transfusions of platelets and red blood cells required by each patient were 3(0–10)(u) and 4(0–12)(u), respectively. The most commonly observed side effect of the regimen was bone marrow proliferation inhibition. Infections, usually respiratoy tract infections, were the second. However, sepsis was rare, which appeared in 1 out of 14 patients. Conclusions DA and CAG regimens sequential treatment as remission induction chemotherapy in patients with newly diagnose de novo AML was highly effective and well tolerated. It would be beneficial for those who might not be sensitive enough to DA regimen chemotherapy only.

High Remission Rates and Long-Term Survival in a High Percentage of Patients Achieved by Intensive Chemotherapy for AML and Further Improvement of Supportive Care.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1052-1052 ◽  
Author(s):  
Taiichi Kyo ◽  
Akiko Kimura ◽  
Kouhei Kyo ◽  
Noriaki Yoshida ◽  
Hideki Asaoku ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Induction Therapy ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Colony Stimulating Factor ◽  
Single Institution ◽  
Postremission Therapy ◽  
Stimulating Factor

Abstract Abstract 1052 Poster Board I-74 Background: Until recently, intensive chemotherapy for acute myeloid leukemia (AML) did not necessarily lead to high success rates, partly because of deaths from infections due to the associated long-term neutropenic phase. However, the advent of effective antifungal agents or the use of granulocyte colony-stimulating factor (G-CSF) or macrophage colony-stimulating factor (M-CSF) has definitely reduced deaths from chemotherapy and has improved the results of treatment with intensive chemotherapy also in elderly patients. Objectives: The complete remission rate after remission induction therapy and the event-free survival (EFS) after postremission therapy were investigated in 165 patients (99 men and 66 women) with untreated de novo AML (excluding subtype M3) who were consecutively registered in a single institution between March 2001 and March 2009. The patients' ages ranged from 16 to 94 years (median: 59 years). There were 3 patients with M0, 18 patients with M1, 25 patients with M2, 25 patients with t(8;21), 35 patients with M4, 12 patients with M4Eo, 35 patients with M5, 10 patients with M6, and 2 patients with M7. Methods: Remission induction therapy consisted of 10 days of behenoyl-ara-C (BHAC) at 350 mg/m2 (300 mg/m2 for patients 70 years or older) and 4 days of idarubicin (IDA) at 12 mg/m2 (10 mg/m2 for 70 years or older). Further, if bone marrow examination revealed 5% or more residual blast cells on day 15, etoposide was additionally administered at a dose of 100 mg/m2 for 4 days. The efficacy of the remission induction therapy was evaluated after 1 course of treatment. The patients who had achieved remission underwent 9 courses of postremission therapy, which lasted 11 months. The details are omitted, but therapy with high-dose (2 g/m2 [1 g/m2 for patients 60 years or older]) cytarabine (HDAC)×10 plus 7 mg/m2 of mitoxantrone (MIT) ×3 was performed during the 1st and 9th courses. No HDAC was performed on the elderly aged above 75 years old. The intensive therapy with Aclarubicin (ACR) of 20 mg/body for 14 days and the maintenance therapy with a combination of BHAC 350 mg/m2×4 with ACR or IDA were repeated alternately every 6 weeks. Chemotherapies other than remission induction therapy and HDAC were performed in an outpatient clinic, and if the patients with the WBC decreasing to 1000/mm3 were hospitalized in the biological clean room. M-CS was administered for 7 days after the day following the end of chemotherapy, and subsequently G-CSF was administered until the WBC becomes to be 1000/mm3. Results: Complete remission (CR) was achieved in 143 of the 165 patients overall (86.7%), 113 of the 123 patients 69 years or younger (92.7%), and 29 of the 42 patients 70 years or older (69.1%). During the remission induction therapy, death occurred in 6 of the 165 patients overall (3.6%), 2 of the 123 patients 69 years or younger (1.6%), and 4 of the 42 patients 70 years or older (9.5%). The EFS in patients with CR was 61.5% at 8 years in patients 69 years or younger, while it was 26.9% at 5 years in patients 70 years or older. There was only a case of death due to chemotherapy during postremission therapy. Seven patients underwent bone marrow transplantation during the first remission, and 6 of these patients have been enjoying EFS. Conclusion: Improvement in supportive care has enabled safe intensive chemotherapy. The patients with good or intermediate prognosis were clearly improved by the present preliminary treatment at a single institution, but the patients with poor prognosis still highly require bone marrow transplantation in the future. Disclosures: No relevant conflicts of interest to declare.

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2637-2644 ◽  
Author(s):  
Teresa Padró ◽  
Sandra Ruiz ◽  
Ralf Bieker ◽  
Horst Bürger ◽  
Martin Steins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Microvessel Density ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Bone Marrow Biopsies ◽  
Acute Myeloid

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (×500 field, 0.126 mm2) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/×500 field vs 11.2 (10.0-12.0)/×500 field, respectively (P < .001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P < .001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with ≥ 5% residual blasts (P < .001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML.

scholarly journals Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information

2020 ◽  
Author(s):  
Harald Hugenschmidt ◽  
Knut Jørgen Labori ◽  
Cathrine Brunborg ◽  
Caroline Sophie Verbeke ◽  
Lars Thomas Seeberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Advanced Disease ◽  
Pancreatic Disease ◽  
Benign Disease ◽  
Tumour Cells ◽  
Prognostic Impact ◽  
Periampullary Carcinoma ◽  
Cox Regression Analysis ◽  
Entire Cohort

Abstract Background: Pancreatic and periampullary carcinoma are aggressive tumours where preoperative assessment is challenging. Disseminated tumour cells (DTC) in the bone marrow (BM) are associated with impaired prognosis in a variety of epithelial cancers. In a cohort of patients with presumed resectable pancreatic and periampullary carcinoma, we evaluated the frequency and the potential prognostic impact of the preoperative presence of DTC, defined as cytokeratin-positive cells detected by immunocytochemistry (ICC).Methods: Preoperative BMsamples from 242 patients selected for surgical resection of presumed resectable pancreatic and periampullary carcinoma from 09/2009 to 12/2014, were analysed for presence of CK-positive cells by ICC. The median observation time was 21.5 months. Overall survival (OS) and disease-free survival (DFS) were calculated by Kaplan-Meier and Cox regression analysis.Results: Successful resections of malignant tumours were performed in 179 of the cases, 30 patients resected had benign pancreatic disease based on postoperative histology, and 33 were deemed inoperable intraoperatively due to advanced disease. Overall survival for patients with resected carcinoma was 21.1 months (95% CI: 18.0-24.1), for those with benign disease OS was 101 months (95% CI: 69.4-132) and for those with advanced disease OS was 8.8 months (95% CI: 4.3-13.3). The frequency of CK-positive cells was 6/168 (3.6%) in resected malignant cases, 2/31 (6.5%) in advanced disease and 4/29 (13.8%) in benign disease. The presence of CK-positive cells was not correlated to OS or DFS, neither in the entire cohort nor in the subgroup negative for circulating tumour cells (CTC). Conclusions: The results indicate that CK-positive cells may be present in both patients with malignant and benign diseases of the pancreas. Detection of CK-positive cells was not associated with differences in prognosis for the entire cohort or any of the subgroups analysed.Trial registration: clinicaltrials.gov (NCT01919151)

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2637-2644 ◽  
Author(s):  
Teresa Padró ◽  
Sandra Ruiz ◽  
Ralf Bieker ◽  
Horst Bürger ◽  
Martin Steins ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Microvessel Density ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Bone Marrow Biopsies ◽  
Acute Myeloid

Abstract The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (×500 field, 0.126 mm2) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/×500 field vs 11.2 (10.0-12.0)/×500 field, respectively (P &lt; .001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P &lt; .001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with ≥ 5% residual blasts (P &lt; .001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML.

Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 43-47 ◽  
Author(s):  
John T. Sandlund ◽  
Patricia L. Harrison ◽  
Gaston Rivera ◽  
Frederick G. Behm ◽  
David Head ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Treatment Protocol ◽  
Cell Lineage ◽  
Remission Induction ◽  
Prognostic Impact ◽  
Dna Index ◽  
Risk Patients

Abstract We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (± 1 day) and 218 on days 22 to 25 (± 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (≥ 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% ± 6%) or on days 22 to 25 (4% ± 3%) as compared to those without lymphoblasts on these dates (78% ± 2% and 76% ± 2%, respectively, P &lt; .001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% ± 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P &lt; .001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.

Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: Utility of day 6 bone marrow biopsy

1983 ◽  
Vol 7 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Harvey Preisler ◽  
Maurice Barcos ◽  
Peter Reese ◽  
Roger L. Priore ◽  
Lillian Pothier
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
Bone Marrow Biopsy ◽  
Induction Therapy ◽  
Lymphocytic Leukemia ◽  
Remission Induction

scholarly journals The Prognostic Significance of Minimal Residual Disease and Possibility of Its Correction in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5751-5751
Author(s):  
Andrey Garifullin ◽  
Sergei Voloshin ◽  
Alexey Kuvshinov ◽  
Anastasiya Kuzyaeva ◽  
Alexander Sсhmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Induction Therapy ◽  
Residual Disease ◽  
Pet Ct ◽  
Minimal Residual

Abstract Introduction. Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients, the optimal methodology to assess MRD is not clear. The results of previous studies demonstrated the potential of multiparameter flow cytometry (MFC) and (PET-CT) in evaluation of MRD in MM. MRD monitoring should be applied in prospective clinical trials to compare and evaluate the efficacy of different treatment strategies, particularly in the consolidation and maintenance settings. The impact of MRD negativity is important, but further studies are needed to quantify the pharmacoeconomic and quality-of-life differences between early and delayed transplant strategies. Therefore, with the currently available evidence, upfront autologous stem cell transplantation (ASCT) is standard of care regardless of MRD status. Aim. We are aiming to determine the role of MRD and role of autologous stem cells transplantation in MM. Materials and methods. We`ve recently started a prospective one-center pilot study in subjects with MM. We analyzed 18 transplant-eligible patients with MM (the median age is 57 years, a male/female ratio is 3.5:1).The induction therapy Bortezomib-based only regimens was used in 12/18 (67%) patients, combination of Bortezomib-Immunomodulator-based regimens - in 6/18 (33%). High dose therapy (Mel200) and ASCT is carried out on 100% patients. The standard risk was established on 15 patients, 1 patient has an intermediate risk and 2 patients have high risk according to mSMART 2.0 stratification. The MFC MRD status of bone marrow was evaluated after 4-6 cycles of induction therapy and after ASCT on 5-color flow cytometry with use anti- CD38, CD138, CD45, CD19, CD20, CD27, CD56 and CD117 antibodies. We were based on two levels: MFC MRD- (<10-4) and MFC MRD- (<10-5) for assessing the significance of factors that affect MRD and for identifying the prognostic potential of MRD-negative status. The evaluation of MRD was carried out by genetic (cytogenetic and FISH) analysis of bone marrow plasma cells and PET-CT with 18-FDG before ASCT and on 100 day post ASCT. The results. The MFC MRD- (<10-4) before carrying out an ASCT reached 22.2% (4/18), the MFC MRD- (<10-5) - 0% and was not depended on the variant of pre-transplantation regimen. After the ASCT had been carried out there was a tendency to decrease the tumor burden in bone marrow from 0.65% to 0.1% and to increase the frequency of MFC MRD- (<10-4) status to 44.4% (8/18), of which MFC MRD- (<10-5) was 16.7% (3/18). MRD status was determined before ASCT and after ASCT by MFC and FISH in patients with high risk. The use of maintenance therapy with bortezomib (n = 5) or lenalidomide (n = 13) did not increase the frequency of MRD status. The PFS median in MFC MRD+ (>10-4) group was 23 months, in the MFC MRD- (<10-4) was not achieved; 2-year PFS was 43% and 100%, respectively (p=.04) We compared PFC between MFC MRD+ (>10-4) before ASCT (n = 4) and MFC MRD- (<10-4) after ASCT (n = 6) to assess the effect of ASCT in MM. The median PFS was not reached in both groups; 2-year PFS was 67% and 100%, respectively. The reliable difference between PFS in MFC MRD- (10-4-10-5) group and MFC MRD- (<10-5) was absent: the median of PFS was not achieved in both groups. PET-CT has been tested on 15 patients, PET-CT- response was achieved in 53% (8/15) patients. The PFS median in PET-CT+ group and PET-CT- group was not achieved. The 2-year PFS was higher in PET-CT+ group then PET-CT- probably due to patients with MFC MRD-. The 2-year PFS in «MFC MRD-PET-CT-» group was 100% to 55% in other patients. Conclusion. Carrying out ASCT demonstrated a tendency to increase the percentage of MFC MRD negative responses and improvement of PFS. The use of MFC in evaluation of MRD should be complemented with PET-CT and genetic methods for further analysis of the MFC MRD role status on MM patients. Disclosures No relevant conflicts of interest to declare.

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