The Use of Day 14 Bone Marrow Characteristics in the Decision to Pursue a Second Course of Induction Chemotherapy in the Treatment of Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2596-2596
Author(s):  
Masumi Ueda ◽  
Hu Xie ◽  
Ravinder K Sandhu ◽  
Roland B. Walter ◽  
John M. Pagel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Blast Count ◽  
Pre Treatment ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract Abstract 2596 Background: Patients with acute myeloid leukemia (AML) receiving induction or salvage chemotherapy often undergo bone marrow evaluation around day 14 to determine early treatment response and guide decision-making regarding need for immediate re-induction therapy. However, the parameters that define whether or not to initiate such therapy are seemingly not always objective. Thus we sought to define what factors influence physicians' decisions to pursue a second course of induction chemotherapy in AML. Methods: We retrospectively reviewed 211 patients with newly diagnosed, relapsed, or refractory AML who received induction chemotherapy at the University of Washington /Fred Hutchinson Cancer Research Center from January 2008 to May 2012. 178 had a marrow aspirate and/or biopsy between days 13 to 17 after start of chemotherapy and were included in our “day 14” analysis. Bone marrows were assessed both morphologically and by multi-parameter flow cytometry (MFC). We used the Wilcoxon signed rank test and Fisher exact test to compare patient age, pre-treatment cytogenetics (SWOG criteria), newly diagnosed vs. relapsed or refractory AML, day 14 marrow cellularity, day 14 blast count by morphology or MFC, and induction regimen given on the first course (ara-C-containing vs. not) among patients who did and did not receive a second course of induction chemotherapy within 1 week of the “day 14” marrow. The second course could either be the same or different than the first course. Results: 81% of the 178 patients had fewer than 10% blasts by morphology and MFC on day 14. None of these patients received course 2 within 1 week. 34 patients (19%) had greater than 10% blasts on the day 14 marrow by morphology or flow cytometry, of whom 18 (53%; 95% confidence interval 36–70%) received course 2 prior to day 21 and 16 (47%; 95% CI 30–64%) patients did not. As the decision of whether or not to begin course 2 within 1 week varied once blasts counts were >10%, we analyzed the 34 patients with >10% blasts between day 13–17 to assess what factors influenced the decision to begin a second course of treatment. The median age in those who received and did not receive course 2 within 1 week was 60 and 50.5, respectively (p=0.269). The fraction of newly diagnosed AML (as opposed to relapsed or refractory disease) in the two groups was 83% and 69%, respectively (p=0.429). The blast count by morphology was 69.5% in those who did vs. 24.4% in those who did not receive a second course within 1 week of the day 14 marrow (p=0.001) and by flow cytometry were 63% and 10%, respectively (p<0.001). 12 out of 27 (44%; 95% confidence interval 26–63%) patients who received ara-C on course 1 (“higher intensity”) received course 2 within 1 week of the first vs. 6 of 7 who received a lower intensity regimen on course 1 (p=0.09). 56% of the 9 patients with unfavorable cytogenetics received a second course within 1 week, as did the only patient with favorable cytogenetics, and 50% of those with intermediate risk cytogenetics. 1 of the 4 patients with hypocellular marrows on day 14 received a second course within 1 week as did 4 of the 5 with normocellular and 10 of the 21 with hypercellular marrows. Conclusions: Although day 14 blast percentages were significantly higher among patients who received a second course of induction chemotherapy within 1 week of the day 14 marrow, 47% of patients with >10% blasts in a day 14 marrow and 56% who received a higher intensity regimen on course 1 did not begin a second course during the next week despite National Comprehensive Cancer Network (NCCN) guidelines that they do. We are studying whether this reflects objective patient and marrow characteristics, such as change in blast count from pre-treatment to day 14 marrow, or other more subjective factors in clinical practice. Disclosures: Becker: Sanofi: Research Funding.

scholarly journals Efficacy and Safety of Decitabine Combined with IA Regimen in the Treatment of Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2341-2341
Author(s):  
Lifen Kuang ◽  
Juan Li
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
High Risk Group ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Acute Myeloid

Abstract Objective: To evaluate the efficacy and safety of decitabine combined with IA regimen in the treatment of newly diagnosed acute myeloid leukemia. Methods: From September 1, 2013 to October 18, 2019, 164 newly diagnosed acute myeloid leukemia patients who received IA or decitabine combined with IA induction chemotherapy who were hospitalized in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University were enrolled. The efficacy and side effects of treatment were analyzed. Results: The complete remission rate of decitabine combined with IA regimen chemotherapy group (n=88) and IA regimen chemotherapy group (n=76) was 83.0% vs. 68.4% (P=0.029, Fig 1). Subgroup analysis (table 1) showed that age ≥40 years old, WBC＜10*10^9/L, Hb＞85g/L, PLT≥50*10^9/L, MCV≥98fL, ratio of bone marrow immature cells ≤45%, NCCN intermediate-risk or high-risk group, patients with FLT3ITD mutation had a higher CR rate in the decitabine combined with IA regimen group. Multivariate analysis showed that combined decitabine was an independent favorable factor affecting the CR rate (OR 3.559, 95% CI: 1.554-8.151, P=0.003). Compared with the IA group, patients in the decitabine combined with IA group took longer to rebuild the granule system (20 days vs 19 days, P=0.026), and the incidence of infection was higher (93.2% vs 78.8%, P=0.028) (table 2). Conclusion: Compared with the IA regimen, the decitabine combined with the IA regimen significantly improves the induction chemotherapy response rate of newly diagnosed non-M3 AML patients, especially for patients with the following characteristics: age ≥ 40 years old, WBC &lt;10*10^ 9/L, Hb＞85g/L, PLT≥50*10^9/L, MCV≥98fL, bone marrow immature cell proportion ≤45%, NCCN risk stratification medium-risk or high-risk group, FLT3ITD mutation. After combining with decitabine, the patient's granular bone marrow suppression increased. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Prospective Clinical Study of the Efficacy and Adverse Reactions of Azacitidine Combined with IA Regimen As the Induction Treatment of Newly Diagnosed AML

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4408-4408
Author(s):  
Lifen Kuang ◽  
Juan Li
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Acute Myeloid

Abstract Objective: This single-arm prospective research (ChiCTR2100044731) aimed to evaluate the efficacy and safety of azacitidine combined with IA regimen in the induction treatment of newly diagnosed acute myeloid leukemia (AML), with a view to further improving the efficacy of acute myeloid leukemia with poor prognosis. Methods: Newly diagnosed AML (non-M3) patients who received azacitidine combined with IA regimen induction chemotherapy in the Department of Hematology of the First Affiliated Hospital of Sun Yat-sen University from November 2019 to February 2021 were enrolled, and the efficacy and side effect were analyzed. Results: A total of 33 patients were enrolled. The median age of the enrolled patients was 43.36 years (17-63), including 16 males (48.5%) and 17 females (51.5%). According to NCCN risk stratification, there were 3 patients (9.1%) in the favor group (9.1%) ,13 cases (39.4%) in the intermediate group and 17 cases (51.5%) in the poor group.The CR rate of one cycle of azacitidine combined with IA regimen was 66.7%, with a PR rate of 12.1% and a NR rate of 21.2%. After propensity score matching with the newly diagnosed AML patients who received IA regimen as induction chemotherapy in our center, a paired study was carried out. The results showed that there was no significant difference between the 2 groups in the treatment CR rate (66.7% for azacitidine combined with IA vs 54.5% for IA, P=0.592, Fig1). Subgroup analysis (table 1) showed combination of azacitidine with IA significantly improved the CR rate of patients with a ratio of blasts in the bone marrow greater than 67% (83.3% vs 30.8%, P=0.014) and patients in the intermediate NCCN risk group (100.0% vs 37.5%, P=0.001).The duration of agranulocytosis in the azacitidine combined with IA chemotherapy group was longer than that in the IA group (21 days vs 19 days, P=0.045). There was no significant difference in the number of platelet transfusions and the number of red blood cell transfusions between the two groups, and there was no significant difference in the incidence of infection between the two groups (table 2). Conclusions: The remission rate of induction chemotherapy for azacitidine combined with IA regimen and IA regimen in newly diagnosed non-M3 AML patients is comparable. Patients with a ratio of immature cells in bone marrow greater than 67% and patients in the intermediate NCCN risk group may benefit from azacitidine combined with the IA regimen. The combination of azacitidine with IA regimen aggravated granular bone marrow suppression. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Clinical Impact of Different Levels of VEGF-C on Leukemic Blasts in the Bone Marrow and Peripheral Blood of Acute Myeloid Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1670-1670
Author(s):  
Sung-Eun Lee ◽  
Ji Yoon Lee ◽  
A-Reum Han ◽  
Woo-Sung Min ◽  
Heeje Kim
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Cancer Cells ◽  
Predictive Model ◽  
Induction Chemotherapy ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Acute Myeloid

Abstract Background: Vascular endothelial growth factor-C (VEGF-C) is a lymph-angiogenic growth factor and in general, transmits intracellular signals, resulting in cell proliferation and survival. Previous studies have reported that VEGF-C is important for cancer progression based on the autocrine VEGF-C loop promoting the invasion and metastasis of cancer cells as well as the spread of cancer cells by active recruitment of new lymphatics by tumor-derived VEGF-C. Acute myeloid leukemia (AML) blasts express VEGF-C and its receptors. A few studies demonstrated that high VEGF-C mRNA expression of AML blasts were related to increased in vitro and in vivo drug resistance and could predict adverse long-term outcomes. However, whether the expression of VEGF-C in the bone marrow (BM) and peripheral blood (PB) has a similar role in the pathophysiology of AML remains unclear. Methods: In this study, we analyzed plasma levels of VEGF-C in both BM and PB samples of AML patients. The levels of VEGF-C were measured using a commercially available ELISA in the newly diagnosed AML patients (58 in BM, 26 in PB), patients in complete remission (CR) (26 in BM, 20 in PB), and refractory/relapsed AML (15 in BM, 10 in PB). In addition, response after 1st induction chemotherapy was assessed in 67 evaluable patients and to create the predictive model for an achievement of CR, logistic regression was used after log transformation of VEGF-C levels. Results: In the BM of patients with newly diagnosed AML, the level of VEGF-C was 47.87 ± 12.4 pg/ml which was significantly lower than that of refractory/relapsed AML [518.3 ± 320.0 pg/ml (P=0.005)] but there was no difference, compared to that of patients in CR [44.57 ± 8.44 pg/ml (P = 0.865)]. In contrast no trend was observed in the PB samples. Next, to create the predictive model for an achievement of CR, sixty-seven evaluable patients who received standard induction chemotherapy were analyzed. Thirty-seven men and 30 women were included. With a median age of 49 years (range, 20-78), the distribution of favorable, intermediate-I, intermediate-II, and adverse cytogenetic risk (ELN) were 25%, 31%, 21%, and 22%, respectively. The patients with continuous values of Log10VEGF-C were divided into 2 groups (low vs. high levels) by a ROC curve analysis. Univariate analysis showed that high levels in BM samples were associated with achievement of CR after 1st induction chemotherapy. Ultimately, multivariate analyses revealed that low levels of Log10VEGF-C showed a trend for failure to achieve a response of CR (RR of 0.24, P = 0.065) and intermediate II/adverse cytogenetic risk was associated with a failure of CR, compared to favorable/intermediate I (RR of 0.21, P = 0.036). In contrast, in the PB samples, a low value of Log10VEGF-C was an independent factor for achievement of CR (RR of 28.7, P = 0.043). Conclusion: Our data demonstrate that the high VEGF-C level in the BM samples at diagnosis was associated with a trend toward higher CR rate and high VEGF-C level in the PB samples was significantly related to a failure of CR, suggesting discrepancy of the role of VEGF-C level in the BM and PB. Further studies on the different mechanism of the VEGF-C/VEGF-receptor pathway in the BM and PB are warranted. Disclosures No relevant conflicts of interest to declare.

scholarly journals Invasive Fungal Disease in Patients with Newly Diagnosed Acute Myeloid Leukemia

2021 ◽  
Vol 7 (9) ◽  
pp. 761
Author(s):  
Anastasia I. Wasylyshyn ◽  
Kathleen A. Linder ◽  
Carol A. Kauffman ◽  
Blair J. Richards ◽  
Stephen M. Maurer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Proportional Hazards ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Antifungal Prophylaxis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Acute Myeloid

This single-center retrospective study of invasive fungal disease (IFD) enrolled 251 adult patients undergoing induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) from 2014–2019. Patients had primary AML (n = 148, 59%); antecedent myelodysplastic syndrome (n = 76, 30%), or secondary AML (n = 27, 11%). Seventy-five patients (30%) received an allogeneic hematopoietic cell transplant within the first year after induction chemotherapy. Proven/probable IFD occurred in 17 patients (7%). Twelve of the 17 (71%) were mold infections, including aspergillosis (n = 6), fusariosis (n = 3), and mucomycosis (n = 3). Eight breakthrough IFD (B-IFD), seven of which were due to molds, occurred in patients taking antifungal prophylaxis. Patients with proven/probable IFD had a significantly greater number of cumulative neutropenic days than those without an IFD, HR = 1.038 (95% CI 1.018–1.059), p = 0.0001. By cause-specific proportional hazards regression, the risk for IFD increased by 3.8% for each day of neutropenia per 100 days of follow up. Relapsed/refractory AML significantly increased the risk for IFD, HR = 7.562 (2.585–22.123), p = 0.0002, and Kaplan-Meier analysis showed significantly higher mortality at 1 year in patients who developed a proven/probable IFD, p = 0.02. IFD remains an important problem among patients with AML despite the use of antifungal prophylaxis, and development of IFD is associated with increased mortality in these patients.

Intensively timed induction therapy followed by autologous or allogeneic bone marrow transplantation for children with acute myeloid leukemia or myelodysplastic syndrome: a Childrens Cancer Group pilot study.

1993 ◽  
Vol 11 (8) ◽  
pp. 1448-1457 ◽  
Author(s):  
W G Woods ◽  
N Kobrinsky ◽  
J Buckley ◽  
S Neudorf ◽  
J Sanders ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Cancer Group ◽  
Acute Myeloid

PURPOSE Childrens Cancer Group (CCG) protocol 2861 was designed to test the feasibility of aggressively timed induction therapy followed by autologous or allogeneic bone marrow transplantation (BMT) as the sole postremission therapy for newly diagnosed children with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). PATIENTS AND METHODS Between April 1988 and October 1989, 142 patients were eligible for study. All patients entered received a timing-intensive five-drug induction of dexamethasone, cytarabine (Ara-C), thioguanine, etoposide, and daunorubicin (DCTER) over 4 days with a second cycle administered after 6 days of rest, irrespective of hematologic status at that time. Most patients subsequently received a second two-cycle induction course. Those who achieved remission were eligible for bone marrow ablative therapy with busulfan and cyclophosphamide, followed by 4-hydroperoxy-cyclophosphamide (4-HC)-purged autologous or allogeneic BMT rescue. RESULTS One hundred eight (76%) patients achieved remission: 19 (13%) died of complications of the leukemia and/or chemotherapy, and 15 (11%) failed to achieve remission. Seventy-four patients subsequently underwent BMT with either autologous (n = 58) or allogeneic (n = 16) rescue. For patients who received autologous rescue with 4-HC-purged grafts, the actuarial disease-free survival (DFS) rate at 3 years from the day of transplant is 51%, compared with 55% for patients who received allogeneic grafts (P = .92). At 3 years, the overall actuarial survival rate for all 142 patients entered on this study is 45%, with an event-free survival (EFS) rate of 37%. Adverse prognostic factors for outcome included an elevated WBC count or the presence of CNS leukemia at the time of AML diagnosis. CONCLUSION Results suggest that aggressively timed induction therapy followed by marrow ablation and BMT rescue with either autologous or allogeneic grafts for children with newly diagnosed AML or MDS is both feasible and effective.

scholarly journals AML Subtype M5 Linked to Pulmonary Leukemic Infiltrates and Respiratory Failure and the Importance of Early Induction Chemotherapy

2018 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Yvonne Chu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Lung Tissue ◽  
Complete Resolution ◽  
Lung Biopsy ◽  
Myeloid Leukemia ◽  
Clinical Question ◽  
Newly Diagnosed ◽  
Acute Myeloid ◽  
Lung Infiltrates

Currently there are no practice guidelines for evaluating lung infiltrates in patients with newly diagnosed acute myeloid leukemia (AML). More specifically, it remains unclear if there is a need to obtain a lung tissue biopsy prior to the initiation of induction chemotherapy. This clinical question is particularly important in instances in which obtaining a lung tissue diagnosis can potentially delay anti-leukemic treatment.  Here we describe a case of such lung infiltrates in which a newly diagnosed AML patient underwent a diagnostic lung biopsy before receiving chemotherapy, was shown to have leukemic infiltration of lung tissue, and subsequently had complete resolution of lung infiltrates following initiation of chemotherapy.

scholarly journals Fatal Idiopathic Hyperammonemia after Induction Chemotherapy for Acute Myeloid Leukemia

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Christophe Angelo ◽  
Marie-Françoise Vincent ◽  
Mina Komuta ◽  
Philippe Hantson ◽  
Nicole Straetmans ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Care Management ◽  
Fatal Complication ◽  
Intensive Care Management ◽  
Brain Dead ◽  
Acute Myeloid

Idiopathic hyperammonemia is a rare but potentially fatal complication occurring in patients with acute leukemia or bone marrow transplantation. The role of some specific anticancer drugs may be discussed, but the etiology of hyperammonemia is often multifactorial. We report the case of a 40-year-old woman who developed fatal idiopathic hyperammonemia two weeks after induction chemotherapy with idarubicin-aracytine for acute myeloid leukemia. Despite intensive care management and extrarenal epuration, the patient was declared brain dead two days after hyperammonemia onset.

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