A New Predictive and Prognostic Marker for De Novo AML: Peripheral Blood CD34 (pCD34) Count at Recovery Following Remission Induction (RI) Therapy (Supp. by Ankara University-2003-0809114).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4517-4517
Author(s):  
Mutlu Arat ◽  
Pervin Topcuoglu ◽  
Meltem K. Yuksel ◽  
Klara Dalva ◽  
Gulhis Gultekin ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Cell Count ◽  
Prognostic Marker ◽  
De Novo ◽  
Negative Impact ◽  
Recovery Period ◽  
Remission Induction ◽  
Incidence And Mortality ◽  
De Novo Aml ◽  
Cd34 Expression

Abstract In EORTC-LCG AML-10 study patients with low CD34 mobilization profile showed a better outcome (Leukemia,2003,17:60-7). We hypothesized that patients with low pCD34 at the recovery period after RI therapy with de novo AML should have a better clinical outcome or vice versa and launched this prospective study. Between Jan 2002 and Oct 2004, 40 patients with AML (median age: 40 yrs, 17–60; 22M/18F) were enrolled to this study. Using flow cytometrical method CD34-expressing cells were measured in peripheral venous blood samples once WBC was between 1x10e9/L to 3x10e9/L at the recovery period after first RI therapy. Results: The median time for estimation of pCD34 was 23 days (7–35) after RI. The pCD34 cell count was lower in patients responding to first RI therapy (12x10e6/L vs 68x10e6/L, p=0.011). We observed a weak, but statistically significant positive correlation between CD34 expression of the blasts at diagnosis and pCD34 at recovery period (p=0.048, r2:0.322). We could not show any significant negative impact of CD34 expression of the blasts at diagnosis and response to first RI (p=0.059). Only two of 8 patients not responding to the 1st RI achieved a complete remission after re-induction. The two-year probability of OS, LFS, relapse incidence and mortality rates were 47.1%, 37.2%, 55% and 42.5%, respectively (fig 1,2). If we set up a cut-off value of 18x10e6/L for pCD34, we did not observe any impact of pCD34 on relapse incidence but the mortality rate was significantly increased in patients with high CD34+ cell count (p=0.025). Conclusion: We were able to show a positive impact of pCD34 estimations after first RI in AML patients on both remission and mortality rate. AML Patients with lower pCD34 after 1st RI tends to have a higher hematological remission rate and lower mortality. This impact of pCD34 as a predictive and prognostic marker in AML should be verified in large cohorts using multivariate analysis. Table 1: Distribution of risk factors at diagnosis according RI response Variables 1stCRafter1stRI (n=32 ) NoCR after 1stRI (n=8 ) P *p<0.05; Abbr: NS: Non-Significant; ND: Not-Done pCD34 (x10e6/L) 12.4 (0–268) 68.6 (4.4–3820) 0.011* CD34 expr at dx 12% (0%–94%) 44% (9–89) 0.059 Age, years 38.5 (17–57) 43 (20–60) NS WBC at dx (x10e9/L) 11.85 (0.7–175.0) 5.10 (2.7–114.7) 0.934 EM involvement (Y/N) 7/25 0/8 NS Table 2: The outcome of AML patients according to median pCD34 at recovery Variables pCD34<Med 18x10e6/kg (n=20 ) pCD34 ≥ Med 18x10.6/kg (n=20) p CR1 (Y/N) after 1st RI 19/1 13/7 0.044* Relapse incidence 44% 54.5% NS Mortality rate 25% 60% 0.025* DFS 46.19%±12.6% 29.2%±10.4 NS OS 64.95%±13.2% 35.6%±11.3 NS Figure Figure

Timed Sequential Induction Therapy with Cytarabine and Mitoxantrone In Acute Myeloid Leukemia (AML): A Well-Tolerated Regimen with High Response Rates In Older Patients and Transformed AML.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1068-1068
Author(s):  
Sheena Sahota ◽  
Melissa L Larson ◽  
Margaret C Keller ◽  
Jamile M. Shammo ◽  
Allison Zindell ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Older Patients ◽  
De Novo ◽  
Response Rates ◽  
High Response ◽  
Remission Induction ◽  
High Dose ◽  
Remission Duration ◽  
Induction Regimen ◽  
De Novo Aml

Abstract Abstract 1068 Background: Patients with AML who are eligible for chemotherapy are traditionally treated with infusional cytarabine and an anthracycline. CR rates with this combination have been approximately 50–60% with an induction mortality of 10–25%. However, this treatment is less effective in older patients in terms of CR attainment, remission duration, and overall survival. We present a retrospective analysis of an induction regimen that was designed based on the concept of timed sequential therapy. An initial pulse of chemotherapy is administered to eradicate cells in S phase. This is followed by a rest period during which previously quiescent cells that enter the cell cycle can be targeted by a second pulse of chemotherapy. The regimen incorporates high dose cytarabine, which has been shown to improve remission duration when used in induction, and dose-intensified anthracycline therapy, which has been shown to improve outcomes in younger patients. This report highlights the responses and tolerability of the study regimen, particularly in elderly patients and patients with prior myelodysplastic syndrome (MDS). Patients and Methods: One hundred sixty six patients were treated with timed sequential chemotherapy from 1998–2009. The treatment consisted of two doses of cytarabine 2 gm/m2 IVPB over 3 hours administered 12 hours apart followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Data on pre-therapy cytogenetics and MDS was collected for each patient. Remission status was assigned per the IWG response criteria for AML. Results: Median age of the patients was 54.5 years (range 17–85). There were eighty males and eighty-six females. Out of 166 patients, 11 (6.6%) patients had favorable, 83 (50%) had intermediate, and 72 (43.4%) had unfavorable karyotypes. One-third of the patients (57 pts) had AML transformed from MDS. The overall response rate (ORR: CR+CRi+CRp) for all patients was 69.9%. In patients who had de novo AML, the ORR was 79.8%, regardless of age. Patients over age 60 with de novo AML had an ORR of 74%. For those patients under the age of 60, the ORR was 82%. The ORR for patients with transformed AML was 52.6% (53% in pts over age 60, 52% in pts less than 60). The 30 day mortality rate was 3.4% (6/166). Five of the six patients who died had an unfavorable karyotype with 2 patients having therapy-related AML. The 30 day mortality for patients older than 60 was 3.3% (2/61) and for all patients was 3.6% (6/166). The 60 day mortality rate in all patients was 10.8% (18/166). Of the additional 12 patients, seven died from progressive disease and only 3 died of suspected therapy-related complications. Grade 3/4 hematologic toxicities were the most common adverse events seen. Conclusion: This is a convenient, 2-day induction regimen that is well-tolerated with comparatively low 30 and 60 day mortality and high response rates in older patients and those patients with AML transformed from MDS. This would be an excellent initial regimen for remission induction in a select population of patients in whom novel consolidation or maintenance therapies can be incorporated to further improve outcome. Disclosures: No relevant conflicts of interest to declare.

Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy.

1997 ◽  
Vol 15 (6) ◽  
pp. 2262-2268 ◽  
Author(s):  
M Wetzler ◽  
M R Baer ◽  
S H Bernstein ◽  
L Blumenson ◽  
C Stewart ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Prognostic Significance ◽  
Poor Response ◽  
Significant Difference ◽  
De Novo Aml ◽  
Cd34 Expression ◽  
Acute Myeloid

PURPOSE c-mpl, the human homolog of v-mpl, is the receptor for thrombopoietin. Given that c-mpl expression carries an adverse prognosis in myelodysplastic syndrome and given the prognostic significance of expression of other growth factor receptors in other diseases, we attempted to determine whether c-mp/mRNA expression is a prognostic factor in acute myeloid leukemia (AML). PATIENTS AND METHODS We analyzed bone marrow samples from 45 newly diagnosed AML patients by reverse-transcription polymerase chain reaction. RESULTS Samples from 27 patients (60%) expressed c-mpl mRNA (c-mpl+); their clinical and laboratory features were compared with those of the 18 patients without detectable levels of c-mpl(c-mpl-). No significant differences in age, sex, leukocyte count, French-American-British subtype, or karyotype group were found. c-mpl+ patients more commonly had secondary AML (41% v 11%; P = .046) and more commonly expressed CD34 (67% v 12%; P = .0004). There was no significant difference in complete remission (CR) rate. However, c-mpl+ patients had shorter CR durations (P = .008; median, 6.0 v > 17.0 months). This was true when only de novo AML patients were considered and when controlling for age, cytogenetics, or CD34 expression. There was a trend toward shorter survival in c-mpl+ patients (P = .058; median, 7.8 v 9.0 months). CONCLUSION These data suggest that c-mpl expression is an adverse prognostic factor for treatment outcome in adult AML that must be considered in the analysis of clinical studies using thrombopoietin in AML.

Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3727-3732 ◽  
Author(s):  
Uma H. Athale ◽  
Bassem I. Razzouk ◽  
Susana C. Raimondi ◽  
Xin Tong ◽  
Frederick G. Behm ◽  
...  
Keyword(s):  
Down Syndrome ◽  
De Novo ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Transplantation ◽  
Remission Induction ◽  
Allogeneic Bone ◽  
Acute Megakaryoblastic Leukemia ◽  
Free Survival ◽  
Megakaryoblastic Leukemia ◽  
De Novo Aml

To describe the clinical and biologic features of pediatric acute megakaryoblastic leukemia (AMKL) and to identify prognostic factors, experience at St Jude Children's Research Hospital was reviewed. Of 281 patients with acute myeloid leukemia treated over a 14-year period, 41 (14.6%) had a diagnosis of AMKL. Six patients had Down syndrome and AMKL, 6 had secondary AMKL, and 29 had de novo AMKL. The median age of the 22 boys and 19 girls was 23.9 months (range, 6.7-208.9 months). The rate of remission induction was 60.5%, with a 48% rate of subsequent relapse. Patients with Down syndrome had a significantly higher 2-year event-free survival (EFS) estimate (83%) than did other patients with de novo AMKL (14%) or with secondary AMKL (20%;P ≤ .038). Among patients who had de novo AMKL without Down syndrome, 2-year EFS was significantly higher after allogeneic bone marrow transplantation (26%) than after chemotherapy alone (0%;P = .019) and significantly higher when performed during remission (46%) than when performed during persistent disease (0%;P = .019). The 5-year survival estimates were significantly lower for de novo AMKL (10%) than for other forms of de novo AML (42%; P &lt; .001). Treatment outcome is very poor for patients with AMKL in the absence of Down syndrome. Remission induction is the most important prognostic factor. Allogeneic transplantation during remission offers the best chance of cure; in the absence of remission, transplantation offers no advantage over chemotherapy alone.

The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2137-2145 ◽  
Author(s):  
Sabine Kayser ◽  
Konstanze Döhner ◽  
Jürgen Krauter ◽  
Claus-Henning Köhne ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
De Novo ◽  
Negative Impact ◽  
Primary Malignancy ◽  
De Novo Aml ◽  
The Impact ◽  
Acute Myeloid

Abstract To study the characteristics and clinical impact of therapy-related acute myeloid leukemia (t-AML). 200 patients (7.0%) had t-AML and 2653 de novo AML (93%). Patients with t-AML were older (P < .0001) and they had lower white blood counts (P = .003) compared with de novo AML patients; t-AML patients had abnormal cytogenetics more frequently, with overrepresentation of 11q23 translocations as well as adverse cytogenetics, including complex and monosomal karyotypes, and with underrepresentation of intermediate-risk karyotypes (P < .0001); t-AML patients had NPM1 mutations (P < .0001) and FLT3 internal tandem duplications (P = .0005) less frequently. Younger age at diagnosis of primary malignancy and treatment with intercalating agents as well as topoisomerase II inhibitors were associated with shorter latency periods to the occurrence of t-AML. In multivariable analyses, t-AML was an adverse prognostic factor for death in complete remission but not relapse in younger intensively treated patients (P < .0001 and P = .39, respectively), relapse but not death in complete remission in older, less intensively treated patients (P = .02 and P = .22, respectively) and overall survival in younger intensively treated patients (P = .01). In more intensively treated younger adults, treatment-related toxicity had a major negative impact on outcome, possibly reflecting cumulative toxicity of cancer treatment.

Outcomes in CCG-2961, a Children’s Cancer Group Phase III Trial for Untreated Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 169-169 ◽  
Author(s):  
Beverly J. Lange ◽  
Franklin O. Smith ◽  
Patricia A. Dinndorf ◽  
Carola A.S. Arndt ◽  
Dorothy R. Barnard ◽  
...  
Keyword(s):  
De Novo ◽  
Interleukin 2 ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Remission Induction ◽  
High Dose ◽  
Free Survival ◽  
Cancer Group ◽  
De Novo Aml

Abstract CCG-2961 tested an intensively timed induction therapy consisting of cytarabine (AC), etoposide, thioguanine, dexamethasone, idarubicin and daunorubicin. Patients in remission after induction were randomized to a second induction course (Arm A) or a 3-drug combination of fludarabine, AC, and idarubicin (Arm B). Course 3 for patients with related donors was bone marrow transplantation (BMT); for those without donors, high dose AC/l-asparaginase. After Course 3 patients without donors were randomized to 14 infusions of Interleukin 2 (IL2) over 18 days or follow-up. CNS prophylaxis was intrathecal AC. Eligibility included all subtypes of de novo AML except acute promyelocytic leukemia and AML in patients with Down syndrome. CCG-2961 opened in Oct.1996 and closed in Dec. 2002. The DSMC suspended the study between Oct. 1999 and May 2000 while the 2961 Committee developed supportive care policies to reduce treatment-related mortality (TRM). CCG-2961 enrolled 900 de novo patients aged 3 days to 21 years, with 495 and 405 patients accruing pre-and post suspension respectively. Remission induction rate is 88.5%. With median follow-up of 3.6 years (range: 0 – 8.1 years), event-free survival (EFS) at 3 years is 44±3% and survival (OS) 57±3%. Disease-free survival (DFS) following Course 2 Arms A and B are not different, although relapse is significantly higher in Arm A (7.3% .vs. 3.1% P=0.018) and TRM more common in Arm B (7.9% vs.4.2% P=0.059), despite 7 less days of neutropenia in Arm B (P&lt;0.001). DFS is 65±9% for patients with a donor versus 50±5% for patients without a donor (P=0.005); respective OS, 74±8% and 66±5% (P=0.221). However, among 98 patients in CR1 with t(8;21) or inv(16) cytogenetics, outcomes in those without and with a donor were no different: DFS (61±12% vs. 72±18%, P = 0.49) and OS (78±10% vs. 77±17%, l P= 0.85). DFS with and without IL2 is 55±9% and 60±8%(P=0.606). Outcomes improved progressively over time. EFS pre- and post-suspension are 41±4% and 47±5%(P=0.038); OS, 52±5% and 63±5%(P=0.005); TRM is 17±3% pre- and 12±3% post-suspension (P=0.039). Factors predictive of inferior EFS are age &gt;17 years, Afro-American and Hispanic ethnicity, body mass index &lt;10th or &gt;95th percentile for age, absence of related marrow donor, WBC &gt; 50,000/mm3, karyotype with −7/7q, −5/5q- or &gt; cytogenetic 5 abnormalities, FLT3/ITD, &gt;15 % morphologic blasts on day 14 or &gt;0.5% immunologically detectable blasts at the end of induction. CCG-2961 confirms the efficacy and high TRM of intensively timed therapy. Neither fludarabine nor IL2 increases DFS or OS, and availability of a donor does not improve outcomes in those with favorable cytogenetics.

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.

Interim Anaiysis of Intention To Treat Analysis, “Multicenter AML-2000 Trial” Based on Cytogenetics Risk Factors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4618-4618
Author(s):  
Yeung-Chul Mun ◽  
S.M. Lee ◽  
S.M. Bang ◽  
S.H. Park ◽  
E.K. Cho ◽  
...  
Keyword(s):  
De Novo ◽  
Risk Groups ◽  
Good Prognosis ◽  
Remission Induction ◽  
Secondary Aml ◽  
Intention To Treat ◽  
Prognostic Groups ◽  
Prognosis Group ◽  
De Novo Aml ◽  
Treat Analysis

Abstract The result of cytogenetics is one of the most important prognostic factors on the prognosis of AML. HDAC, auto PBPCT and allogeneic BMT after 1 or 2 times of post remission therapy based on 4 prognostic groups(APL: Acute promyelocytic leukemia, GPG: Good prognosis group, IPG: Intermediate prognosis group, PPG: Poor prognosis group by MRC definition) were underwent based on cytogenetics data. We studied CR, relapse, toxic death, DFS and OS. Inclusion criteria were age<65, PS<3 with reasonable organ functions in de novo AML, secondary AML and RAEB-T. The aims of this prospective intention to treat analysis was to compare the CR, recovery kinetics, DFS and OS by giving different therapies of intensity in the different prognostic groups based on cytogentics data. Three plus seven(Idarubicin 12mg/m2(D1–D3), Ara-C 100mg/m2(D1–D7)) were given to de novo AML, secondary AML and RAEB-T. Intermediate dose(8gm/m2) of Ara-C was given followed by HDAC or auto PBPCT to the patients with GPG(t(8:21) & inv(16)). Three times of post remission therapy including HDAC, or auto PBPCT were given to the patients with IPG or PPG(−5, −7, del 5q, complex). If HLA-identical sibling was available, then allo BMT was underwent after 1st post-remission therapy. In cases of APL, three times of post-remission therapy with idarubicin alone were given. ATRA was given to APL group during remission induction therapy and after post-remission maintenance period for 2 years. Up to Mar., 2005, 422 patients(18 centers) were enrolled. Median follow-up was 48months. Among them, 92.3% was de novo AML, and APL, GPG, IPG and PPG were 10.0%, 21.6%, 51.4%, and 14.7% respectively. Overall CR after 1st induction(3+7) were 69.9%(APL: 87.2%, GPG: 84.7%, IPG: 63.8%, PPG: 55.66%, P<0.01). Relapse rate was 12.8%(APL), 40.5%(GPG), 40.5%(IPG) and 45.6%(PPG) respectively(P<0.01). Toxicities profiles including mucositis, hepatic, cardiac and bleeding episodes were similar on 3 different therapy modalities(HDAC, auto PBPCT and allo BMT). In conclusions, this trial seems to be tolerable in terms of toxicities after induction and during post remission therapies. Among GPG, there were no significant statistical differences on OS and LFS in all the therapy modalities(ie, HDAC, Auto, Allo). In IPG, auto arm had a tendency of superior OS and LFS comparing to HDA & allo arm. In PPG, there was significant surperior LFS in allo arm. There were no statistical differences on OS in all the therapy modalities in PPG. This intention to treattrial, which had started in Jan, 2000, has been going on until now. Through this risk based trial using cytogenetics, we might be able to find optimal post-remission therapies for different risk groups with less toxicities.

scholarly journals Redefining Remission Induction Chemotherapy Ineligibility by Early Mortality in De Novo Acute Myeloid Leukemia

2021 ◽  
Vol 10 (24) ◽  
pp. 5768
Author(s):  
You-Cheng Li ◽  
Yu-Hsuan Shih ◽  
Tsung-Chih Chen ◽  
Jyh-Pyng Gau ◽  
Yu-Chen Su ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Mortality Rate ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Group Performance ◽  
De Novo ◽  
Early Mortality ◽  
Remission Induction ◽  
Acute Myeloid

The therapeutic strategies for acute myeloid leukemia (AML) patients ineligible for remission induction chemotherapy have been improving in the past decade. Therefore, it is important to define ineligibility for remission induction chemotherapy. We retrospectively assessed 153 consecutive adult de novo AML patients undergoing remission induction chemotherapy and defined early mortality as death within the first 60 days of treatment. The 153 patients were stratified into the early mortality group (n = 29) and the non-early mortality group (n = 124). We identified potential factors to which early mortality could be attributed, investigated the cumulative incidence of early mortality for each aspect, and quantified the elements. The early mortality rate in our study cohort was 19.0%. Age ≥ 65 years (odds ratio (OR): 3.15; 95% confidence interval (CI): 1.05–9.44; p = 0.041), Eastern Cooperative Oncology Group performance status ≥ 2 (OR: 4.87; 95% CI: 1.77–13.41; p = 0.002), and lactate dehydrogenase ≥ 1000 IU/L (OR: 4.20; 95% CI: 1.57–11.23; p = 0.004) were the risk factors that substantially increased early mortality in AML patients. Patients with two risk factors had a significantly higher early mortality rate than those with one risk factor (68.8% vs. 20.0%; p < 0.001) or no risk factors (68.8% vs. 9.2%; p < 0.001). In conclusion, older age, poor clinical performance, and a high tumor burden were risks for early mortality in AML patients receiving remission induction chemotherapy. Patients harboring at least two of these three factors should be more carefully assessed for remission induction chemotherapy.

scholarly journals Long-Term Outcomes of De Novo Acute Myeloid Leukemia (AML) Patients (pts) with Life Threating Complications

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5898-5898
Author(s):  
Aleksei Bazhenov ◽  
Elena N. Parovichnikova ◽  
Gennadiy M. Galstyan ◽  
Vera V. Troitskaya ◽  
Elena O. Gribanova ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
De Novo ◽  
Univariate Analysis ◽  
Categorical Variables ◽  
Remission Induction ◽  
Long Term Outcomes ◽  
Icu Mortality ◽  
Icu Admission ◽  
De Novo Aml

Abstract Background. Induction of remission in pts with AML is often associated with the life-threating complication and ICU admission. The long-term outcomes of these AML pts discharged from ICU are unknown. The aim was to estimate the long-term outcomes of de novo AML pts required ICU admission due to life-threating complications during induction of remission. Methods. All de novo AML pts, younger than 60 y.o, median age 34 (17-60 yo), from 2013 to 2016 were enrolled in the study. All pts were divided into 2 groups: pts who required ICU admission during induction chemotherapy due to life-threating complications and pts who didn't require ICU admission during induction chemotherapy. Overall survival (OS) and disease free survival (DSF) were assessed by the Kaplan - Meier method, log rank value p<0.05 consider as significant. Univariate analysis was performed with χ 2 tests or Fisher's exact tests for categorical variables to find an independent ICU mortality predictor. Results In total, 73 AML pts included in study, 26 (36%) of them were admitted in ICU during induction of remission (tab. 1). ICU pts had more advanced AML. Reasons for ICU admissions were acute respiratory failure (ARF) (62%); neurological events (16%); septic shock (SS) (16%); cardiac arrhythmia (7%). ICU survival rate was 69%. 8 pts died in ICU (5 SS and 3 ARF). Needs for mechanical ventilation, vasopressors and ≥2 organ dysfunctions were independent predictors (p<0.05) of ICU mortality. 18 of 26 (69%) pts received chemotherapy during their stay in ICU. Modifications of chemotherapy were required in 46% of ICU pts and in 36% in non-ICU pts (p>0.05). There were differences in 30-day OS between ICU and non-ICU pts (69% vs. 0%, p=0.001). However, a landmark analysis for long term OS for patients who survived the first 30 days of treatment were the similar in ICU and non-ICU groups (p=0.946)( picture1, A). DSF also were the similar in ICU and non-ICU groups (p=0.946) (picture 1,B) Conclusion. During remission induction 36% of AML pts needed ICU admission due to life-threating complications. Mortality rate in ICU is high (31%). However, after discharging from ICU AML patents had the similar long-term outcomes as well as non-ICU AML pts. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Attenuated Dose of Idarubicin for the Elderly De Novo Acute Myeloid Leukemia with Normal Karyotype.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4608-4608
Author(s):  
June-Won Cheong ◽  
Yuri Kim ◽  
Sun Young Park ◽  
In Hae Park ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
De Novo ◽  
Normal Karyotype ◽  
The Elderly ◽  
Remission Induction ◽  
Conventional Dose ◽  
The Difference ◽  
Group 2 ◽  
De Novo Aml ◽  
Group 1

Abstract The incidence of acute myeloid leukemia (AML) increases with age. Because of poor performance status, co-morbidity and treatment-related side effects, a conventional dose chemotherapy containing anthracyclins may be toxic to the majority of elderly patients. In contrast, the administration of suboptimal dose of myelosuppressive chemotherapy could lead to an unsuccessful clinical outcome including lower complete remission (CR) rate. To evaluate the effect of attenuated dose of idarubicin, compared to the standard dose, on the clinical outcome and chemotherapy-related complications, we analyze the consecutive 32 elderly de novo AML patients (range, 60 – 74 years) with normal karyotype. Eleven patients received one cycle of conventional-dose remission induction chemotherapy (idarubicin, 12 mg/m2/day on days 1–3 and cytarabine 100mg/m2/day on days 1–7) (Group 1) and 21 patients received attenuated-dose idarubicn (8 mg/m2/day on days 1–3) and cytarabine (100mg/m2/day on days 1–7) (Group 2). Six cases (54.5%) in Group 1 and 12 cases (57.1%) in Group 2 had CR. The difference of CR between the two groups was not significant (P = 0.59). The intervals from the chemotherapy-starting date to the date of CR documentation were not also different between two groups (median 31.5 days on Group 1 vs 27.0 days on Group 2) (P = 0.29). The median number of transfusion requirement during the induction therapy was not different in the red blood cells (10 units, each) and platelets (16.5 units in Group 1 vs 18.0 units in Group 2; P > 0.05). Thirty patients received the recombinant human granulocyte colony-stimulating factor (G-CSF) three days after termination of chemotherapy. The duration of G-CSF administration was not different between two groups (P = 0.86). However, the frequency of septicemia and septic shock after induction chemotherapy was statistically significantly higher in Group 1 (54.5% and 9.5%, respectively) compared to that in Group 2 (36.3% and 0.5%, respectively) (P < 0.01). We also observed a higher incidence of clinically-documented invasive fungal infection in Group 1 (45.5%) compared to Group 2 (15.0%), although the difference was not statistically significant (P = 0.095). The incidence of other regimen-related toxicities including renal dysfunction, hepatic dysfunction and heart failure was not different between two groups. Overall survival and disease-free survival also were not different between the groups. In conclusion, the attenuated dose of idarubicin can be recommended for the remission induction chemotherapy for the elderly de novo AML patients with normal karyotype since it is associated with lower incidence of sepsis and septic shock with comparable CR rate.

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