scholarly journals ADE as Induction Therapy Results in Treatment of Children with Non-M3 High-Risk Acute Myeloid Leukemia, an Extrapolable Achievement in Developing Countries

2016 ◽  
Vol 07 (03) ◽  
pp. 197-202
Author(s):  
Marta Zapata-Tarrés ◽  
Rocío Cárdenas-Cardós ◽  
Liliana Velasco-Hidalgo ◽  
Martín Pérez-García ◽  
Alberto Olaya-Vargas ◽  
...  
Keyword(s):  
Developing Countries ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Elderly Patients with Acute Myeloid Leukemia Are Not All the Same: Results of the Prospective DSIL AML96 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1840-1840
Author(s):  
Markus Andreas Schaich ◽  
Walter E. Aulitzky ◽  
Heinrich Bodenstein ◽  
Martin Bornhaeuser ◽  
Thomas Illmer ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
High Risk ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Severe Toxicity ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract The majority of patients with acute myeloid leukemia (AML) are older than 60 years at diagnosis. However, treatment results for these elderly patients are still unsatisfactory. This is thought to be due to a more aggressive disease, preexisting co-morbidities or a decreased tolerance for intensive treatment approaches. As for younger patients there is growing evidence that elderly AML patients may be divided into prognostic subgroups. So far data on prognostic factors in this group of patients are still sketchy. Between February 1996 and March 2005 a total of 827 elderly AML patients with a median age of 67 (61–87) years were treated within the prospective AML96 trial of the German Study Initiative Leukemia (DSIL). 643 patients had de novo and 184 patients secondary disease. All patients were scheduled to receive a double induction therapy with Daunorubicin and Ara-C (DA3+7). The consolidation therapy consisted of one course of m-Amsacrine and intermediate-dose (10g/m2) Ara-C. 265 (32%) patients reached CR criteria after double induction therapy. Forty-two patients (5%) had only a PR, 307(37%) displayed refractory disease, 126(15%) died during induction therapy and 77(10%) received only one course of induction therapy due to severe toxicity. Out of the 265 patients in CR 120 (45%) patients received the consolidation course. The strongest independent prognostic factors for achieving a CR were less than 10% blasts in the day 15 bone marrow, the presence of a NPM mutation or a low-risk karyotype (p<0.0001 each). The 3-year overall (OS) and relapse-free survival (RFS) rates were 18% for all patients and 17% for all patients in CR, respectively. In the multivariate analysis the strongest prognostic factors for survival were age, LDH and cytogenetics (p<0.0001 each). Using these three parameters a prognostic model for survival was established. Patients older than 70 years with intermediate- or high-risk cytogenetics and a high LDH level at diagnosis (n=213) had a 3-year OS of only 9%, whereas patients with low-risk cytogenetics or patients with intermediate-risk cytogenetics, younger than 70 years and a low LDH level (n=237) had a 3-year OS of 32%. All other patients (n=377) had an intermediate 3-year OS of 15% (p<0.0001). In conclusion, elderly AML patients can be stratified into prognostic groups. AML patients older than 70 years with high LDH levels and intermediate- or high-risk cytogenetics at diagnosis do not profit from conventional chemotherapy.

scholarly journals CLAG-Based Induction Therapy in Previously Untreated High Risk AML Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4892-4892
Author(s):  
Karen Seiter ◽  
Stephanie Germani ◽  
Julie Martin ◽  
Rosemarie Raffa ◽  
Michele Reilly ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Early Death ◽  
High Dose ◽  
Cell Transplant ◽  
Kaplan Meier ◽  
Duration Of Response ◽  
Acute Myeloid

Abstract The CLAG regimen (G-CSF 300 mcg sc, cladribine 5 mg/m2 over 2 hours, and cytarabine 2 gm/m2 over 4 hours beginning 2 hours after cladribine, all daily times 5 days) was originally devised by Robak et al (Leuk Lymphoma 2000; 36:121-9) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Fifty percent of patients achieved a CR with a median duration of 22.5 weeks. This group subsequently added mitoxantrone to the regimen (Wrzesien-Kus A, et al. Ann Hematol 2005; 84:557-64). We treated 20 patients with previously untreated acute myeloid leukemia who were considered unsuitable for our intensive high-dose cytarabine, high-dose mitoxantrone frontline induction regimen either due to age or cardiac dysfunction with CLAG-based therapy. Patients with a cardiac ejection fraction above 50% additionally received either mitoxantrone (mito) or idarubicin (ida), 12 mg/m2 times 3 days, concurrently with CLAG. Of 20 patients treated, 5 received CLAG, 12 received CLAG-ida and 3 received CLAG-mito. The median age was 64 years (range 42-79 years). There were 13 men and 7 women. Six patients had received prior chemo and/or RT for a previous malignancy. In addition 3 patients had a prior MPD and 1 had prior MDS (total of 10 patients with secondary AML). Patients had a median of 3 comorbidities (range 0-7). Cytogenetic risk was good: 2 patients (however one was FLT3 ITD+), intermediate: 10 patients, poor: 8 patients. Only one patient was FLT3 ITD+. Responding patients (CR or PR) received 1 (5 pts), 2 (2 pts), 3 (8 pts) or 4 (2 pts) cycles of CLAG+/- ida or mito followed by allogeneic stem cell transplant (4 pts), hidac (2 pts) or decitabine maintenance (4 pts). Most patients responded to therapy. There were 13 formal CRs (65%), 1 CRp (5%), 3 PR (15%, defined as 6-10% blasts on marrow with complete hematologic recovery in the peripheral blood), 2 failures (10%) and one early death (5%). Other than the early death, treatment was well tolerated with few toxicities other than neutropenic fever and cytopenias. Estimated overall survival by Kaplan Meier analysis is 29.6 months (95% CI 20.1-39.2 months). Duration of response is 32.3 months (95% CI 21.6-43.1 months). CLAG-based therapy is a well-tolerated, efficacious induction strategy in previously-untreated patients with high risk AML. CLAG-based regimens should be studied in a broader group of newly diagnosed AML patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Off Label Use: Use of cladribine in AML.

CLAG-based induction therapy in previously untreated high risk acute myeloid leukemia patients

2016 ◽  
Vol 46 ◽  
pp. 74-78 ◽  
Author(s):  
Karen Seiter ◽  
Nasir Ahmed ◽  
Azfar Shaikh ◽  
Paul Baskind ◽  
Delong Liu
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Induction Therapy with Idarubicin and Etoposide Combined with Sequential or Concurrent Azacitidine In Patients with High-Risk Acute Myeloid Leukemia: Pilot-Phase of the AMLSG 12-09 Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2184-2184
Author(s):  
Frank G. Rücker ◽  
Stephan Stilgenbauer ◽  
Martin Bommer ◽  
Daniela Späth ◽  
Silja Mack ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Single Agent ◽  
Severe Toxicity ◽  
Overall Response ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 2184 Background: Treatment outcome in patients with cytogenetically and/or molecularly defined high-risk acute myeloid leukemia (AML) is dismal with low complete remission (CR) rates after intensive induction therapy and 5-year overall survival of about 25% in patients 60 years and younger and far below 5% in patients above the age of 60 years. In younger patients, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched related or unrelated donors results in significantly better clinical outcome especially if patients are transplanted early in first CR (Schlenk et al., J. Clin. Oncol. 2010, in press). Azacitidine is a demethylating agent showing promising results as a single agent in AML patients with bone marrow blast counts between 20 and 30%. Therefore, the randomized AMLSG 12-09 trial will evaluate the combination of idarubicin/etoposide chemotherapy combined with azacitidine instead of cytarabine as compared to induction with idarubicin/etoposide/cytarabine (ICE) in an attempt to increase CR rates in these high-risk patients. Aim: To evaluate feasibility of the investigational induction therapy with idarubicin and etoposide in combination with sequentially or concurrently administered subcutaneous (sc) azacitidine. Methods: Patients were treated according to the investigational treatment schedules of the AMLSG 12-09 protocol. Patients received idarubicin 12 mg/sqm on days 1, 3 and 5 and etoposide 100 mg/sqm on days 1, 2 and 3 (patients above the age of 65 years received idarubicin 12 mg/sqm and etoposide 100 mg/sqm only on days 1 and 3, respectively). Azacitidine 100 mg/sqm sc was added on days -5 to -1 in 7 patients (schedule A), days 1 to 5 in 6 patients (schedule B), and days 4 to 8 in 5 patients (schedule C). Results: 18 patients have been treated (13 males and 5 females). Median age was 62.5 years (range, 28–76). The cytogenetic and molecular risk profile of the 18 AML was as follows: Eight AML had MDS-related cytogenetic changes (WHO 2008) including five exhibiting a complex karyotype and two had 3q abnormalities; three AML had balanced t(v;11q23), and six exhibited a normal karyotype together with triple negative genotype (NPM1-wt, FLT3-wt and CEBPA-wt). In one case, there were no metaphases available, however molecularly NPM1-wt, FLT3-wt, CEBPA-wt, no core binding factor AML, no t(15;17) and or t(9;11) were present. Median WBC was 4.6/nl (range, 0–6-75/nl). Overall response to induction therapy was CR n=7, partial remission (PR) n=3, refractory disease (RD) n=7 and one patient died during induction therapy (ED). Moreover, two patients with RD achieved CR after additional cycles of single agent azacitidine treatment. Overall response rates (CR and PR) according to treatment schedule were 43% (3/7), 67% (4/6) and 80% (4/5) for schedules A, B and C, respectively. Most common azacitidine-related toxicity was local reactions at injection site not exceeding CTC-grade 2. As expected, fever in neutropenia was the most common severe toxicity (83%). In addition, one patient with history of epilepsy had seizures during induction therapy and one patient with history of Crohn‘s disease had mucositis CTC-grade 3. Allo-HSCT has been performed in three patients and is planned in five. After a median time of 7.5 months, 16 of 18 patients are alive. Conclusion: Azacitidine administered sc can be given safely either sequentially or concurrently in combination with idarubicine/etoposide induction chemotherapy. Response rate of this high-risk population appears promising and the toxicity profile was favorable. The question which schedule is the most effective will be addressed in the randomized AMLSG trial (NCT01180322) Disclosures: Stilgenbauer: Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Döhner: Pfizer: Research Funding. Schlenk: Celgene, Pfizer, Novartis, Cephalon, Amgen: Research Funding.

scholarly journals Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome

2015 ◽  
Vol 90 (6) ◽  
pp. 483-486 ◽  
Author(s):  
Mazyar Shadman ◽  
Raya Mawad ◽  
Carol Dean ◽  
Tara L. Chen ◽  
Kathleen Shannon-Dorcy ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Risk-Adapted Therapy in Younger Adults with Acute Myeloid Leukemia: Results of the AMLHD98A Trial of the AMLSG.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 14-14 ◽  
Author(s):  
Richard F. Schlenk ◽  
Konstanze Dohner ◽  
Hans Pralle ◽  
Katharina Götze ◽  
Michael Pfreundschuh ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Normal Karyotype ◽  
Low Risk ◽  
High Dose ◽  
Intermediate Risk ◽  
Consolidation Therapy ◽  
Acute Myeloid

Abstract Objective: To evaluate outcome of younger adult patients with acute myeloid leukemia (AML) allocated to different treatment strategies according to the risk factors “karyotype” and “response to first induction cycle”. Methods: Between 1998 and 2004, 871 patients (age 16–60 yrs) were enrolled. 77% of pts had de novo AML, 16% s-AML, and 7% t-AML. Risk stratification was based on cytogenetics and response to first induction therapy: i) low-risk: t(8;21); ii) intermediate-risk: normal karyotype, inv(16), t(11q23) or other rare aberrations; iii) high-risk: abn(3q), −5/5q-, −7/7q-, abn(12p), abn(17p) or complex karyotype and/or all pts having refractory disease (RD) after the 1st or not achieving complete remission (CR) after the 2nd induction. All pts received first induction with ICE (idarubicin, cytarabine, etoposide) followed by a second cycle ICE in case of CR/PR; pts with RD after first induction were assigned to high-dose cytarabine based salvage therapy. Pts achieving CR after response-adapted induction received first consolidation therapy with HAM. Second consolidation therapy was stratified according to the risk definition: i) low-risk pts were assigned to a second course of HAM; ii) intermediate-risk pts with an MRD were assigned to a HLA-matched related donor (MRD) stem cell transplantation (SCT), whereas the remaining pts were either randomized between autologous SCT and a second course of HAM in case of normal karyotype or assigned to autologous SCT if cytogenetic aberrations were present; iii) all high-risk pts were assigned to allogeneic SCT from a MRD or unrelated donor (MUD). Results: Response after response-adapted double induction therapy was as follows: CR 70%, RD 18%, death 12%. In 69 pts risk assessment could not be performed due to unsuccessful cytogenetics; 701 (91%) were assigned to a specific risk: i) high-risk n=255 (36%); ii) intermediate-risk: 408 (58%) pts, comprising 254 pts with normal karyotype and 154 with aberrations; iii) low-risk: 38 pts. (5%) with t(8;21). The median follow-up time was 47 months. Overall survival (OS) for the whole study population at 4 years was 40% (95%-CI 37-42%). All 38 low-risk pts received intensive chemotherapy translating in an OS of 75% (95%-CI 61%-92%). Intention to treat-analysis for intermediate-risk patients exhibiting a normal karyotype revealed a relapse free survival (RFS) of 63%, 38% and 46% for patients assigned to MRD-SCT, autologous SCT and HAM, respectively (p=0.01). However, this difference in RFS did not translate into a difference (p=0.36) in OS due to effective salvage treatment, i.e. mainly MUD-SCT. Within the intermediate-risk group defined by cytogenetic abnormalities no difference in RFS (p=0.16) and OS (p=0.61) was evident between the intended MRD-SCT and autologous SCT. High-risk: 93 pts received MUD-SCT, 57 MRD-SCT, and 93 no allogeneic SCT, resulting in a feasibility of 58% and an OS of 28%, 29% and 5%, respectively (p<0.0001). Conclusions: In this prospective study, allogeneic SCT from MRD or MUD improved outcome of patients with high-risk features. In addition, pts with normal karyotype had a significant better RFS after allogeneic SCT.

Hydroxyurea in the Early Management of Acute Myeloid Leukemia and Hyperleukocytosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4368-4368 ◽  
Author(s):  
Asmaa M. Quessar ◽  
Nisrine R. Khoubila ◽  
Raul C.U. Ribeiro ◽  
Mohamed A. Rachid ◽  
Saadia D. Zafad ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Mortality Rate ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Early Mortality ◽  
Early Management ◽  
The Mean ◽  
Wbc Count ◽  
Acute Myeloid

Abstract BACKGROUND: Patients with acute myeloid leukemia (AML) and hyperleukocytosis are at high risk of early mortality due to pulmonary, renal, and central nervous system complications. Leukapheresis and low-dose continuous infusion of cytarabine and hydroxyurea (HU) have been used but their advantages and limitations are not well characterized. The University hospital in Casablanca, Morocco has a limited number of beds, and hence admissions must be prioritized. Here we report the effects of HU on the white blood cell (WBC) count and early mortality rate of patients with hyperleukocytic AML. METHODS: Between April 2003 and December 2006, patients with AML were enrolled on the AML-MA2003 protocol (2 induction courses of cytarabine and daunorubicin and 2 postremission courses that include intermediate-dose cytarabine). Patients with AML and hyperleukocytosis (WBC count >50 x 109/L) were immediately started on HU (50 mg/kg/day orally x 4 days), regardless of hospital bed availability. Response was evaluated after 4 days of HU; patients were considered responders if >50% reduction of the initial WBC count was observed. RESULTS: Ninety of 260 (34.6%) patients enrolled had hyperleukocytosis. Three patients were excluded, induction therapy started on the day of admission. Therefore, 87 patients (48 females, 39 males) were evaluable. The mean age was 32 years (range, 2–60); 29% were children (ages 2–20 years). The mean initial WBC count was 104x109/L (range 50–260 x109/L); 37 (42.5%) patients had WBC counts > 100x109/L. The French-American-British subtypes were M1 (45%), M2 (26%), M4 (12%), M5 (7%), and M0, M3, M6 and M7 (2.5% each); 5 cases were unclassified. Karyotypes determined for 65/87 cases revealed 13 (20%) favorable karyotypes [9 had the t(8;21); 3 had inv16; 1 had the t(15;17)], 30 (46%) intermediate-risk karyotypes, including normal karyotypes, and 22 (34%) unfavorable-risk karyotypes. Sixty-two (71%) patients were classified as responders. In an additional 3, the WBC count was reduced 25%–50%. In 22 (25%) patients, including 4 whose WBC counts increased, HU showed no cytoreductive effect. The mean WBC count after 4 days of HU was 24 x 109/L (range, 1.5–125 x109/L); 15 (17%) patients’ WBC counts remained >100x109/L. Four patients developed acute tumor lysis syndrome (TLS) (hyperuricemia and renal dysfunction) in response to HU. There were 5 (8%) early deaths (mean, 7 days after the start of HU; range, 4–14 days). All 5 patients had WBC counts > 100x109/L at diagnosis, and only 1 was a responder. This mortality rate does not differ from that (9%) observed among the 170 protocol patients who did not have hyperleukocytosis. Causes of death included infection (n=1), pulmonary and CNS leukostasis (n=1 each), TLS (renal failure and hyperkalemia, n=1), and intracranial hemorrhage (n=1). Among several factors (age, sex, FAB type, karyotype, WBC counts), only WBC count of ≤ 100x109/L was significantly associated with response to HU (P=0.01). The complete remission rate after first course of induction therapy was 43.5% for responders and 16% for non-responders (P=0.02). CONCLUSION: HU given orally for 4 days rapidly reduces the WBC count in pediatric and adult AML with hyperleukocytosis. The early mortality rate in this high-risk group treated with HU compares favorably with rates reported for similar patients. It remains to be determined whether initial response to HU is associated with overall outcome in AML.

Induction Intensified Regimens Including Fludarabine or Mylotarg for Acute Myeloid Leukemia Patients: Comparison by Response and Follow-up.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 941-941
Author(s):  
Cristina Papayannidis ◽  
Anna Candoni ◽  
Stefania Paolini ◽  
Emanuela Ottaviani ◽  
Ilaria Iacobucci ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Median Time ◽  
Induction Therapy ◽  
Safety Profile ◽  
Myeloid Leukemia ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Background . Conventional induction treatment in young Acute Myeloid Leukemia (AML) patients (<= 60 years old) is still represented by the association of antracycline and cytarabine, which offers a complete remission (CR) rate not inferior to 63%. Since many non-randomized trials have recently demonstrated the superiority of intensified regimens, the present gold standard therapy includes the addition of at least a third drug to the classic 3/7 schedule. Aim of the study . We evaluated the safety profile and the efficacy of two four-drugs induction schedules, adding either fludarabine (25 mg/sqm days 1–5) or mylotarg (3 mg/sqm day 6) to idarubicin (6 mg/sqm days 1, 3, 5), cytarabine (1 g/sqm days 1–5), etoposide (100 mg/sqm days 1–5) (FLAIE and MyAIE, respectively). Methods . Sixty-six consecutive AML patients were enrolled either in the FLAIE (N=44, from 2002 to 2005) or in the MyAIE (N=22, from 2005 to April 2007) schedule, with similar clinical and biological characteristics. The median age was 45 and 48 years, respectively. According to kariotype, WBC count and FLT3 status, seventy and sixty-four percent of cases, respectively, were considered at high risk. Consolidation therapy consisted of 2 cycles of ID-AraC and Ida. Results . The complete remission rate was 75% and 59% for FLAIE and MyAIE, respectively (p=n.s.). Death during treatment rates were 5% and 0. After 1 consolidation course the overall CR rate was 80% and 73%. After a similar median follow up, 27 months (1–62) and 21 months (5–42) respectively, 41% of patients are alive in CR in the FLAIE group (12 SCT and 3 ASCT) and 64% in the MyAIE group (7 SCT and 4 ASCT) (p=n.s.; Chi-square, Fisher’s exact test). Toxicity was comparable in the two regimens. The median time to ANC recovery (>1.0 x 10^9/L) was 31 and 23 days for FLAIE and MyAIE, respectively. The median time to PLT recovery (>100 x 10^9/L) was 28 and 24 days, respectively. The median time of neutropenic fever episodes for patients was 1 and 1.4 in the 2 groups, respectively. Grade III/IV GI toxicities occurred in 11% and 22% of cases, respectively. Conclusions . These data showed that four-drugs intensified induction therapy is a feasible approach in young AML patients. Recent published trials have demonstrated that fludarabine-based induction chemotherapy in high risk AML patients is able to increase the CR rate offered by conventional treatment. Therefore, the limited number of patients involved in this study, the low administration dosage of idarubicin, and the relevant role of fludarabine in induction therapy, can reasonably justify the lower CR rate obtained in patients treated in the MyAIE schedule, if compared with FLAIE regimen and, above all, with standard chemotherapy. In the light of their efficacy and safety profile, fludarabine and mylotarg, in combination with conventional chemotherapy, represent a promising induction regimen in young AML patients; further analyses and randomized pilot trials will define their definite role.

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