scholarly journals Dose intensity for induction in acute myeloid leukemia: what, when, and for whom?

Haematologica ◽  
2021 ◽  
Author(s):  
Shannon R. McCurdy ◽  
Selina M. Luger
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Dose Intensity ◽  
Gemtuzumab Ozogamicin ◽  
Cytotoxic Agents ◽  
Binding Factor ◽  
Flt3 Inhibitors ◽  
Acute Myeloid

Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a deeper understanding of the genetic makeup of AML, has led to remission-inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered singleagent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.

The Survival Of The Elderly Acute Myeloid Leukemia Patients Do Not Depend On The Intensity Of Induction Chemotherapy. Retrospective Study Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5029-5029
Author(s):  
Sebastian Grosicki ◽  
Ewa Bodzenta ◽  
Marek Kriegler ◽  
Ilona Szypula ◽  
Marcin Fejklowicz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Remission Rate ◽  
Standard Dose ◽  
Study Results ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Abstract The aims of this study were comparison of overall survival (OS) and complete remission rate (CR) in whole group of acute myeloid leukemia (AML) >60 patients, and in younger older (61 – 70) AML patients in dependency of qualification to risk group according to PALG stratification and a schedule of treatment. Patients with AML >60 after diagnosis were qualified into the risk groups according to PALG stratification for AML >60. The patients from group 1 patients were receiving intensive induction chemotherapy DAC (daunorubicin, cytarabine, cladribine) or DA (daunorubicin, cytarabine), those from group 2 were receiving cytarabine+thioguanine induction chemotherapy, and those from group 3 chemotherapy with low doses of cytarabine. Patients from first group, who reached CR after induction were receiving consolidation with mitoxantrone + standard dose of cytarabine, and next they were qualified to HSCT or maintenance phase. Patients from group 2 and 3 independently of results of induction were receiving successive cycles of chemotherapy like in first course every 4 weeks to 2 years with very intensive supportive care. One hundred sixteen patients with untreated AML treated In period 02.2009-12.2012, age 73 (61-89), men 50% were included to this study. Thirty three patients were qualified to group 1, 50 to second and 33 to third. After preliminary analysis, because of similar early and late outcomes of the therapy in group 2 and 3, those groups of patients were joint for next analysis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical and experimental efficacy of gemtuzumab ozogamicin in core binding factor acute myeloid leukemia

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Michele Gottardi ◽  
Federico Mosna ◽  
Sergio De Angeli ◽  
Cristina Papayannidis ◽  
Anna Candoni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Core Binding Factor ◽  
Free Survival ◽  
Binding Factor ◽  
Clonogenic Potential ◽  
Acute Myeloid

Leukemia-initiating cells of core binding factor (CBF) acute myeloid leukemia (AML) likely derive from early committed hematopoietic precursors expressing CD33. As such, targeting CD33 could ameliorate the chance of cure of CBF AML patients. We compared 12 CBF AML patients treated with Fludarabine, Cytarabine, Idarubicin and Gemtuzumab Ozogamicin (FLAI-GO regimen) with 25 CBF AML patients treated with the same schedule, but without GO. With the limit of small numbers, we observed a consistent trend toward better overall survival, disease free survival and event free survival in the FLAI-GO group. We also demonstrated the ability of GO to induce the disappearance <em>in vitro</em> of the AML1-ETO molecular transcript in a polymerase chain reaction-positive graft without decreasing the clonogenic potential of CD34+/CD38- cells. This represent the proof of principle for using GO in a purging strategy before autologous stem cell transplantation. Therefore, our data argue in favor of the reinstitution of GO in the therapy of CBF AML.

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group

Blood ◽  
2004 ◽  
Vol 103 (2) ◽  
pp. 479-485 ◽  
Author(s):  
Jacob M. Rowe ◽  
Donna Neuberg ◽  
William Friedenberg ◽  
John M. Bennett ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Growth Factor ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Gm Csf ◽  
Acute Myeloid

Abstract The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixty-two older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P = .03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate.

Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 3869-3876 ◽  
Author(s):  
Jeanne E. Anderson ◽  
Kenneth J. Kopecky ◽  
Cheryl L. Willman ◽  
David Head ◽  
Margaret R. O'Donnell ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
P Value ◽  
Term Survival ◽  
Acute Myeloid

Complete remission and long-term survival rates are low for older adults treated for acute myeloid leukemia (AML). Because of favorable phase 2 data using mitoxantrone and etoposide, we conducted a phase 3 study (SWOG-9333) in which patients over 55 years of age with previously untreated AML were randomized to receive mitoxantrone (10 mg/m2 per day × 5) and etoposide (100 mg/m2per day × 5) [ME], or cytarabine (200 mg/m2 per day × 7) and daunorubicin (45 mg/m2 per day × 3) [AD] as induction therapy. The randomization was stratified by age, onset of leukemia, and multidrug resistance phenotype. Over a 4-year period, 328 eligible patients from 66 institutions were enrolled. The complete remission rate was 34% (95% confidence interval [CI] 26%-41%) for patients in the ME and 43% (CI 35%-51%) for patients in the AD treatment arm (one-tailedP value .96). The rates of resistant disease were 43% (CI 35%-51%) and 34% (CI 27%-42%), respectively, for the 2 treatment arms (one-tailed P value .95). The estimated overall survival at 2 years was 11% (CI 6%-15%) and 19% (CI 12%-25%) for patients randomized to ME and to AD induction therapy, respectively (one-tailed P value .99). After accounting for the independent prognostic factors associated with survival (karyotype, performance status, age, white blood cell count), exploratory analysis suggested there was a worse survival for patients who received ME compared with AD induction therapy (2-tailed P value .0066). We conclude that the results of our study do not demonstrate any benefit to the use of ME induction chemotherapy instead of AD in older patients with AML.

scholarly journals Updates in the Management of Newly Diagnosed Acute Myeloid Leukemia

2021 ◽  
Vol 19 (11.5) ◽  
pp. 1358-1361
Author(s):  
Alice S. Mims
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Chemotherapy Patients ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

For patients with newly diagnosed acute myeloid leukemia (AML) who are candidates for intensive induction regimens, all therapies include anthracycline- and cytarabine-based backbones. Core-binding factor AML is typically treated with gemtuzumab ozogamicin and 7 + 3 chemotherapy. Patients with FLT3-mutated (ITD or TKD) disease should have midostaurin + 7 + 3 and consolidation, and those with secondary or therapy-related AML should be considered for CPX-351. For patients ineligible for intensive induction regimens, venetoclax has changed the game and should be used in combination with hypomethylating agents or cytarabine. Glasdegib is also approved in combination with low-dose cytarabine. Patients with IDH1/2-mutated disease can be treated with ivosidenib and enasidenib, respectively. Although enasidenib has yet to secure its spot in the up-front setting, data support its use in newly diagnosed AML. An ongoing question in the field concerns how to treat patients with TP53-mutated AML, because most patients do not respond well to currently available therapies and continue to have poor overall outcomes.

The Influence of Induction Chemotherapy Dose and Dose Intensity on the Duration of Remission in Acute Myeloid Leukemia

1994 ◽  
Vol 15 (1-2) ◽  
pp. 79-84 ◽  
Author(s):  
James F. Bishop ◽  
Jane P. Matthews ◽  
Graham Young ◽  
Jeff Szer ◽  
Douglas E. Joshua ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Dose Intensity ◽  
Chemotherapy Dose ◽  
Acute Myeloid
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