Timed sequential therapy with high-dose cytarabine and mitoxantrone as an induction regimen for acute myeloid leukemia: An update on adverse events.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18524-e18524
Author(s):  
Kristin J. Richardson ◽  
Revathi Kollipara ◽  
Deborah Ann Katz ◽  
Maura Hoyt ◽  
Kirstin Gallas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Day Treatment ◽  
Sequential Therapy ◽  
Neutropenic Fever ◽  
High Response ◽  
High Dose ◽  
Acceptable Safety Profile ◽  
Induction Regimen ◽  
High Dose Cytarabine

e18524 Background: Traditionally, patients eligible for induction chemotherapy for AML are treated with the “7+3” regimen, standard doses of infusional cytarabine and an anthracycline, with historical CR rates of 50-60%. We present a retrospective analysis of an alternate induction regimen. Based on timed sequential therapy, it consists of a 2-day treatment with high dose cytarabine, which improves remission rates when used in induction, and dose intensified anthracycline therapy, which improves outcomes while maintaining an acceptable safety profile. Methods: 200 patients were treated from 2010-2015. Patients received 2 doses of cytarabine 2 gm/m2 (1.5 gm/m2 age > 70 years) IVPB over 3 hours, 12 hours apart followed by 1 dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Cytogenetics and adverse events data were collected. IWG remission criteria were used to determine remission status. Results: Median age 57.6 years (range 23-79); 105 (53%) age > 60. 119 male; 81 female. Risk stratification: 12 favorable; 108 intermediate; 80 unfavorable . Overall CR rate (CRR: CR+CRi+CRp) for all patients was 68.5%. CR rates based on risk karyotypes: favorable 100%, intermediate 76.8%, unfavorable 52.5%. Most common G3-4 adverse events: anemia (60% G3, 40% G4), neutropenia (1% G3, 99% G4), thrombocytopenia (0.5% G1, 99.5% G4). 196 patients (98%) had neutropenic fever; 134 (67%) documented infections (100 with G3/4), 62 (31%) neutropenic fever with no source. 52 (26%) experienced bleeding (15 G1, 31 G2, 4 G3, 1 G4, 1 G5). G3/4 renal or hepatic toxicity was rare. No cerebellar toxicity occurred during induction. 30 day mortality 0.5%; 60 day mortality 3%. 62 (31%) patients are still alive; 122 died, 16 lost to follow-up. Conclusions: This two-day induction regimen is an effective treatment for AML with an acceptable safety profile including patients age >60. There is a high response rate, particularly for favorable and intermediate risk karyotypes, with a low rate of early mortality. The high response rates and tolerability with this regimen provides a platform for further clinical trials to enhance outcome by combining with novel targeted therapies for AML.

Timed sequential therapy with high-dose cytarabine and mitoxantrone as an effective and safe induction regimen for acute myeloid leukemia.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7055-7055
Author(s):  
Melissa L. Larson ◽  
Sakina Burhani ◽  
Kirstin Gallas ◽  
Deborah Ann Katz ◽  
Maura Hoyt ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Sequential Therapy ◽  
High Dose ◽  
Induction Regimen ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Favorable Outcome In Patients with Poor Prognosis Acute Myeloid Leukemia (AML) Using a 2-Day Induction Regimen Incorporating High Dose Cytarabine and Mitoxantrone.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1069-1069
Author(s):  
Melissa L Larson ◽  
Sheena Sahota ◽  
Margaret C Keller ◽  
Bharathi Muthusamy ◽  
Allison Zindell ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Induction Therapy ◽  
Older Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Remission Induction ◽  
High Dose ◽  
Younger Patients ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract Abstract 1069 Background: Cytogenetic data plays an important role in assessing prognosis and determining choice of therapy for AML. Traditionally, patients with AML are treated with infusional cytarabine and an anthracycline. CR rates with this regimen have been reported at 50–60%. Evaluation of novel treatment regimens for AML should include determination of the impact of the regimen on intermediate and unfavorable cytogenetics. We present a retrospective analysis of a 2-day remission induction regimen, based on the concept of timed sequential therapy. The regimen combines high dose cytarabine, which has been shown to improve remission rates when used in induction therapy, and dose intensified anthracycline therapy, which has been shown to improve outcome in younger patients. The cycling cells are eradicated during an initial pulse of therapy, then, previously quiescent cells are targeted during the second pulse of therapy. Here we present the analysis of the study regimen and the response rates of patients with intermediate and unfavorable cytogenetic profiles. Patients and Methods: One hundred fifty five patients categorized as having intermediate or unfavorable cytogenetics were treated with timed sequential chemotherapy from 1998–2009. The treatment regimen consisted of two doses of cytarabine 2 gm/m2 IVPB given over 3 hours, administered 12 hours apart. This was followed by one dose of mitoxantrone 30 mg/m2 IVPB over 1 hour on days 1 and 5. Pre-therapy cytogenetic data was collected for each patient. Responses to therapy were determined based on IWG response criteria for AML. Results: One hundred fifty five patients with intermediate and unfavorable karyotypes received high dose cytarabine and mitoxantrone for remission induction therapy. Median age of patients was 55 years (ranged from 17–85). Sixty patients were 60 years or older. Eighty three patients (53.5%) had intermediate and 72 (46.5%) had unfavorable karyotypes. The younger patients (under 60 years of age) with intermediate cytogenetics achieved the following responses: 34 CR, 6 CRi, and 2 CRp. The overall response rate (ORR) was 80.8% for these younger patients, while the ORR for the older patients (over 60 years of age) with intermediate cytogenetics was 77.4% (15 CR, 4 CRi, 5 CRp). In the unfavorable cytogenetic category, the ORR of the younger patients (under 60 years of age) was 60.5% with 13CR, 8 CRi, and 5 CRp, while an ORR of 44.8% was shown in the older patients (over 60 years of age) with 9 CR, 1 CRi, and 3 CRp. Overall, twenty two out of seventy two (30.5%) had CR in the unfavorable group, 9 (12.5%) had CRi, and 8 (11%) had CRp for an overall response rate of 54%. The 30 day mortality rate was 3.8% (6/155). The 60 day mortality rate was 11.6%. The most common adverse events were Grade 3/4 hematologic toxicities. Conclusion: This convenient, 2-day induction regimen leads to high response rates with low treatment-related mortality in older patients and patients with unfavorable cytogenetic characteristics. Based on the tolerability and effectiveness, this regimen could potentially be useful in high risk transplant-eligible patients for remission induction. It appears that this regimen would also be appropriate for initial cytoreduction in elderly patients with AML prior to introduction of novel therapeutic strategies, such as hypomethylating agents or oral clofarabine for consolidation and maintenance. Disclosures: No relevant conflicts of interest to declare.

Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19037-e19037 ◽  
Author(s):  
Venkata Vosuri ◽  
Ravi Kaisreddy ◽  
Somasekhar Bandi
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Cell Lymphoma ◽  
Meta Analysis ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
High Dose Cytarabine ◽  
Large B Cell

e19037 Background: Salvage chemotherapy followed by autologous stem cell transplantation(ASCT) is the standard second-line treatment for relapsed or refractory diffuse large b-cell lymphoma(DLBCL). Rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE) and rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP) are the two widely used regimens worldwide but quest for optimal regimen continues. Our objective is to compare currently available salvage therapies based on complete response and adverse events. Methods: Pubmed, EMBASE and Clinicaltrials.gov were queried for salvage therapies in relapsed or refractory DLBCL. Only randomized clinical trials including phase 2 and 3 trials involving salvage therapies for relapsed or refractory DLBCL were selected. Data was extracted based on meta-analysis guidelines by two independent reviewers. Network meta-analyses of treatment effects and adverse outcomes were calculated with a frequentist approach. Results: Overall, 5 studies(1480 patients) were included. The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). Of the 6 regimens in the network, treatment with R-DHAP (OR:0.36,95%CI:0.24-0.54), R-GDP(OR:0.37,95%CI: 0.21-0.65), O-ICE(OR:0.16,95%CI: 0.05-0.53), O-DHAP(OR:0.30,95%CI:0.17-0.52), DR-ICE(OR:0.77,95%CI:0.40-1.49) were not superior against network placebo(R-ICE) in achieving complete response. Higher odds of occurring severe adverse events was observed in R-DHAP(OR:2.02,95%CI: 1.35-3.01) and O-DHAP(OR:2.15,95%CI: 1.24-3.72) salvage regimens when compared to R-ICE. Conclusions: R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease.

Effective Remission Induction for AML Using Two Days of Chemotherapy: Older Patients Tolerate and Respond Equally Well

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4004-4004
Author(s):  
Neel B. Shah ◽  
Melissa L. Larson ◽  
Nitin Goyal ◽  
Ann M. Thomas ◽  
Jamile M. Shammo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Older Patients ◽  
Response Rates ◽  
Remission Induction ◽  
High Dose ◽  
Refractory Disease ◽  
Toxicity Profile ◽  
Induction Regimen ◽  
High Dose Cytarabine

Abstract Background: The remission induction regimen used for treatment of adult AML has traditionally been the “7+3” regimen, which has not changed significantly since 1981. CR rates have been in the 55–60% range, historically. We present a single institution, retrospective analysis of a regimen consisting of two pulses of chemotherapy 96 hours apart with high-dose cytarabine and mitoxantrone. It is based on the concept of timed sequential therapy where the first pulse of chemotherapy recruits leukemic cells into the cell cycle and is followed by the second pulse at the time of peak cell recruitment. Cytarabine is a cell cycle-specific drug, and mitoxantrone was chosen because of its resistance to the effects of the gene MDR1, which is commonly expressed in adult leukemia, as well as its favorable cardiac toxicity profile. Patients and Methods: One hundred four patients with AML were treated with timed sequential chemotherapy from April 1997 to April 2008. Each pulse of chemotherapy consisted of 2 doses of cytarabine 2gm/m2 given 12 hours apart (at t=0 and t=12) followed by one dose of mitoxantrone 30 mg/m2 administered after the second cytarabine dose (t=15) given on days 1 and 5. Bone marrow biopsies were performed to assess for leukemia free-state (day 14) and subsequently for remission documentation. Responses were defined per the Revised IWG Recommendations (Cheson, J Clin Onc21: 4642, 2003). Toxicities, response rates, relapse rates, and preexisting conditions were also recorded. Results: Median age of the 104 patients was 57 y [range 17–79]. There were 47 males and 57 females. Forty-two patients (40%) were 60 years of age or older with 17 (16%) of them older than 70 years. Forty patients (38%) had preexisting MDS. Five patients (4.8%) had favorable cytogenetics, 61 (58.7%) had intermediate cytogenetics, and 38 (36.5%) had unfavorable cytogenetics. Seventy-four patients (71%) achieved a leukemia free state based on the day 14 bone marrow biopsy. At the time of the remission documentation bone marrow biopsy, the IWG-defined responses seen are the following: 56 CR (53.8%), 9 CRi (8.6%), and 10 CRp (9.6%). Three additional patients (2.9%) had a return to MDS (RMDS). Twenty patients (19.2%) had refractory disease. Overall, 78 patients had a response, (ORR=75%). The 30-day mortality rate was 2.8% (3/104). In the 62 patients under 60 years of age, 51 (82%) responded to chemotherapy. In the 42 patients age 60 and older, 27 had a response (64%). Thirteen of the seventeen patients age 70 and older had a response (10 CR, 2 CRp, 1 CRi) for an ORR of 76.4%. The remaining 4 patients in this age group had refractory disease. Conclusion: This remission induction regimen of high dose cytarabine and mitoxantrone produces very high response rates, even in the older AML patients. The response rates in both younger patients and older patients compare favorably with the rates historically seen with the standard 7 + 3 regimen. The 30-day mortality rate of less than 3% is less than that previously reported with the 7 + 3 regimen. This may be attributable to improvements in supportive care; although, this could also represent the favorable toxicity profile of this effective, novel regimen.

Modified VR-CAP, Alternating With Rituximab and High-dose Cytarabine: An Effective Pre-transplant Induction Regimen for Mantle Cell Lymphoma

2019 ◽  
Vol 19 (1) ◽  
pp. 48-52
Author(s):  
Stephen D. Smith ◽  
Shruti Gandhy ◽  
Ajay K. Gopal ◽  
Prathima Reddy ◽  
Mazyar Shadman ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose ◽  
Mantle Cell ◽  
Induction Regimen ◽  
High Dose Cytarabine

scholarly journals HIGH-DOSE SUBLINGUAL ALLERGEN IMMUNOTHERAPY: ADVISABILITY AND SAFETY

2014 ◽  
Vol 11 (3) ◽  
pp. 63-67
Author(s):  
O M KURBACHEVA ◽  
K S PAVLOVA
Keyword(s):  
Allergic Rhinitis ◽  
Adverse Events ◽  
Safety Profile ◽  
Allergen Immunotherapy ◽  
Evidence Base ◽  
High Dose ◽  
Future Studies ◽  
High Profile ◽  
Good Safety Profile ◽  
High Doses

Efficacy of the allergen immunotherapy (ait) in the treatment of allergic rhinitis and asthma has been proved in many studies and systematic reviews. Higher safety profile of sublingual ait (slit) relative subcutaneous ait (sCit) defines preferences of slit. although the results of the first study of slit were published about 25 years ago and a lot of allergenic products for slit appeared during this period, poor evidence base and a lack of direct comparative controlled studies on the efficacy of slit vs sCit support debate about what way of allergen administration is more effective. it is possible, that lower efficacy of slit showed in earlier studies explains for the use of regimes with low daily and cours doses of allergens. in a recent review of the eaaCi it was shown the dosedependent therapeutic effect of ait, and was noted that an increase of the maintenance allergen dose while sCit increases the risk of adverse events, vs high doses slit demonstrates good safety profile with a significant increase of efficacy. it is possible that future studies using high doses of standardized allergens for slit will show not only more high profile of slit safety, but also its higher efficacy vs sCit.

scholarly journals Outcomes of Non-anesthesiologist-Administered Propofol in Pediatric Gastroenterology Procedures

2021 ◽  
Vol 8 ◽  
Author(s):  
Frances C. Lee ◽  
Karen Queliza ◽  
Bruno P. Chumpitazi ◽  
Amber P. Rogers ◽  
Catherine Seipel ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
General Anesthesia ◽  
Safety Profile ◽  
Event Rate ◽  
Adverse Event Rate ◽  
Gastrointestinal Adverse Event ◽  
Acceptable Safety Profile ◽  
Physical Classification ◽  
American Society

Background and Aims: Non-anesthesiologist-administered propofol (NAAP) has been found to have an acceptable safety profile in adult endoscopy, but its use remains controversial and pediatric data is limited. Our aim was to examine the safety and efficacy of NAAP provided by pediatric hospitalists in pediatric endoscopy.Methods: We retrospectively reviewed 929 esophagogastroduodenoscopy (EGD), colonoscopy, and combined EGD/colonoscopy cases in children aged 5–20 years between April 2015 and December 2016 at a large children's hospital. We analyzed the data for adverse events in relation to demographics and anthropometrics, American Society of Anesthesiologists physical classification score, presence of a trainee, comorbid conditions, and procedure time.Results: A total of 929 cases were included of which 496 (53%) were completed with NAAP. Seventeen (3.4%) of NAAP cases had an adverse event including the following: 12 cases of hypoxia, 2 cardiac, and 3 gastrointestinal adverse events. General anesthesia cases had 62 (14.3%) adverse events including the following: 54 cases of hypoxia, 1 cardiac, 7 gastrointestinal, and 1 urologic adverse event. No adverse events in either group required major resuscitation. NAAP vs. general anesthesia had a lower overall adverse event rate (3.4 vs. 14.3%, p < 0.0004) and respiratory adverse event rate (2.4% vs. 12.5%, p < 0.0004). Overall, cardiac and gastrointestinal adverse event rates between the two groups were comparable. When accounting for all captured factors via logistic regression, both younger age (P < 0.001) and general anesthesia (P < 0.0001) remained risk factors for an adverse event.Conclusion: The overall adverse event rate of NAAP was low (3.4%) with none requiring major resuscitation or hospitalization. This is comparable to studies of NAAP in adult endoscopy and suggests that NAAP provided by pediatric hospitalists has an acceptable safety profile.

scholarly journals Comparison of Pegfilgrastim and Filgrastim to Prevent Neutropenic Fever during Consolidation with High Dose Cytarabine for Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1404-1404
Author(s):  
Evan Field ◽  
Paolo F Caimi ◽  
Brenda Cooper ◽  
Jane Little ◽  
Ehsan Malek ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Advisory Board ◽  
Neutropenic Fever ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract Background: Granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever is a well-accepted standard of care to minimize the risk of neutropenic fever during consolidation chemotherapy for acute myeloid leukemia (AML). Although prospective, randomized clinical trials of filgrastim versus depot pegfilgrastim demonstrated biologic equivalency, retrospective studies in patients with solid tumors suggest the use of pegfilgrastim results in reduced rates of admission for neutropenic fever. Patients undergoing AML consolidation may be at higher risk for admission, as with solid tumors. Biosimilars for filgrastim (filgrastim-sndz and tbo-filgrastim) and pegfilgrastim (pegfilgrastim-jmdb) are creating market forces that may make daily administered agents an attractive alternative to pegfilgrastim, and therefore additional observational studies to clarify of the safety of daily administered G-CSF vs depot injections. We hypothesize that the use filgrastim over pegfilgrastim may result in higher hospital admission rates in AML patients undergoing consolidation chemotherapy outside the setting of prospective trials. Methods: Patient charts from the year 2004 through early 2017 diagnosed with AML at the Seidman Cancer Center of University Hospitals Cleveland Medical Center (UHCMC) were reviewed as a retrospective cohort study. Patient were included who received at least one cycle of high dose cytarabine during 1st complete remission, and received filgrastim or pegfilgrastim were considered available for analysis. Individual cycles of chemotherapy were assessed for potential adverse outcomes with the use of different forms of GCSF. The primary outcome of interest is hospitalization during consolidation chemotherapy. The incidence of hospitalization was analyzed using longitudinal logistic regression with generalized estimating equations for statistical inference assuming exchangeable variance-covariance structure of multiple hospitalizations from the same patients. Results 436 patient charts were reviewed identifying 165 patients receiving at least one cycle of HiDAC chemotherapy. Of these, 156 patients received either filgrastim or pegfilgrastim, representing 256 cycles of high dose cytarabine chemotherapy supported with GCSF. Patients receiving filgrastims vs pegfilgrastim differed in the number of HiDAC cycles received (1.64 vs 1.97, p = 0.046), the distribution of favorable risk AML (11.9% vs 32.7%, p = 0.035). Groups did not differ based on age, sex, race, initial response to therapy, and proportion of secondary AML. After controlling the effects of age, sex, race and initial clinical response, treatment (filgrastim vs. pegfilgrastim) was significantly associated with hospitalization during consolidation therapy (p = 0.005). Specifically, the odds of having hospitalization for patients treated with Filgrastim is estimated to be 2.31 times the odds of having hospitalization for patients treated Pegfilgrastim with 95% CI (1.28, 4.17). Also, the estimated probability of having hospitalization for patients treated with filgrastim was 0.59 (95% CI: 0.43- 0.73) vs. 0.38 (95% CI: 0.27 - 0.51) for patients treated with pegfilgrastim. Conclusions: The use of filgrastim was found to be statistically significantly associated with and increased risk of hospitalization. Disclosures Caimi: Kite Pharma: Other: Advisory Board Participation; Celgene: Speakers Bureau; Genentech: Other: Advisory Board PArticipation, Research Funding; Kite Pharma: Other: Advisory Board Participation. Little:PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding. Malek:Sanofi: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

Gemtuzumab-Ozogamicin in Combination with Fludarabine, Cytarabine, Idarubicin (FLAI-GO) as Induction Therapy in CD33-Positive AML patients Younger Than 65 Years. Report of a Multicentric Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3998-3998
Author(s):  
Anna Candoni ◽  
Giovanni Martinelli ◽  
Cristina Papayannidis ◽  
Erica Simeone ◽  
Eleonora Toffoletti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Response Rate ◽  
Residual Disease ◽  
Target Therapy ◽  
Prospective Trial ◽  
Gemtuzumab Ozogamicin ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Induction Regimen

Abstract INTRODUCTION. The addition of Gemtuzumab-ozogamicin (GO) to an induction regimen including synergistic drugs, such as intermediate dose of cytarabine (Ara-C), idarubicin and fludarabine (FLAI), could reduce treatment failure in AML patients. Nevertheless, the role and safety of this antibody target-therapy in first-line chemotherapy in patients younger than 65 years has not yet been defined. PATIENTS and METHODS. The primary goal of this multicenter prospective trial (EUDRACT Number 2007-005248-26) was to evaluate the efficacy and the safety profile of FLAI plus GO as induction regimen. Sixty-eight consecutive AML patients were included from five Italian hematological centres. All patients were younger than 65 with a median age of 48 years and CD33 expression exceeded 20% in all cases. The M/F ratio was 37/31, and 54/68 (79%) of patients were poor-risk at diagnosis. The induction regimen (FLAI-GO) included fludarabine (30 mg/sqm) and Ara-C (2 g/sqm) on days 1–5, idarubicin (10 mg/sqm) on days 1, 3, and 5 and GO (3 mg/sqm) on day 6. Hematopoietic stem cell transplant (HSCT) was planned for all high risk AML patients in first complete remission (CR) after consolidation with intermediate doses of Ara-C and idarubicin (IDAC-IDA). Cytogenetic, multidrug-resistance phenotype, FLT3 mutation status, and WT1 quantitative expression analyses were performed at diagnosis in all patients. WT1 expression and cytogenetic (in positive cases) analyses were performed after induction to detect and follow Minimal Residual Disease. RESULTS. Patients were evaluated for response rate, treatment-related adverse events, overall survival and relapse free survival. After induction with FLAI-GO, CR rate was 86% (54 of 63 evaluable pts); one patient achieved partial remission and eight were resistant. There were only two cases of death during induction (DDI). After FLAI-GO, the mean value of WT1 dropped from 4540±2342 copies/104ABL to 180±277 copies/104ABL. The toxicity of FLAI-GO was acceptable; 58% of patients experienced transient and reversible GO infusion-related adverse events (especially fever and chills), but no cases of veno-occlusive disease occurred during CHT or after HSCT. After a median follow-up of 9 months (range 1–32), 60/68 (88%) patients are alive (57/60 in CR). The probability of 12 and 18 mths OS a was 91% and 78%, respectively. The probability of 12 and 18 mths RFS was 87 % and 78%, respectively. Allogeneic and autologus HSCT was performed in 30 (44%) and 8 (12%) patients. CONCLUSIONS. The preliminary results of this multicentric trial confirm that FLAI-GO is an effective and well tolerated induction regimen for CD33 positive AML patients younger than 65 years, with a high complete response rate, favourable safety profile and low DDI.

Tolerability of An Effective Two Day Induction Regimen for Newly Diagnosed AML

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4035-4035
Author(s):  
Melissa L. Larson ◽  
Nitin Goyal ◽  
Ann M. Thomas ◽  
Jamile M. Shammo ◽  
John J. Maciejewski ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Induction Therapy ◽  
Dose Intensity ◽  
Remission Induction ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Refractory Disease ◽  
Induction Regimen ◽  
High Dose Cytarabine ◽  
Grade 3

Abstract Background: The standard remission induction regimen for treating Acute Myeloid Leukemia consists of seven days of continuous infusion cytarabine and three days of an anthracycline, the “7 + 3” regimen. We present a single institution, retrospective analysis of toxicity associated with a regimen that requires only two days of chemotherapy using high dose cytarabine and mitoxantrone. The regimen is based on the timed sequential therapy concept where two pulses of chemotherapy are given. The first pulse recruits cells into the cell cycle, while the second pulse is given at the time of peak recruitment. Methods: One hundred four patients with AML were treated with two days of chemotherapy given 96 hours apart from April 1997 to April 2008. Each day of chemotherapy consisted of two doses of cytarabine 2gm/m2 (at t=0 and t=12) followed by one dose of mitoxantrone 30 mg/m2 administered after the second cytarabine dose (t=15). Each patient’s chart and electronic record were thoroughly reviewed, and toxicities associated with induction therapy were analyzed and graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events v3.0. Responses were defined per the Revised IWG Recommendations (Cheson, J Clin Onc21: 4642, 2003). Results: One hundred four patients were eligible for toxicity evaluation. Hematologic toxicities were the most common toxicities seen with this induction therapy. Overall, all patients experienced hematologic toxicity of some grade with 98% of patients having one or more Grade 3/4 hematologic toxicity. The incidences of grade 3/4 hematologic toxicities are the following: Hemoglobin 65.3% (Gr 3 59.6%, Gr 4 5.7%), thrombocytopenia 93.2% (Gr 3 9.6%, Gr 4 83.6%), and neutropenia 89.4% (Gr 3 1.9%, Gr 4 87.5%). Febrile neutropenia occurred in 64% of the patients, and grade 3 and 4 infections occurred in 25%. Common non-hematologic toxicities included fatigue, nausea, vomiting, diarrhea, and electrolyte abnormalities. The vast majority of non-hematologic toxicities were grade 1 and 2. Three patients (2.9%) died within the first 30 days of induction therapy. One patient died before completing therapy due to massive hemoptysis. One died from complications of refractory disease, and the third patient died from disseminated fungal infection. An additional 10 patients (6 TF-RD, 1 TF-aplasia, 1 CR, 1 CRi, 1 CRp) died within the first 60 days. Of the 6 patients with refractory disease, 4 received re-induction therapy to which 3 did not have a response and the fourth died of sepsis while aplastic. Two patients had intracerebral hemorrhage (TF-aplasia and CRp). One patient died suddenly in CR of unknown causes and one patient (CRi) died from complications of pneumonia/ARDS. Conclusion: Although this regimen incorporating high dose cytarabine into remission induction presents a significantly higher dose intensity of cytarabine and mitoxantrone compared to that of the “7+3” regimen, the toxicity profile and 30-day mortality rate compare favorably to the “7 + 3” regimen. This regimen has been shown to produce a CR rate comparable to that of the “7+3” regimen with equal efficacy and better tolerance in elderly patients with AML. We conclude that this regimen effectively administers a high yet apt dosage of chemotherapy, and it can even be used for remission induction in elderly patients. This induction regimen could serve as a platform for future studies of maintenance and biologic therapies in the elderly AML patients.

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