Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1754-1762 ◽  
Author(s):  
Xavier Thomas ◽  
Mohamed Elhamri ◽  
Emmanuel Raffoux ◽  
Aline Renneville ◽  
Cécile Pautas ◽  
...  
Keyword(s):  
Risk Groups ◽  
High Dose ◽  
Consolidation Therapy ◽  
Sequential Chemotherapy ◽  
Younger Adults ◽  
Significant Difference ◽  
High Dose Cytarabine ◽  
First Remission ◽  
The Difference ◽  
Cytogenetically Normal Aml

Abstract To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association–9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1+ or CEBPA+ and FLT3-ITD− had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.

Impact of Pegfilgrastim and Dosing Schedule of Cytarabine on Hematological Reconstitution Times, Incidences of Severe Infection and Duration of Hospitalization after Consolidation Therapy with High-Dose Cytarabine in Acute Myeloid Leukaemia - Interim Results from AMLSG 07-04 Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1836-1836
Author(s):  
Richard F. Schlenk ◽  
Konstanze Döhner ◽  
Silja Groner ◽  
Peer C. Hartmann ◽  
Jürgen Krauter ◽  
...  
Keyword(s):  
Severe Infection ◽  
Risk Groups ◽  
Control Group ◽  
High Dose ◽  
Consolidation Therapy ◽  
Intention To Treat ◽  
Single Center Experience ◽  
High Dose Cytarabine ◽  
Duration Of Hospitalization ◽  
Number Of Cycles

Abstract Introduction: Therapy using high-dose cytarabine (HiDAC) according to the CALGB scheme (3g/m2 bid. days 1,3,5) is recognized as a standard consolidation treatment for younger adult patients (pts) with AML. Pegfilgrastim (PF) has been shown to be effective in reducing the duration of neutropenia in treatment of solid tumors and it seems to be even more effective than Filgrastim in reducing the incidence of infection. Methods: The AMLSG 07-04 trial (NCT00151242) was initiated in September 2004 (age 18–60 yrs). Consolidation therapy for cytogenetic favorable- and intermediate-risk groups consists of 3 cycles of HiDAC (3g/m2 bid. days 1,3,5) with PF 6mg given at day 10 (1-3-5 schedule) or after amendment no. 2 of HiDAC (3g/m2 bid. days 1,2,3) with PF 6mg given at day 8 (1-2-3 schedule). As a control group, pts randomized from AMLSG into the German AML Intergroup protocol using the standard 1-3-5 schedule for consolidation therapy with allowed interventional application of G-CSF were used. Results: Data from 251 pts and a total of 584 cycles are available (137 pts and 324 cycles, 1-3-5 schedule; 78 pts and 185 cycles, 1-2-3 schedule; 36 pts and 75 cycles, German AML Intergroup standard arm). Data from all three consolidation cycles were pooled for the comparison between the AMLSG 07-04 1-3-5 schedule and the German AML Intergroup standard arm. The duration of leukopenia (LP) and neutropenia (NP) were significantly shorter in pts receiving PF within the AMLSG 07-04 trial compared to pts within the German AML Intergroup standard arm (intention-to-treat, p=0.08 and p=0.03; as-treated, p=0.01 and 0.008, respectively). This beneficial effect of PF on LP and NP increased with the number of cycles. This was paralleled by a lower incidence of infection ≥CTC grade 3 with 40% in the 1-3-5 schedule and 67% in the German AML Intergroup standard arm (p<0.0001). The comparison of the 1-2-3 schedule with the 1-3-5 schedule within the AMLSG 07-04 protocol revealed significantly shorter LP and NP in favor for the 1-2-3 schedule (p=0.03 and p=0.004, respectively). In median, pts after the 1-3-5 and the 1-2-3 schedule achieved a leukocyte count above 1.0/μl and a neutrophil count above 0.5/μl at day 20 and day 22 as well as 16 and 17, respectively. In a single center experience using out patient platelet and red blood cell support, the median time of hospitalization for the 1-3-5 (n=32 cycles) and the 1-2-3 (n=25) schedule could be reduced to 7.5 and 5 days with incidences for readmission of 33% and 12.5%, respectively. Conclusion: The administration of PF after HiDAC-based consolidation therapy in AML significantly shortened the duration of leuko- and neutropenia, reduced the rate of severe infections, and reduced the period of hospitalization.

scholarly journals Aminoglycoside trough levels in neonates

2010 ◽  
Vol 138 (1-2) ◽  
pp. 50-55 ◽  
Author(s):  
Biljana Pejovic ◽  
Milica Rankovic-Janevski ◽  
Niveska Bozinovic-Prekajski
Keyword(s):  
Gestational Age ◽  
Trough Level ◽  
Inverse Correlation ◽  
Risk Groups ◽  
Target Range ◽  
Group I ◽  
Significant Difference ◽  
Group Ii ◽  
The Difference ◽  
Trough Levels

Introduction. Drug safety depends on trough levels. Objective. Objective of the study was to measure gentamicin and amikacin trough levels in neonates and to identify risk groups by gestational and postnatal age. Methods. Gentamicin and amikacin were applied according to the clinical practice guidelines. Trough levels (mg/l) were deter- mined using fluorescence polarization immunoassay methodology. Target trough levels were <2 mg/l for gentamicin, and <10 mg/l for amikacin. Patients were divided in 3 groups by gestational age: I ?32, II 33-36, and III ?37 gestational weeks and, by postnatal age, in 2 groups: ?7 and >7 days. Results. Out of 163 neonates, 111 were receiving gentamicin and 52 amikacin. Mean amikacin trough level was 7.8?4.8 mg/l and, in group I 10.5?4.9 mg/l, which was above the target range and significantly higher than in group II (LSD, p<0.05). In the amikacin group, 26 patients were 7 and less, and 26 more than 7 days old, without significant differences in trough levels between the groups. In the gentamicin group, 52.3% of neonates had trough values within the target range. Gentamicin trough level in group I was above the trough range, 3.7?1.8, 2.3?1.5 in group II and, 1.8?1.4 mg/l in group III. The difference in trough levels among the groups was highly significant (F=9.015, p<0.001, ?2=17. 576, p<0.001). Further analysis revealed that differences between groups I and II (LSD, p=0.002) and between I and III (LSD, p=0.000) were highly significant. Conclusion. Obtained gentamicin and amikacin trough levels are high. Inverse correlation has been confirmed between trough level and gestational age, with highly significant difference, and the risk group has been identified. There is obviously a need to change the dosing regimen in terms of those with extended intervals, particularly for neonates of the lowest gestational age, along with pharmacokinetic measurements.

scholarly journals Varying intensity of postremission therapy in acute myeloid leukemia

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1924-1930 ◽  
Author(s):  
PA Cassileth ◽  
E Lynch ◽  
JD Hines ◽  
MM Oken ◽  
JJ Mazza ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Mortality Rate ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Postremission Therapy ◽  
Acute Myeloid

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6- thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four- year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

Safety and feasibility of outpatient high-dose cytarabine and intermediate-dose cytarabine for consolidation therapy in acute myeloid leukemia

2021 ◽  
pp. 107815522110465
Author(s):  
Wenhui Li ◽  
Katherine Richter ◽  
Jamie Lee ◽  
Kevin McCarthy ◽  
Timothy Kubal
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Outpatient Setting ◽  
Cancer Center ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Incidence Of Hospitalization ◽  
Acute Myeloid ◽  
Intermediate Dose

Introduction The standard of care consolidation therapy for acute myeloid leukemia is high-dose cytarabine or intermediate-dose cytarabine, which are traditionally given inpatient. At Moffitt Cancer Center, we have moved the administration of high-dose cytarabine and intermediate-dose cytarabine to the outpatient setting through the inpatient/outpatient program. To facilitate outpatient administration, high-dose cytarabine and intermediate-dose cytarabine are given in a shorter interval of every 10 h instead of 12 h. The safety of a shorter duration interval of high-dose cytarabine and intermediate-dose cytarabine is unknown. This study aims to assess the safety and feasibility of administering high-dose cytarabine and intermediate-dose cytarabine consolidation therapy in the inpatient/outpatient setting. Methods This is a retrospective chart review to analyze acute myeloid leukemia patients treated with inpatient/outpatient high-dose cytarabine or intermediate-dose cytarabine consolidation therapy at Moffitt Cancer Center from January 1, 2015, through November 1, 2018. The primary objective was to determine the incidence of hospitalization during the inpatient/outpatient administration of high-dose cytarabine or intermediate-dose cytarabine. Results Two hundred fifty-three of 255 cycles of high-dose cytarabine/intermediate-dose cytarabine were delivered outpatient over the reviewed time period to 118 patients. No patients receiving outpatient high-dose cytarabine/intermediate-dose cytarabine consolidation required hospitalization during chemotherapy. Our incidence of hospitalization (24%) after chemotherapy is consistent with the reported literature. Through the inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine, 1265 inpatient days were saved with an approximate revenue of $3,135,176 generated in our study period. Conclusion Inpatient/outpatient administration of high-dose cytarabine and intermediate-dose cytarabine is both safe and feasible. Moving high-dose cytarabine/intermediate-dose cytarabine administration to the outpatient setting resulted in significant additional revenue vs. inpatient administration.

Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.

1992 ◽  
Vol 10 (4) ◽  
pp. 644-646 ◽  
Author(s):  
L F Verdonck ◽  
A W Dekker ◽  
G C de Gast ◽  
H M Lokhorst ◽  
H K Nieuwenhuis
Keyword(s):  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Lymphoblastic Lymphoma ◽  
Adult Patients ◽  
High Dose ◽  
Consolidation Therapy ◽  
Poor Risk ◽  
First Remission ◽  
Autologous Bone

PURPOSE Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.

Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.

1992 ◽  
Vol 10 (1) ◽  
pp. 41-46 ◽  
Author(s):  
G J Schiller ◽  
S D Nimer ◽  
M C Territo ◽  
W G Ho ◽  
R E Champlin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Disease Free Survival ◽  
High Dose ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
High Dose Cytarabine ◽  
First Remission ◽  
Disease Free

PURPOSE Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission. PATIENTS AND METHODS The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy. RESULTS After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%). CONCLUSIONS Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.

Repetitive Cycles of High-Dose Cytarabine Benefit Patients With Acute Myeloid Leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461

2004 ◽  
Vol 22 (6) ◽  
pp. 1087-1094 ◽  
Author(s):  
John C. Byrd ◽  
Amy S. Ruppert ◽  
Krzysztof Mrózek ◽  
Andrew J. Carroll ◽  
Colin G. Edwards ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
The Impact ◽  
To Receive ◽  
Acute Myeloid

Purpose To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22). Patients and Methods We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy. Results Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. Conclusion We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.

In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission.

1996 ◽  
Vol 14 (8) ◽  
pp. 2206-2216 ◽  
Author(s):  
A S Stein ◽  
M R O'Donnell ◽  
A Chai ◽  
G M Schmidt ◽  
A Nademanee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adult Patients ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Acute Myelogenous ◽  
Intent To Treat ◽  
First Complete Remission

PURPOSE To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT.

Cologne High-Dose Sequential Chemotherapy in Relapsed and Refractory Hodgkin Lymphoma - Results of a Large Multicenter Study of the German Hodgkin Lymphoma Study Group (GHSG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 309-309 ◽  
Author(s):  
Andreas Josting ◽  
Christian Rudolph ◽  
Markus Mapara ◽  
Jan-Peter Glossmann ◽  
Markus Sieber ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Hodgkin Lymphoma ◽  
Late Relapse ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Eligibility Criteria ◽  
First Results ◽  
First Remission ◽  
Multiple Relapse ◽  
Lymphoma Study Group

Abstract Purpose: Combination chemotherapy can cure patients (pts) with Hodgkin lymphoma (HD), but those with treatment failure or relapse still have a poor prognosis. We thus, designed a dose- and time-intensified high-dose sequential chemotherapy regimen with a final myeloablative course. Patients and Methods: Eligibility criteria included age 18–65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consists of two cycles DHAP (dexamethasone 40mg d1-4, high-dose cytarabin 2g/m2 12q d2, cisplatinum 100mg/m2 d1); pts with partial (PR) or complete remission (CR) received cyclophosphamide 4g/m2, followed by peripheral blood stem cell (PBSC) harvest; methotrexate 8g/m2 plus vincristine 1,4mg/m2; and etoposide 2g/m2. The final myeloblative course was BEAM followed by PBSCT. Results: 102 pts (median age 34 years, range 18–64) were enrolled. The response rate (RR) at the final evaluation (100 days posttransplantation) was 80% (72% CR, 8% PR). PBSC harvest was succesful in 96% of pts. Toxicity was tolerable. With a median follow-up of 30 months (range 3–61 months) freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD: 41% and 48% and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after 2 cycles of DHAP (p &lt; 0.0001) and duration of first remission (PD and multiple relapse vs. early and late relapse; p = 0.0127) were prognostic factors for FF2F. Response after DHAP (p &lt; 0.0081), duration of first remission (p = 0.0017) and anemia (p = 0.019) were identified as prognostic factors for OS. Conclusion: We conclude that this regimen is feasible, tolerable and highly effective in poor risk patients with relapsed and refractory HD. Based on these results a prospective randomized european intergoup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol). First results of the second interim analysis of this study will be presented.

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