Is Consolidation and/or Maintenance Treatment a Standard Therapy in Elderly AML in First Complete Remission?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2775-2775
Author(s):  
Elise Corre ◽  
Jean-Pierre Marie ◽  
Ollivier Legrand
Keyword(s):  
Complete Remission ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
P Value ◽  
Consolidation Therapy ◽  
Term Survival ◽  
Postremission Therapy ◽  
Wbc Count ◽  
First Complete Remission

Abstract The treatment of elderly patients with acute myeloid leukemia (AML) is very disappointing. Studies have established that if half of the intensivity treated patients achieve complete remission (CR), the high rate of relapse within the first year jeopardize the long term survival. No clearly effective postremission therapy had been established. Therefore we retrospective analyzed 141 elderly patients (>60 yo) in first CR, to evaluate the effectiveness of postremission therapy, consolidation (3+7or 2+5) and/or maintenance (low dose AraC). All patiens received a 3+7 induction therapy. In these 141 patients DFS and OS at 4 years are respectively 14%, and 19%. According to the clinical status of the patient after induction, 20 (14%) patients did not receive therapy after induction, 30 (21%) patients received only maintenance therapy, 53 (38%) patients received only consolidation therapy, and 38 patients (27%) received both consolidation and maintenance therapy. These 4 groups were stratified according to age (< >70 yo) and WBC (< or > 30 x 109/l) (See Tables). The outcome of these patients receiving or not post induction therapy is shown in these Tables. Patients DFS at 4 years OS at 4 years Consolidation No consolidation P value consolidation No consolidation P value Outcome of patients receiving or not consolidation therapy in 4 groups stratified according to age and WBC count < 70yo and WBC< 30x109/l 19% 13% p=0.01 27% 13% p=0.0074 <70yo and WBC>30x109/l 26% 0% p=0.08 38% 0% p=0.05 >70 yo and WBC < 30x109/l 0% 30% p=0.001 6% 30% p=0.01 >70 yo and WBC> 30x109/l 2% 0% NS 4% 0% NS In patients > 70 yo and WBC < 30 x 109/l patients who received consolidation have a poorer prognosis than patients who did not because the mortality in first complete remission (mortality during consolidation) was high (25% versus 0% respectively, P=0.01). Patients DFS at 4 years OS at 4 years Maintenance No Maintenance p value Maintenance No Maintenance P value Outcome of patients receiving or not maintenance therapy in 4 groups stratified according to age and WBC count <70yo and WBC<30x109/ 17% 20% NS 22% 25% NS <70 yo and WBC>30x109/l 23% 14% p=0.05 32% 23% NS >70 yo and WBC<30x109/l 25% 5% p=0.01 25% 5% p=0.008 >70 yo and WBC >30x109/l 2% 0% NS 4% 0% NS In conclusion, in patients < 70 yo consolidation ± maintenance therapy (for DFS in patients with > 30 x109/l) improves the outcome of these patients (DFS and OS). In patients > 70 yo and with WBC < 30 x109/l maintenance therapy without consolidation, improves outcome. In these later patients (> 70 yo and with WBC < 30 x 109/l) consolidation therapy decrease outcome. In patients > 70yo and with WBC > 30 x 109/l, both consolidation and/or maintenance therapy does not improve outcome.

Reduction of Relapse Incidence and Improvement of Leukemia Free Survival by Allogeneic Stem Cell Transplantation in Patients with AML and Normal Karyotype Irrespective of the FLT3-ITD Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1612-1612
Author(s):  
Frank Schueler ◽  
Nadezda Basara ◽  
Georg Maschmeyer ◽  
Thomas Fischer ◽  
Michael Herold ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Poor Prognosis ◽  
Normal Karyotype ◽  
Consolidation Therapy ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Postremission Therapy ◽  
Treat Analysis ◽  
First Complete Remission

Abstract Abstract 1612 Poster Board I-638 Cytogenetically normal AML (CN-AML) is a heterogeneous disease with molecular markers impacting considerably on survival. Acquired gene mutations such as the internal tandem duplication (ITD) of the FLT3 gene has been shown to be associated with poor prognosis. Furthermore, it has been shown that the poor prognosis in the group of patients with high risk cytogenetics could be improved, when a consolidation therapy with allogeneic stem cell transplantation (HCT) was performed. To investigate the importance of a postremission consolidation therapy in CN-AML patients according their mutational status for the FLT3-ITD mutation we compared the clinical outcome in these patients on an intention to treat analysis. A total of 800 patients have been entered into two OSHO (East German study group for hematology and oncology) studies between 1997 and now. The first protocol (AML 96) compared two different induction schedules employing different schedules of intermediate AraC and Idarubicin. The second protocol (AML 2002) studied the role of two different induction therapies in patients failing to reach CR after the first induction therapy. From the 800 patients treated within these protocols 338 pts. had a normal karyotype. Complete remissions were obtained in 277 patients after one or two induction cycles. Out of these patients 78 pts received a consolidation therapy by allogeneic HCT whereas 169 pts were further treated by conventional chemotherapy or by autologous transplantation. HCT was performed after conditioning with cytoxan and 1200 cGy total body irradiation followed by GvH-D prophylaxis with cyclosporine and methotrexate. Material at the time of diagnosis to analyse the presence of a FLT3-ITD mutation was available in 116 pts. Of those, 70 patients received conventional chemotherapy whereas 46 pts. were transplanted from an allogeneic donor as postremission therapy. Data were analyzed on an intend-to-treat-analysis in 116/277 patients being in CR1 after induction therapy from whom a FLT3-ITD mutation analysis was available. The EFS in this cohort of 116 patients was 38% after 5 years. Within the subgroup of patients (n=46) who received a HCT from an allogeneic donor the EFS was 44% compared to 33% (p=0.19) within the subgroup of conventional treated patients(n=70). As previously described, the detection of a FLT3-ITD mutation had a negative impact on event free survival which was calculated with 25% after 5 years in contrast to 46% in FLT3-ITD negative patients (p=0.06). In a further step EFS was analyzed according to the FLT3 status and the postremission treatment given. The EFS in conventional treated patients was significantly different (FLT3-ITD negative: LFS=50% vs. FLT3-ITD positive: LFS=19%; p=0.05). But, allogeneic HCT in first complete remission equalizes this difference (FLT3-ITD negative: LFS=50% vs. FLT3-ITD positive: LFS=35%; p=0.58). Major significant differences were seen in relapse incidences (RI) between the four subgroups of patients (FLT3-ITD positive and negative, conventional postremission therapy or allogeneic HCT; p=0.003). FLT3-ITD positive patients treated with conventional chemotherapy had a RI of 80% that could be reduced to a RI of 48% in the group of HCT patients. Within the two different treatment groups of FLT3-ITD negative patients the RI in the conventional treated group was 55% compared to 26% in HCT patients. To conclude, the worse prognostic impact of the presence FLT3-ITD mutation on the outcome of CN-AML pts. can be improved by allogeneic HCT performed in first complete remission after two courses of induction therapy. Allogeneic HCT reduces the relapse incidence in FLT3-ITD positive as well as in FLT3-ITD negative pts. Disclosures No relevant conflicts of interest to declare.

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.

High-dose cytosine arabinoside and m-AMSA is effective therapy in relapsed acute nonlymphocytic leukemia.

1984 ◽  
Vol 2 (6) ◽  
pp. 545-549 ◽  
Author(s):  
J D Hines ◽  
M M Oken ◽  
J J Mazza ◽  
A M Keller ◽  
R R Streeter ◽  
...  
Keyword(s):  
Complete Remission ◽  
Maintenance Therapy ◽  
Median Time ◽  
Induction Therapy ◽  
Cytosine Arabinoside ◽  
Partial Remission ◽  
De Novo ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Consolidation Therapy

High-dose cytosine arabinoside ( HDARAC ) and 4'-(9 acridinylamino) methane sulfon -m-anisidine (m-AMSA) was administered as induction therapy to 40 patients with relapsed or refractory acute nonlymphocytic leukemia (ANLL) with the following results: 28 patients (70%) achieved complete remission, one patient achieved a partial remission; five patients died with hypoplastic bone marrows containing less than 5% blasts; four patients died with hypoplastic marrowing containing greater than 5% blasts; and three patients failed to achieve marrow aplasia and died without significant cytoreduction in percentage of blasts. Consolidation therapy was not used and maintenance therapy was given to less than 10% (three patients) of remission patients. The median duration of remission for all patients was 6.0 months and the median time for the complete remission patients exceeded eight months. This regimen has acceptable toxicity and the results are equivalent to those obtained from conventional induction therapy of de novo ANLL patients.

scholarly journals Characteristics and Outcome of Elderly Patients (> 55 Years) with Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3365-3365
Author(s):  
Daniela V. Wenge ◽  
Klaus Wethmar ◽  
Corinna Klar ◽  
Hedwig Kolve ◽  
Tim Sauer ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Conventional Treatment ◽  
Advisory Board ◽  
Intensive Treatment ◽  
Consolidation Therapy ◽  
Group Status

Abstract Introduction: Prognosis of elderly ALL patients is generally considered to be poor. Nonetheless, data on disease characteristics, treatment and outcome of this group of patients is scarce. Methods: Between May 2003 and October 2020, 96 patients (pts) aged > 55 years with B-precursor ALL (91 pts) or T-ALL (5 pts), received first-line induction chemotherapy (84 pts) or were admitted for salvage treatment (8 pts) or allogeneic stem cell transplantation (alloSCT, 4 pts) at the University Hospital Muenster, Germany. 78 patients were diagnosed with a common-ALL (27 pts were BCR/ABL positive) and 13 patients with a pro-B-ALL. Age adapted BFM (Berlin-Frankfurt-Muenster)-like treatment regimens, according to the recommendations of the GMALL (German multicenter ALL study group) for younger (18-55 years, 25 pts) or elderly patients (> 55 years, 68 pts) were used. In general, these protocols consisted of two cycles of induction therapy followed by consolidation, reinduction and consolidation therapy blocks in the 1 st year as well as a consecutive maintenance therapy in the 2 nd year. 3 patients (3%) received no intensive treatment due to poor performance status and comorbidities. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank-test and Cox proportional hazards model for RFS and OS, respectively. Results: Median patient age at diagnosis was 66 years (range 55-89 years). 94% of all patients had an ECOG (Eastern Cooperative Oncology Group) status of 0-2 and 92% had a Charlson comorbidity index of 0-2. The median follow-up of all patients was 2.0 years (range 20 days - 16.9 years) and of surviving patients 3.7 years (range 8.8 months - 16.9 years). A complete remission (CR) after induction therapy was documented in 62 of 81 (77%) patients receiving their initial induction therapy at our center. Minimal residual disease (MRD) status was analyzed by quantitative real time PCR in 44 of these patients and 19 patients had an MRD negative CR (43%) after induction therapy. The rate of early death after intensive therapy (death within 100 days after start of treatment) was 6%. The 3 patients not treated with intensive chemotherapy died within 3 months. 27 of 93 patients finished the first year of treatment. Subsequent maintenance therapy was administered to 12 patients. The reasons for discontinuation of conventional treatment in the first and second year were relapsed disease (31 pts), alloSCT in 1 st CR (23 pts), toxicity/patients' preference (17 pts) and death in CR under conventional therapy (7 pts). 3 patients have not completed their therapy yet. OS and RFS of the entire cohort at 1 year were 73% (95% CI: 64-82%) and 57% (95% CI: 47-67%) and at 3 years 46% (95% CI: 36-56%) and 32% (95% CI: 22-42%), respectively. The cumulative incidence of relapse at 1 and 3 years was 29% (95% CI: 20-41%) and 56% (95% CI: 45-69%), respectively. OS of those patients receiving an alloSCT (23 pts in 1 st CR, 7 pts in 2 nd CR, 3 pts with active disease, median age at alloSCT 62 years) at 1 and 3 years was 82% (95% CI: 68-95%) and 49% (95% CI: 32-67%), respectively. The cumulative incidence of relapse after alloSCT at 1 and 3 years was 16% (95% CI: 7-35%) and 32% (95% CI: 18-56%), respectively. Regarding the entire patient cohort, older age (> 75 years, 15 pts) was significantly associated with an inferior OS (p < .001). BCR/ABL status, ALL phenotype (T- or B-ALL) or intensity of conventional treatment applied (protocol originally intended for patients ≤ 55 years vs > 55 years) had no significant impact on OS. In multivariate analysis, ECOG status >2 and persisting disease after 1 st consolidation therapy were risk factor associated with inferior OS (p < .05). Conclusion: Intensive treatment is feasible in selected elderly ALL patients (> 55 years). High relapse rates and impaired survival rates underline the need for novel therapeutic strategies. Disclosures Khandanpour: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; Sanofi: Honoraria, Research Funding; BMS/Celgene: Honoraria. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Brüggemann: Incyte: Other: Advisory Board; Amgen: Other: Advisory Board, Travel support, Research Funding, Speakers Bureau; Janssen: Speakers Bureau. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Stelljes: Celgene/BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau.

Different Prognosis According to Subtype-Oriented Protocols in Elderly Patients with Acute Lymphoblastic Leukemia (ALL). Comparison of Three Prospective Parallel Trials from the Pethema Group

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3869-3869
Author(s):  
Josep-Maria Ribera ◽  
Olga Garcia ◽  
Pascual Fernandez ◽  
Pau Montesinos ◽  
Salut Brunet ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Early Death ◽  
Hematological Toxicity ◽  
P Value ◽  
Phase Ii Trials ◽  
Bulky Disease ◽  
Wbc Count

Abstract Background and objective ALL in elderly patients is associated with poor prognosis and many patients are not included in therapeutic trials. Consequently, the results of subtype-oriented protocols in elderly ALL are poorly known. We present the results of three prospective parallel subtype-oriented protocols from the Spanish PETHEMA group in ALL patients older than 55 years. Patients and Methods In 2008 three prospective phase II trials for ALL patients older than 55 yr with the Charlson Comorbidity Index ≤3 were activated: ALLOld07 (Ph-negative patients, NCT01366898, n=54), ALLOPh07 (Ph-positive patients, NCT01376427, n=48) and BURKIMAB08 (mature B-ALL, NCT00388193, n=18). The ALL0ld07 protocol included moderate-dose induction chemotherapy without genotoxic drugs, followed by consolidation and maintenance therapy for 2 years (Gökbuget et al, ASH 2008), the ALL OPh07 included imatinib and dexamethasone for induction followed by maintenance therapy with mercaptopurine and methotrexate and imatinib for 2 years, followed by imatinib for one additional year (Ribera et al, Br J Haematol 2012; 159: 485-488), and the BURKIMAB08 protocol included specific therapy for Burkitt’s lymphoma/leukemia together with rituximab (Ribera et al, Cancer 2013; 119:1660-8). The main outcomes (early death [ED], complete remission [CR], remission duration [RD] and overall survival [OS]) and toxicity (CTCAE v4.0) were compared. Results 40, 45 and 16 patients from ALLOld07, ALLOPh07 and BURKIMAB08, respectively, were evaluable for this study. Patients with mature B-ALL were more frequently male, with poorer general status, higher frequency of bulky disease and higher LDH serum levels, whereas no significant differences were observed on comparison of ALLOld07 and ALLOPh07 patients. The comparison of the main outcomes of the three trials is shown in Table 1. By multivariate analyses for RD the protocol and WBC count were identified as prognostic factors (BURKIMAB08 was considered as reference category), with HR [95%CI] of 6.8 [0.9-52.1], p=0.064, when compared with ALL Old07 and 3.1 [0.4-24.8], p=0.278 when compared with ALL OPh07, global p value=0.042, and HR [95%CI]: 1.004 [1-1.009], p=0.058 for the WBC count, respectively. The ECOG score was the only variable influencing OS (HR [95%CI]: 0.4 [0.2;0.8], p=0.003). Hematological toxicity in induction and consolidation as well as infections were significantly less frequent in ALLOPh07 than in other two trials, whereas renal toxicity was more frequent in BURKIMAB08. Conclusion Risk-adapted therapy in elderly patients with ALL was feasible and produced significantly different results in terms of CR duration, being the best for mature B-ALL and the poorest for Ph-negative ALL. Supported by the grants PI10/01417 from FIS and RD12-0036-0029 from Instituto Carlos III Disclosures: No relevant conflicts of interest to declare.

The Impact Of European Leukemia Net (ELN) Genetic Classification On The Outcome Of Allogeneic Stem Cell Transplantation (ALLOHCT) For Acute Myeloid Leukemia (AML) In First Complete Remission

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2107-2107
Author(s):  
Jorge Sierra ◽  
Ana Garrido ◽  
Mar Tormo ◽  
Ramon Guardia ◽  
Josep F Nomdedeu ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
P Value ◽  
Term Survival ◽  
Factors Influencing ◽  
The Impact ◽  
First Complete Remission ◽  
Reduced Intensity

Abstract Introduction The improvements in genetic characterization of AML allowed the ELN to propose a prognostic classification into 4 categories: Favorable, Intermediate I, Intermediate II and Adverse. Several groups have tested the outcome of AML patients based on these genetic subgroups in registries and databases from prospective trials. Since ALLOSCT recommendations are being established based on the ELN risk categories, we considered of interest to investigate whether these also have an impact on the results of allogeneic transplants. This could be helpful to identify the patients that may benefit the most from ALLOHCT in the first complete remission (CR1). Objectives To investigate whether the ELN genetic groups of AML have any impact on the results of ALLOHCT performed in CR1. To identify the patients who are best candidates for transplantation, based on the ELN categories as well as in other characteristics. Methods Patients were transplanted between 1990 and 2012. In all cases, treatment prior to transplant had consisted of anthracycline based induction and intermediate-dose cytarabine consolidation according to the CETLAM AML-88, AML-94, AML-99 and AML-03 trials. Upper age limit for transplantation was 60 years until 2002 and 70 years thereafter. Most patients above 50 years received either CD34 selected grafts or reduced intensity conditioning. GVHD prophylaxis after transplant was usually based on cyclosporine and prednisone or methotrexate. The main characteristics of patients and transplants were included in the exploratory analysis of variables influencing survival; those with a p- value up to 0.1 were incorporated as covariates to the multivariable model. Results One hundred ninety two patients in CR1 received an ALLOHCT from HLA-identical siblings (n=140), adult unrelated donors (n=26) or umbilical cord blood (n= 26). Age distribution of the patients was as follows: 16-35 years-old (y-o) n=65 (34%), 36-50 y-o n= 55 (29%), 51-60 y-o n= 54 (28%), >60 y-o n=18 (9%). Twenty-three patients (12%) were classified as in the favorable ELN category, 54 (28%) in the intermediate I, 41 (21%) in the intermediate II and 74 (39%) in the adverse. One-hundred fifty-seven patients (82%) had achieved CR1 after a single course of chemotherapy. Conditioning was myeloablative (MA) in 139 (72%) patients and reduced-intensity (RIC) in 53 (28%). In 76 cases of the MA regimens total body irradiation was included. Thirty-eight patients (20%) died due to transplant complications other than relapse and 47 (24%) experienced a leukemia recurrence. Overall survival (OS) and leukemia-free survivals at 8-years were 55±4% and 53±4%, respectively. Multivariate analysis of factors influencing OS included as covariates age at diagnosis of AML, ELN categories, courses to CR1 and conditioning regimen (MA versus RIC), since they had a p-value <0.1 in the univariate comparisons. The variables with independent on OS impact were age (p=0.01), courses to CR (p=001) and ELN classification (p=0.01). OS at 8 years in the favorable, intermediate I, intermediate II and adverse categories were 69±10%, 53±8%, 69±7% and 42±6%, respectively. In patients from the adverse ELN category, independent factors influencing OS in the multivariate analysis of this subgroup were age (16-60 y-o vs>60, p=0.01) and courses to CR (1 vs more, p=0.03). Conclusions The ELN genetic categories have impact on OS of AML patients who receive an ALLOHCT in CR1. The results were very good in the favorable category and, most important, in intermediate II patients. Even patients in the adverse category had a substantial probability of long-term survival. This is remarkable, since the outcome of patients with adverse genetic features when treated with CT only is very poor. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Increased Idarubicin Dosage during Consolidation Therapy for Adult Acute Myeloid Leukemia Improves Leukemia-Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 338-338
Author(s):  
Bradstock Kenneth ◽  
Emma Link ◽  
Juliana Di Iulio ◽  
Jeff Szer ◽  
Paula Marlton ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Consolidation Therapy ◽  
Advisory Committees ◽  
Free Survival ◽  
Acute Myeloid

Abstract Background: Anthracylines are one of the major classes of drugs active against acute myeloid leukemia (AML). Increased doses of daunorubicin during induction therapy for AML have been shown to improve remission rates and survival. The ALLG used idarubicin in induction therapy at a dose of 9 mg/m2 x 3 days (total dose 27 mg/m2) in combination with high-dose cytarabine and etoposide (Blood 2005, 105:481), but showed that a total idarubicin dose of 36 mg/m2 was too toxic in this context (Leukemia 2001, 15:1331). In order to further improve outcomes in adult AML by anthracycline dose escalation, we conducted a phase 3 trial comparing standard to an increased idarubicin dose during consolidation therapy. Methods: Patients achieving complete remission after 1 or 2 cycles of intensive induction therapy (idarubicin 9 mg/m2 daily x3, cytarabine 3 g/m2 twice daily on days 1,3,5 and 7, and etoposide 75 mg/m2 daily x7; ICE protocol) were randomized to receive 2 cycles of consolidation therapy with cytarabine 100 mg/m2 per day for 5 days, etoposide 75 mg/m2 for 5 days, and idarubicin 9mg/m2 daily for either 2 or 3 days (standard and intensive arms respectively). No further protocol therapy was given. The primary endpoint was leukemia-free survival from randomization to consolidation therapy (LFS) with overall survival (OS) as secondary endpoint. Results: A total of 422 patients with AML (excluding cases with CBF rearrangements or APL) aged 16 to 60 years were enrolled between 2003-10, with 345 (82%) achieving complete remission, and 293 being randomized to standard (n=146) or intensive (n=147) consolidation arms. The median age was 45 years in both arms (range 16- 60), and both groups were balanced for intermediate versus unfavorable karyotypes and for frequency of mutations involving FLT3-ITD and NPM1 genes. Of the randomized patients, 120 in the standard arm (82%) and 95 in the intensive arm (65%) received the second consolidation cycle (p<0.001). The median total dose of idarubicin received in the 2 consolidation courses was 36 mg/m2 (range 17-45), or 99% (47-125%) of the protocol dose in the standard arm, versus 53 mg/m2 (18-73), or 98% (33-136%) of the protocol dose in the intensive arm. The durations of grades 3-4 neutropenia and thrombocytopenia were significantly longer in the intensive arm, but there were no differences in grade 3 or 4 non-hematological toxicities. There were no non-relapse deaths during consolidation on the standard arm and 2 in the intensive (0% vs 1%; p =0.50). Subsequently, 41 patients in the standard arm and 37 in the intensive arm underwent elective allogeneic BMT during first remission. On intention to-treat analysis uncensored for transplant and with a median follow-up time of 5.3 years (range 0.6 - 9.9), there was improvement in LFS in the intensive arm compared with the standard arm (3 year LFS 47% (95% CI 40-56%) versus 35% (28-44%); HR 0.74 (95% CI 0.55-0.99); p=0.045) (Figure 1). The 3 year OS for the intensive arm was 61% (95% CI 54-70%) and 50% (95% CI 43-59%) for the standard arm; HR 0.75 (95% CI 0.54-1.05); p=0.092). Although adverse cytogenetics, presence of FLT3-ITD mutation, and absence of NPM1 mutation were all associated with poorer outcomes, there was no evidence of a benefit of intensive consolidation being confined to specific cytogenetic or gene mutation sub-groups. Conclusion: We conclude that in adult patients in complete remission after intensive induction chemotherapy an increased dose of idarubicin delivered during consolidation therapy results in improved LFS, without increased non-hematologic toxicity. Figure 1. Figure 1. Disclosures Szer: Ra Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alnylam: Honoraria, Membership on an entity's Board of Directors or advisory committees. Marlton:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wei:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; CTI: Consultancy, Honoraria; Abbvie: Honoraria, Research Funding; Servier: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Cartwright:ROCHE: Consultancy, Membership on an entity's Board of Directors or advisory committees. Roberts:Servier: Research Funding; Janssen: Research Funding; Genentech: Research Funding; AbbVie: Research Funding. Mills:Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Meeting attendance sponsorship. Gill:Janssen: Membership on an entity's Board of Directors or advisory committees. Seymour:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission

2017 ◽  
Vol 35 (20) ◽  
pp. 2260-2267 ◽  
Author(s):  
Daniel J. Landsburg ◽  
Marissa K. Falkiewicz ◽  
Joseph Maly ◽  
Kristie A. Blum ◽  
Christina Howlett ◽  
...  
Keyword(s):  
Complete Remission ◽  
Intensive Therapy ◽  
Front Line ◽  
Term Survival ◽  
Disease Response ◽  
Line Therapy ◽  
Double Hit Lymphoma ◽  
Double Hit ◽  
First Complete Remission

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

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