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  • Buchner, Thomas  (12)
  • Sauerland, Maria Cristina  (12)
  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2696-2696
    Abstract: Abstract 2696 Introduction: The prognosis of older patients (≥ 60 years) with acute myeloid leukemia (AML) is generally poor. The decision whether or not to use intensive chemotherapy in this patient cohort is challenging since only half of all older AML patients will eventually achieve a complete remission (CR) with an intensive approach. We therefore sought to develop a clinically relevant risk score for estimating the chance to obtain a CR compared to the risk of early death (ED). Patients and Methods: 1406 patients ≥ 60 years of age with AML and evaluable for an induction result after treatment with an intensive induction regimen (1-2 courses of either standard-dose araC containing TAD - high-dose araC containing HAM or HAM - HAM) within the AMLCG1999 study of the German AML Cooperative Group (AMLCG) were analyzed. External validation was performed on 801 patients ≥ 61 years of age treated in the AML96 study of the Study Alliance Leukemia (SAL) treated with 1–2 courses of a ‘7+3’ induction. 16 clinical parameters as well as cytogenetic and molecular risk factors were evaluated for risk prediction in an exploratory analysis. Results: Among the analyzed parameters, age, de novo versus secondary leukemia, body temperature, hemoglobin, thrombocyte count, LDH, fibrinogen and the cytogenetic and molecular risk were significantly associated with a CR and/or with an ED within 60 days (p 〈 0.05) in a multivariate logistic regression analysis. For comparison, patients were grouped into quarters by their predicted CR and ED score. The comparison of the predicted with the observed CR and ED rates within these quarters and additionally within the highest and lowest 5% showed a valid prediction of the CR and ED rates by the individual risk prediction (figure 1A & B). This could also be demonstrated when applying these CR and ED scores on an independent patient population (figure 1C & D). Conclusions: These scores based on pretreatment clinical, cytogenetic and molecular variables provide a reasonable estimate for CR and the ED rate of elderly AML patients. An online calculation tool for the prediction of the CR and the ED rate has been implemented (www.aml-score.org). This tool might be helpful to determine the treatment strategy for older patients with AML. Comparison of the predicted CR and ED rate with the corresponding observed CR and ED rates. Patients were grouped into quarters by their predicted CR or ED rates and the boxplot of the predicted rate of each quarter is plotted against the observed rate of this quarter. In addition, the predicted versus the observed rates of the extreme 5% by predicted rates are shown. A: AMLCG population, CR rates; B: AMLCG population, ED rates; C: SAL population, CR rates; D: SAL population, ED rates. Disclosure: Haferlach: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 2
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1447-1447
    Abstract: Data on benefit and toxicity by treatment intensification for AML are now available and allow rediscussing current dosing. Methods In a multicenter trial involving patients between 16 and 86 years of age, patients below 60 years received uniform double induction by the 1st course with standard dose araC/ daunorubicin (60mg/m²x3)/ thioguanine followed by the 2nd course with high-dose araC (3g/m²x6)/ mitoxantrone (10mg/m²x3), or randomly two high-dose courses. As age adaption patients of 60y or older received the 2nd course only in case of persistent blasts, and high-dose araC at 1 instead of 3g/m². Post remission treatment was consolidation and maintenance or randomly autologous stem cell transplantation in younger patients. Results 3369 patients entered the trial with 1843 patients 60y or older. A multivariate analysis identified age as continuous variable, favorable cytogenetics/ molecular genetics, unfavorable cytogenetics, white blood cell count and lactate dehydrogenase as categorical variables to be risk factors predicting complete remission, overall survival as well as relapse free survival. To separate the age effect from the treatment effect, two subgroups of similar age and baseline characteristics but different treatment were compared. Thus, the 239 patients aged 57-59 and the 336 patients aged 60-62 years shared not only similar age but also similar baseline characteristics, while their treatment by protocol and age adaption differed substantially. The difference as expressed by the cumulative araC dosis amounted to a factor of 3.6, which however did not translate into a different overall survival (equally 28%) or relapse rate (equally 70%) at 5 years. In contrast to different treatment, different age had a strong effect on outcome. Thus, the survival in patients aged 16-46y was 65% at 5 years versus 40% in those of 47-59y receiving the same treatment (p 〈 0.001). A corresponding age related difference was also found between the patients of 60-66y and those of 67-86y (p 〈 0.001) receiving the same age adapted treatment. As shown by others in patients of 18-60y doubling an intermediate cumulative dose of araC produced excessive toxicity without therapeutic benefit (Löwenberg B et al. NEJM 2011; 364: 1027-36), while high dose daunorubicin (90mg/m²) instead of standard dose (45mg/m²) improved the remission rate and survival in younger patients (Fernandez H et al. NEJM 2009; 361: 1249-59) and older patients of 60-65y (Löwenberg B et al. NEJM 2009; 361: 1235-48). No comparable data are available about daunorubicin 60mg/m² the standard in present study. Conclusion Age and disease biology rather than chemotherapy intensity are the main determinants of outcome in AML. Once a certain intensity and antileukemic effect has been achieved, a further escalation does not seem to overcome the age factor in AML. Present data require rediscussing current chemotherapy dosing and treatment alternatives. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 3
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 593-593
    Abstract: In order to test current risk factors in a prospective multicenter setting we evaluated the AMLCG 99 trial. Patients were randomly assigned to induction by TAD-HAM (HAM with araC 3 for age 〈 60y and 1 for age ≥60y g/m2 × 6), or HAM-HAM, and also to TAD consolidation and maintenance or (age 〈 60y) myeloablative chemotherapy and autologous SCT. Patients with histocompatible family donors preferentially underwent allogeneic SCT. Since any randomization was done up-front, informations from completely unselected patients were available. 2547 patients of 16–85 (median 61) y entered the trial. 1858 pts had de-novo and 689 pts secondary AML. The CR rate was 61%, 54% in older (60) and 69% in younger patients. The overall survival (OS) at 4 years was 27%, 15% in older and 41% in younger patients. The relapse risk (RR) was 65%, 80% in older and 50% in younger patients and the relapse-free survival (RFS) was 30%, 14% and 44%, respectively. In the entire patients complete outcome (CR, OS, RR, RFS) was predicted by favorable and unfavorable karyotype. Among patients with any abnormal karyotype complete outcome was predicted by unfavorable karyotype in the older and favorable karyotype in the younger age group. In both age groups with normal karyotype outcome for the complete parameters was predicted by the NPM1+/FLT3- ITD- mutation status. As a new finding in patients of 〈 60 years with normal karyotype female sex turned out being an independent predictive factor for longer OS (HR 1.45;95%CI 1.04–2.03), longer RFS (HR1.64;95%CI 1.10–2.44), and lower RR (HR 0.59;95%CI 0.38–0.92). Female sex was the only predictive factor besides the NPM1/FLT3 mutation status in this group. The OS at 4 years in patients of 〈 60y with normal karyotype is 52% in women and 40% in men (log-rank P=0.047), the RR is 37% and 52% (P=0.016), and the RFS is 55% in women and 42% in men (P=0.025). Furthermore, the favorable NPM1+/FLT3- mutation status was more frequent in women than in men (35% vs 26%; P=0.0075). Remarkably, the NPM1+/FLT3- mutation status was equally predictive in patients of ≥60y as in those of 〈 60y with HR for OS of 2.51 (95% CI 1.75–3.61) and 3.27 (95%CI 2.11–5.05) and HR for RR of 0.33 (95% C 0.21–0.51) and 0.29 (95%CI 0.17–0.49). The difference in the OS at 4 years between patients with NPM1+/FLT3- mutation and those with other NPM1/FLT3 combinations was 42% vs 18% (P= 〈 0.001) in the older, and 69% vs 34% (P 〈 0.001) in the younger patients. The related differences in RR were 58% vs 84% (P 〈 0.001) in the older, and 22% vs 59% (P 〈 0.001) in the younger patients. Among the NPM1/FLT3 mutations the favorable +/− constellation accounted for 27% of older, and 35% of younger patients (P=0.0197). Besides karyotypes and mutations, also age, de-novo AML, blast clearance, LDH and WBC partly predicted outcomes. In contrast no prognostic impact was found by multi-and univariate analyses of treatment alternatives. Conclusion: As from a large multicenter prospective trial the outcome in AML is mainly determined by cytogenetics, NPM1/FLT3 mutation, age and sex, but not by the assigned treatment variables.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2773-2773
    Abstract: Abstract 2773 Introduction: For patients with high-risk myelodysplastic syndromes an epigenetic therapy with hypomethylating agents is considered standard of care. Intensive chemotherapy can be offered to a subset of patients; however, data about the long-term outcome of MDS patients receiving intensive chemotherapy are scarce. Methods: For this evaluation, 104 adult patients with IPSS intermediate-2 or high-risk MDS with at least 10% bone marrow blasts of all age groups treated within the AMLCG1999 trial were included. Patients were randomized upfront to receive 1. double induction therapy with either standard-dose containing TAD - versus high-dose containing HAM–HAM, 2. TAD consolidation therapy followed by either a monthly maintenance therapy for 3 years after achievement of CR or an autologous stem cell transplantation (patients aged ≥ 60 years were all assigned to maintenance therapy), and 3. blast priming with filgastrim starting on day -1 of chemotherapy in selected centers. Results: Fifty-four patients had IPSS Score intermediate-2 and 50 patients were IPSS high risk. Median bone marrow blast count at diagnosis was 15%. The median age was 63.5 years (range: 27–76 years), 39 patients (37.5 %) were female. Median lactate dehydrogenase (LDH) serum level was 296 U/l, median leukocyte count at diagnosis was 5,950 per μl. The cytogenetic risk groups were as follows: favorable 3, intermediate 57, unfavourable 37, missing 7. Among 38 patients with normal karyotype, NPM1/FLT3 mutational status was available for 22 with 5 patients having the combination NPM1 mutated/FLT3 wildtype. Comparison with 2051 patients with de novo AML within the same trial revealed the following significant differences: patients with MDS were older, had a higher male to female ratio, a lower LDH serum level at diagnosis, a lower leukocyte count at diagnosis and were more likely to have adverse cytogenetic risk. Compared to 636 patients with secondary AML after MDS, cytotoxic therapy or irradiation, the cohort of patients with MDS did not display any significant differences except the sex distribution. Patients with MDS displayed a CR rate of 48% (50/104 patients), which was significantly lower than de novo AML patients (67%) and not different to secondary AML patients (47%). Median overall survival in MDS patients was 320 (95% CI: 236 to 505) days with a 2-year and 5-year survival of 33.4% (95% CI: 23.6% to 43.2%) and 22.7% (95% CI: 13.5% to 31.9%), respective, which was significantly (p=0.03) lower than in patients with de novo AML (median 484, 95% CI 435 to 541 days) and comparable to patients with secondary AML (median 282, 95% CI 224 to 311 days, p=0.13). Median relapse-free survival in responding MDS patients was 536 (95% CI: 264 to 1299) days with no significant differences of RFS compared to de novo or secondary AML patients. In multivariate analyses, the diagnosis of MDS remained an independent prognostic factor for CR probability but had no independent influence on survival compared with de novo AML patients. Nine patients proceeded to allogeneic stem cell transplantation in first complete remission of whom six remain in first complete remission between 1354 and 1911 days after achievement of CR. In addition, 16 patients remained in CR for more than one year without allogeneic transplantation. Discussion: Taken together, outcome of patients with intermediate-2 or high-risk MDS after intensive chemotherapy is comparable to the outcome of patients with secondary AML. Adjustment for known risk factors such as age, cytogenetic risk and LDH revealed that inferior outcome of MDS patients compared to patients with de novo AML is attributable to the higher incidence of adverse risk factors. CR-rates appear to be higher compared to hypomethylating therapy and a fraction of MDS patients experiences long-term survival by intensive chemotherapy. Allogeneic transplantation can improve long-term survival for patients achieving remission. Disclosures: Krug: MedA Pharma: Honoraria; Novartis: Honoraria; Alexion: Honoraria; Boehringer Ingelheim: Research Funding; Sunesis: Honoraria. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 485-485
    Abstract: Abstract 485 In order to assess the relative value of major treatment variables for AML and subgroups in a representative setting 2693 patients were treated in a multicenter trial. To avoid a selection during treatment and to provide intention-to-treat conditions in a factorial design patients were randomized up-front in one step to receive TAD-HAM versus HAM-HAM induction, G-CSF priming with all chemotherapy courses during the 1st year versus no G-CSF, and for postremission therapy TAD consolidation followed by monthly myelosuppressive maintenance versus autologous stem cell transplantation instead of maintenance (TAD, thioguanine, araC standard dose and daunorubicin; HAM, araC 3 (age 〈 60) or 1 (age 60+) g/m2 × 6 with mitoxantrone; G-CSF 150μg/m2/day from 48h before until the end of the chemotherapy course; maintenance, 5-day standard dose araC with daunorubicin or with thioguanine or with cyclophosphamide alternatingly). The median age was 61 (range 16-85) years with 55% of patients 60 years or older, 27% patients had AML secondary to cytotoxic treatment or myelodysplasia. Favorable, intermediate, and unfavorable cytogenetics were found in 7.5%, 67% and 25.5% of patients, respectively. Among 956 patients with normal cytogenetics the mutation status was availabel with NPM1 mut/ FLT3-ITD neg in 33% and other combinations in 67%. The median observation time for the entire patients was 4.4 years . In the patients 〈 60 years the overall survival (OS) at 5 years is 40%. 65% went into complete remission (CR). Their relapse rate (RR) at 5 years is 52%. Patients of 60+years show an OS of 13% at 5 years, a CR rate of 54%, and a RR of 81% at 5 years. There were no significant differences in these parameters with respect to randomizations between TAD-HAM versus HAM-HAM, G-CSF priming versus no G-CSF, maintenance versus autologous stem cell transplantation. In a multivariate analysis including all patients and ages the main determinants of OS were age 60+y (HR 2.00; 95% CI 1.82-2.21), de-novo AML (0.79; 0.71-0.88), unfavorable karyotype (2.05; 1.84-2.28), favorable karyotype (0.47; 0.37-0.60), day 16 b.m. blast clearance (0.66; 0.61-0.74), and LDH (1.36; 1.19-1.54). Corresponding factors for the RR were age 60+ (1.90; 1.65-2.18), unfavorable karyotype (1.83; 1.54-2.17), favorable karyotype (0.41; 0.30-0.55), LDH (1.33; 1.11-1.59), and day 16 b.m. blast clearance (0.79; 0.68-0.93). In patients with normal karyotype the main determinants of OS were age 60+ (2.12; 1.77-2.54), NPM1mut/ FLT3-ITD neg (0.45; 0.36-0.56), and for the RR age 60+ (1.87; 1.49-2.35), and NPM1mut/ FLT3-ITD neg (0.37; 0.29-0.48). Even in patients 〈 60 years age older than the median (47y) is a major risk factor for OS (1.56; 1.33-1.82) and RR (1.35; 1.10-1.66). Conclusion: In a prospective analysis of representative and unselected patients with AML the outcome of therapy is mainly determined by chromosomal and molecular abnormalities and by older age as an own risk factor. The influence of treatment variables such as substantial increase in high-dose araC, G-CSF priming, or autologous SCT is neglectable. Present data may contribute a basis for novel molecular and immunologic approaches. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 327-327
    Abstract: Abstract 327 Introduction: Older patients (≥ 60 years) with acute myeloid leukemia (AML) display a dismal prognosis with only half of the patients reaching a complete remission after intensive induction therapy. The decision whether or not to use intensive chemotherapy is often difficult given the limited number of known markers that might predict the chance to achieve a complete remission. The aim of this study was to establish a risk score for therapy-failure based on clinical variables for older but medically fit AML patients. Patients and Methods: 1379 patients ≥ 60 years of age with AML evaluable for an induction result after treatment with an intensive induction regimen (randomized standard-dose cytarabine containing TAD or high-dose cytarabine (1g/sqm × 6) containing HAM, with a second induction course HAM in case of blast persistence after the first course) within the AMLCG1999 study of the German AML Co-operative Group were evaluated. The following parameters were evaluated for risk prediction in an exploratory analysis: Age, sex, de novo versus secondary leukemia, performance status, body mass index, body temperature, presence of extramedullary manifestations, spleen size, presence of lymph node enlargement, hemoglobin, peripheral blood leukocytes, platelets, blast percentage in peripheral blood and bone marrow, total protein in serum, alanine aminotransferase (ALT), alkaline phosphatase (AP), bilirubin, lactate dehydrogenase (LDH), FAB classification, prothrombin time (PT) and fibrinogen. Since cytogenetics and molecular markers are often not available at the time of decision making, these data were not included. Results: Within this cohort of patients, 744 (54 %) achieved a complete remission. Among the analyzed parameters, age, de novo versus secondary leukaemia, body mass index, body temperature, hemoglobin, peripheral blood leukocytes, platelets, bone marrow and peripheral blood blasts, ALT, AP, LDH, PT and fibrinogen were significantly associated with a CR (p 〈 0.05) in a univariate log rank analysis. In a multivariate logistic regression model, the following parameters retained its significance: age (60 – 63 years, 64 – 67 years, 68 – 72 years, ≥ 73 years) de novo versus secondary leukemia, body temperature (≤ 36°C, 〉 36°C – 38°C, 〉 38°C), hemoglobin (≤ 10.3 g/dl versus 〉 10.3 g/dl), platelets (≤ 28,000, 〉 28,000 - 53000, 〉 53,000 – 103,000, 〉 103,000 per μl), AP (≤ 89 U/l versus 〉 89 U/l), PT (≤ 75 %, 〉 75 – 87 %, 〉 87 – 98 %, 〉 98 %) and fibrinogen (≤ 150 mg/dl versus 〉 150 mg/dl). Based on these parameters, the predicted remission rates were: minimum, 18.3 %; 1st quartile, 43.9 %; median, 54.4 %;3rd quartile, 64.3 %; maximum: 88.1 %. The observed remission rates were: 1st quarter, 35.7 %; 2nd quarter, 50.3 %; 3rd quarter, 60.2 %; 4th quarter, 69.8 %. Conclusions: Taken together, this risk prediction score based on pre-treatment values predicted the remission probability in patients ≥ 60 years of age with AML receiving an intensive induction therapy. This score may be useful for the determination of the therapy strategy in elderly patients with AML. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 7
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-01), p. 2001-2001
    Abstract: Therapy - related acute myeloid leukemia (t-AML) is one of the most severe long - term complications of successful cancer treatment using chemo- and/or radiotherapy. Its frequency is increasing, also in patients with autoimmune disease after cytostatic therapy. Cytogenetic and molecular biological analysis have identified several subgroups, however large prospective trials on optimal treatment are lacking. In 1999 the German AMLCG started a prospective multicenter randomized trial including patients with t-AML. Patients received induction treatment, randomized to either TAD (standard dose thioguanine, araC, daunorubicin) followed by HAM (HAM, high-dose araC 1 or 3 g/m2x6/mitoxantrone 10mg/m2x3), or to induction by two courses of HAM. Above the age of 60 years, the second induction course was given only to patients with 5 % or more residual bone marrow blasts. Postremission therapy was randomized to either TAD followed by three year maintenance, or to autologous stem cell transplantation. Patients under the age of 60 years with a suitable donor received an allogeneic stem cell transplantation. 137 patients were included. The most frequent primary diagnoses were breast cancer (n = 43), Non Hodgkin’s lymphoma (n = 18), Hodgkin’s lymphoma (n = 9), autoimmune disease (n = 9), multiple myeloma (n = 5), germ cell tumor (n = 5) and ovarian cancer (n = 5). The median age was 57 years (23 – 77). 64 of 119 currently evaluable patients achieved CR (53,8 %), 34 (29 %) had persistent leukaemia, 20 (17,1 %) were classified as early death without evidence of disease. The CR rate was significantly lower than in 1532 patients with de novo AML (65,6 %), but higher than in patients with AML after MDS (46,8 %). Cytogenetic analysis was routinely performed in all patients with t-AML. 21 (17,7 %) had a favourable karyotype, 47 (39,5 %) an unfavourable karyotype, 51 (42,9 %) were classified as intermediate. Patients with favourable karyotype had a median survival of 25 months and an estimated survival rate at 5 yrs of 47,4 %. Median survival was 3 months for patients with unfavourable karyotype with an estimated survival rate of 12,5 %, while the intermediate group had a median survival of 19 months and an estimated survival rate of 24,2 %. This is one of the largest prospective studies on the therapy of patients with t-AML. The CR rate of all patients was inferior to patients with de novo AML. However, this difference was mainly due to the high number of patients with unfavourable karyotype. Within cytogenetically defined subgroups, the prognosis of t-AML patients does not differ significantly from patients with de novo AML.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6610-6610
    Abstract: 6610 Background: Patients’ age is an important issue in treatment decisions for AML, while its role in this disease remains poorly explained. Methods: In the AMLCG 1999 trial 1223 patients (pts) were 16-59y and 1470 pts were 60-85y of age. Their treatment was randomized between TAD-HAM vs HAM-HAM induction (TAD, standard dose thioguanine, cytarabine, daunorubicin 60mg/m² x 3; HAM, high-dose cytarabine 3g/m² x 6, mitoxantrone 10mg/m² x 3), TAD consolidation and monthly maintenance vs autologous SCT, any chemotherapy + vs - G-CSF priming. All randomization was done upfront. Pts of 〈 60y received routine double induction and full dose HAM while pts of 60+y preferentially received only one course induction and HAM at 1g instead of 3g cytarabine /m² x 6. Results: With little differences according randomizations, pts 〈 60y and 60+y achieved a complete remission rate (CR) of 70.2% and 53.5% (p 〈 .001), overall survival (OS) at 5y of 41.3% and 12.9% (p 〈 .001) and a relapse rate (RR) of 49.0 and 72.0% (p 〈 .001). We also focussed on pts around 60y of age and compared the 172 pts of 57-59y with the 261 pts of 60-62y excluding pts undergoing allogeneic stem cell transplantation. According to their similar age the two groups showed similar baseline characteristics. In contrast and due to the cut-off point for age adaption at 60y they differed considerably in treatment. Expressed by the cumulative dosage of cytarabine, the difference between the two groups was by factor 2.9. This difference, however, did not translate into a different outcome being 62% vs 60% CR, 28% vs 21% 5y OS (p=0.25), and 73% vs 73% RR at 5y. A multivariable analysis in all pts between 16 and 85y of age identified cytogenetik/ molecular risk and age as a continuous variable, to be risk factors predicting CR, OS, as well as RR. In pts of 16-60y those below and above the median age of 47y differed in their CR rate by 75% vs 66% (p 〈 .001), their OS by 49% vs 35% (p 〈 .001) and in their RR by 45% vs 53% (p=.007). In pts of 60-85y those below and above the median age of 67y differed in their CR rate by 57% vs 51% (p=.023), and their OS by 16% vs 11% (p 〈 .001), while their RR was similarly 71%. Conclusions: The outcome in pts with AML is substantially determined by patients’ age as its own risk factor, and not by treatment intensity.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
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  • 9
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1856-1856
    Abstract: We have previously shown that a monthly myelosuppressive chemotherapy proved superior to high-dose cytarabine consolidation therapy (J Clin Oncol2003,21:4496) after induction therapy and induction-type consolidation therapy. In the multicenter AMLCG 1999 trial, we reported that this maintenance therapy resulted in equal results with lower therapy-related morbidity and death-rate compared to autologous stem cell transplantation in patients & lt;60 years of age. However, data about the feasibility and compliance of this prolonged maintenance therapy are still lacking. In the AMLCG 1999 trial, patients & lt;60 years of age were randomized upfront to receive either an autologous stem cell transplantation or a maintenance therapy for three years from achievement of complete remission after consolidation therapy TAD. Patients ≥60 years of age were assigned to maintenance therapy following consolidation therapy. Maintenance courses were araC 100mg/m2 q 12 hr sc × 10 and either daunorubicin 45mg/m2 × 2 (AD), or thioguanine 100mg/m2 q 12hr × 10 (AT), or cyclophosphamide 1g/m2 iv (AC), and again AT-AD-AT-AC-. In patients with a leukopenia & lt;1.000/μl or thrombocytopenia & lt;20.000/μl after two following cycles, dosage was permanently reduced by 50%. Of all patients who achieved a CR before July 1st 2004, 269 patients & lt;60 years were randomized to receive maintenance, and all 423 patients ≥60 years were assigned to maintenance. Out of the 692 patients, 211 patients (30.5%) did not receive maintenance therapy due to: allogeneic (49, 7.1%) or autologous (6, 0.9%) stem cell transplantation, early relapse (52, 7.5%), withdrawal of consent (17, 2.5%), medical reasons other than relapse (53, 7.7%), other reasons not classified (7, 1.0%) or death in CR (27, 3.9%). In 78 patients (11.3%) the application of maintenance therapy cannot be followed due to loss of follow-up or incomplete documentation. For the remaining 403 (58.2%) patients with a documented start of the maintenance therapy, the median number of maintenance courses applied was 6 (1st to 3rd quartile: 2–16) over a median duration from achievement of CR of 10 months (1st to 3rd quartile: 5–24). Due to fixed dose adjustment rules, the median dosage of the applied chemotherapy declined from 90.5% (range 8.2–183.3%) in the first course to 47.1% (range 6.6–128.6%) in the third course. From the fifth course on, the median dosage was between 22.2 and 26.3%. Out of the 403 patients who started maintenance, therapy was terminated early in 346 patients (85.9%) due to: an allogeneic stem cell transplantation in 1st CR (3 patients, 0.7%); relapse (175, 43.4%); withdrawal of consent (17, 4.2%); medical reasons other than relapse (72, 17.9%); other reasons not classified (13, 3.2%), loss of follow-up or incomplete documentation (56, 13.9%); and death in CR (10, 2.5%). Of the latter, 5 patients (1.2%) succumbed to therapy-related death. Of the 129 patients experiencing a relapse free survival of ≥ three years, the median number of applied courses was 20 (1st to 3rd quartile: 4–29) over a median duration of 31 months after achieving CR (1st to 3rd quartile: 11–36). Taken together, this results show that a prolonged monthly myelosuppressive maintenance therapy as part of a postremission therapy in AML is feasible and shows a high compliance and acceptance among patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 1978-1978
    Abstract: As recently reported modifications, dose or duration of treatment had no impact on outcome of AML in older patients (Burnett et al. Blood 106: 162a, 2005). We therefore evaluated 764 patients 60 years of age or older and their various prognostic subgroups in the 1992 and 1999 mulitcenter randomized trials by the German AMLCG where patients received uniform postremission consolidation by one course of TAD (standard dose thioguanine, araC, daunorubicin) and maintenance by monthly 5 day courses of reduced TAD. For maximum homogeneity this analysis was restricted to de-novo AML and to patients with known karyotype. Before treatment started, patients were assigned to induction treatment by either TAD followed by HAM (HAM, high-dose araC 1g/m2x6 / mitoxantrone 10mg/m2x3), or to induction by two courses of HAM. The second induction course (HAM) was given to only patients with 5% or more residual bone marrow blasts. Therapy administered to the two randomized groups differed by a factor 2 in their araC dose. Despite this difference in treatment intensity patients in the two arms show similar response rate, overall survival (OS), ongoing CR, and relapse-free survival (see table). The same similarity in outcome as for de-novo AML overall is true for established prognostic subgroups as listed below. Conclusion: Intensification of induction therapy by high-dose araC has no effect on outcome in older age de-novo AML. Since potential influences other than the randomized treatment were minimized, present results do not support a risk adapted intensification strategy. TAD-HAM HAM-HAM P TAD-HAM HAM-HAM P OS 4y % OS 4y % CR 4y % CR 4y % Total 18 13 .28 22 22 .53 Favorable Karyotype 17 16 .48 41 33 .82 Intermediate Karyotype 24 18 .31 24 26 .38 Unfavorable Karyotype 4 - .81 - - .37 LDH ≤ 700U/L 21 13 .86 23 24 .47 LDH 〉 700U/L 12 10 .07 - 16 .27 WBC ≤ 20x103/ccm 21 11 .91 22 21 .81 WBC 〉 20x103/ccm 15 16 .08 22 26 .19 Day 16 Blasts 〈 10% 26 16 .87 23 22 .81 Day 16 Blasts ≥ 10% 14 8 .28 18 19 .26
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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