Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes

Krug, Utz; Röllig, Christoph; Koschmieder, Anja; Heinecke, Achim; Sauerland, Maria Cristina; Schaich, Markus; Thiede, Christian; Kramer, Michael; Braess, Jan; Spiekermann, Karsten; Haferlach, Torsten; Haferlach, Claudia; Koschmieder, Steffen; Rohde, Christian; Wörmann, Bernhard; Hiddemann, Wolfgang; Ehninger, Gerhard; Berdel, Wolfgang E.; Büchner, Thomas; Müller‐Tidow, Carsten

doi:10.1016/s0140-6736(10)62105-8

Cited by 282 publications

(216 citation statements)

References 31 publications

Supporting

Mentioning

206

Contrasting

Unclassified

Order By: Relevance

“…Based on data from a large study in elderly patients (N = 1406), patient and disease factors significantly associated with CR and/or early death were identified and risk scores were developed based on multivariate regression analysis. 147 The predictive model was subsequently validated in an independent cohort of elderly patients (N = 801) treated with 2 courses of induction therapy with cytarabine and daunorubicin. The algorithm, with or without knowledge of cytogenetic or molecular risk factors, predicts the probability of achieving a CR and the risk for an early death for elderly patients with untreated AML, who are medically fit and therefore considered eligible for standard treatments.…”

Section: Induction Therapymentioning

confidence: 99%

“…The algorithm, with or without knowledge of cytogenetic or molecular risk factors, predicts the probability of achieving a CR and the risk for an early death for elderly patients with untreated AML, who are medically fit and therefore considered eligible for standard treatments. 147 The factors included in the algorithm are the following: body temperature (≤38°C, >38°C), hemoglobin levels (≤10.3, >10.3 g/dL), platelet counts (≤28K, >28K-≤53K, >53K-≤10K, >10K counts/mcL), fibrinogen levels (≤150, >150 mg/dL), age at diagnosis (60-64, >64-67, >67-72, and >72 years), and type of leukemia (de novo, secondary). The algorithm can be accessed online at http://www.aml-score.org/.…”

Section: Induction Therapymentioning

confidence: 99%

See 1 more Smart Citation

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Mizutani

Hara

Fujita

et al. 2016

Bone Marrow Transplant

View full text Add to dashboard Cite

Section: Induction Therapymentioning

confidence: 99%

Section: Induction Therapymentioning

confidence: 99%

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Mizutani

Hara

Fujita

et al. 2016

Bone Marrow Transplant

View full text Add to dashboard Cite

“…13,[20][21][22][23] Various covariates including age, PS, platelet counts, albumin level, primary vs secondary AML, white blood cell count (WBC), peripheral blood blast percentage and creatinine were included in the model by Walter et al 13 Older patients with lower TRM score (p3.9) had 1% TRM, whereas patients with higher TRM score (13.1-22.8) had 41% probability of TRM. In the British model, the Medical Research Council (MRC) AML11 trial (n ¼ 1071) was used to develop the index that included cytogenetic group, age, white blood count, PS and type of AML (de novo, secondary).…”

Section: Induction Therapymentioning

confidence: 99%

“…These models were also predictive of CR and early TRM. 20 An MDACC study (only for patients X70 years, n ¼ 446) found that age X80 years, complex karyotypes (X3 abnormalities), poor performance (Eastern Cooperative Oncology Group (ECOG) performance scores 2-4) and elevated creatinine were associated with high induction (8-week) mortality. Patients with none of the adverse prognostic factors had lowest TRM (16%) vs patients with X3 factors with the highest mortality (71%).…”

Section: Induction Therapymentioning

confidence: 99%

To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century

Üstün

Lazarus

Weisdorf

2013

Bone Marrow Transplant

View full text Add to dashboard Cite

AML treatment presents significant challenges in the elderly, who more often have poor risk cytogenetic and molecular markers, comorbidities and compromised performance status. Although population-based studies indicate that treated patients' survival is better than those who are not treated, there is an understandable reluctance of physicians to choose aggressive therapy. Even in this older population 40-60% CR rates are achievable. Several scoring systems and web-based programs help to predict TRM and CR rates. These sources can assist physicians in the difficult decision-making process of aggressive therapy in an individual patient. Clofarabine and hypomethylating agents are reasonable options and can induce CR in patients who cannot receive standard induction with anthracyclines and cytarabine. Despite encouraging CR rates, median survival remains short (o12 months) in elderly AML patients. Even those patients achieving CR have limited long-term survival (B20% at 3 years) without allogeneic hematopoietic cell transplantation (alloHCT). AlloHCT is feasible and can provide approximately 40% survival at 2 years in appropriately selected patients. Although increased age is associated with poorer survival, higher comorbidities and poor performance status have more negative impact than age per se. The short duration of CR demands that leukemia and transplant physicians collaborate immediately after diagnosis to move quickly toward alloHCT. This collaboration is also essential to choosing the right individuals to transplant and to bridging post-remission therapy (intermediate-dose cytarabine, a hypomethylating agent or FLT-3 inhibitor) in this sometimes frail population. Future studies should be designed not only to address who should receive alloHCT, but also to improve our understanding of AML biology and the process of its cure.

show abstract

“…Toxicities were consistent with those seen in this patient population and difficult to distinguish from disease-related complications. To address this issue further, we calculated the expected induction death rate for the cohort of patients with untreated AML (de novo or sAML), [37] and determined the expected and observed 60-day mortality (27% vs. 31%) were not significantly different.…”

Section: Discussiosnmentioning

confidence: 99%

Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia

et al. 2011

View full text Add to dashboard Cite

Temozolomide sensitivity is determined by methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can ''prime'' blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m 2 orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m 2 orally for 14 days followed by 200 mg/m 2 orally for 7 days every 6 weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count <50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247. Am. J. Hematol. 87:45-50, 2012. V

show abstract

Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes

Cited by 282 publications

References 31 publications

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

To transplant or not: a dilemma for treatment of elderly AML patients in the twenty-first century

Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia

Contact Info

Product

Resources

About