Current standard of care for consolidation therapy for AML varies based on age and induction regimen, among other factors. Many trials have sought to determine the optimal dose, number of cycles, and ...schedule for consolidation with cytarabine. For AML patients under age 60, mid-dose cytarabine is as effective as high-dose cytarabine, results after 3 or 4 cycles of cytarabine in consolidation are comparable but are both superior to only one cycle, and giving cytarabine every 12 h on days 1, 2, and 3 appears to have the same benefit but less toxicity than cytarabine given on days 1, 3, and 5. For those over age 60, the best dose of cytarabine is unknown, but post-remission therapy appears to improve survival for some patients who achieve remission after standard induction, depending on induction regimen used and MRD status at time of remission.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (pre-imatinib cohort). In 2003 ...imatinib was introduced as a single-agent course following induction (N = 86, late imatinib). In 2005 imatinib was added to the second phase of induction (N = 89, early imatinib). The complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P = .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS = 0.64, 95% confidence interval 0.44-0.93, P = .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.
•Imatinib improves outcomes for adults with Ph+ ALL at least in part by facilitating allogeneic stem cell transplant.•Allogeneic hematopoietic stem cell transplant is not dispensible in Ph+ ALL in the imatinib era.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How can one optimize induction therapy in AML? Luger, Selina M.
Best practice & research. Clinical haematology,
December 2017, 2017-12-00, 20171201, Volume:
30, Issue:
4
Journal Article
Peer reviewed
Induction therapy for acute myeloid leukemia has not changed much since 1973, when the 7 + 3 regimen of cytarabine and daunorubicin was born. Since then, various strategies have been evaluated to ...improve patient response, including dose intensification, the incorporation of additional agents into the regimen, the development of novel agents, and modified approaches for older patients. Recently, two novel agents, CPX-351 and gemtuzumab ozogamicin, have been approved by the US Food and Drug Administration. This review discusses each of the induction strategies and their impact on patient outcomes.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Intensive chemotherapy has been the backbone of the treatment of acute myeloid leukemia (AML) for decades. However, an increase in novel targeted agents, which has been brought about in part by a ...deeper understanding of the genetic makeup of AML, has led to remission-inducing regimens that do not require traditional cytotoxic agents. Combinations of a hypomethylating agent (HMA) and venetoclax have doubled the chance of remission for patients considered unfit for induction chemotherapy who would have traditionally been offered singleagent HMA. In fact, this regimen may rival the complete remission rate achieved with induction chemotherapy for certain populations such as the very elderly and those with secondary AML, but equivalency has yet to be established. Further advances include the addition of gemtuzumab ozogamicin and FLT3 inhibitors to induction chemotherapy, which improves survival for patients with core-binding factor and FLT3-mutated AML, respectively. Still, much work is needed to improve the outcomes of the highest-risk subgroups: frail patients and those with high-risk cytogenetics and/or TP53 mutations. Promisingly, the landscape of AML therapy is shifting dramatically and no longer is intensity, when feasible, always the best answer for AML.
Patients with AML who were between 17 and 60 years of age were randomly assigned to receive induction therapy with the standard dose of daunorubicin or twice the standard dose; the two groups also ...received a standard dose of cytarabine. Rates of complete remission and overall survival were best in the high-dose group, especially among patients with a favorable or an intermediate cytogenetic risk profile.
Patients with AML who were between 17 and 60 years of age were randomly assigned to receive induction therapy with the standard dose of daunorubicin or twice the standard dose. Rates of complete remission and overall survival were best in the high-dose group.
The survival of patients with acute myeloid leukemia (AML) is affected by many variables, including therapy that induces complete remission and appropriate consolidation therapy. Currently, anthracycline plus cytarabine is the usual induction therapy for patients with AML.
1
The widely used intravenous combination of daunorubicin (at a dose of 45 mg per square meter of body-surface area), given daily for 3 days, and cytarabine (at a dose of 100 mg per square meter), given daily for 7 days, results in complete remission in 50 to 75% of patients.
1
,
2
Neither the addition of other drugs to daunorubicin and cytarabine
3
nor intensification . . .
Survival rates for patients with acute myeloid leukemia (AML) older than 75 years are still quite dismal. Recent approvals, therefore, of two agents specifically to treat older patients—glasdegib and ...venetoclax—have created excitement among the medical community. Clinical data, particularly complete response (CR) rates and CR with incomplete hematologic recovery (CRi), look quite promising and are reviewed here. Yet the question remains whether fit elderly patients should receive combination therapy containing the newer agents, particularly since intensive chemotherapy remains the only treatment that has demonstrated the ability to achieve long-term disease-free survival.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This study examines the long‐term OS of relapsed AML patients who were enrolled to 9 successive ECOG‐ACRIN trials for newly diagnosed AML, during 1984‐2008. The objectives were to examine whether ...there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long‐term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.1%) achieved CR1 and of these, 58.9% relapsed. The median follow‐up was 9.7 years. The median OS from relapse was 0.5 years and the 5‐year OS was 10 (±1)%. These results were similar even for the most recent studies. A multivariate model showed that age, cytogenetics at diagnosis, duration of CR1 and undergoing allogeneic transplantation were significantly associated with OS from relapse. Even among patients who relapsed with better prognostic factors; age < 40 and CR1 > 12 months, there was no significant OS difference between the studies. In conclusion, this large cohort appears to confirm that the survival of AML patients postrelapse continues to be dismal and has not improved during the past quarter of a century.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose Extramedullary disease (EMD) at diagnosis in patients with acute myeloid leukemia (AML) has been recognized for decades. Reported herein are results from a large study of patients with AML ...who were treated in consecutive ECOG-ACRIN Cancer Research Group frontline clinical trials in an attempt to define the incidence and clinical implications of EMD. Methods Patients with newly diagnosed AML, age 15 years and older, who were treated in 11 clinical trials, were studied to identify EMD, as defined by physical examination, laboratory findings, and imaging results. Results Of the 3,522 patients enrolled, 282 were excluded, including patients with acute promyelocytic leukemia, incorrect diagnosis, or no adequate assessment of EMD at baseline. The overall incidence of EMD was 23.7%. The sites involved were: lymph nodes (11.5%), spleen (7.3%), liver (5.3%), skin (4.5%), gingiva (4.4%), and CNS (1.1%). Most patients (65.3%) had only one site of EMD, 20.9% had two sites, 9.5% had three sites, and 3.4% had four sites. The median overall survival was 1.035 years. In univariable analysis, the presence of any EMD ( P = .005), skin involvement ( P = .002), spleen ( P < .001), and liver ( P < .001), but not CNS ( P = .34), nodal involvement ( P = .94), and gingival hypertrophy ( P = .24), was associated with a shorter overall survival. In contrast, in multivariable analysis, adjusted for known prognostic factors such as cytogenetic risk and WBC count, neither the presence of EMD nor the number of specific sites of EMD were independently prognostic. Conclusion This large study demonstrates that EMD at any site is common but is not an independent prognostic factor. Treatment decisions for patients with EMD should be made on the basis of recognized AML prognostic factors, irrespective of the presence of EMD.
PDF
