The prognostic relevance of flt3 and npm1 mutations on older patients treated intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16 trial

Lazenby, Michelle; Gilkes, Amanda F.; Marrin, Ceri; Evans, Anna; Hills, Robert Kerrin; Burnett, Alan Kenneth

doi:10.1038/leu.2014.90

Cited by 53 publications

(40 citation statements)

References 26 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is much less prognostic molecular information available in older patients and, because the overall results of therapy are poorer, such information has less prognostic impact. 23 More extensive characterization of larger numbers of older patients may improve this situation. Attention to this population of patients was stimulated by our investigators, who realized that the therapeutic options on offer, which were exclusively a conventional chemotherapy approach, were not suitable for the "frail" patients who frequently presented (see the supplemental data for the investigators who recruited patients to the trial).…”

Section: Discussionmentioning

confidence: 99%

Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

Dennis

Russell

Hills

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

Dennis

Russell

Hills

et al. 2015

Blood

View full text Add to dashboard Cite

show abstract

“…As noted above, inclusion of information about NPM and FLT3 alters Wheatley prognostic score in only 11% of older patients aged 60 [19]. Hence, older patients who are in the Wheatley poor risk group (Table II) will largely fall into the ELN adverse group and as such are typically candidates for clinical trials.…”

Section: Older Patientsmentioning

confidence: 99%

“…Information about NPM1 and FLT3 ITD resulted in a change in prognostic group ("good," "standard", "poor", Ref. 20, Table II) in only 11% of patients from status based only on covariates such as cytogenetics or secondary AML [19]. SWOG found no effect of NPM11/FLT3 ITD-status on, relapse or survival rates in the 25% of 58 patients aged >65 with this genotype, largely because their outcomes were poor enough to be indistinguishable from those in similarly aged patients with the other three genotypes [21].…”

Section: Factors Associated With Trmmentioning

confidence: 99%

See 1 more Smart Citation

Acute myeloid leukemia: 2016 Update on risk‐stratification and management

Estey

2016

American J Hematol

View full text Add to dashboard Cite

Evidence suggest that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment related mortality and resistance to therapy, the latter the principal cause of failure even in patients aged 70 or above. We emphasize the limitations of prediction of resistance based only on pre‐ treatment factors and stress the need to incorporate post‐treatment factors, for example indicators of minimal residual disease. We review various newer therapeutic options and considerations that underlie the decision to recommend allogeneic hematopoietic cell transplant. Am. J. Hematol. 91:825–846, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

“…3,17 As might be expected, older FLT3-ITD+ patients treated with chemotherapyonly regimens fare even worse with 79% relapsing and a 3-year overall survival of only 14%. 18 These statistics provide a sobering comparator to Song and colleagues' data.…”

mentioning

confidence: 99%

Allogeneic transplant for FLT3-ITD+ AML: room for improvement

Perl

Luger

2016

Bone Marrow Transplant

View full text Add to dashboard Cite

Fms-like tyrosine kinase 3 internal tandem duplication mutations (FLT3-ITD+) occur in 25% of newly diagnosed patients with AML. In patients younger than age 60 with normal karyotype AML, FLT3-ITD mutations consistently have been shown to be associated with high relapse rates and short time to relapse, particularly, in patients who receive chemotherapy alone as post-remission treatment. Remission rates after relapse are low and consequently survival is poor.1,2 Accordingly, allogeneic transplantation has been employed in appropriate patients to attempt to mitigate the negative prognostic impact of FLT3-ITD mutation.Whether allogeneic transplant for FLT3-ITD+ AML actually improves overall survival over traditional chemotherapy has not been specifically studied in a randomized prospective fashion. Instead, one must infer these results from a number of pediatric and younger adult AML trials, where AML patients in first remission with matched siblings received myeloablative transplants.3-5 Although initial results of donor versus no-donor analyses from these trials were conflicting and analyses complicated by low rates of transplant among patients with available donors, subsequent data with higher protocol adherence suggest rather substantial protection from relapse among FLT3-ITD+ patients. The magnitude of this benefit is sufficient to expect an improved survival from the approach and transplant is now an accepted frontline therapy for FLT3-ITD+ AML patients. Still, even within the FLT3-ITD+ population, relapse risk is variable. Although based upon a number of clinical and leukemia-specific factors, selection of optimal FLT3-ITD+ patients for transplant remains challenging. In this issue, Song and colleagues 6 report addresses these questions; their report is both welcome and topical.Song and colleagues 6 report is notable not only for being among the largest single-center experiences reporting transplant outcomes in the FLT3-ITD+ population but also for its inclusion of patients transplanted with both myeloablative and reduced intensity conditioning, inclusion of unrelated donors as well as matched siblings and a wide range of patient ages from pediatric to older adults. From this broad experience, the authors show not only an impressively favorable tolerability of transplant among FLT3-ITD+ patients but a 3 year overall survival of only 38% with a strikingly high relapse rate (63%) post transplant. Such high relapse rates are concerning, and the authors convincingly show FLT3-ITD+ status at diagnosis-once controlled for a number of confounders-is an independent risk factor for relapse and mortality following transplant. Leukemic relapse was far and away the dominant cause of mortality among FLT3-ITD+ patients (26/28 of the post-transplant deaths due to relapse, 4% non-relapse mortality). Overall, the data unfortunately suggest purported survival benefits from transplant may be modest when applied to a broader population than that enrolled to multicenter prospective trials noted above.Similarly, Song and colleague...

show abstract

The prognostic relevance of flt3 and npm1 mutations on older patients treated intensively or non-intensively: a study of 1312 patients in the UK NCRI AML16 trial

Cited by 53 publications

References 26 publications

Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia

Acute myeloid leukemia: 2016 Update on risk‐stratification and management

Allogeneic transplant for FLT3-ITD+ AML: room for improvement

Contact Info

Product

Resources

About