Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation

Schmid, Christoph; Labopin, Myriam; Socié, Gérard; Daguindau, Étienne; Volin, Liisa; Huynh, Anne; Bourhis, Jean; Milpied, Noël; Cornelissen, Jan J.; Chevallier, Patrice; Maertens, Johan; Jindra, Pavel; Blaise, Didier; Lenhoff, Stig; Ifrah, Norbert; Baron, Frédéric; Ciceri, Fabio; Gorin, Claude; Savani, Bipin N.; Giebel, Sebastian; Polge, Emmanuelle; Esteve, Jordi; Nagler, Arnon; Mohty, Mohamad

doi:10.1182/blood-2015-06-651562

Cited by 96 publications

(83 citation statements)

References 40 publications

(52 reference statements)

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“…Patients with FLT3-ITD AML are candidates for allo-SCT due to the poor prognosis conferred by this mutation and are at increased risk of developing post-transplant relapse compared with FLT3-WT patients. 15,16 A phase I trial designed to identify the maximum tolerated dose of sorafenib in the post-SCT maintenance period for FLT3-ITD+ AML demonstrated a 1-year RFS of 85% and a 1-year OS of 95%. In patients that were in CR1/CR2 at SCT, the 1-year RFS and OS were 95% and 100%, respectively.…”

Section: Post-transplant Therapymentioning

confidence: 99%

“…[10][11][12][13][14][15] Therefore, the basic prognostic scheme proposed by the European Leukemia Net (ELN) working group also has applicability in the allo-SCT setting. 16 In addition, advanced disease status at transplant is a significant adverse-risk factor for post-SCT relapse. Patients that undergo allo-SCT with advanced disease are also prone to poor outcomes.…”

Section: Identification Of Patients At High Risk For Relapse After Almentioning

confidence: 99%

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Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Tsirigotis

Byrne

Schmid

et al. 2016

Bone Marrow Transplant

169

131

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Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.

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Section: Post-transplant Therapymentioning

confidence: 99%

Section: Identification Of Patients At High Risk For Relapse After Almentioning

confidence: 99%

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Tsirigotis

Byrne

Schmid

et al. 2016

Bone Marrow Transplant

169

131

View full text Add to dashboard Cite

show abstract

“…Similarly, Song and colleagues' data describe generally higher relapse rates and worse post-transplant survivals for FLT3-ITD+ AML than that of large registry reports, from EBMT, 7,8 and CIBMTR. 9 These registry studies report relapse rates after first remission transplant in the range of~30%, with expected cure rate of~50% for transplanted patients.…”

mentioning

confidence: 86%

“…9 These registry studies report relapse rates after first remission transplant in the range of~30%, with expected cure rate of~50% for transplanted patients. Notably, outside of a recent EBMT analysis of transplant for normal karyotype AML that included patients up to 71 years of age and both myeloablative and reduced intensity conditioning, 8 prior registry reports examining the merits of transplant for FLT3-ITD+ AML focused upon considerably younger patients who received T-cell replete, myeloablative allografts from HLA-matched siblings and/or 8/8 antigen-matched unrelated donors. The higher relapse rates reported by Song and colleagues may in part relate to the older age of their patients (median age of 55, with 28% older than 60 years), variations in preparative regimens or other transplant-specific treatments.…”

mentioning

confidence: 99%

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

Perl

Luger

2016

Bone Marrow Transplant

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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...

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“…It should be noted that as NRM rates decrease justification for allo HCT in CR1 may increase even in certain "favorable" molecular subgroups (e.g. NPM mutated/FLT3 wild type) not now considered indications for allo HCT [96].…”

Section: Allogeneic Hematopoietic Cell Transplant Allo (Hct)mentioning

confidence: 99%

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

Estey

2016

American J Hematol

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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.

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Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation

Cited by 96 publications

References 40 publications

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT

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

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

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