Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

Oran, Betül; Jorgensen, Jeff; Marín, David; Wang, Sa; Ahmed, Sairah; Alousi, Amin M.; Andersson, Börje S.; Bashir, Qaiser; Bassett, Roland L.; Lyons, Genevieve; Chen, Julianne; Rezvani, Katy; Kebriaei, Partow; Patel, Keyur P.; Rondón, Gabriela; Shpall, Elizabeth J.; Champlin, Richard E.

doi:10.3324/haematol.2016.144253

Cited by 51 publications

(42 citation statements)

References 42 publications

(34 reference statements)

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“…Despite similar immunophenotypes, the differing cytogenetics in our twins could be due to additional mutational “hits” (secondary events) in twin A. The presence of pre‐HCT MRD was likely the determining prognostic factor, as persistent pre‐HCT MRD is associated with poor outcomes in pediatric and adult AML …”

Section: Discussionmentioning

confidence: 91%

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Abu‐Arja

Dargart

Bajwa

et al. 2018

Pediatric Transplantation

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AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.

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Section: Discussionmentioning

confidence: 91%

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Abu‐Arja

Dargart

Bajwa

et al. 2018

Pediatric Transplantation

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“…Note, Flu/Mel conditioning was associated with lower relapse rate compared with fludarabine and busulfan conditioning . While this conditioning did not overcome the negative impact of MRD positivity in HLA‐matched transplants, in haplo‐SCT the opposite appears to be the case. This supports the idea that a stronger GVL effect might exist with haploidentical grafts, and raises the question whether the negative MRD on transplant outcomes can be potentially mitigated.…”

Section: Discussionmentioning

confidence: 98%

Haploidentical transplantation for acute myeloid leukemia patients with minimal/measurable residual disease at transplantation

et al. 2019

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There have been conflicting results regarding the impact of minimal/measurable disease at transplant on acute myeloid leukemia (AML) outcomes after haploidentical transplantation (haplo-SCT). We assessed the impact of pre-transplant disease status on posttransplant outcomes of 143 patients treated with haplo-SCT using fludarabine-melphalan (FM) conditioning and post-transplant cyclophosphamide (PTCy). With a median followup of 29 months, the two-year PFS for all patients was 41%. Compared to patients in complete remission (CR) at transplant, those with active disease (n = 29) and CR with incomplete count recovery (CRi) (n = 39) had worse PFS. They had hazard ratios (HR) of 3.5 (95% CI: 2.05-6.1; P < .001) and 2.3 (95% CI: 1.3-3.9; P = .002), respectively. Among patients who were in CR at transplant, there were no differences in PFS between those who had minimal residual disease (MRD) positive (n = 24), and MRD negative (n = 41) (HR 1.85, 95%CI: 0.9-4.0; P = .1). In multivariable analysis for patients in CR, only age was predictive for outcomes, while MRD status at transplant did not influence the treatment outcomes. Our findings suggest that haplo-SCT with FM conditioning regimen and PTCy-based GVHD prophylaxis has a protective effect, and may potentially abrogate the inferior outcomes of MRD positivity for patients with AML. Patients with positive MRD may benefit from proceeding urgently to a haplo-SCT, as this does not appear to negatively impact transplant outcomes.

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“…These results can improve prognostication accuracy in patients referred for HCT in MRD‐negative state. Previous studies of MRD in the transplant setting either did not consider prior consolidation in analysis or had too few patients without consolidation . On the other hand, previous studies showing no impact of consolidation did not take MRD status into account and the heterogeneity in MRD status might have masked the effect of consolidation specifically in MRD‐negative patients .…”

Section: Discussionmentioning

confidence: 99%

“…Achieving minimal residual disease (MRD) negativity before allogeneic hematopoietic cell transplantation (allo-HCT) is associated with a reduced risk of relapse in acute myeloid leukemia (AML). 1,2 Furthermore, MRD status at the time of HCT is arguably the most important prognostic determinant of relapse risk, dominating a number of other potential prognostic factors (e.g., cytogenetic risk group, graft source, conditioning intensity). 1,3 However, still about 30% of patients who undergo allo-HCT in a MRD-negative state relapse, 1 We hypothesized that among MRD-negative patients, where MRD status is no longer a variable, specifics of previous treatments may reflect varying depths of remission and hence be prognostic.…”

Section: Introductionmentioning

confidence: 99%

History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease‐negative first complete remission

et al. 2017

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Background Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? Methods The inclusion criteria were: (i) Age >18 years, (ii) AML in CR1 after 1–2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. Results A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35–0.99], P = .046), relapse-free survival (0.60 [0.37–0.96], P = .036), and relapse (0.50 [0.27–0.92], P = .025). Analysis of potential sources of bias was unrevealing. Conclusions In AML patients undergoing allo-HCT in MRD-negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts.

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Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia

Cited by 51 publications

References 42 publications

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Monozygotic twins diagnosed simultaneously with RAM immunophenotype acute myeloid leukemia

Haploidentical transplantation for acute myeloid leukemia patients with minimal/measurable residual disease at transplantation

History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease‐negative first complete remission

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