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

Tsirigotis, Panagiotis; Byrne, Michael; Schmid, Christoph; Baron, Frédéric; Ciceri, Fabio; Esteve, Jordi; Gorin, Norbert Claude; Giebel, Sebastian; Mohty, Mohamad; Savani, Bipin N.; Nagler, Arnon

doi:10.1038/bmt.2016.167

Cited by 166 publications

(127 citation statements)

References 95 publications

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“…Thereby, PRF-AML with poor cytogenetic characteristics were associated with statistically significant lower LFS, higher RI, and lower OS at 2 years in multivariate analysis. These data pave the road for investigating more intensive additional approaches relying on sequential conditioning regimens and/or post-transplant treatments such as 5-azacytidine, prophylactic donor lymphocytes infusions, or targeted therapy in order to further improve in the prognosis of this devastating subgroup of patients [39]. …”

Section: Discussionmentioning

confidence: 99%

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

et al. 2017

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BackgroundPrimary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML.MethodsThe current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.ResultsHSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality.ConclusionsHSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0498-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

et al. 2017

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“…A prospective study needs to clarify these questions. However, currently MRD analysis is—if available—clearly preferable …”

Section: Discussionmentioning

confidence: 99%

Digital droplet PCR‐based chimerism analysis for monitoring of hematopoietic engraftment after allogeneic stem cell transplantation

Mika

Baraniskin

Ladigan

et al. 2019

Int J Lab Hematology

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Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a curative approach for multiple hematologic diseases. The success of alloHSCT is evaluated by analyzing the proportion of living donor cells in blood and bone marrow samples of the recipient (chimerism analysis). To monitor the engrafted cells, donor's individual genetic markers are analyzed in peripheral blood and bone marrow samples, usually by using short tandem repeat (STR) analysis. An alternative method to measure chimerism is based on insertion and deletion markers (InDels) analyzed by digital droplet PCR (ddPCR); however, this approach is rarely evaluated in clinical practice. Methods In this study, we examined the usefulness of ddPCR‐based chimerism analysis against the standard STR analysis in samples around day+30 after alloHSCT in clinical practice using peripheral blood and bone marrow samples. Results The median absolute difference between ddPCR and STR analysis was 0.55% points for bone marrow chimerisms and 0.25% points for peripheral blood chimerisms, respectively, including variation in the range of maximum 2% for both methods. The results of every single sample gave the same clinical message. Conclusion According to our data, chimerism analysis by ddPCR has an excellent correlation with STR‐based analyses. Due to its fast and easy applicability, the ddPCR technique is suitable for chimerism monitoring in clinical practice.

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“…Allogeneic stem cell transplantation is the most preferred postremission therapy for patients with AML . However, approximately 30%‐40% of patients with AML experience relapse after allo‐HSCT, and their outcomes are dismal . Thus, refining the risk stratification that could be used to identify patients at a higher risk of relapse is crucial for reducing relapse and improving prognosis.…”

Section: Discussionmentioning

confidence: 99%

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

Wang

Guo

Zhang

et al. 2019

Int J Lab Hematology

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Background The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia‐associated immunophenotypes. Methods We compared the MRD status detected using MFC and real‐time quantitative polymerase chain reaction (RT‐qPCR) in the same 158 bone marrow samples collected from 44 AML patients carrying leukemia‐specific fusion genes. The clinical performance of the MFC‐based MRD status was analyzed in 168 AML patients who exhibited morphologic CR (135) or active disease (33) before HSCT. Results Strong concordance was found between MFC‐based and RT‐qPCR‐based MRD status (κ = 0.868). Among the patients displaying CR, the positive MRD status detected using MFC was correlated with a worse prognosis [HRs (P values) for relapse, event‐free survival, and overall survival: 4.83 (<0.001), 2.23 (0.003), and 1.79 (0.049), respectively]; the prognosis was similar to patients with an active disease before HSCT. Patients with a positive MRD before HSCT might experience a benefit from developing chronic graft‐vs‐host disease. Conclusions The assessment of MRD using our self‐built different‐from‐normal AML‐MRD detection panel exhibited reliable sensitivity, specificity, and accuracy. In addition, patients with a positive MRD status before transplantation may have higher risk of relapse and worse survival.

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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

Cited by 166 publications

References 95 publications

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Digital droplet PCR‐based chimerism analysis for monitoring of hematopoietic engraftment after allogeneic stem cell transplantation

The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

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