ISSN 1866-8836
Клеточная терапия и трансплантация

Significance of minimal residual disease before allogeneic hematopoietic cell transplantation for acute myeloid leukemia

Sergey N. Bondarenko 1, Ivan S. Moiseev 1, Elena I. Darskaya 1, Anna G. Smirnova 1, Irina A. Samorodova 1, Olga S. Uspenskaya 2, Elena V. Babenko 1, Ildar M. Barkhatov 1, Tatyana L. Gindina 1, Nikolay N. Mamaev 1, Alexander D. Kulagin 1, Boris V. Afanasyev 1
1 R. M. Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First St. Petersburg State Medical University, St. Petersburg, Russian Federation
2 Leningrad Regional Clinical Hospital, Hematology Department, St. Petersburg, Russian Federation

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Cellular Therapy and Transplantation (CTT)
Volume 7, Number 3
Contents 

Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for many patients with acute myeloid leukemia (AML). The relapse after allo-HSCT is the most common cause of treatment failure. However, multiparameter flow cytometry, cytogenetic and molecular studies in the onset of the disease makes it possible to detect the minimal residual disease (MRD) in AML remission in order to determine the prognosis and the therapy strategy.

Aim

To evaluate the impact of MRD before allo-HSCT in patients with AML on the results of treatment.

Patients and methods

We analysed 195 consecutive patients with AML since 2012 to 2016. Median age was 36 (18-70) years. The median follow-up was 23 (23-467) months. Disease status before allo-HSCT: CR1 – 148 (76%), CR2 – 47 (24%) patients. Molecular and genetic low-risk group was defined in 31(17%), standard risk in 119 (59%) and 45 (24%) high-risk patients. MRD was not determined (MRD (-)) in 155 (80%) patients. A positive result of MRD (MRD (+)) before alloHSCT was in 40 (20%) patients, including mutations, gene overexpression and leukemia associated immunophenotypes.

Results

Disease-free survival (DFS) after alloHSCT in CR1MRD(-) was 67% (95%CI 57-77), and in MRD(+) 54% (95%CI 36-72) (p=.03), whereas in patients with CR2MRD(-) 57% (95%CI 41-73) and CR2MRD(+) – 33% (95%CI 1-88) (p=ns). The relapse incidence (RI) in the CR1MRD(-) was 22% (95%CI 13-32), and in MRD(+) – 36% (95%CI 19-53), whereas in the CR2MRD(-) 17% (95%CI 7-32), and in MRD(+) 66% (95%CI 15-91). With myeloablative conditioning (MAC), the DFS and RI after allo-HSCT in CR1 did not depended on MRD: patients with MRD(-) 70% (95%CI 59-81) vs MRD(+) 64% (95%CI 36-92) and 17% (95%CI 7-39) vs 23% (95%CI 12-35) respectively. Whereas after reduced intensity conditioning (RIC), the DFC was higher, and the RI was lower in patients with MRD(-): 67% (95%CI 54-80) vs 50% (95%CI 27-77) (p=.03) and 50% (95%CI 25-70) vs 23% (95%CI 12-35) (p <.000). The cytogenetic risk group (intermediate and high) and the donor type (related and unrelated) had no effect on DFS and RI: 74% vs 63% and 47% vs 38%, 16% vs 19% and 59% vs 63 %; 68% vs 57% and 65% vs 42%, 20% vs 29% and 29% vs 58%. In the absence of chronic graft-versus-host disease (cGVHD), DFS and RI were better in patients with MRD(-) 64% (95%CI 45-83) vs 52% (95%CI 32-72) (p = 0.01) and 34% (95%CI 15-54) vs 44% (95%CI 23-63)(p =.03). In patients with cGVHD, the difference was insignificant: 70% vs 80% and 17% vs 20%. In multivariate analysis, the impact on the RI has had the status of the disease (MRD(+)/MRD(-)) (HR2.3, 95%CI, 1.1-4.9, p=.03) and the presence of cGVHD(yes/no) (HR0.3, 95%CI, 0.2-1.0, =.05). DFS was lower with MRD(+) (HR1.8, 95%CI, 1.0-3.5, p =.05).

Conclusion

Immunophenotypic, cytogenetic and molecular data in the onset of the disease is necessary for monitoring the MRD in AML remission. The presence of MRD has a negative effect on DFS and RI after allo-HSCT. MRD(+) status in front of the allo-HSCT is an indication for the intensification of the conditioning regimen.

Disclosure

The authors report no conflicts of interest in this work.

Keywords

Acute myeloid leukemia, minimal residual disease, allogeneic hematopoietic stem cell transplantation.


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