Dataset Information

Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT.

ABSTRACT: Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia (AML) is a common high-risk feature that is referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with AML harboring -5/5q- having their first allogeneic transplantation between 2000 and 2015. Five hundred and one patients with -5/5q- have been analyzed. Three hundred and thirty-eight patients (67%) were in first remission and 142 (28%) had an active disease at time of allogeneic transplantation. The 2-year probabilities of overall survival and leukemia-free survival were 27% and 20%, respectively. The 2-year probability of treatment-related mortality was 20%. We identified four different cytogenetic groups according to additional abnormalities with prognostic impact: -5/5q- without complex karyotype, monosomal karyotype or abn(17p), -5/5q- within a complex karyotype, -5/5q- within a monosomal karyotype and the combination of -5/5q- with abn(17p). In multivariate analysis, factors associated with worse overall survival and leukemia-free survival across the four groups were active disease, age, monosomal karyotype, and abn(17p). The presence of -5/5q- without monosomal karyotype or abn(17p) was associated with a significantly better survival rate while -5/5q- in conjunction with monosomal karyotype or abn(17p) translated into a worse outcome. The patients harboring the combination of -5/5q- with abn(17p) showed very limited benefit from allogeneic transplantation.

SUBMITTER: Poire X

PROVIDER: S-EPMC7012466 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT.

Poiré Xavier X Labopin Myriam M Polge Emmanuelle E Forcade Edouard E Ganser Arnold A Volin Liisa L Michallet Mauricette M Blaise Didier D Yakoub-Agha Ibrahim I Maertens Johan J Espiga Carlos Richard CR Cornelissen Jan J Finke Jürgen J Mohty Mohamad M Esteve Jordi J Nagler Arnon A

Haematologica 20200131 2

Deletion 5q or monosomy 5 (-5/5q-) in acute myeloid leukemia (AML) is a common high-risk feature that is referred to allogeneic stem cell transplantation. However, -5/5q- is frequently associated with other high-risk cytogenetic aberrations such as complex karyotype, monosomal karyotype, monosomy 7 (-7), or 17p abnormalities (abn (17p)), the significance of which is unknown. In order to address this question, we studied adult patients with AML harboring -5/5q- having their first allogeneic trans ...[more]

PMID: 31048355

Similar Datasets

Project description:BACKGROUND:Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. METHODS:In this retrospective registry study, we explored whether measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia is associated with different outcomes in recipients of myeloablative total body irradiation (TBI)-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38?years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated donors. RESULTS:In 1816 of patients, no disease was detectable, and in 964 patients, MRD was positive. Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), and 1.51 (1.26-1.8). TBI was associated with a higher OS, LFS, and lower RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82), and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS and LFS and higher RI in the TBI group, and with higher RI in the chemotherapy group. TBI-based conditioning was associated with improved outcomes in both MRD-negative and MRD-positive patients. CONCLUSIONS:In this large study, we confirmed that patients who are MRD-negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI-based conditioning in the myeloablative setting.

Project description:Primary refractory or relapsed acute myeloid leukemia is associated with a dismal prognosis. Allogeneic stem cell transplantation is the only therapeutic option that offers prolonged survival and cure in this setting. In the absence of a matched sibling donor, transplantation from unrelated 10/10 HLA allele-matched or 9/10 HLA allele-mismatched donors and haploidentical donors are potential alternatives. The current study aimed to compare the outcomes of acute myeloid leukemia patients with active disease who received allogeneic stem cell transplantation from a haploidentical donor with post-transplant cyclophosphamide (n=199) versus an unrelated 10/10-matched donor (n=1111) and versus an unrelated 9/10-mismatched donor (n=383) between 2007 and 2014 and who were reported to the European Society for Blood and Marrow Transplantation registry. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. The leukemia-free survival rates at 2 years of recipients of grafts from a haploidentical donor, an unrelated 10/10-matched donor and an unrelated 9/10-mismatched donor were 22.8%, 28% and 22.2%, respectively (P=NS). In multivariate analysis, there were no significant differences in leukemia-free survival, overall survival, relapse incidence, non-relapse mortality, or graft-versus-host-disease-free relapse-free survival between the three groups. Two predictive factors were associated with a higher relapse incidence: transplantation during first or second relapse compared to primary refractory acute myeloid leukemia and poor cytogenetics. Allogeneic stem cell transplantation may rescue about 25% of acute myeloid leukemia patients with active disease. Importantly, the outcomes of transplants from haploidentical donors were comparable to those from 10/10-matched and 9/10-mismatched unrelated donors. Therefore, a haploidentical donor is a valid option for acute myeloid leukemia patients with active disease.

Dataset Information

Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT.

Publications

Allogeneic stem cell transplantation using HLA-matched donors for acute myeloid leukemia with deletion 5q or monosomy 5: a study from the Acute Leukemia Working Party of the EBMT.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets