PROGNOSTIC IMPACT OF COMPLEX KARYOTYPE ON OUTCOME OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN ACUTE MYELOID LEUKEMIAWITH CHROMOSOME 5 AND/OR 7 ABNORMALITIES
(Abstract release date: 05/19/16)
EHA Library. Gindina T. 06/09/16; 134535; PB1635
Dr. Tatiana Gindina
Contributions
Contributions
Abstract
Abstract: PB1635
Type: Publication Only
Background
Chromosome 5 and 7 abnormalities often occur in acute myeloid leukemia (AML) both as a single chromosomal aberration and a part of the complex karyotype (CK), and constitute a high-risk group. Breems et al., 2008 have identified a monosomal karyotype (MK), defined by the presence of at least 1 autosomal monosomy and 1 structural chromosomal abnormality or at least 2 autosomal monosomies, which associated with dismal outcome in AML patients. However, whether or not the prognostic impact of MK and CK remains relevant for patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still unclear.
Aims
To evaluate the prognostic impact of chromosome 5 and 7 abnormalities both as a single chromosome aberration and a part of the complex or monosomal karyotype on outcome of allogeneic hematopoietic stem cell transplantation in AML patients.
Methods
In this study, outcomes in 44 AML patients with 5q-, 7q-/monosomy 7, who were transplanted in our University between 2008 and 2015, were analyzed. All patients and transplant characteristics are listed in Table I.
Results
CK and MK were identified in 19 (43 %) and 8 (18 %) cases, respectively. The median follow-up was 525 (46 – 2186) days. Overall survival (OS) was 39 % (95 % CI 22 - 55) and event free survival (EFS) was 20 % (95% CI 8 - 35) at 3 years estimated with Kaplan-Meier method. In univariate analysis, prognostic factors associated with increased OS and EFS were age (>18 vs <18 years; p=0.01, p=0.05, respectively), the disease status at transplant (complete remission vs active diease; p=0.10, p=0.01, respectively), complex karyotype (CK- vs CK+; p=0.05, p=0.002, respectively), and stem cells source (bone marrow vs other source; p=0.03 for OS only); monosomal karyotype (MK- vs MK+; p=0.009 for EFS only). Other factors including variant of AML, patient sex, donor type, conditioning regimen, number of transplanted CD34+ cells, and type of chromosome abnormality were not associated with survival. In multivariate analysis, age (HR-3.67; P=0.01), the disease status at allo-HSCT (HR-2.64; P=0.03), the stem cell source (HR-3.04; P=0.02), and complex karyotype (HR-2.48; P=0.03) remained statistically significant for OS. Moreover, age (HR-2.63; P=0.01), the disease status at transplant (HR-2.63; P=0.01) and complex karyotype (HR-3.29; P=0.002) were independent predictors of EFS.
Conclusion
The results indicate, that chromosome 5 and 7 abnormalities as a part of the complex karyotype but not monosomal karyotype is high-risk factor in AML patients undergoing allo-HSCT.
Session topic: E-poster
Keyword(s): Allo-SCT, AML, Complex aberrant karyotype, Prognosis
Type: Publication Only
Background
Chromosome 5 and 7 abnormalities often occur in acute myeloid leukemia (AML) both as a single chromosomal aberration and a part of the complex karyotype (CK), and constitute a high-risk group. Breems et al., 2008 have identified a monosomal karyotype (MK), defined by the presence of at least 1 autosomal monosomy and 1 structural chromosomal abnormality or at least 2 autosomal monosomies, which associated with dismal outcome in AML patients. However, whether or not the prognostic impact of MK and CK remains relevant for patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still unclear.
Aims
To evaluate the prognostic impact of chromosome 5 and 7 abnormalities both as a single chromosome aberration and a part of the complex or monosomal karyotype on outcome of allogeneic hematopoietic stem cell transplantation in AML patients.
Methods
In this study, outcomes in 44 AML patients with 5q-, 7q-/monosomy 7, who were transplanted in our University between 2008 and 2015, were analyzed. All patients and transplant characteristics are listed in Table I.
| Number of patients | 44 (100 %) |
| AMLDe novo AMLSecondary AML | 27 (61 %)17 (39 %) |
| Patient sex, n (%)MaleFemale | 22 (50 %)22 (50 %) |
| Age at HSCT, median, (range) years | 31.2 (1.2-67) |
| Age group≤18 yo≥18 yo | 15 (34 %)29 (66 %) |
| Cytogenetics, n (%) 5q--7/7q-5q- together with -7/7q-Complex karyotype -Complex karyotype + Monosomal karyotype –Monosomal karyotype + | 15 (34 %)24 (55 %) 5 (11 %)25 (57 %)19 (43 %)36 (82 %) 8 (18 %) |
| Clinical stage at HSCT, n (%)CR1≥CR2Active disease | 13 (30 %)7 (16 %)24 (54 %) |
| HSC source, n (%)Bone marrowPeripheral bloodBoth | 24 (55 %)15 (34 %)5 (11 %) |
| Conditioning regimen, n (%)MANon-MA | 10 (23 %)34 (77 %) |
| Donor type, n (%)HLA-id siblingMatched unrelatedHaploidentical | 13 (30 %)20 (45 %)11 (25 %) |
| Number of transplanted CD34+ cells, mediana (range) x106/kg | 6.3 (1.6-17.9) |
Results
CK and MK were identified in 19 (43 %) and 8 (18 %) cases, respectively. The median follow-up was 525 (46 – 2186) days. Overall survival (OS) was 39 % (95 % CI 22 - 55) and event free survival (EFS) was 20 % (95% CI 8 - 35) at 3 years estimated with Kaplan-Meier method. In univariate analysis, prognostic factors associated with increased OS and EFS were age (>18 vs <18 years; p=0.01, p=0.05, respectively), the disease status at transplant (complete remission vs active diease; p=0.10, p=0.01, respectively), complex karyotype (CK- vs CK+; p=0.05, p=0.002, respectively), and stem cells source (bone marrow vs other source; p=0.03 for OS only); monosomal karyotype (MK- vs MK+; p=0.009 for EFS only). Other factors including variant of AML, patient sex, donor type, conditioning regimen, number of transplanted CD34+ cells, and type of chromosome abnormality were not associated with survival. In multivariate analysis, age (HR-3.67; P=0.01), the disease status at allo-HSCT (HR-2.64; P=0.03), the stem cell source (HR-3.04; P=0.02), and complex karyotype (HR-2.48; P=0.03) remained statistically significant for OS. Moreover, age (HR-2.63; P=0.01), the disease status at transplant (HR-2.63; P=0.01) and complex karyotype (HR-3.29; P=0.002) were independent predictors of EFS.
Conclusion
The results indicate, that chromosome 5 and 7 abnormalities as a part of the complex karyotype but not monosomal karyotype is high-risk factor in AML patients undergoing allo-HSCT.
Session topic: E-poster
Keyword(s): Allo-SCT, AML, Complex aberrant karyotype, Prognosis
Abstract: PB1635
Type: Publication Only
Background
Chromosome 5 and 7 abnormalities often occur in acute myeloid leukemia (AML) both as a single chromosomal aberration and a part of the complex karyotype (CK), and constitute a high-risk group. Breems et al., 2008 have identified a monosomal karyotype (MK), defined by the presence of at least 1 autosomal monosomy and 1 structural chromosomal abnormality or at least 2 autosomal monosomies, which associated with dismal outcome in AML patients. However, whether or not the prognostic impact of MK and CK remains relevant for patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still unclear.
Aims
To evaluate the prognostic impact of chromosome 5 and 7 abnormalities both as a single chromosome aberration and a part of the complex or monosomal karyotype on outcome of allogeneic hematopoietic stem cell transplantation in AML patients.
Methods
In this study, outcomes in 44 AML patients with 5q-, 7q-/monosomy 7, who were transplanted in our University between 2008 and 2015, were analyzed. All patients and transplant characteristics are listed in Table I.
Results
CK and MK were identified in 19 (43 %) and 8 (18 %) cases, respectively. The median follow-up was 525 (46 – 2186) days. Overall survival (OS) was 39 % (95 % CI 22 - 55) and event free survival (EFS) was 20 % (95% CI 8 - 35) at 3 years estimated with Kaplan-Meier method. In univariate analysis, prognostic factors associated with increased OS and EFS were age (>18 vs <18 years; p=0.01, p=0.05, respectively), the disease status at transplant (complete remission vs active diease; p=0.10, p=0.01, respectively), complex karyotype (CK- vs CK+; p=0.05, p=0.002, respectively), and stem cells source (bone marrow vs other source; p=0.03 for OS only); monosomal karyotype (MK- vs MK+; p=0.009 for EFS only). Other factors including variant of AML, patient sex, donor type, conditioning regimen, number of transplanted CD34+ cells, and type of chromosome abnormality were not associated with survival. In multivariate analysis, age (HR-3.67; P=0.01), the disease status at allo-HSCT (HR-2.64; P=0.03), the stem cell source (HR-3.04; P=0.02), and complex karyotype (HR-2.48; P=0.03) remained statistically significant for OS. Moreover, age (HR-2.63; P=0.01), the disease status at transplant (HR-2.63; P=0.01) and complex karyotype (HR-3.29; P=0.002) were independent predictors of EFS.
Conclusion
The results indicate, that chromosome 5 and 7 abnormalities as a part of the complex karyotype but not monosomal karyotype is high-risk factor in AML patients undergoing allo-HSCT.
Session topic: E-poster
Keyword(s): Allo-SCT, AML, Complex aberrant karyotype, Prognosis
Type: Publication Only
Background
Chromosome 5 and 7 abnormalities often occur in acute myeloid leukemia (AML) both as a single chromosomal aberration and a part of the complex karyotype (CK), and constitute a high-risk group. Breems et al., 2008 have identified a monosomal karyotype (MK), defined by the presence of at least 1 autosomal monosomy and 1 structural chromosomal abnormality or at least 2 autosomal monosomies, which associated with dismal outcome in AML patients. However, whether or not the prognostic impact of MK and CK remains relevant for patients who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still unclear.
Aims
To evaluate the prognostic impact of chromosome 5 and 7 abnormalities both as a single chromosome aberration and a part of the complex or monosomal karyotype on outcome of allogeneic hematopoietic stem cell transplantation in AML patients.
Methods
In this study, outcomes in 44 AML patients with 5q-, 7q-/monosomy 7, who were transplanted in our University between 2008 and 2015, were analyzed. All patients and transplant characteristics are listed in Table I.
| Number of patients | 44 (100 %) |
| AMLDe novo AMLSecondary AML | 27 (61 %)17 (39 %) |
| Patient sex, n (%)MaleFemale | 22 (50 %)22 (50 %) |
| Age at HSCT, median, (range) years | 31.2 (1.2-67) |
| Age group≤18 yo≥18 yo | 15 (34 %)29 (66 %) |
| Cytogenetics, n (%) 5q--7/7q-5q- together with -7/7q-Complex karyotype -Complex karyotype + Monosomal karyotype –Monosomal karyotype + | 15 (34 %)24 (55 %) 5 (11 %)25 (57 %)19 (43 %)36 (82 %) 8 (18 %) |
| Clinical stage at HSCT, n (%)CR1≥CR2Active disease | 13 (30 %)7 (16 %)24 (54 %) |
| HSC source, n (%)Bone marrowPeripheral bloodBoth | 24 (55 %)15 (34 %)5 (11 %) |
| Conditioning regimen, n (%)MANon-MA | 10 (23 %)34 (77 %) |
| Donor type, n (%)HLA-id siblingMatched unrelatedHaploidentical | 13 (30 %)20 (45 %)11 (25 %) |
| Number of transplanted CD34+ cells, mediana (range) x106/kg | 6.3 (1.6-17.9) |
Results
CK and MK were identified in 19 (43 %) and 8 (18 %) cases, respectively. The median follow-up was 525 (46 – 2186) days. Overall survival (OS) was 39 % (95 % CI 22 - 55) and event free survival (EFS) was 20 % (95% CI 8 - 35) at 3 years estimated with Kaplan-Meier method. In univariate analysis, prognostic factors associated with increased OS and EFS were age (>18 vs <18 years; p=0.01, p=0.05, respectively), the disease status at transplant (complete remission vs active diease; p=0.10, p=0.01, respectively), complex karyotype (CK- vs CK+; p=0.05, p=0.002, respectively), and stem cells source (bone marrow vs other source; p=0.03 for OS only); monosomal karyotype (MK- vs MK+; p=0.009 for EFS only). Other factors including variant of AML, patient sex, donor type, conditioning regimen, number of transplanted CD34+ cells, and type of chromosome abnormality were not associated with survival. In multivariate analysis, age (HR-3.67; P=0.01), the disease status at allo-HSCT (HR-2.64; P=0.03), the stem cell source (HR-3.04; P=0.02), and complex karyotype (HR-2.48; P=0.03) remained statistically significant for OS. Moreover, age (HR-2.63; P=0.01), the disease status at transplant (HR-2.63; P=0.01) and complex karyotype (HR-3.29; P=0.002) were independent predictors of EFS.
Conclusion
The results indicate, that chromosome 5 and 7 abnormalities as a part of the complex karyotype but not monosomal karyotype is high-risk factor in AML patients undergoing allo-HSCT.
Session topic: E-poster
Keyword(s): Allo-SCT, AML, Complex aberrant karyotype, Prognosis
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