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Overall Survival (OS) of Older Patients with Acute Myeloid Leukemia (AML) and Association with Socioeconomic and Health Care System Factors
Abstracts AML-031
Figure 2 Overall Survival
Overall Survival (OS) of Older Patients with Acute Myeloid Leukemia (AML) and Association with Socioeconomic and Health Care System Factors Vijaya Bhatt Baojiang Chen University of Nebraska Medical Center, Omaha, NE, United States
GvHD prophylaxis with PT-Cy is reproducible and effective. Different posttransplant strategies can be used in case of relapse or graft dysfunction (DLI, second transplantation).
Context: Non-biological factors may influence OS of older patients with AML. Objective: To determine the predictors of OS of older patients with AML. Design: Retrospective study from 19982012. Setting: Data from National Cancer Database. Patients: AML patients >60 years Main Outcome Measures: Multivariate analysis of determinants of OS Results: 63,463 patients >60 years had a median OS of 2.9 months (95% CI 2.8-3.0). In a multivariate analysis, OS was worse in non-academic versus academic centers (HR 1.13; 95% CI 1.10-1.16; p <0.0001), with Medicare insurance (HR 1.35; 95% CI 1.30-1.40; p<0.0001) or unknown insurance status (HR 1.38; 95% CI 1.27-1.49; p<0.0001), and Charlson comobidity score of 1 (HR 1.20; 95% CI 1.16-1.24; p<0.0001) or 2 versus 0 (HR 1.45; 95% CI 1.38-1.52; p<0.0001)
Table 1 Cox Proportional Hazard Model for OS Variable
Hazards ratio
Academic
1.00
Non-Academic
1.13
95% confidence interval
Pair-wise P-value
1.09-1.16
<0.0001
0.93-0.98
0.001
0.36
Sex Male
1.00
Female
0.96
Annual Income <$38,000
1.00
$38,000-47,999
0.98
0.94-1.03
$48,000-62,999
0.93
0.89-0.98
0.003
$63,000 +
0.89
0.83-0.93
<0.0001
Insurance Status Private insurance/managed care
1.00
Not insured
1.04
0.92-1.18
0.54
Medicaid
1.07
0.97-1.18
0.18 <0.0001
Medicare
1.35
1.30-1.40
Other government
0.97
0.83-1.14
0.74
Unknown
1.38
1.27-1.49
<0.0001
Charlson co-morbidity score 0
1.00
1
1.20
1.16-1.24
<0.0001
2
1.45
1.38-1.52
<0.0001
1.76-1.95
<0.0001
2.08-2.52
<0.0001
Receipt of chemotherapy Yes
1.00
No
1.85
Receipt of transplant Yes
1.00
No
2.29
Clinical Lymphoma, Myeloma & Leukemia September 2016
- S21
Abstracts (Table 1). Lack of receipt of chemotherapy and hematopoietic cell transplant were associated with worse OS. OS was significantly better in women (HR 0.96; 95% CI 0.93-0.98; p¼0.001), and with higher annual income (p<0.0001). OS did not differ based on race, and education status. Conclusion: Various socioeconomic and health system factors are associated with varying OS in older patients with AML. Deeper understanding of such factors and improved delivery of care have potential to improve outcomes. Grant Acknowledgement: University of Nebraska Medical Center, College of Medicine, Physician-Scientist Training Program Grant 2016-2017 to Vijaya Bhatt.
AML-033 Role of the Methylenetetrahydrofolate Reductase (MTHFR) A1982C Gene Polymorphism in Predicting Clinical Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantationin Patients with Myeloid Leukemia Essam El Beih ,1 Raafat Abdel-Fattah,2,3 Hosam Kamel,2,3 Mohamed Samra,2,3 Alaa El-Haddad,2,3 Omar Fahmy,4 Gamal Fathy,3 Gamal Ebid,5 Eman Radwan,6 Azza Kamel5 1
Clinical Hematology Unit, Internal Medicine Department, Faculty of
Medicine, Assiut University Hospital, Assiut, Egypt; 2Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 3Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt; 4Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 5
Clinical Pathology Department, National Cancer Institute, Cairo
University, Cairo, Egypt; 6Clinical and Chemical Pathology Depart-
Background: Role of 5,10-methylenetetrahydrofolate reductase (MTHFR) A1298G polymorphism in Methotrexate Pharmacodynamics, used as GVHD prophylaxis, in myeloid leukemic patients undergoing HSCT is still uncertain. Objectives: To assess impact of the A1298G polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) on the clinical outcomes of leukemic patients treated using HLA-matched sibling HSCT as acute graft versus host disease (GVHD), severe oral mucositis, VOD, drug induced hepatic and renal toxicity, transplant related mortality (TRM) and overall survival (OS). Patients and Methods: 20 leukemic patients, 15 (9/ 6) AML (CR1/CR2-3) and 5(4/1) CML (CP1/CP3), received allogeneic HSCT were recruited. We examined the association of a single nucleotide polymorphism (A>C) at position 1298 in the MTHFR gene with outcomes HSCT of. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Median age at the time of HSCT was 23 years (range 8e44 years); 9 patients (45%) are males, and the median (range) follow-up period of survivors was 24.8 (0.3-50.1) months. BU/CY was as conditioning regimen in 14 patients (70%). All received peripheral blood stem as a stem cell source with mean CD34+ stem cell dose (6.2 1.7) 106/kg and GVHD prophylaxis was standard combination of CsA and MTX. Results: The frequencies of the MTHFR A1298C genotypes in patients were 60% (12 patients) for 1298AA (wild type), 40% (8 patients) for combined variant genotypes (AC+CC). Recipient MTHFR1298 in AC or CC genotypes versus AA genotypes showed non-statistically significant higher incidence of acute GVHD (12.5% vs 8.3%); p¼0.76, chronic GVHD (37.5% vs 16.7%); p¼ 0.29, VOD (12.5% vs 0%); p¼0.21, TRM (25% vs 8.3%); p¼0.31 (Table 1). Recipients with variant allele MTHFR 1298C were associated with lower non statistically significant overall survival; p¼0.12 (Figure 1). Conclusion: MTHFR 1298C variant allele might be a predictor of GVHD and mortality of myeloid leukemic patients undergoing HSCT, albeit larger studies warranted for verification.
ment, Cairo University, Cairo, Egypt
Table 1 Univariate Analysis of Association of Recipient MTHFR1298 Polymorphism with HSCT Outcomes of 21 Myeloid Leukemic Patients 1298AA (n[12)
S22
-
1298AC or CC (n[9)
Event
N
%
N
%
P value
Acute GVHD (n[2)
1
8.3
1
12.5
0.76
Chronic GVHD (n[5) Hepatic toxicity (n[10)
2
16.7
3
37.5
0.29
7
58.3
3
37.5
0.36
Renal toxicity (n[6) VOD (n[1)
4
33.3
2
25
0.69
0
0
1
12.5
0.21
Severe oral mucositis (n[10) TRM (n[3)
6
50
4
50
1.00
2
25
0.31
1
8.3
Clinical Lymphoma, Myeloma & Leukemia September 2016
Figure 1 Variant Allele MTHFR 1298C were Associated with Lower Non Statistically Significant Overall Survival
Figure 2 Overall Survival
Overall Survival (OS) of Older Patients with Acute Myeloid Leukemia (AML) and Association with Socioeconomic and Health Care System Factors Vijaya Bhatt Baojiang Chen University of Nebraska Medical Center, Omaha, NE, United States
GvHD prophylaxis with PT-Cy is reproducible and effective. Different posttransplant strategies can be used in case of relapse or graft dysfunction (DLI, second transplantation).
Context: Non-biological factors may influence OS of older patients with AML. Objective: To determine the predictors of OS of older patients with AML. Design: Retrospective study from 19982012. Setting: Data from National Cancer Database. Patients: AML patients >60 years Main Outcome Measures: Multivariate analysis of determinants of OS Results: 63,463 patients >60 years had a median OS of 2.9 months (95% CI 2.8-3.0). In a multivariate analysis, OS was worse in non-academic versus academic centers (HR 1.13; 95% CI 1.10-1.16; p <0.0001), with Medicare insurance (HR 1.35; 95% CI 1.30-1.40; p<0.0001) or unknown insurance status (HR 1.38; 95% CI 1.27-1.49; p<0.0001), and Charlson comobidity score of 1 (HR 1.20; 95% CI 1.16-1.24; p<0.0001) or 2 versus 0 (HR 1.45; 95% CI 1.38-1.52; p<0.0001)
Table 1 Cox Proportional Hazard Model for OS Variable
Hazards ratio
Academic
1.00
Non-Academic
1.13
95% confidence interval
Pair-wise P-value
1.09-1.16
<0.0001
0.93-0.98
0.001
0.36
Sex Male
1.00
Female
0.96
Annual Income <$38,000
1.00
$38,000-47,999
0.98
0.94-1.03
$48,000-62,999
0.93
0.89-0.98
0.003
$63,000 +
0.89
0.83-0.93
<0.0001
Insurance Status Private insurance/managed care
1.00
Not insured
1.04
0.92-1.18
0.54
Medicaid
1.07
0.97-1.18
0.18 <0.0001
Medicare
1.35
1.30-1.40
Other government
0.97
0.83-1.14
0.74
Unknown
1.38
1.27-1.49
<0.0001
Charlson co-morbidity score 0
1.00
1
1.20
1.16-1.24
<0.0001
2
1.45
1.38-1.52
<0.0001
1.76-1.95
<0.0001
2.08-2.52
<0.0001
Receipt of chemotherapy Yes
1.00
No
1.85
Receipt of transplant Yes
1.00
No
2.29
Clinical Lymphoma, Myeloma & Leukemia September 2016
- S21
Abstracts (Table 1). Lack of receipt of chemotherapy and hematopoietic cell transplant were associated with worse OS. OS was significantly better in women (HR 0.96; 95% CI 0.93-0.98; p¼0.001), and with higher annual income (p<0.0001). OS did not differ based on race, and education status. Conclusion: Various socioeconomic and health system factors are associated with varying OS in older patients with AML. Deeper understanding of such factors and improved delivery of care have potential to improve outcomes. Grant Acknowledgement: University of Nebraska Medical Center, College of Medicine, Physician-Scientist Training Program Grant 2016-2017 to Vijaya Bhatt.
AML-033 Role of the Methylenetetrahydrofolate Reductase (MTHFR) A1982C Gene Polymorphism in Predicting Clinical Outcomes of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantationin Patients with Myeloid Leukemia Essam El Beih ,1 Raafat Abdel-Fattah,2,3 Hosam Kamel,2,3 Mohamed Samra,2,3 Alaa El-Haddad,2,3 Omar Fahmy,4 Gamal Fathy,3 Gamal Ebid,5 Eman Radwan,6 Azza Kamel5 1
Clinical Hematology Unit, Internal Medicine Department, Faculty of
Medicine, Assiut University Hospital, Assiut, Egypt; 2Medical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 3Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt; 4Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 5
Clinical Pathology Department, National Cancer Institute, Cairo
University, Cairo, Egypt; 6Clinical and Chemical Pathology Depart-
Background: Role of 5,10-methylenetetrahydrofolate reductase (MTHFR) A1298G polymorphism in Methotrexate Pharmacodynamics, used as GVHD prophylaxis, in myeloid leukemic patients undergoing HSCT is still uncertain. Objectives: To assess impact of the A1298G polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) on the clinical outcomes of leukemic patients treated using HLA-matched sibling HSCT as acute graft versus host disease (GVHD), severe oral mucositis, VOD, drug induced hepatic and renal toxicity, transplant related mortality (TRM) and overall survival (OS). Patients and Methods: 20 leukemic patients, 15 (9/ 6) AML (CR1/CR2-3) and 5(4/1) CML (CP1/CP3), received allogeneic HSCT were recruited. We examined the association of a single nucleotide polymorphism (A>C) at position 1298 in the MTHFR gene with outcomes HSCT of. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Median age at the time of HSCT was 23 years (range 8e44 years); 9 patients (45%) are males, and the median (range) follow-up period of survivors was 24.8 (0.3-50.1) months. BU/CY was as conditioning regimen in 14 patients (70%). All received peripheral blood stem as a stem cell source with mean CD34+ stem cell dose (6.2 1.7) 106/kg and GVHD prophylaxis was standard combination of CsA and MTX. Results: The frequencies of the MTHFR A1298C genotypes in patients were 60% (12 patients) for 1298AA (wild type), 40% (8 patients) for combined variant genotypes (AC+CC). Recipient MTHFR1298 in AC or CC genotypes versus AA genotypes showed non-statistically significant higher incidence of acute GVHD (12.5% vs 8.3%); p¼0.76, chronic GVHD (37.5% vs 16.7%); p¼ 0.29, VOD (12.5% vs 0%); p¼0.21, TRM (25% vs 8.3%); p¼0.31 (Table 1). Recipients with variant allele MTHFR 1298C were associated with lower non statistically significant overall survival; p¼0.12 (Figure 1). Conclusion: MTHFR 1298C variant allele might be a predictor of GVHD and mortality of myeloid leukemic patients undergoing HSCT, albeit larger studies warranted for verification.
ment, Cairo University, Cairo, Egypt
Table 1 Univariate Analysis of Association of Recipient MTHFR1298 Polymorphism with HSCT Outcomes of 21 Myeloid Leukemic Patients 1298AA (n[12)
S22
-
1298AC or CC (n[9)
Event
N
%
N
%
P value
Acute GVHD (n[2)
1
8.3
1
12.5
0.76
Chronic GVHD (n[5) Hepatic toxicity (n[10)
2
16.7
3
37.5
0.29
7
58.3
3
37.5
0.36
Renal toxicity (n[6) VOD (n[1)
4
33.3
2
25
0.69
0
0
1
12.5
0.21
Severe oral mucositis (n[10) TRM (n[3)
6
50
4
50
1.00
2
25
0.31
1
8.3
Clinical Lymphoma, Myeloma & Leukemia September 2016
Figure 1 Variant Allele MTHFR 1298C were Associated with Lower Non Statistically Significant Overall Survival