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Introduction Autologous blood/bone marrow transplantation (BMT) is the currently accepted treatment for many hematological malignancies
.
Although improvements in supportive care regimens have resulted in a significant reduction in early mortality, autologous BMT recipients remain at higher risk of long-term mortality due to long-term disease burden
.
The main causes of long-term death include disease recurrence or progression and secondary malignancy (SMN)
.
However, the cumulative effect of long-term morbidity and mortality on life expectancy is unclear
.
Transplant protocols have changed significantly over the past 30 years, including: increasing patient age at transplant; increasing selection of autologous BMT for plasma cell disease (PCD); decline in total body irradiation (TBI) as a pre-transplant treatment; selection of peripheral blood Increase in stem cells (PBSC) as a source of stem cells
.
However, researchers are not yet clear about the impact of these factors on mortality and life expectancy
.
Based on this, some researchers conducted a BMT survivor study to explore the trends of long-term mortality and life expectancy in patients who survived ≥2 years after BMT treatment
.
Research Methods The BMT Survivor Study is a collaborative research project between City of Hope National Medical Center, the University of Minnesota and the University of Alabama at Birmingham
.
The study included patients who survived ≥2 years after receiving BMT at three medical centers in 2014 and prior
.
The primary exposure variables in the study population were four different periods of BMT treatment: 1981-1999; 2000-2005; 2006-2010; and 2011-2014
.
The follow-up deadline was April 19, 2021
.
Results Patient Baseline Characteristics A total of 4702 patients were included in the study, the median age at BMT was 53 years (range: 0-78 years), 58.
7% were male, 67.
8% were non-Hispanic Caucasian, 28.
3 % of patients received BMT between 2011-2014
.
Median follow-up after BMT was 9 years (range: 2-36 years)
.
PCD was the most common cause of BMT (42.
3%)
.
91.
6% of patients chose PBSC as the source of stem cells during transplantation, and 23.
1% received TBI as pre-transplant treatment
.
Stratified by four periods (1981-1999; 2000-2005; 2006-2010; 2011-2014), the median age at BMT increased from 40 to 58 years, the proportion of PCD patients increased from 13.
7% to 60.
0%, The proportion of patients receiving PBSC as a stem cell source increased from 66.
6% to 99.
5%; while patients receiving TBI as pre-transplant therapy decreased from 56.
4% to 5.
2%, and patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) ) in patients receiving BMT decreased from 15.
4% to 0.
2%
.
The specific baseline characteristics are shown in Table 1
.
Table 1 Mortality and life expectancy Mortality 2-30 years after BMT was higher than expected, with a U-shaped curve, with greater differences between patients with the shortest and longest follow-up; 2-year mortality after BMT was 39.
2/1000 Person/year, the 30-year mortality rate after BMT was 54.
1/1000 person/year
.
Mortality rates were higher than expected for transplant patients of all ages; mortality rates for transplant patients >30 years of age were increasing compared with the general population
.
The risk of all-cause mortality in this study cohort was 2.
1 times that of the general population (95% CI, 2.
0-2.
2)
.
Specifically as shown in Figure 1
.
Figure 1 With the premise of ≥2 years of survival after BMT, the patient's life expectancy was reduced by 7.
0 years, or a reduction of 25.
8%
.
Younger patients lost more years of life, and older patients lost the least
.
Specifically as shown in Figure 2
.
Figure 2 is stratified by four periods, with a 9.
4% reduction in life expectancy in 2011-2014 and an 18.
5% reduction in life expectancy in 1981-1999
.
After adjusting for relevant demographic and clinical variables, the 5-year hazard ratio for all-cause mortality was referenced from 1981 to 1999, and decreased for the remaining three periods
.
Specifically as shown in Figure 3
.
Figure 3 Unadjusted 5-year hazard ratios for all-cause mortality for the four periods are comparable
.
Adjusting for age at BMT and primary diagnosis, both reduced the hazard ratio for mortality
.
After adjustment for age at BMT, primary diagnosis, and TBI, late mortality was further reduced from 1981-1999 to 2011-2014
.
Results of analyses stratified by age at BMT (≤40 years; 41-64 years; ≥65 years) showed significant reductions in long-term all-cause mortality in patients ≥65 years across four periods; results of stratified analyses by early diagnosis , PCD and Hodgkin lymphoma patients had a significant reduction in long-term all-cause mortality in four periods; stratified analysis according to TBI results showed a significant reduction in long-term all-cause mortality in four periods in patients who did not receive TBI
.
The long-term mortality risk was predicated on survival in the first 2 years after BMT, and the 25-year overall survival rate for the entire study cohort was 41.
0%
.
Factors associated with long-term all-cause mortality included older age at BMT (41-64 years: HR=2.
47, 95%CI, 2.
14-2.
86; ≥65 years: HR=3.
69, 95%CI, 3.
08-4.
42; ref.
Age group: 0-40 years), male (HR=1.
17, 95%CI, 1.
07-1.
28) and high-risk disease (HR=1.
34; 95%CI, 1.
20-1.
50)
.
The details are shown in Table 2
.
Table 2 Among the 2132 patients who died, 1898 (89.
0%) could know the cause of death
.
Causes of death included relapse-related death (RRM, 47.
4%), non-relapse death (NRM, 44.
0%), and external causes (1.
6%)
.
The 25-year cumulative incidence of RRM was 23.
8% (95% CI, 22.
5-25.
2) and NRM was 25.
9% (95% CI, 24.
0-27.
7)
.
The most common causes of NRM included infection (n=361), SMN (n=346), cardiovascular disease (n=260) and renal disease (n=165)
.
The 25-year cumulative incidence of infection-related death was 9.
7%, with a standard mortality ratio (SMR) of 8.
1
.
Multivariate analysis indicated that older age at BMT, high-risk disease, and PCD were predictors of infection-related mortality
.
The 25-year cumulative incidence of SMN-related death was 9.
8%, with an SMR of 5.
7
.
Types of SMN include hematologic SMN (treatment-related myeloid tumors [t-MN: n=124] and others [n=23]) and solid SMN (gastrointestinal tumors [n=56], lung tumors [n=23]) 47] and others [n=93])
.
Multivariate analysis indicated that older age at BMT was a predictor of mortality associated with all SMN, t-MN, and solid SMN, whereas male sex was a predictor of mortality associated with solid SMN
.
Mortality and life expectancy of BMT recipients in recent years The study collated data from 2546 patients who received BMT between 2006 and 2014
.
With survival ≥2 years as a precondition, the risk of all-cause mortality in this subgroup was 9.
1 times higher than that in the general population (95% CI, 8.
51-9.
69), and the 15-year overall survival rate was 53.
4%
.
The 15-year cumulative incidence of RRM was 22.
3% and NRM was 17.
4%
.
Factors associated with RRM include older age at BMT, high-risk disease, and PCD
.
Factors associated with NRM included older age at BMT, male gender, Asian ethnicity, high-risk disease, pre-transplant TBI treatment, and use of bone marrow as a source of stem cells
.
Compared with the normal population, the life expectancy of this group of patients was shortened by 4.
4 years
.
CONCLUSIONS The findings suggest that long-term mortality in BMT recipients decreased over a 30-year period
.
However, further control of the development of infections, secondary tumors, cardiovascular and renal diseases is needed to reduce long-term mortality
.
References: Smita Bhatia, Chen Dai, Wendy Landier, et al.
Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report.
J Clin Oncol.
2022 Mar 9; JCO2102372.
doi: 10.
1200/ JCO.
21.
02372.
Review: Quinta Typesetting: Uni Execution: Uni stamp "read the original text", we will make progress together
.
Although improvements in supportive care regimens have resulted in a significant reduction in early mortality, autologous BMT recipients remain at higher risk of long-term mortality due to long-term disease burden
.
The main causes of long-term death include disease recurrence or progression and secondary malignancy (SMN)
.
However, the cumulative effect of long-term morbidity and mortality on life expectancy is unclear
.
Transplant protocols have changed significantly over the past 30 years, including: increasing patient age at transplant; increasing selection of autologous BMT for plasma cell disease (PCD); decline in total body irradiation (TBI) as a pre-transplant treatment; selection of peripheral blood Increase in stem cells (PBSC) as a source of stem cells
.
However, researchers are not yet clear about the impact of these factors on mortality and life expectancy
.
Based on this, some researchers conducted a BMT survivor study to explore the trends of long-term mortality and life expectancy in patients who survived ≥2 years after BMT treatment
.
Research Methods The BMT Survivor Study is a collaborative research project between City of Hope National Medical Center, the University of Minnesota and the University of Alabama at Birmingham
.
The study included patients who survived ≥2 years after receiving BMT at three medical centers in 2014 and prior
.
The primary exposure variables in the study population were four different periods of BMT treatment: 1981-1999; 2000-2005; 2006-2010; and 2011-2014
.
The follow-up deadline was April 19, 2021
.
Results Patient Baseline Characteristics A total of 4702 patients were included in the study, the median age at BMT was 53 years (range: 0-78 years), 58.
7% were male, 67.
8% were non-Hispanic Caucasian, 28.
3 % of patients received BMT between 2011-2014
.
Median follow-up after BMT was 9 years (range: 2-36 years)
.
PCD was the most common cause of BMT (42.
3%)
.
91.
6% of patients chose PBSC as the source of stem cells during transplantation, and 23.
1% received TBI as pre-transplant treatment
.
Stratified by four periods (1981-1999; 2000-2005; 2006-2010; 2011-2014), the median age at BMT increased from 40 to 58 years, the proportion of PCD patients increased from 13.
7% to 60.
0%, The proportion of patients receiving PBSC as a stem cell source increased from 66.
6% to 99.
5%; while patients receiving TBI as pre-transplant therapy decreased from 56.
4% to 5.
2%, and patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) ) in patients receiving BMT decreased from 15.
4% to 0.
2%
.
The specific baseline characteristics are shown in Table 1
.
Table 1 Mortality and life expectancy Mortality 2-30 years after BMT was higher than expected, with a U-shaped curve, with greater differences between patients with the shortest and longest follow-up; 2-year mortality after BMT was 39.
2/1000 Person/year, the 30-year mortality rate after BMT was 54.
1/1000 person/year
.
Mortality rates were higher than expected for transplant patients of all ages; mortality rates for transplant patients >30 years of age were increasing compared with the general population
.
The risk of all-cause mortality in this study cohort was 2.
1 times that of the general population (95% CI, 2.
0-2.
2)
.
Specifically as shown in Figure 1
.
Figure 1 With the premise of ≥2 years of survival after BMT, the patient's life expectancy was reduced by 7.
0 years, or a reduction of 25.
8%
.
Younger patients lost more years of life, and older patients lost the least
.
Specifically as shown in Figure 2
.
Figure 2 is stratified by four periods, with a 9.
4% reduction in life expectancy in 2011-2014 and an 18.
5% reduction in life expectancy in 1981-1999
.
After adjusting for relevant demographic and clinical variables, the 5-year hazard ratio for all-cause mortality was referenced from 1981 to 1999, and decreased for the remaining three periods
.
Specifically as shown in Figure 3
.
Figure 3 Unadjusted 5-year hazard ratios for all-cause mortality for the four periods are comparable
.
Adjusting for age at BMT and primary diagnosis, both reduced the hazard ratio for mortality
.
After adjustment for age at BMT, primary diagnosis, and TBI, late mortality was further reduced from 1981-1999 to 2011-2014
.
Results of analyses stratified by age at BMT (≤40 years; 41-64 years; ≥65 years) showed significant reductions in long-term all-cause mortality in patients ≥65 years across four periods; results of stratified analyses by early diagnosis , PCD and Hodgkin lymphoma patients had a significant reduction in long-term all-cause mortality in four periods; stratified analysis according to TBI results showed a significant reduction in long-term all-cause mortality in four periods in patients who did not receive TBI
.
The long-term mortality risk was predicated on survival in the first 2 years after BMT, and the 25-year overall survival rate for the entire study cohort was 41.
0%
.
Factors associated with long-term all-cause mortality included older age at BMT (41-64 years: HR=2.
47, 95%CI, 2.
14-2.
86; ≥65 years: HR=3.
69, 95%CI, 3.
08-4.
42; ref.
Age group: 0-40 years), male (HR=1.
17, 95%CI, 1.
07-1.
28) and high-risk disease (HR=1.
34; 95%CI, 1.
20-1.
50)
.
The details are shown in Table 2
.
Table 2 Among the 2132 patients who died, 1898 (89.
0%) could know the cause of death
.
Causes of death included relapse-related death (RRM, 47.
4%), non-relapse death (NRM, 44.
0%), and external causes (1.
6%)
.
The 25-year cumulative incidence of RRM was 23.
8% (95% CI, 22.
5-25.
2) and NRM was 25.
9% (95% CI, 24.
0-27.
7)
.
The most common causes of NRM included infection (n=361), SMN (n=346), cardiovascular disease (n=260) and renal disease (n=165)
.
The 25-year cumulative incidence of infection-related death was 9.
7%, with a standard mortality ratio (SMR) of 8.
1
.
Multivariate analysis indicated that older age at BMT, high-risk disease, and PCD were predictors of infection-related mortality
.
The 25-year cumulative incidence of SMN-related death was 9.
8%, with an SMR of 5.
7
.
Types of SMN include hematologic SMN (treatment-related myeloid tumors [t-MN: n=124] and others [n=23]) and solid SMN (gastrointestinal tumors [n=56], lung tumors [n=23]) 47] and others [n=93])
.
Multivariate analysis indicated that older age at BMT was a predictor of mortality associated with all SMN, t-MN, and solid SMN, whereas male sex was a predictor of mortality associated with solid SMN
.
Mortality and life expectancy of BMT recipients in recent years The study collated data from 2546 patients who received BMT between 2006 and 2014
.
With survival ≥2 years as a precondition, the risk of all-cause mortality in this subgroup was 9.
1 times higher than that in the general population (95% CI, 8.
51-9.
69), and the 15-year overall survival rate was 53.
4%
.
The 15-year cumulative incidence of RRM was 22.
3% and NRM was 17.
4%
.
Factors associated with RRM include older age at BMT, high-risk disease, and PCD
.
Factors associated with NRM included older age at BMT, male gender, Asian ethnicity, high-risk disease, pre-transplant TBI treatment, and use of bone marrow as a source of stem cells
.
Compared with the normal population, the life expectancy of this group of patients was shortened by 4.
4 years
.
CONCLUSIONS The findings suggest that long-term mortality in BMT recipients decreased over a 30-year period
.
However, further control of the development of infections, secondary tumors, cardiovascular and renal diseases is needed to reduce long-term mortality
.
References: Smita Bhatia, Chen Dai, Wendy Landier, et al.
Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report.
J Clin Oncol.
2022 Mar 9; JCO2102372.
doi: 10.
1200/ JCO.
21.
02372.
Review: Quinta Typesetting: Uni Execution: Uni stamp "read the original text", we will make progress together
