Leukemia, Myelodysplasia, Transplantation

Analysis of data from blood transfusions that took place in Sweden and Denmark over a 30-year period showed no indication that chronic lymphocytic leukemia (CLL) risk is higher among recipients of blood from donors who subsequently developed CLL, according to researchers.

The study compared 7,413 recipients of blood from 796 donors who subsequently developed CLL (exposed group), with 80,431 recipients from 7,477 donors free of CLL (unexposed group). In total, 12 recipients in the exposed group and 107 in the unexposed group were later diagnosed with CLL, for an incidence rate ratio of 0.94 (95% confidence interval, 0.52-1.71). When defining “exposed” as receiving blood less than 10 years before donor CLL diagnosis, the incidence rate ratio was 0.46 (95% CI, 0.12-1.85).

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The analyses provided little evidence that donor MBL [monoclonal B-cell lymphocytosis]/CLL transmission in blood products influences recipient CLL risk,” wrote Dr. Henrik Hjalgrim of the department of epidemiology research at Statens Serum Institut, Copenhagen, and his colleagues (Blood 2015 doi: 10.1182/blood-2015-03-632844).

MBL is fairly common in healthy individuals (estimated at 7.1% in a study of American blood donors aged 45-91 years) and may progress to CLL at various rates depending on the MBL cell count. Results from previous studies investigating the association between transfusion and risk of CLL or small lymphocytic lymphoma have been mixed, they noted.

Using a retrospective approach, Dr. Hjalgrim and his associates first identified donors subsequently diagnosed with CLL, then identified control donors free from CLL who were matched for age, sex, county, number of donations, and blood type.

In case MBL may have progressed in the recipient but not the donor, investigators also examined whether CLL clustered among recipients from an individual donor, regardless of donor CLL status, but found no such clusters.

Limiting the analysis was the lack of donor MBL status, for which postdonation CLL diagnosis substituted. Some recipients in the exposed group may have received blood drawn before the donor developed MBL.

Dr. Hjalgrim and his coauthors reported having no disclosures.

Analysis of data from blood transfusions that took place in Sweden and Denmark over a 30-year period showed no indication that chronic lymphocytic leukemia (CLL) risk is higher among recipients of blood from donors who subsequently developed CLL, according to researchers.

The study compared 7,413 recipients of blood from 796 donors who subsequently developed CLL (exposed group), with 80,431 recipients from 7,477 donors free of CLL (unexposed group). In total, 12 recipients in the exposed group and 107 in the unexposed group were later diagnosed with CLL, for an incidence rate ratio of 0.94 (95% confidence interval, 0.52-1.71). When defining “exposed” as receiving blood less than 10 years before donor CLL diagnosis, the incidence rate ratio was 0.46 (95% CI, 0.12-1.85).

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The analyses provided little evidence that donor MBL [monoclonal B-cell lymphocytosis]/CLL transmission in blood products influences recipient CLL risk,” wrote Dr. Henrik Hjalgrim of the department of epidemiology research at Statens Serum Institut, Copenhagen, and his colleagues (Blood 2015 doi: 10.1182/blood-2015-03-632844).

MBL is fairly common in healthy individuals (estimated at 7.1% in a study of American blood donors aged 45-91 years) and may progress to CLL at various rates depending on the MBL cell count. Results from previous studies investigating the association between transfusion and risk of CLL or small lymphocytic lymphoma have been mixed, they noted.

Using a retrospective approach, Dr. Hjalgrim and his associates first identified donors subsequently diagnosed with CLL, then identified control donors free from CLL who were matched for age, sex, county, number of donations, and blood type.

In case MBL may have progressed in the recipient but not the donor, investigators also examined whether CLL clustered among recipients from an individual donor, regardless of donor CLL status, but found no such clusters.

Limiting the analysis was the lack of donor MBL status, for which postdonation CLL diagnosis substituted. Some recipients in the exposed group may have received blood drawn before the donor developed MBL.

Dr. Hjalgrim and his coauthors reported having no disclosures.

Analysis of data from blood transfusions that took place in Sweden and Denmark over a 30-year period showed no indication that chronic lymphocytic leukemia (CLL) risk is higher among recipients of blood from donors who subsequently developed CLL, according to researchers.

The study compared 7,413 recipients of blood from 796 donors who subsequently developed CLL (exposed group), with 80,431 recipients from 7,477 donors free of CLL (unexposed group). In total, 12 recipients in the exposed group and 107 in the unexposed group were later diagnosed with CLL, for an incidence rate ratio of 0.94 (95% confidence interval, 0.52-1.71). When defining “exposed” as receiving blood less than 10 years before donor CLL diagnosis, the incidence rate ratio was 0.46 (95% CI, 0.12-1.85).

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“The analyses provided little evidence that donor MBL [monoclonal B-cell lymphocytosis]/CLL transmission in blood products influences recipient CLL risk,” wrote Dr. Henrik Hjalgrim of the department of epidemiology research at Statens Serum Institut, Copenhagen, and his colleagues (Blood 2015 doi: 10.1182/blood-2015-03-632844).

MBL is fairly common in healthy individuals (estimated at 7.1% in a study of American blood donors aged 45-91 years) and may progress to CLL at various rates depending on the MBL cell count. Results from previous studies investigating the association between transfusion and risk of CLL or small lymphocytic lymphoma have been mixed, they noted.

Using a retrospective approach, Dr. Hjalgrim and his associates first identified donors subsequently diagnosed with CLL, then identified control donors free from CLL who were matched for age, sex, county, number of donations, and blood type.

In case MBL may have progressed in the recipient but not the donor, investigators also examined whether CLL clustered among recipients from an individual donor, regardless of donor CLL status, but found no such clusters.

Limiting the analysis was the lack of donor MBL status, for which postdonation CLL diagnosis substituted. Some recipients in the exposed group may have received blood drawn before the donor developed MBL.

Dr. Hjalgrim and his coauthors reported having no disclosures.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans, with many new treatment options now available. Data on patterns of treatment in elderly veteran patients with CLL is limited. We sought to assess initial treatment patterns over a 13-year period among veteran patients in the Minneapolis VA Health Care System.

Methods: We identified 6,756 CLL cases diagnosed from 2000 to 2013 and are presenting interim data on 2015. We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics and treatment information were collected. The objective of this study was to assess initial treatment patterns, time to initial treatment, and variation of these parameters by age.

Results: At diagnosis, median age was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). The majority of patients were white (n = 1,752, 87%); followed by African American (n = 203, 10%); and Hispanic (n = 33, 2%). Of the 2,015 patients, 751 (37%) received therapy over this period of follow-up. Median time from diagnosis to initial treatment was 1.3 years (range, 0-13 years). The most common initial therapies utilized were chlorambucil (39.4%); fludarabine/cyclophosphamide/ritux-imab (FCR) (12.4%); and single-agent fludarabine (10.5%). When examining these parameters by age in decades, we found that there were no differences in Rai stage at diagnosis by age-decade. There was a progressive increase in initial chlorambucil usage by advancing age. Likewise, the majority of FCR usage was in patients aged < 70 years.

Conclusions: In this veteran population, including many elderly patients, the majority of patients requiring therapy initiated it within 2 years of diagnosis. These patients were most commonly treated with chlorambucil. These patterns of care will be changing with the introduction of newer oral agents, such as ibrutinib and idelalisib, but at a significantly higher cost. The National VA Tumor Registry data will allow future opportunity to examine evolving treatment patterns in both an elderly as well as a veteran population. Updated data will be presented at the AVAHO annual meeting.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans, with many new treatment options now available. Data on patterns of treatment in elderly veteran patients with CLL is limited. We sought to assess initial treatment patterns over a 13-year period among veteran patients in the Minneapolis VA Health Care System.

Methods: We identified 6,756 CLL cases diagnosed from 2000 to 2013 and are presenting interim data on 2015. We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics and treatment information were collected. The objective of this study was to assess initial treatment patterns, time to initial treatment, and variation of these parameters by age.

Results: At diagnosis, median age was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). The majority of patients were white (n = 1,752, 87%); followed by African American (n = 203, 10%); and Hispanic (n = 33, 2%). Of the 2,015 patients, 751 (37%) received therapy over this period of follow-up. Median time from diagnosis to initial treatment was 1.3 years (range, 0-13 years). The most common initial therapies utilized were chlorambucil (39.4%); fludarabine/cyclophosphamide/ritux-imab (FCR) (12.4%); and single-agent fludarabine (10.5%). When examining these parameters by age in decades, we found that there were no differences in Rai stage at diagnosis by age-decade. There was a progressive increase in initial chlorambucil usage by advancing age. Likewise, the majority of FCR usage was in patients aged < 70 years.

Conclusions: In this veteran population, including many elderly patients, the majority of patients requiring therapy initiated it within 2 years of diagnosis. These patients were most commonly treated with chlorambucil. These patterns of care will be changing with the introduction of newer oral agents, such as ibrutinib and idelalisib, but at a significantly higher cost. The National VA Tumor Registry data will allow future opportunity to examine evolving treatment patterns in both an elderly as well as a veteran population. Updated data will be presented at the AVAHO annual meeting.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans, with many new treatment options now available. Data on patterns of treatment in elderly veteran patients with CLL is limited. We sought to assess initial treatment patterns over a 13-year period among veteran patients in the Minneapolis VA Health Care System.

Methods: We identified 6,756 CLL cases diagnosed from 2000 to 2013 and are presenting interim data on 2015. We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics and treatment information were collected. The objective of this study was to assess initial treatment patterns, time to initial treatment, and variation of these parameters by age.

Results: At diagnosis, median age was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). The majority of patients were white (n = 1,752, 87%); followed by African American (n = 203, 10%); and Hispanic (n = 33, 2%). Of the 2,015 patients, 751 (37%) received therapy over this period of follow-up. Median time from diagnosis to initial treatment was 1.3 years (range, 0-13 years). The most common initial therapies utilized were chlorambucil (39.4%); fludarabine/cyclophosphamide/ritux-imab (FCR) (12.4%); and single-agent fludarabine (10.5%). When examining these parameters by age in decades, we found that there were no differences in Rai stage at diagnosis by age-decade. There was a progressive increase in initial chlorambucil usage by advancing age. Likewise, the majority of FCR usage was in patients aged < 70 years.

Conclusions: In this veteran population, including many elderly patients, the majority of patients requiring therapy initiated it within 2 years of diagnosis. These patients were most commonly treated with chlorambucil. These patterns of care will be changing with the introduction of newer oral agents, such as ibrutinib and idelalisib, but at a significantly higher cost. The National VA Tumor Registry data will allow future opportunity to examine evolving treatment patterns in both an elderly as well as a veteran population. Updated data will be presented at the AVAHO annual meeting.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans. Some veterans have a history of Agent Orange exposure, which may potentially impact their presentation and disease course. We sought to assess initial patterns of cytogenetic aberrations among patients with CLL within the Minneapolis VA Health Care System (MVAHCS).

Methods: For this interim analysis, we evaluated a subset (30%) of a larger sample (6,756). We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics, including bone marrow/cytogenetic findings and treatment information were collected. The objective of this study was to assess initial cytogenetic patterns and variation of these parameters by age and Agent Orange exposure.

Results: Median age at diagnosis was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). Cytogenetic data were available on 590 of 2,015 (29%) patients. Cytogenetic findings were normal in 258 (44%) patients. Abnormal cytogenetic findings in the remaining 330 cases included del 13q (28%); trisomy 12 (15%); del 11q (11%); del 17p (6%); and other abnor-malities (13%). Of 330 patients with noted abnormalities, 191 (58%) had 1 abnormality; 60 (18%) had 2; and 79 (24%) had > 2 abnormalities. Out of 2,015 patients, 283 (14%) had a reported exposure to Agent Orange; cytogenetic information was available in 130 (46%). Chromosomal abnormalities were detected in 80 of 130 cases (62%). The most frequent abnormality was del 13q (40%); trisomy 12 (19%); other abnormalities (18%); and del 11q (17%). Of the 80 pa-tients with noted abnormalities, 44 (55%) had 1 abnormality;14 (18%) had 2; and 22 (28%) had > 2 abnormalities.

Conclusions: Cytogenetic abnormalities in CLL play an important role in predicting disease progression and survival. These abnormalities paired with Agent Orange exposure have yet to be explored. Utilization of the National VA Tumor Registry data will allow the opportunity to examine the impact, if any, of Agent Orange exposure on the presentation and disease course of veterans with CLL. Updated cytogenetic findings will be presented at the AVAHO annual meeting.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans. Some veterans have a history of Agent Orange exposure, which may potentially impact their presentation and disease course. We sought to assess initial patterns of cytogenetic aberrations among patients with CLL within the Minneapolis VA Health Care System (MVAHCS).

Methods: For this interim analysis, we evaluated a subset (30%) of a larger sample (6,756). We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics, including bone marrow/cytogenetic findings and treatment information were collected. The objective of this study was to assess initial cytogenetic patterns and variation of these parameters by age and Agent Orange exposure.

Results: Median age at diagnosis was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). Cytogenetic data were available on 590 of 2,015 (29%) patients. Cytogenetic findings were normal in 258 (44%) patients. Abnormal cytogenetic findings in the remaining 330 cases included del 13q (28%); trisomy 12 (15%); del 11q (11%); del 17p (6%); and other abnor-malities (13%). Of 330 patients with noted abnormalities, 191 (58%) had 1 abnormality; 60 (18%) had 2; and 79 (24%) had > 2 abnormalities. Out of 2,015 patients, 283 (14%) had a reported exposure to Agent Orange; cytogenetic information was available in 130 (46%). Chromosomal abnormalities were detected in 80 of 130 cases (62%). The most frequent abnormality was del 13q (40%); trisomy 12 (19%); other abnormalities (18%); and del 11q (17%). Of the 80 pa-tients with noted abnormalities, 44 (55%) had 1 abnormality;14 (18%) had 2; and 22 (28%) had > 2 abnormalities.

Conclusions: Cytogenetic abnormalities in CLL play an important role in predicting disease progression and survival. These abnormalities paired with Agent Orange exposure have yet to be explored. Utilization of the National VA Tumor Registry data will allow the opportunity to examine the impact, if any, of Agent Orange exposure on the presentation and disease course of veterans with CLL. Updated cytogenetic findings will be presented at the AVAHO annual meeting.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, including elderly veterans. Some veterans have a history of Agent Orange exposure, which may potentially impact their presentation and disease course. We sought to assess initial patterns of cytogenetic aberrations among patients with CLL within the Minneapolis VA Health Care System (MVAHCS).

Methods: For this interim analysis, we evaluated a subset (30%) of a larger sample (6,756). We reviewed clinical data from 2,015 patients with CLL diagnosed from 2000 to 2013 and identified through the National VA Tumor Registry. Baseline demographics, including bone marrow/cytogenetic findings and treatment information were collected. The objective of this study was to assess initial cytogenetic patterns and variation of these parameters by age and Agent Orange exposure.

Results: Median age at diagnosis was 69 years (range, 37-96 years); 98% were male (1,979); Rai stage was 0 (n = 1,331, 66%), 1 (n = 317, 16%), 2 (n = 156, 8%), 3 (n = 91, 5%), 4 (n = 113, 6%). Cytogenetic data were available on 590 of 2,015 (29%) patients. Cytogenetic findings were normal in 258 (44%) patients. Abnormal cytogenetic findings in the remaining 330 cases included del 13q (28%); trisomy 12 (15%); del 11q (11%); del 17p (6%); and other abnor-malities (13%). Of 330 patients with noted abnormalities, 191 (58%) had 1 abnormality; 60 (18%) had 2; and 79 (24%) had > 2 abnormalities. Out of 2,015 patients, 283 (14%) had a reported exposure to Agent Orange; cytogenetic information was available in 130 (46%). Chromosomal abnormalities were detected in 80 of 130 cases (62%). The most frequent abnormality was del 13q (40%); trisomy 12 (19%); other abnormalities (18%); and del 11q (17%). Of the 80 pa-tients with noted abnormalities, 44 (55%) had 1 abnormality;14 (18%) had 2; and 22 (28%) had > 2 abnormalities.

Conclusions: Cytogenetic abnormalities in CLL play an important role in predicting disease progression and survival. These abnormalities paired with Agent Orange exposure have yet to be explored. Utilization of the National VA Tumor Registry data will allow the opportunity to examine the impact, if any, of Agent Orange exposure on the presentation and disease course of veterans with CLL. Updated cytogenetic findings will be presented at the AVAHO annual meeting.

Road traffic

A French study has revealed an increased incidence of acute myeloid leukemia (AML) among children living close to heavily used roads.

The incidence of AML was 30% higher among children who lived within 150 m of heavily used roads and where the combined length of road sections

within this radius exceeded 260 m.

The researchers believe the association between AML and road proximity may be driven by traffic-related benzene exposure.

Previous research has shown an increased risk of leukemia among adults with a history of occupational exposure to benzene.

The current study did not suggest an increased risk of acute lymphoblastic leukemia (ALL) among children living closed to heavily used roads.

Jacqueline Clavel, MD, PhD, of INSERM in Paris, France, and her colleagues reported these findings in the American Journal of Epidemiology.

The team analyzed 2760 cases of leukemia diagnosed in children younger than 15 years of age in metropolitan France between 2002 and 2007, including 418 cases of AML and 2275 cases of ALL.

The researchers compared these cases to a contemporary sample of 30,000 control children representative of the metropolitan population.

The data showed that neither distance from the nearest major road(s) nor the length of major roads within 150 m of a child’s residence was associated with ALL.

However, there was an association for AML. For children whose home was less than 150 m from the nearest major road(s), the odds ratio (OR) was 1.2.

When the total length of major road(s) within 150 m from the child’s residence was 257-308 m (second tertile) or 309 m or greater (third tertile), the OR was 1.3. When the total length of major roads was 1-256 m (first tertile), the OR was 0.90.

The researchers noted that traffic-related nitrogen dioxide concentration was not associated with ALL or AML. But their data indicated that benzene concentration was associated with AML.

To assess this potential association, the team studied the Île-de-France region of Paris, the most urbanized region, for which the mean annual concentration of benzene, mainly from road traffic, was estimated in the vicinity of each residence.

The median estimated benzene concentration for controls living in the Île-de-France region was 1.3 μg/m³ (range, 0.3 to 8.5 μg/m³). And the length of major roads within 150 m of a child’s residence was positively and significantly correlated with log benzene concentration (r=0.3, P<0.001).

So it followed that exposure to an estimated benzene concentration greater than the median was associated with AML (OR=1.6).

The researchers also used a composite variable based on the estimated benzene concentration and the length of major roads around a child’s residence.

The association with AML was largest among children with at least 309 m of major roads within 150 m of their residence and estimated benzene concentrations of 1.3 μg/m³ or greater (OR=2.2).

The researchers said these results support a role for traffic-related benzene exposure in the etiology of childhood AML.

Road traffic

A French study has revealed an increased incidence of acute myeloid leukemia (AML) among children living close to heavily used roads.

The incidence of AML was 30% higher among children who lived within 150 m of heavily used roads and where the combined length of road sections

within this radius exceeded 260 m.

The researchers believe the association between AML and road proximity may be driven by traffic-related benzene exposure.

Previous research has shown an increased risk of leukemia among adults with a history of occupational exposure to benzene.

The current study did not suggest an increased risk of acute lymphoblastic leukemia (ALL) among children living closed to heavily used roads.

Jacqueline Clavel, MD, PhD, of INSERM in Paris, France, and her colleagues reported these findings in the American Journal of Epidemiology.

The team analyzed 2760 cases of leukemia diagnosed in children younger than 15 years of age in metropolitan France between 2002 and 2007, including 418 cases of AML and 2275 cases of ALL.

The researchers compared these cases to a contemporary sample of 30,000 control children representative of the metropolitan population.

The data showed that neither distance from the nearest major road(s) nor the length of major roads within 150 m of a child’s residence was associated with ALL.

However, there was an association for AML. For children whose home was less than 150 m from the nearest major road(s), the odds ratio (OR) was 1.2.

When the total length of major road(s) within 150 m from the child’s residence was 257-308 m (second tertile) or 309 m or greater (third tertile), the OR was 1.3. When the total length of major roads was 1-256 m (first tertile), the OR was 0.90.

The researchers noted that traffic-related nitrogen dioxide concentration was not associated with ALL or AML. But their data indicated that benzene concentration was associated with AML.

To assess this potential association, the team studied the Île-de-France region of Paris, the most urbanized region, for which the mean annual concentration of benzene, mainly from road traffic, was estimated in the vicinity of each residence.

The median estimated benzene concentration for controls living in the Île-de-France region was 1.3 μg/m³ (range, 0.3 to 8.5 μg/m³). And the length of major roads within 150 m of a child’s residence was positively and significantly correlated with log benzene concentration (r=0.3, P<0.001).

So it followed that exposure to an estimated benzene concentration greater than the median was associated with AML (OR=1.6).

The researchers also used a composite variable based on the estimated benzene concentration and the length of major roads around a child’s residence.

The association with AML was largest among children with at least 309 m of major roads within 150 m of their residence and estimated benzene concentrations of 1.3 μg/m³ or greater (OR=2.2).

The researchers said these results support a role for traffic-related benzene exposure in the etiology of childhood AML.

Road traffic

A French study has revealed an increased incidence of acute myeloid leukemia (AML) among children living close to heavily used roads.

The incidence of AML was 30% higher among children who lived within 150 m of heavily used roads and where the combined length of road sections

within this radius exceeded 260 m.

The researchers believe the association between AML and road proximity may be driven by traffic-related benzene exposure.

Previous research has shown an increased risk of leukemia among adults with a history of occupational exposure to benzene.

The current study did not suggest an increased risk of acute lymphoblastic leukemia (ALL) among children living closed to heavily used roads.

Jacqueline Clavel, MD, PhD, of INSERM in Paris, France, and her colleagues reported these findings in the American Journal of Epidemiology.

The team analyzed 2760 cases of leukemia diagnosed in children younger than 15 years of age in metropolitan France between 2002 and 2007, including 418 cases of AML and 2275 cases of ALL.

The researchers compared these cases to a contemporary sample of 30,000 control children representative of the metropolitan population.

The data showed that neither distance from the nearest major road(s) nor the length of major roads within 150 m of a child’s residence was associated with ALL.

However, there was an association for AML. For children whose home was less than 150 m from the nearest major road(s), the odds ratio (OR) was 1.2.

When the total length of major road(s) within 150 m from the child’s residence was 257-308 m (second tertile) or 309 m or greater (third tertile), the OR was 1.3. When the total length of major roads was 1-256 m (first tertile), the OR was 0.90.

The researchers noted that traffic-related nitrogen dioxide concentration was not associated with ALL or AML. But their data indicated that benzene concentration was associated with AML.

To assess this potential association, the team studied the Île-de-France region of Paris, the most urbanized region, for which the mean annual concentration of benzene, mainly from road traffic, was estimated in the vicinity of each residence.

The median estimated benzene concentration for controls living in the Île-de-France region was 1.3 μg/m³ (range, 0.3 to 8.5 μg/m³). And the length of major roads within 150 m of a child’s residence was positively and significantly correlated with log benzene concentration (r=0.3, P<0.001).

So it followed that exposure to an estimated benzene concentration greater than the median was associated with AML (OR=1.6).

The researchers also used a composite variable based on the estimated benzene concentration and the length of major roads around a child’s residence.

The association with AML was largest among children with at least 309 m of major roads within 150 m of their residence and estimated benzene concentrations of 1.3 μg/m³ or greater (OR=2.2).

The researchers said these results support a role for traffic-related benzene exposure in the etiology of childhood AML.

Exosomes released by chronic lymphocytic leukemia (CLL) cells induce stromal cells to adopt a cancer-associated fibroblast phenotype, thereby creating a microenvironment conducive to CLL cell adhesion, survival, and growth.

Although the role of exosomes in other cancers has been well studied, their role in hematologic malignancies has not been well characterized. Also, this study confirmed that exosomes are present in CLL lymph nodes and promote tumor growth in vivo.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“Our in vitro and in vivo data show that CLL exosomes harbor an oncogenic potential by stimulating stromal cells to induce an inflammatory and protumorigenic milieu, including increased angiogenesis, thus supporting the survival and outgrowth of CLL cells,” wrote Jerome Paggetti, Ph.D., of the laboratory of experimental hemato-oncology, Luxembourg Institute of Health (Blood 2015 Aug 27. doi:10.1182/blood-2014-12-618025).

Cells were obtained from 21 CLL patients; all patients had an absolute lymphocyte count of more than 30,000/mcL and were untreated for 3 months. The researchers established 30-day cocultures of bone marrow mesenchymal stem cells with primary CLL cells in culture inserts or they treated bone marrow mesenchymal stem cells weekly with exosomes. Similar experiments were performed with the Burkitt lymphoma cell line Namalwa to investigate whether the impact on stromal cells is CLL specific.

Based on gene expression analysis, CLL exosomes and CLL cells cocultured in inserts induced similar gene expression changes in bone marrow mesenchymal stem cells, highlighting the relevance of exosomes for microenvironment changes. “Importantly, lymphoma cells induced a distinct gene expression pattern in bone marrow mesenchymal stem cells, suggesting a specific response to CLL exosomes,” wrote Dr. Paggetti and coauthors.

The impact of CLL exosomes on tumor growth was studied in vivo by subcutaneously injecting cells with and without CLL exosomes into immunocompromised mice. Cells supplemented with exosomes resulted in an increased tumor size compared with tumor cells injected without additional exosomes. Also, the cells supplemented with exosomes accumulated in mice kidneys, confirming the renal involvement observed in CLL patients. “Our data demonstrate a protumorigenic effect of CLL-derived exosomes in vivo and their importance in the early onset of the disease when tumor cells impact the microenvironment to proliferate and promote angiogenesis,” the researchers concluded.

Exosomes released by chronic lymphocytic leukemia (CLL) cells induce stromal cells to adopt a cancer-associated fibroblast phenotype, thereby creating a microenvironment conducive to CLL cell adhesion, survival, and growth.

Although the role of exosomes in other cancers has been well studied, their role in hematologic malignancies has not been well characterized. Also, this study confirmed that exosomes are present in CLL lymph nodes and promote tumor growth in vivo.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“Our in vitro and in vivo data show that CLL exosomes harbor an oncogenic potential by stimulating stromal cells to induce an inflammatory and protumorigenic milieu, including increased angiogenesis, thus supporting the survival and outgrowth of CLL cells,” wrote Jerome Paggetti, Ph.D., of the laboratory of experimental hemato-oncology, Luxembourg Institute of Health (Blood 2015 Aug 27. doi:10.1182/blood-2014-12-618025).

Cells were obtained from 21 CLL patients; all patients had an absolute lymphocyte count of more than 30,000/mcL and were untreated for 3 months. The researchers established 30-day cocultures of bone marrow mesenchymal stem cells with primary CLL cells in culture inserts or they treated bone marrow mesenchymal stem cells weekly with exosomes. Similar experiments were performed with the Burkitt lymphoma cell line Namalwa to investigate whether the impact on stromal cells is CLL specific.

Based on gene expression analysis, CLL exosomes and CLL cells cocultured in inserts induced similar gene expression changes in bone marrow mesenchymal stem cells, highlighting the relevance of exosomes for microenvironment changes. “Importantly, lymphoma cells induced a distinct gene expression pattern in bone marrow mesenchymal stem cells, suggesting a specific response to CLL exosomes,” wrote Dr. Paggetti and coauthors.

The impact of CLL exosomes on tumor growth was studied in vivo by subcutaneously injecting cells with and without CLL exosomes into immunocompromised mice. Cells supplemented with exosomes resulted in an increased tumor size compared with tumor cells injected without additional exosomes. Also, the cells supplemented with exosomes accumulated in mice kidneys, confirming the renal involvement observed in CLL patients. “Our data demonstrate a protumorigenic effect of CLL-derived exosomes in vivo and their importance in the early onset of the disease when tumor cells impact the microenvironment to proliferate and promote angiogenesis,” the researchers concluded.

Exosomes released by chronic lymphocytic leukemia (CLL) cells induce stromal cells to adopt a cancer-associated fibroblast phenotype, thereby creating a microenvironment conducive to CLL cell adhesion, survival, and growth.

Although the role of exosomes in other cancers has been well studied, their role in hematologic malignancies has not been well characterized. Also, this study confirmed that exosomes are present in CLL lymph nodes and promote tumor growth in vivo.

VashiDonsk/Wikimedia Commons/Creative Commons BY-SA 3.0

“Our in vitro and in vivo data show that CLL exosomes harbor an oncogenic potential by stimulating stromal cells to induce an inflammatory and protumorigenic milieu, including increased angiogenesis, thus supporting the survival and outgrowth of CLL cells,” wrote Jerome Paggetti, Ph.D., of the laboratory of experimental hemato-oncology, Luxembourg Institute of Health (Blood 2015 Aug 27. doi:10.1182/blood-2014-12-618025).

Cells were obtained from 21 CLL patients; all patients had an absolute lymphocyte count of more than 30,000/mcL and were untreated for 3 months. The researchers established 30-day cocultures of bone marrow mesenchymal stem cells with primary CLL cells in culture inserts or they treated bone marrow mesenchymal stem cells weekly with exosomes. Similar experiments were performed with the Burkitt lymphoma cell line Namalwa to investigate whether the impact on stromal cells is CLL specific.

Based on gene expression analysis, CLL exosomes and CLL cells cocultured in inserts induced similar gene expression changes in bone marrow mesenchymal stem cells, highlighting the relevance of exosomes for microenvironment changes. “Importantly, lymphoma cells induced a distinct gene expression pattern in bone marrow mesenchymal stem cells, suggesting a specific response to CLL exosomes,” wrote Dr. Paggetti and coauthors.

The impact of CLL exosomes on tumor growth was studied in vivo by subcutaneously injecting cells with and without CLL exosomes into immunocompromised mice. Cells supplemented with exosomes resulted in an increased tumor size compared with tumor cells injected without additional exosomes. Also, the cells supplemented with exosomes accumulated in mice kidneys, confirming the renal involvement observed in CLL patients. “Our data demonstrate a protumorigenic effect of CLL-derived exosomes in vivo and their importance in the early onset of the disease when tumor cells impact the microenvironment to proliferate and promote angiogenesis,” the researchers concluded.

Reovirus, a naturally occurring oncolytic virus, appears to exert direct cytotoxic activity against chronic lymphocytic leukemia (CLL) and “phenotypically and functionally” activates patient natural killer cells using a monocyte-derived interferon alpha–dependent mechanism, according to preclinical data published in Leukemia.

Reovirus also enhances antibody-dependent cellular cytotoxicity – mediated killing of CLL cells in combination with anti-CD20 antibodies.

Wikimedia Commons

“Reovirus together with anti-CD20 antibodies represents a promising combination strategy for the treatment of CLL … and now warrants clinical evaluation,” wrote Christopher Parrish, Ph.D., of the Leeds (England) Institute of Cancer and Pathology and his colleagues (Leukemia. 2015;29:1799-1810. doi: 10.1038/leu.2015.88).Reovirus is a naturally occurring double-stranded RNA virus, and it exerts its effects against cancer cells by direct oncolysis and activation of antitumor immunity. The researchers investigated the efficacy of reovirus for the treatment of CLL, both as a direct cytotoxic agent and as an immunomodulator, using CLL cell lines and primary CLL cells from 24 patients.

Dr. Parrish and his team treated human CLL cells with live or UV-inactivated reovirus for 7 days. They assessed the ability of reovirus to stimulate immune-mediated killing of CLL using peripheral blood mononuclear cells from healthy volunteers and CLL patients. Reovirus activated natural killer (NK) cells from CLL patients, as well as stimulating innate antitumor immunity.

Rituximab, which is believed to act in part via NK cell–mediated antibody-dependent cellular cytotoxicity, was added to peripheral blood mononuclear cells that were treated with reovirus. Compared with rituximab alone, reovirus treatment significantly increased NK-cell CD107a/b degranulation. Reovirus was then paired with ofatumumab and GA101 to see if the effects observed with reovirus/rituximab could be translated to other anti-CD20 antibodies in which NK cells also play a role. The results were similar.

Absolute monocyte count and the type 1 interferon-alpha response could be used to predict the generation of antitumor innate immunity by reovirus. In cells from 24 CLL patients, about 75% responded to reovirus, with NK-cell activation. Further, NK-cell activation correlated with absolute monocyte count. The role of interferon-alpha is further supported by identification of an interferon gene signature within NK cells from reovirus-treated patients, the researchers said.

The study was supported by Yorkshire Cancer Research and Cancer Research UK. One of the investigators is an employee of Oncolytics Biotech and holds company stock and options. All the other authors declared no conflicts of interest.

Reovirus, a naturally occurring oncolytic virus, appears to exert direct cytotoxic activity against chronic lymphocytic leukemia (CLL) and “phenotypically and functionally” activates patient natural killer cells using a monocyte-derived interferon alpha–dependent mechanism, according to preclinical data published in Leukemia.

Reovirus also enhances antibody-dependent cellular cytotoxicity – mediated killing of CLL cells in combination with anti-CD20 antibodies.

Wikimedia Commons

“Reovirus together with anti-CD20 antibodies represents a promising combination strategy for the treatment of CLL … and now warrants clinical evaluation,” wrote Christopher Parrish, Ph.D., of the Leeds (England) Institute of Cancer and Pathology and his colleagues (Leukemia. 2015;29:1799-1810. doi: 10.1038/leu.2015.88).Reovirus is a naturally occurring double-stranded RNA virus, and it exerts its effects against cancer cells by direct oncolysis and activation of antitumor immunity. The researchers investigated the efficacy of reovirus for the treatment of CLL, both as a direct cytotoxic agent and as an immunomodulator, using CLL cell lines and primary CLL cells from 24 patients.

Dr. Parrish and his team treated human CLL cells with live or UV-inactivated reovirus for 7 days. They assessed the ability of reovirus to stimulate immune-mediated killing of CLL using peripheral blood mononuclear cells from healthy volunteers and CLL patients. Reovirus activated natural killer (NK) cells from CLL patients, as well as stimulating innate antitumor immunity.

Rituximab, which is believed to act in part via NK cell–mediated antibody-dependent cellular cytotoxicity, was added to peripheral blood mononuclear cells that were treated with reovirus. Compared with rituximab alone, reovirus treatment significantly increased NK-cell CD107a/b degranulation. Reovirus was then paired with ofatumumab and GA101 to see if the effects observed with reovirus/rituximab could be translated to other anti-CD20 antibodies in which NK cells also play a role. The results were similar.

Absolute monocyte count and the type 1 interferon-alpha response could be used to predict the generation of antitumor innate immunity by reovirus. In cells from 24 CLL patients, about 75% responded to reovirus, with NK-cell activation. Further, NK-cell activation correlated with absolute monocyte count. The role of interferon-alpha is further supported by identification of an interferon gene signature within NK cells from reovirus-treated patients, the researchers said.

The study was supported by Yorkshire Cancer Research and Cancer Research UK. One of the investigators is an employee of Oncolytics Biotech and holds company stock and options. All the other authors declared no conflicts of interest.

Reovirus, a naturally occurring oncolytic virus, appears to exert direct cytotoxic activity against chronic lymphocytic leukemia (CLL) and “phenotypically and functionally” activates patient natural killer cells using a monocyte-derived interferon alpha–dependent mechanism, according to preclinical data published in Leukemia.

Reovirus also enhances antibody-dependent cellular cytotoxicity – mediated killing of CLL cells in combination with anti-CD20 antibodies.

Wikimedia Commons

“Reovirus together with anti-CD20 antibodies represents a promising combination strategy for the treatment of CLL … and now warrants clinical evaluation,” wrote Christopher Parrish, Ph.D., of the Leeds (England) Institute of Cancer and Pathology and his colleagues (Leukemia. 2015;29:1799-1810. doi: 10.1038/leu.2015.88).Reovirus is a naturally occurring double-stranded RNA virus, and it exerts its effects against cancer cells by direct oncolysis and activation of antitumor immunity. The researchers investigated the efficacy of reovirus for the treatment of CLL, both as a direct cytotoxic agent and as an immunomodulator, using CLL cell lines and primary CLL cells from 24 patients.

Dr. Parrish and his team treated human CLL cells with live or UV-inactivated reovirus for 7 days. They assessed the ability of reovirus to stimulate immune-mediated killing of CLL using peripheral blood mononuclear cells from healthy volunteers and CLL patients. Reovirus activated natural killer (NK) cells from CLL patients, as well as stimulating innate antitumor immunity.

Rituximab, which is believed to act in part via NK cell–mediated antibody-dependent cellular cytotoxicity, was added to peripheral blood mononuclear cells that were treated with reovirus. Compared with rituximab alone, reovirus treatment significantly increased NK-cell CD107a/b degranulation. Reovirus was then paired with ofatumumab and GA101 to see if the effects observed with reovirus/rituximab could be translated to other anti-CD20 antibodies in which NK cells also play a role. The results were similar.

Absolute monocyte count and the type 1 interferon-alpha response could be used to predict the generation of antitumor innate immunity by reovirus. In cells from 24 CLL patients, about 75% responded to reovirus, with NK-cell activation. Further, NK-cell activation correlated with absolute monocyte count. The role of interferon-alpha is further supported by identification of an interferon gene signature within NK cells from reovirus-treated patients, the researchers said.

The study was supported by Yorkshire Cancer Research and Cancer Research UK. One of the investigators is an employee of Oncolytics Biotech and holds company stock and options. All the other authors declared no conflicts of interest.

 

 

Hannah Karlsson, PhD

 

NEW YORK—For the first time, according to researchers, chimeric antigen receptor (CAR) T-cell therapy has been tested in a clinical trial in Sweden.

Early results have shown the treatment can produce complete responses (CRs) in leukemia and lymphoma, although most patients ultimately progressed.

Hannah Karlsson, PhD, of Uppsala University in Sweden, presented data from the phase 1/2a trial of the third-generation CD19 CAR T-cell therapy (abstract A041*) at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trial is a collaboration between Uppsala University and Baylor College of Medicine and was funded by AFA Insurances AB and the Swedish Cancer Society.

“Third-generation CAR T cells are being tested in clinical trials for leukemia patients in the United States with success,” said senior study author Angelica Loskog, PhD, also of Uppsala University.

“[T]he main purpose of our clinical trial was to evaluate whether we could reproduce the successful results in leukemia patients in Sweden and to also test if patients with lymphoma will also respond to this treatment.”

So the investigators enrolled 13 patients, 11 of whom were evaluable for efficacy at 3 months after CAR T-cell infusion. All patients had relapsed or refractory, CD19-positive, B-cell disease.

Two patients had acute lymphoblastic leukemia (ALL), 2 had chronic lymphocytic leukemia (CLL), and 7 had lymphoma—3 with diffuse large B-cell lymphoma (DLBCL), 2 with mantle cell lymphoma (MCL), 1 with follicular lymphoma (FL)/DLBCL, and 1 with Burkitt lymphoma.

All of the lymphoma patients received chemotherapy before CAR T-cell infusion to shrink their tumors. Seven patients—3 with leukemia and 4 with lymphoma—received pre-conditioning with cyclophosphamide plus fludarabine to reduce their immunosuppressive cell counts.

The investigators used CAR T cells containing signaling domains from both CD28 and 4-1BB and manufactured using a gamma retrovirus.

Patients received a single infusion of the CAR T cells, 2 patients at a dose of 2 x 10⁷ cells/m², 4 at a dose of 1 x 10⁸ cells/m², and 5 at 2 x 10⁸ cells/m².

Response and toxicity

Six patients had achieved a CR at the time of evaluation.

One patient with DLBCL experienced mild cytokine release syndrome (CRS) before achieving CR. However, the patient relapsed after a second CRS occurred (after 3 months).

Another DLBCL patient achieved a CR prior to T-cell infusion and remained in CR for 6 months before progressing.

One CLL patient and another DLBCL patient responded prior to T-cell infusion and remained in CR for more than 3 months. The CLL patient was still in CR at the time of the meeting.

One of the ALL patients achieved a CR after transient central nervous system toxicity but relapsed at 3 months with CD19-negative ALL. The other ALL patient was in CR for more than a month after experiencing CRS but ultimately progressed.

One CLL patient and 2 MCL patients had all progressed by 3 months.

The FL/DLBCL patient progressed after 1 month, with mild CRS. And the patient with Burkitt lymphoma had major CRS and progressive disease.

The investigators noted that 5 of the 6 patients who received pre-conditioning treatment had initial CRs.

The team is now analyzing whether there is any correlation between the level of immunosuppressive cells and patient response.

*Information presented at the meeting differs from the abstract.

 

 

Hannah Karlsson, PhD

 

NEW YORK—For the first time, according to researchers, chimeric antigen receptor (CAR) T-cell therapy has been tested in a clinical trial in Sweden.

Early results have shown the treatment can produce complete responses (CRs) in leukemia and lymphoma, although most patients ultimately progressed.

Hannah Karlsson, PhD, of Uppsala University in Sweden, presented data from the phase 1/2a trial of the third-generation CD19 CAR T-cell therapy (abstract A041*) at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trial is a collaboration between Uppsala University and Baylor College of Medicine and was funded by AFA Insurances AB and the Swedish Cancer Society.

“Third-generation CAR T cells are being tested in clinical trials for leukemia patients in the United States with success,” said senior study author Angelica Loskog, PhD, also of Uppsala University.

“[T]he main purpose of our clinical trial was to evaluate whether we could reproduce the successful results in leukemia patients in Sweden and to also test if patients with lymphoma will also respond to this treatment.”

So the investigators enrolled 13 patients, 11 of whom were evaluable for efficacy at 3 months after CAR T-cell infusion. All patients had relapsed or refractory, CD19-positive, B-cell disease.

Two patients had acute lymphoblastic leukemia (ALL), 2 had chronic lymphocytic leukemia (CLL), and 7 had lymphoma—3 with diffuse large B-cell lymphoma (DLBCL), 2 with mantle cell lymphoma (MCL), 1 with follicular lymphoma (FL)/DLBCL, and 1 with Burkitt lymphoma.

All of the lymphoma patients received chemotherapy before CAR T-cell infusion to shrink their tumors. Seven patients—3 with leukemia and 4 with lymphoma—received pre-conditioning with cyclophosphamide plus fludarabine to reduce their immunosuppressive cell counts.

The investigators used CAR T cells containing signaling domains from both CD28 and 4-1BB and manufactured using a gamma retrovirus.

Patients received a single infusion of the CAR T cells, 2 patients at a dose of 2 x 10⁷ cells/m², 4 at a dose of 1 x 10⁸ cells/m², and 5 at 2 x 10⁸ cells/m².

Response and toxicity

Six patients had achieved a CR at the time of evaluation.

One patient with DLBCL experienced mild cytokine release syndrome (CRS) before achieving CR. However, the patient relapsed after a second CRS occurred (after 3 months).

Another DLBCL patient achieved a CR prior to T-cell infusion and remained in CR for 6 months before progressing.

One CLL patient and another DLBCL patient responded prior to T-cell infusion and remained in CR for more than 3 months. The CLL patient was still in CR at the time of the meeting.

One of the ALL patients achieved a CR after transient central nervous system toxicity but relapsed at 3 months with CD19-negative ALL. The other ALL patient was in CR for more than a month after experiencing CRS but ultimately progressed.

One CLL patient and 2 MCL patients had all progressed by 3 months.

The FL/DLBCL patient progressed after 1 month, with mild CRS. And the patient with Burkitt lymphoma had major CRS and progressive disease.

The investigators noted that 5 of the 6 patients who received pre-conditioning treatment had initial CRs.

The team is now analyzing whether there is any correlation between the level of immunosuppressive cells and patient response.

*Information presented at the meeting differs from the abstract.

 

 

Hannah Karlsson, PhD

 

NEW YORK—For the first time, according to researchers, chimeric antigen receptor (CAR) T-cell therapy has been tested in a clinical trial in Sweden.

Early results have shown the treatment can produce complete responses (CRs) in leukemia and lymphoma, although most patients ultimately progressed.

Hannah Karlsson, PhD, of Uppsala University in Sweden, presented data from the phase 1/2a trial of the third-generation CD19 CAR T-cell therapy (abstract A041*) at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

The trial is a collaboration between Uppsala University and Baylor College of Medicine and was funded by AFA Insurances AB and the Swedish Cancer Society.

“Third-generation CAR T cells are being tested in clinical trials for leukemia patients in the United States with success,” said senior study author Angelica Loskog, PhD, also of Uppsala University.

“[T]he main purpose of our clinical trial was to evaluate whether we could reproduce the successful results in leukemia patients in Sweden and to also test if patients with lymphoma will also respond to this treatment.”

So the investigators enrolled 13 patients, 11 of whom were evaluable for efficacy at 3 months after CAR T-cell infusion. All patients had relapsed or refractory, CD19-positive, B-cell disease.

Two patients had acute lymphoblastic leukemia (ALL), 2 had chronic lymphocytic leukemia (CLL), and 7 had lymphoma—3 with diffuse large B-cell lymphoma (DLBCL), 2 with mantle cell lymphoma (MCL), 1 with follicular lymphoma (FL)/DLBCL, and 1 with Burkitt lymphoma.

All of the lymphoma patients received chemotherapy before CAR T-cell infusion to shrink their tumors. Seven patients—3 with leukemia and 4 with lymphoma—received pre-conditioning with cyclophosphamide plus fludarabine to reduce their immunosuppressive cell counts.

The investigators used CAR T cells containing signaling domains from both CD28 and 4-1BB and manufactured using a gamma retrovirus.

Patients received a single infusion of the CAR T cells, 2 patients at a dose of 2 x 10⁷ cells/m², 4 at a dose of 1 x 10⁸ cells/m², and 5 at 2 x 10⁸ cells/m².

Response and toxicity

Six patients had achieved a CR at the time of evaluation.

One patient with DLBCL experienced mild cytokine release syndrome (CRS) before achieving CR. However, the patient relapsed after a second CRS occurred (after 3 months).

Another DLBCL patient achieved a CR prior to T-cell infusion and remained in CR for 6 months before progressing.

One CLL patient and another DLBCL patient responded prior to T-cell infusion and remained in CR for more than 3 months. The CLL patient was still in CR at the time of the meeting.

One of the ALL patients achieved a CR after transient central nervous system toxicity but relapsed at 3 months with CD19-negative ALL. The other ALL patient was in CR for more than a month after experiencing CRS but ultimately progressed.

One CLL patient and 2 MCL patients had all progressed by 3 months.

The FL/DLBCL patient progressed after 1 month, with mild CRS. And the patient with Burkitt lymphoma had major CRS and progressive disease.

The investigators noted that 5 of the 6 patients who received pre-conditioning treatment had initial CRs.

The team is now analyzing whether there is any correlation between the level of immunosuppressive cells and patient response.

*Information presented at the meeting differs from the abstract.

Drug production

Photo courtesy of the FDA

Despite recent progress in the fight against cancers, these diseases continue to exert “an immense toll” in the US, according to the AACR Cancer Progress Report 2015.

The report highlights the recent approval by the US Food and Drug Administration (FDA) of several anticancer therapies, a vaccine, and 2 diagnostic aids.

But the report also includes data suggesting that cancer cases, and costs related to cancer care, are on the rise.

The report states that, between Aug. 1, 2014, and July 31, 2015, the FDA approved 9 anticancer therapies, either for the first time or for new indications.

During the same period, the FDA approved a new cancer vaccine, a new cancer screening test, and a new use for a previously approved imaging agent.

Despite these advances, cancers continue to exert personal and economic tolls, according to the report.

It states that cancer is the number 1 cause of disease-related death among US children. And more than 589,000 people in the US are projected to die from cancer in 2015.

The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035.

In addition, estimates suggest the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs are predicted to rise to $156 billion in 2020.

These data underscore the need for more research to develop new approaches to cancer prevention and treatment, according to the report.

Its authors call for Congress and the administration to provide the National Institutes of Health, National Cancer Institute, and FDA with annual funding increases.

“We have made spectacular progress against cancer, which has saved the lives of millions of individuals in the United States and around the world,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, without increased federal funding for cancer research, we will not be able to realize the promise of recent discoveries and technological advances.”

Drug production

Photo courtesy of the FDA

Despite recent progress in the fight against cancers, these diseases continue to exert “an immense toll” in the US, according to the AACR Cancer Progress Report 2015.

The report highlights the recent approval by the US Food and Drug Administration (FDA) of several anticancer therapies, a vaccine, and 2 diagnostic aids.

But the report also includes data suggesting that cancer cases, and costs related to cancer care, are on the rise.

The report states that, between Aug. 1, 2014, and July 31, 2015, the FDA approved 9 anticancer therapies, either for the first time or for new indications.

During the same period, the FDA approved a new cancer vaccine, a new cancer screening test, and a new use for a previously approved imaging agent.

Despite these advances, cancers continue to exert personal and economic tolls, according to the report.

It states that cancer is the number 1 cause of disease-related death among US children. And more than 589,000 people in the US are projected to die from cancer in 2015.

The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035.

In addition, estimates suggest the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs are predicted to rise to $156 billion in 2020.

These data underscore the need for more research to develop new approaches to cancer prevention and treatment, according to the report.

Its authors call for Congress and the administration to provide the National Institutes of Health, National Cancer Institute, and FDA with annual funding increases.

“We have made spectacular progress against cancer, which has saved the lives of millions of individuals in the United States and around the world,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, without increased federal funding for cancer research, we will not be able to realize the promise of recent discoveries and technological advances.”

Drug production

Photo courtesy of the FDA

Despite recent progress in the fight against cancers, these diseases continue to exert “an immense toll” in the US, according to the AACR Cancer Progress Report 2015.

The report highlights the recent approval by the US Food and Drug Administration (FDA) of several anticancer therapies, a vaccine, and 2 diagnostic aids.

But the report also includes data suggesting that cancer cases, and costs related to cancer care, are on the rise.

The report states that, between Aug. 1, 2014, and July 31, 2015, the FDA approved 9 anticancer therapies, either for the first time or for new indications.

During the same period, the FDA approved a new cancer vaccine, a new cancer screening test, and a new use for a previously approved imaging agent.

Despite these advances, cancers continue to exert personal and economic tolls, according to the report.

It states that cancer is the number 1 cause of disease-related death among US children. And more than 589,000 people in the US are projected to die from cancer in 2015.

The number of new cancer cases in the US is predicted to rise from 1.7 million in 2015 to 2.4 million in 2035.

In addition, estimates suggest the direct medical costs of cancer care in the US in 2010 were nearly $125 billion, and these costs are predicted to rise to $156 billion in 2020.

These data underscore the need for more research to develop new approaches to cancer prevention and treatment, according to the report.

Its authors call for Congress and the administration to provide the National Institutes of Health, National Cancer Institute, and FDA with annual funding increases.

“We have made spectacular progress against cancer, which has saved the lives of millions of individuals in the United States and around the world,” said Margaret Foti, PhD, MD, chief executive officer of the AACR.

“However, without increased federal funding for cancer research, we will not be able to realize the promise of recent discoveries and technological advances.”

Patients with Ph+ CML-CP (Philadelphia chromosome–positive chronic myeloid leukemia, chronic phase) who fail to achieve and maintain treatment response at key milestones should be considered for mutation screening, based on data from the DASISION trial.

Patients with mutations had poor outcomes and high rates of treatment discontinuation in an extended 4-year minimum follow-up of patients in the trial; 14 of 17 dasatinib-treated patients and 14 of 18 imatinib-treated patients with mutations discontinued treatment. The primary reason for treatment discontinuation was protocol-defined disease progression (dasatinib, n = 11; imatinib, n = 8); patients with mutations accounted for 61% of discontinuations on dasatinib (n = 11/18) and 42% on imatinib (n = 8/19).

Courtesy Wikimedia Commons

“With the introduction of generic imatinib into the market in 2016, choosing the most appropriate second-line tyrosine-kinase inhibitor for patients, based on factors such as mutation status, will become increasingly important,” Dr. Tim Hughes of the South Australian Health and Medical Research Institute in Adelaide and his colleagues wrote. Having the option to choose the most suitable second-line therapy may ensure improved outcomes and decreased health care costs.

In the DASISION (Dasatinib vs. Imatinib Study in Treatment-Naive CML-CP) trial, all participants had newly diagnosed Ph+ CML-CP; they were treated with dasatinib (n = 259) or imatinib (n = 260) and followed for a minimum of 3 years (Leukemia. 2015 Sep;29[9]:1832-8). Dr. Hughes and his colleagues conducted a retrospective study of the patients who were potentially at a higher risk for developing mutations. This included patients on treatment who had at least one clinically relevant event – no confirmed complete cytogenetic response (cCCyR) within 12 months, no major molecular response (MMR) within 12 months; a fivefold increase in BCR-ABL1 transcript levels with loss of MMR; loss of CCyR – and/or who discontinued treatment for any reason.

Screening identified only a small number of patients with mutations (dasatinib, n = 17; imatinib, n = 18). Those on dasatinib had a narrower spectrum of mutations (4 sites for dasatinib vs. 12 sites for imatinib), fewer phosphate-binding loop mutations (1 mutation for dasatinib vs, 9 mutations for imatinib), and fewer multiple mutations (1 patient on dasatinib vs. 6 patients on imatinib).

However, patients on dasatinib had a greater occurrence of T315I mutations (11 patients on dasatinib vs. 0 patients on imatinib). The researchers hypothesized that this finding resulted from differences in competitive advantage between mutant clones. For example, P-loop mutations Y253F, E255K were found to have higher transformation potency and proliferation rates, compared with T315I, even in the absence of BCR-ABL1 inhibitors. If one assumes that imatinib has lower activity than dasatinib against these mutations, then mutant clones with select P-loop mutations might expand more rapidly than clones with the T315I mutation when exposed to imatinib.

Consistent with this idea, T315I is less common than all P-loop mutations in CML-CP patients with imatinib resistance. In addition, dasatinib suppresses P-loop mutations to a greater extent than does T315I; therefore, T315I may be able to develop during dasatinib treatment with relatively little competition from rapidly proliferating clones.

“Dasatinib, nilotinib, bosutinib, and ponatinib have enabled many patients, including those with mutations, to overcome imatinib resistance; however, each lack[s] efficacy against a small number of different leukemic clones, and all except ponatinib lack efficacy against T315I,” the researchers wrote.

The study was sponsored by Bristol-Myers Squibb. Dr. Hughes reported receiving honoraria and research funding from ARIAD, the maker of ponatinib; Bristol-Myers Squibb, the maker of dasatinib; and Novartis, the maker of imatinib.

Patients with Ph+ CML-CP (Philadelphia chromosome–positive chronic myeloid leukemia, chronic phase) who fail to achieve and maintain treatment response at key milestones should be considered for mutation screening, based on data from the DASISION trial.

Patients with mutations had poor outcomes and high rates of treatment discontinuation in an extended 4-year minimum follow-up of patients in the trial; 14 of 17 dasatinib-treated patients and 14 of 18 imatinib-treated patients with mutations discontinued treatment. The primary reason for treatment discontinuation was protocol-defined disease progression (dasatinib, n = 11; imatinib, n = 8); patients with mutations accounted for 61% of discontinuations on dasatinib (n = 11/18) and 42% on imatinib (n = 8/19).

Courtesy Wikimedia Commons

“With the introduction of generic imatinib into the market in 2016, choosing the most appropriate second-line tyrosine-kinase inhibitor for patients, based on factors such as mutation status, will become increasingly important,” Dr. Tim Hughes of the South Australian Health and Medical Research Institute in Adelaide and his colleagues wrote. Having the option to choose the most suitable second-line therapy may ensure improved outcomes and decreased health care costs.

In the DASISION (Dasatinib vs. Imatinib Study in Treatment-Naive CML-CP) trial, all participants had newly diagnosed Ph+ CML-CP; they were treated with dasatinib (n = 259) or imatinib (n = 260) and followed for a minimum of 3 years (Leukemia. 2015 Sep;29[9]:1832-8). Dr. Hughes and his colleagues conducted a retrospective study of the patients who were potentially at a higher risk for developing mutations. This included patients on treatment who had at least one clinically relevant event – no confirmed complete cytogenetic response (cCCyR) within 12 months, no major molecular response (MMR) within 12 months; a fivefold increase in BCR-ABL1 transcript levels with loss of MMR; loss of CCyR – and/or who discontinued treatment for any reason.

Screening identified only a small number of patients with mutations (dasatinib, n = 17; imatinib, n = 18). Those on dasatinib had a narrower spectrum of mutations (4 sites for dasatinib vs. 12 sites for imatinib), fewer phosphate-binding loop mutations (1 mutation for dasatinib vs, 9 mutations for imatinib), and fewer multiple mutations (1 patient on dasatinib vs. 6 patients on imatinib).

However, patients on dasatinib had a greater occurrence of T315I mutations (11 patients on dasatinib vs. 0 patients on imatinib). The researchers hypothesized that this finding resulted from differences in competitive advantage between mutant clones. For example, P-loop mutations Y253F, E255K were found to have higher transformation potency and proliferation rates, compared with T315I, even in the absence of BCR-ABL1 inhibitors. If one assumes that imatinib has lower activity than dasatinib against these mutations, then mutant clones with select P-loop mutations might expand more rapidly than clones with the T315I mutation when exposed to imatinib.

Consistent with this idea, T315I is less common than all P-loop mutations in CML-CP patients with imatinib resistance. In addition, dasatinib suppresses P-loop mutations to a greater extent than does T315I; therefore, T315I may be able to develop during dasatinib treatment with relatively little competition from rapidly proliferating clones.

“Dasatinib, nilotinib, bosutinib, and ponatinib have enabled many patients, including those with mutations, to overcome imatinib resistance; however, each lack[s] efficacy against a small number of different leukemic clones, and all except ponatinib lack efficacy against T315I,” the researchers wrote.

The study was sponsored by Bristol-Myers Squibb. Dr. Hughes reported receiving honoraria and research funding from ARIAD, the maker of ponatinib; Bristol-Myers Squibb, the maker of dasatinib; and Novartis, the maker of imatinib.

Patients with Ph+ CML-CP (Philadelphia chromosome–positive chronic myeloid leukemia, chronic phase) who fail to achieve and maintain treatment response at key milestones should be considered for mutation screening, based on data from the DASISION trial.

Patients with mutations had poor outcomes and high rates of treatment discontinuation in an extended 4-year minimum follow-up of patients in the trial; 14 of 17 dasatinib-treated patients and 14 of 18 imatinib-treated patients with mutations discontinued treatment. The primary reason for treatment discontinuation was protocol-defined disease progression (dasatinib, n = 11; imatinib, n = 8); patients with mutations accounted for 61% of discontinuations on dasatinib (n = 11/18) and 42% on imatinib (n = 8/19).

Courtesy Wikimedia Commons

“With the introduction of generic imatinib into the market in 2016, choosing the most appropriate second-line tyrosine-kinase inhibitor for patients, based on factors such as mutation status, will become increasingly important,” Dr. Tim Hughes of the South Australian Health and Medical Research Institute in Adelaide and his colleagues wrote. Having the option to choose the most suitable second-line therapy may ensure improved outcomes and decreased health care costs.

In the DASISION (Dasatinib vs. Imatinib Study in Treatment-Naive CML-CP) trial, all participants had newly diagnosed Ph+ CML-CP; they were treated with dasatinib (n = 259) or imatinib (n = 260) and followed for a minimum of 3 years (Leukemia. 2015 Sep;29[9]:1832-8). Dr. Hughes and his colleagues conducted a retrospective study of the patients who were potentially at a higher risk for developing mutations. This included patients on treatment who had at least one clinically relevant event – no confirmed complete cytogenetic response (cCCyR) within 12 months, no major molecular response (MMR) within 12 months; a fivefold increase in BCR-ABL1 transcript levels with loss of MMR; loss of CCyR – and/or who discontinued treatment for any reason.

Screening identified only a small number of patients with mutations (dasatinib, n = 17; imatinib, n = 18). Those on dasatinib had a narrower spectrum of mutations (4 sites for dasatinib vs. 12 sites for imatinib), fewer phosphate-binding loop mutations (1 mutation for dasatinib vs, 9 mutations for imatinib), and fewer multiple mutations (1 patient on dasatinib vs. 6 patients on imatinib).

However, patients on dasatinib had a greater occurrence of T315I mutations (11 patients on dasatinib vs. 0 patients on imatinib). The researchers hypothesized that this finding resulted from differences in competitive advantage between mutant clones. For example, P-loop mutations Y253F, E255K were found to have higher transformation potency and proliferation rates, compared with T315I, even in the absence of BCR-ABL1 inhibitors. If one assumes that imatinib has lower activity than dasatinib against these mutations, then mutant clones with select P-loop mutations might expand more rapidly than clones with the T315I mutation when exposed to imatinib.

Consistent with this idea, T315I is less common than all P-loop mutations in CML-CP patients with imatinib resistance. In addition, dasatinib suppresses P-loop mutations to a greater extent than does T315I; therefore, T315I may be able to develop during dasatinib treatment with relatively little competition from rapidly proliferating clones.

“Dasatinib, nilotinib, bosutinib, and ponatinib have enabled many patients, including those with mutations, to overcome imatinib resistance; however, each lack[s] efficacy against a small number of different leukemic clones, and all except ponatinib lack efficacy against T315I,” the researchers wrote.

The study was sponsored by Bristol-Myers Squibb. Dr. Hughes reported receiving honoraria and research funding from ARIAD, the maker of ponatinib; Bristol-Myers Squibb, the maker of dasatinib; and Novartis, the maker of imatinib.