Sharon Worcester

CHICAGO – Despite exciting new advances in the understanding of chronic lymphocytic leukemia, particularly with respect to prognostic features that predict risk for relapse, a watch-and-wait approach remains appropriate for asymptomatic disease pending outcomes data for newer approaches, according to Dr. John G. Gribben.

“When the disease is diagnosed, if it is asymptomatic, the correct approach – of course – is to continue to watch and wait,” Dr. Gribben of Barts Cancer Institute, Queen Mary University of London, said at the American Society of Hematology Meeting on Hematologic Malignancies.

Numerous clinical trials have demonstrated no advantage of early treatment vs. watch and wait, he said, adding that all of the trials published to date have used treatment of all-comers, and have used chlorambucil (CLB) as the treatment.

“There has been a whole variety of more modern trials that have used select prognostic features to identify subgroups of people who are at higher risk of relapse, who then go on to receive earlier treatment with either FCR [fludarabine, cyclophosphamide, rituximab], or more recently, ibrutinib,” he said.

These treatments are interesting, and the trials have demonstrated that prognostic features can identify patients who will progress more rapidly, but none have reported, he explained.

“In the absence of any published trial, I continue to ‘watch and wait’ patients, and there are no high-risk features which will make me alter that approach. Even the highest-risk features of complex karyotype and p53 abnormalities are not indications to treat patients until they become symptomatic,” he said.

It is striking how white counts vary widely in both asymptomatic and symptomatic patients, he noted.

“I don’t personally have any particular white count which is the number at which I’ll treat a patient. I don’t treat white counts, I treat patients,” he said.

When patients become symptomatic, the treatment of choice is now immunochemotherapies, irrespective of performance status, he said.

“Within the past year we have seen approval of obinutuzumab and ofatumumab for treatment of previously untreated CLL, as well as ibrutinib and idelalisib plus rituximab for treatment of both previously untreated CLL and those with 17p deletions for relapsed/refractory disease, as well as for up-front treatment,” he said, adding that these new agents greatly increase the available options for treating CLL.

Dr. Gribben said he considers these questions when it comes to treating CLL:

• Does the patient require treatment, or is watching and waiting appropriate?

• What is the goal of therapy? This is determined through conversation with the patient and the patient’s family regarding the side-effect profile they are willing to tolerate vs. the potential longer duration of response.

• What comorbidities are present to determine “fitness” for specific immunochemotherapy? Specifically, is the patient fit for an FCR-type approach, or is an alternative more appropriate?

• Is there a 17p deletion or P53 mutation that would make chemotherapy a less attractive option, and use of novel agents a more attractive option?

His approach, based on the answers to these questions, is as follows:

• In Rai stage 0-II patients with inactive disease, fitness and 17p deletion or p53 mutation status is irrelevant; no therapy is given.

• For active disease or Rai III-IV disease, a “go-go” patient, (or patient in good physical condition) is treated based on the presence or absence of 17p deletion or p53 mutation status. Those without 17p deletions or p53 mutations can be treated with FCR (his preference), or fludarabine-rituximab (FR). Bendamustine-rituximab (BR) is also an attractive option in certain cases, he said.

• For patients with active disease or Rai stage III-IV disease who do have a 17p deletion, his treatment of choice is either ibrutinib or idelalisib plus rituximab, depending on the patient.

• In “slow-go” patients (those with poorer physical condition) treatment is again based on mutational analysis. Those without mutation receive either FR, BR, or CLB plus obinutuzumab. These are very good options, and represent a spectrum to choose from based on the patient’s core abilities and ability to withstand particular types of treatments, he said.

“If they do have a 17p deletion, these patients are just as eligible for ibrutinib or idelalisib plus rituximab as the younger patients,” he noted.

His choices are based largely on the findings from the CLL8 trial (Lancet 2010 Oct;376[9747]:1164-74) which demonstrated an overall survival advantage with chemoimmunotherapy for front-line therapy vs. chemotherapy alone (hazard ratio, 0.68).

Over time, the advantage has become even more pronounced, according to follow-up data.

Starting with something “gentle” and saving the best treatment for later in the event of relapse was recently considered a reasonable approach, but in the wake of the CLL8 findings, this is no longer an acceptable plan, Dr. Gribben said.

“That’s why for my choice, FCR remains the treatment of choice for those patients who are fit enough to tolerate this type of approach,” he said.

In those with 17p deletions or P53 mutations, the CLL8 trial showed poor outcomes with FCR.

“This is a group of patients whom I believe chemoimmunotherapy would no longer be the treatment of choice,” he said, adding that newer findings suggest outcomes in these patients are better with novel agents.

He also noted that patients with 11q abnormalities, which were previously associated with a poor prognosis, were found in CLL8 to respond well to chemoimmunotherapy when used front line.

While there are special considerations in the elderly, and different strategies in relapsed and refractory disease, the future of CLL treatment is promising. The benefit of adding rituximab to combination chemotherapy is well established, the benefit of novel agents is also now established, and the future likely involves combining targeted therapies with each other and with immunochemotherapies, and combining targeted therapies across different pathways.

“And of course the hope is that we’re going to use the biology of the disease to decide what specific therapy is ideal for that patient. Better understanding of biology and genetics is facilitating rational development of new treatments,” he said, adding that whenever possible, patients should be treated within clinical trials.

Dr. Gribben has received research funding from the NIH, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

sworcester@frontlinemedcom.com

CHICAGO – Despite exciting new advances in the understanding of chronic lymphocytic leukemia, particularly with respect to prognostic features that predict risk for relapse, a watch-and-wait approach remains appropriate for asymptomatic disease pending outcomes data for newer approaches, according to Dr. John G. Gribben.

“When the disease is diagnosed, if it is asymptomatic, the correct approach – of course – is to continue to watch and wait,” Dr. Gribben of Barts Cancer Institute, Queen Mary University of London, said at the American Society of Hematology Meeting on Hematologic Malignancies.

Numerous clinical trials have demonstrated no advantage of early treatment vs. watch and wait, he said, adding that all of the trials published to date have used treatment of all-comers, and have used chlorambucil (CLB) as the treatment.

“There has been a whole variety of more modern trials that have used select prognostic features to identify subgroups of people who are at higher risk of relapse, who then go on to receive earlier treatment with either FCR [fludarabine, cyclophosphamide, rituximab], or more recently, ibrutinib,” he said.

These treatments are interesting, and the trials have demonstrated that prognostic features can identify patients who will progress more rapidly, but none have reported, he explained.

“In the absence of any published trial, I continue to ‘watch and wait’ patients, and there are no high-risk features which will make me alter that approach. Even the highest-risk features of complex karyotype and p53 abnormalities are not indications to treat patients until they become symptomatic,” he said.

It is striking how white counts vary widely in both asymptomatic and symptomatic patients, he noted.

“I don’t personally have any particular white count which is the number at which I’ll treat a patient. I don’t treat white counts, I treat patients,” he said.

When patients become symptomatic, the treatment of choice is now immunochemotherapies, irrespective of performance status, he said.

“Within the past year we have seen approval of obinutuzumab and ofatumumab for treatment of previously untreated CLL, as well as ibrutinib and idelalisib plus rituximab for treatment of both previously untreated CLL and those with 17p deletions for relapsed/refractory disease, as well as for up-front treatment,” he said, adding that these new agents greatly increase the available options for treating CLL.

Dr. Gribben said he considers these questions when it comes to treating CLL:

• Does the patient require treatment, or is watching and waiting appropriate?

• What is the goal of therapy? This is determined through conversation with the patient and the patient’s family regarding the side-effect profile they are willing to tolerate vs. the potential longer duration of response.

• What comorbidities are present to determine “fitness” for specific immunochemotherapy? Specifically, is the patient fit for an FCR-type approach, or is an alternative more appropriate?

• Is there a 17p deletion or P53 mutation that would make chemotherapy a less attractive option, and use of novel agents a more attractive option?

His approach, based on the answers to these questions, is as follows:

• In Rai stage 0-II patients with inactive disease, fitness and 17p deletion or p53 mutation status is irrelevant; no therapy is given.

• For active disease or Rai III-IV disease, a “go-go” patient, (or patient in good physical condition) is treated based on the presence or absence of 17p deletion or p53 mutation status. Those without 17p deletions or p53 mutations can be treated with FCR (his preference), or fludarabine-rituximab (FR). Bendamustine-rituximab (BR) is also an attractive option in certain cases, he said.

• For patients with active disease or Rai stage III-IV disease who do have a 17p deletion, his treatment of choice is either ibrutinib or idelalisib plus rituximab, depending on the patient.

• In “slow-go” patients (those with poorer physical condition) treatment is again based on mutational analysis. Those without mutation receive either FR, BR, or CLB plus obinutuzumab. These are very good options, and represent a spectrum to choose from based on the patient’s core abilities and ability to withstand particular types of treatments, he said.

“If they do have a 17p deletion, these patients are just as eligible for ibrutinib or idelalisib plus rituximab as the younger patients,” he noted.

His choices are based largely on the findings from the CLL8 trial (Lancet 2010 Oct;376[9747]:1164-74) which demonstrated an overall survival advantage with chemoimmunotherapy for front-line therapy vs. chemotherapy alone (hazard ratio, 0.68).

Over time, the advantage has become even more pronounced, according to follow-up data.

Starting with something “gentle” and saving the best treatment for later in the event of relapse was recently considered a reasonable approach, but in the wake of the CLL8 findings, this is no longer an acceptable plan, Dr. Gribben said.

“That’s why for my choice, FCR remains the treatment of choice for those patients who are fit enough to tolerate this type of approach,” he said.

In those with 17p deletions or P53 mutations, the CLL8 trial showed poor outcomes with FCR.

“This is a group of patients whom I believe chemoimmunotherapy would no longer be the treatment of choice,” he said, adding that newer findings suggest outcomes in these patients are better with novel agents.

He also noted that patients with 11q abnormalities, which were previously associated with a poor prognosis, were found in CLL8 to respond well to chemoimmunotherapy when used front line.

While there are special considerations in the elderly, and different strategies in relapsed and refractory disease, the future of CLL treatment is promising. The benefit of adding rituximab to combination chemotherapy is well established, the benefit of novel agents is also now established, and the future likely involves combining targeted therapies with each other and with immunochemotherapies, and combining targeted therapies across different pathways.

“And of course the hope is that we’re going to use the biology of the disease to decide what specific therapy is ideal for that patient. Better understanding of biology and genetics is facilitating rational development of new treatments,” he said, adding that whenever possible, patients should be treated within clinical trials.

Dr. Gribben has received research funding from the NIH, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

sworcester@frontlinemedcom.com

CHICAGO – Despite exciting new advances in the understanding of chronic lymphocytic leukemia, particularly with respect to prognostic features that predict risk for relapse, a watch-and-wait approach remains appropriate for asymptomatic disease pending outcomes data for newer approaches, according to Dr. John G. Gribben.

“When the disease is diagnosed, if it is asymptomatic, the correct approach – of course – is to continue to watch and wait,” Dr. Gribben of Barts Cancer Institute, Queen Mary University of London, said at the American Society of Hematology Meeting on Hematologic Malignancies.

Numerous clinical trials have demonstrated no advantage of early treatment vs. watch and wait, he said, adding that all of the trials published to date have used treatment of all-comers, and have used chlorambucil (CLB) as the treatment.

“There has been a whole variety of more modern trials that have used select prognostic features to identify subgroups of people who are at higher risk of relapse, who then go on to receive earlier treatment with either FCR [fludarabine, cyclophosphamide, rituximab], or more recently, ibrutinib,” he said.

These treatments are interesting, and the trials have demonstrated that prognostic features can identify patients who will progress more rapidly, but none have reported, he explained.

“In the absence of any published trial, I continue to ‘watch and wait’ patients, and there are no high-risk features which will make me alter that approach. Even the highest-risk features of complex karyotype and p53 abnormalities are not indications to treat patients until they become symptomatic,” he said.

It is striking how white counts vary widely in both asymptomatic and symptomatic patients, he noted.

“I don’t personally have any particular white count which is the number at which I’ll treat a patient. I don’t treat white counts, I treat patients,” he said.

When patients become symptomatic, the treatment of choice is now immunochemotherapies, irrespective of performance status, he said.

“Within the past year we have seen approval of obinutuzumab and ofatumumab for treatment of previously untreated CLL, as well as ibrutinib and idelalisib plus rituximab for treatment of both previously untreated CLL and those with 17p deletions for relapsed/refractory disease, as well as for up-front treatment,” he said, adding that these new agents greatly increase the available options for treating CLL.

Dr. Gribben said he considers these questions when it comes to treating CLL:

• Does the patient require treatment, or is watching and waiting appropriate?

• What is the goal of therapy? This is determined through conversation with the patient and the patient’s family regarding the side-effect profile they are willing to tolerate vs. the potential longer duration of response.

• What comorbidities are present to determine “fitness” for specific immunochemotherapy? Specifically, is the patient fit for an FCR-type approach, or is an alternative more appropriate?

• Is there a 17p deletion or P53 mutation that would make chemotherapy a less attractive option, and use of novel agents a more attractive option?

His approach, based on the answers to these questions, is as follows:

• In Rai stage 0-II patients with inactive disease, fitness and 17p deletion or p53 mutation status is irrelevant; no therapy is given.

• For active disease or Rai III-IV disease, a “go-go” patient, (or patient in good physical condition) is treated based on the presence or absence of 17p deletion or p53 mutation status. Those without 17p deletions or p53 mutations can be treated with FCR (his preference), or fludarabine-rituximab (FR). Bendamustine-rituximab (BR) is also an attractive option in certain cases, he said.

• For patients with active disease or Rai stage III-IV disease who do have a 17p deletion, his treatment of choice is either ibrutinib or idelalisib plus rituximab, depending on the patient.

• In “slow-go” patients (those with poorer physical condition) treatment is again based on mutational analysis. Those without mutation receive either FR, BR, or CLB plus obinutuzumab. These are very good options, and represent a spectrum to choose from based on the patient’s core abilities and ability to withstand particular types of treatments, he said.

“If they do have a 17p deletion, these patients are just as eligible for ibrutinib or idelalisib plus rituximab as the younger patients,” he noted.

His choices are based largely on the findings from the CLL8 trial (Lancet 2010 Oct;376[9747]:1164-74) which demonstrated an overall survival advantage with chemoimmunotherapy for front-line therapy vs. chemotherapy alone (hazard ratio, 0.68).

Over time, the advantage has become even more pronounced, according to follow-up data.

Starting with something “gentle” and saving the best treatment for later in the event of relapse was recently considered a reasonable approach, but in the wake of the CLL8 findings, this is no longer an acceptable plan, Dr. Gribben said.

“That’s why for my choice, FCR remains the treatment of choice for those patients who are fit enough to tolerate this type of approach,” he said.

In those with 17p deletions or P53 mutations, the CLL8 trial showed poor outcomes with FCR.

“This is a group of patients whom I believe chemoimmunotherapy would no longer be the treatment of choice,” he said, adding that newer findings suggest outcomes in these patients are better with novel agents.

He also noted that patients with 11q abnormalities, which were previously associated with a poor prognosis, were found in CLL8 to respond well to chemoimmunotherapy when used front line.

While there are special considerations in the elderly, and different strategies in relapsed and refractory disease, the future of CLL treatment is promising. The benefit of adding rituximab to combination chemotherapy is well established, the benefit of novel agents is also now established, and the future likely involves combining targeted therapies with each other and with immunochemotherapies, and combining targeted therapies across different pathways.

“And of course the hope is that we’re going to use the biology of the disease to decide what specific therapy is ideal for that patient. Better understanding of biology and genetics is facilitating rational development of new treatments,” he said, adding that whenever possible, patients should be treated within clinical trials.

Dr. Gribben has received research funding from the NIH, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

sworcester@frontlinemedcom.com

LAS VEGAS – A higher-than-expected proportion of trauma-related deaths occur in the months and years after hospital discharge, according to findings from a prospective cohort study.

In 908 trauma patients followed for up to 9.8 years (median, 1.7 years), overall mortality was 27%, and in 509 patients followed for at least 2 years, overall mortality was 38%. Mortality was highest among those who were severely injured (43% at 5 years), Dr. Rachael A. Callcut reported at the annual meeting of the American Association for the Surgery of Trauma.

Spotmatik/ThinkStock

The median Injury Severity Scale score was 18, but for all ISS groups, survival was significantly worse than predicted actuarial survival for that group – even after exclusion of deaths that occurred within 30 days, she said.

For example, at 5 years, predicted actuarial survival was greater than 95%, but actual survival was about 90% for those with ISS less than 15, about 85% for those with ISS of 15-24, and about 57% for those with ISS greater than 24. This dose-response–like relationship between injury severity and mortality demonstrates that the deaths are not just occurring in “patients who are old and would have died from a heart attack anyway” she explained.

The 30-day mortality in the cohort was 22%, and in-hospital mortality was 22.9%, as eight patients who died after the first 30 days did so in the hospital. Forty-five of the 245 deaths (18%) occurred after 30 days, and 36 of those (80%) occurred after hospital discharge, meaning the out-of-hospital mortality rate was 5.3% overall, and 10% for the most severely injured (hazard ratio, 2.7 for the most severe vs. the least severe injuries).

“I personally found this quite striking given that when a patient leaves the hospital, we feel, to some degree, that we won – only to find out that at least 5% of these patients will go on to subsequently die,” said Dr. Callcut of the University of California San Francisco, adding that “if you look at it slightly differently, which is even more concerning, 37 of the out-of-hospital deaths of the total of 245 deaths, mean that out-of-hospital deaths account for 15% of the total mortality following trauma.”

Further, of the deaths that occurred after 30 days, 53% occurred between 31 days and 1 year after trauma, and trauma was the leading cause of postdischarge death, accounting for 41% of the late deaths, she said.

The patients included in this analysis were all highest level trauma activation patients enrolled in the ongoing study between 2005 and 2012. Comprehensive prospective data were collected, and patients were followed throughout their hospitalization and after discharge. Institutional medical records or death certificates were used to determine timing and cause of death, and survival status was determined based on the last date of care in the institution or by query of the National Death Index for 2013.

These findings provide a rare glimpse of trauma-related outcomes among patients discharged from the hospital. Most prior studies focused on 30-day outcomes, with a few extended out to 90 days, but very few studies have looked at long-term outcomes, Dr. Callcut noted.

“You could say that despite having survived to leave the hospital alive, long-term survival is actually worse than predicted actuarial survival, and this suggests to us that successful hospital discharge does not mean success for your patient,” she concluded.

Dr. Callcut was supported in part by a National Institutes of Health award.

sworcester@frontlinemedcom.com

LAS VEGAS – A higher-than-expected proportion of trauma-related deaths occur in the months and years after hospital discharge, according to findings from a prospective cohort study.

In 908 trauma patients followed for up to 9.8 years (median, 1.7 years), overall mortality was 27%, and in 509 patients followed for at least 2 years, overall mortality was 38%. Mortality was highest among those who were severely injured (43% at 5 years), Dr. Rachael A. Callcut reported at the annual meeting of the American Association for the Surgery of Trauma.

Spotmatik/ThinkStock

The median Injury Severity Scale score was 18, but for all ISS groups, survival was significantly worse than predicted actuarial survival for that group – even after exclusion of deaths that occurred within 30 days, she said.

For example, at 5 years, predicted actuarial survival was greater than 95%, but actual survival was about 90% for those with ISS less than 15, about 85% for those with ISS of 15-24, and about 57% for those with ISS greater than 24. This dose-response–like relationship between injury severity and mortality demonstrates that the deaths are not just occurring in “patients who are old and would have died from a heart attack anyway” she explained.

The 30-day mortality in the cohort was 22%, and in-hospital mortality was 22.9%, as eight patients who died after the first 30 days did so in the hospital. Forty-five of the 245 deaths (18%) occurred after 30 days, and 36 of those (80%) occurred after hospital discharge, meaning the out-of-hospital mortality rate was 5.3% overall, and 10% for the most severely injured (hazard ratio, 2.7 for the most severe vs. the least severe injuries).

“I personally found this quite striking given that when a patient leaves the hospital, we feel, to some degree, that we won – only to find out that at least 5% of these patients will go on to subsequently die,” said Dr. Callcut of the University of California San Francisco, adding that “if you look at it slightly differently, which is even more concerning, 37 of the out-of-hospital deaths of the total of 245 deaths, mean that out-of-hospital deaths account for 15% of the total mortality following trauma.”

Further, of the deaths that occurred after 30 days, 53% occurred between 31 days and 1 year after trauma, and trauma was the leading cause of postdischarge death, accounting for 41% of the late deaths, she said.

The patients included in this analysis were all highest level trauma activation patients enrolled in the ongoing study between 2005 and 2012. Comprehensive prospective data were collected, and patients were followed throughout their hospitalization and after discharge. Institutional medical records or death certificates were used to determine timing and cause of death, and survival status was determined based on the last date of care in the institution or by query of the National Death Index for 2013.

These findings provide a rare glimpse of trauma-related outcomes among patients discharged from the hospital. Most prior studies focused on 30-day outcomes, with a few extended out to 90 days, but very few studies have looked at long-term outcomes, Dr. Callcut noted.

“You could say that despite having survived to leave the hospital alive, long-term survival is actually worse than predicted actuarial survival, and this suggests to us that successful hospital discharge does not mean success for your patient,” she concluded.

Dr. Callcut was supported in part by a National Institutes of Health award.

sworcester@frontlinemedcom.com

LAS VEGAS – A higher-than-expected proportion of trauma-related deaths occur in the months and years after hospital discharge, according to findings from a prospective cohort study.

In 908 trauma patients followed for up to 9.8 years (median, 1.7 years), overall mortality was 27%, and in 509 patients followed for at least 2 years, overall mortality was 38%. Mortality was highest among those who were severely injured (43% at 5 years), Dr. Rachael A. Callcut reported at the annual meeting of the American Association for the Surgery of Trauma.

Spotmatik/ThinkStock

The median Injury Severity Scale score was 18, but for all ISS groups, survival was significantly worse than predicted actuarial survival for that group – even after exclusion of deaths that occurred within 30 days, she said.

For example, at 5 years, predicted actuarial survival was greater than 95%, but actual survival was about 90% for those with ISS less than 15, about 85% for those with ISS of 15-24, and about 57% for those with ISS greater than 24. This dose-response–like relationship between injury severity and mortality demonstrates that the deaths are not just occurring in “patients who are old and would have died from a heart attack anyway” she explained.

The 30-day mortality in the cohort was 22%, and in-hospital mortality was 22.9%, as eight patients who died after the first 30 days did so in the hospital. Forty-five of the 245 deaths (18%) occurred after 30 days, and 36 of those (80%) occurred after hospital discharge, meaning the out-of-hospital mortality rate was 5.3% overall, and 10% for the most severely injured (hazard ratio, 2.7 for the most severe vs. the least severe injuries).

“I personally found this quite striking given that when a patient leaves the hospital, we feel, to some degree, that we won – only to find out that at least 5% of these patients will go on to subsequently die,” said Dr. Callcut of the University of California San Francisco, adding that “if you look at it slightly differently, which is even more concerning, 37 of the out-of-hospital deaths of the total of 245 deaths, mean that out-of-hospital deaths account for 15% of the total mortality following trauma.”

Further, of the deaths that occurred after 30 days, 53% occurred between 31 days and 1 year after trauma, and trauma was the leading cause of postdischarge death, accounting for 41% of the late deaths, she said.

The patients included in this analysis were all highest level trauma activation patients enrolled in the ongoing study between 2005 and 2012. Comprehensive prospective data were collected, and patients were followed throughout their hospitalization and after discharge. Institutional medical records or death certificates were used to determine timing and cause of death, and survival status was determined based on the last date of care in the institution or by query of the National Death Index for 2013.

These findings provide a rare glimpse of trauma-related outcomes among patients discharged from the hospital. Most prior studies focused on 30-day outcomes, with a few extended out to 90 days, but very few studies have looked at long-term outcomes, Dr. Callcut noted.

“You could say that despite having survived to leave the hospital alive, long-term survival is actually worse than predicted actuarial survival, and this suggests to us that successful hospital discharge does not mean success for your patient,” she concluded.

Dr. Callcut was supported in part by a National Institutes of Health award.

sworcester@frontlinemedcom.com

LAS VEGAS – Damage control laparotomy is a safe and reliable approach to the surgical management of patients with severe nontrauma secondary peritonitis who require bowel resection, according a review of 182 cases.

For example, the deferred ostomy rate was 16.7% among 72 patients who underwent damage control laparotomy (DCL), which was significantly lower than the primary ostomy rate of 53.6% in 110 patients who underwent a definitive surgical procedure (DSP), Dr. Maria P. Garcia-Garcia reported at the annual meeting of the American Association for the Surgery of Trauma.

Ryan McVay/Thinkstock

Further, the fistula rate was lower among 60 DCL patients who underwent delayed anastomosis, compared with 51 DSP patients who underwent primary anastomosis (26.7% vs. 37.2%), and the mortality rate was lower in the DCL vs. DSP patients (16.7% vs. 24.5%). These differences did not meet statistical significance due to the sample size. Deaths in the DCL group all occurred in those who underwent delayed anastomosis; deaths in the DSP group occurred in 14 ostomy patients and 13 anastomosis patients, said Dr. Garcia-Garcia of Fundacion Valle del Lili, Cali, Colombia.

Disease severity, as measured by APACHE II scores, was similar in the two groups (mean of about 17 for each group). Septic shock was present in 37% at the time of admission. Mean hospital length of stay and mean intensive care unit length of stay did not differ significantly between the groups, nor did the systemic complication rate, or the rates of multiple organ failure and acute respiratory distress syndrome.

Small-bowel perforation occurred in 77 (42.3%), and colon perforation occurred in 105 (57.7%).

The patients included teens and adults aged 16 years or older (mean of 60.3 years) with severe nontrauma secondary peritonitis (NSPT) who were undergoing bowel resection after enteric perforations between 2003 and 2013. The DSP patients underwent either primary anastomosis or primary ostomy, and the DCL patients underwent segmental bowel resection, temporary abdominal closure, and subsequent delayed anastomosis or deferred ostomy.

DCL is a recognized strategy for managing bowel injuries in trauma patients. It was developed in response to the poor outcomes associated with attempting definitive repair, but evidence regarding the role and timing of anastomosis in DCL in NTSP – a condition associated with high morbidity and a 30% in-hospital mortality rate – is lacking, Dr. Garcia-Garcia said, noting that the current findings suggest it is the preferred approach.

“When a definite surgical repair is chosen, there is a 50/50 chance of performing anastomosis or ostomy. However, when a damage control abbreviated laparotomy is performed, there is a high bowel reconstruction success rate of about 80%. Therefore, damage control abbreviated laparotomy is a reliable and safe option in critically ill nontrauma secondary peritonitis patients. At the end of the day it’s your choice: Would you rather leave your patient with an ostomy or tube, or would you give your patient a chance of successful reconstruction without an ostomy?” she said.

Dr. Garcia-Garcia reported having no disclosures.

sworcester@frontlinemedcom.com

LAS VEGAS – Damage control laparotomy is a safe and reliable approach to the surgical management of patients with severe nontrauma secondary peritonitis who require bowel resection, according a review of 182 cases.

For example, the deferred ostomy rate was 16.7% among 72 patients who underwent damage control laparotomy (DCL), which was significantly lower than the primary ostomy rate of 53.6% in 110 patients who underwent a definitive surgical procedure (DSP), Dr. Maria P. Garcia-Garcia reported at the annual meeting of the American Association for the Surgery of Trauma.

Ryan McVay/Thinkstock

Further, the fistula rate was lower among 60 DCL patients who underwent delayed anastomosis, compared with 51 DSP patients who underwent primary anastomosis (26.7% vs. 37.2%), and the mortality rate was lower in the DCL vs. DSP patients (16.7% vs. 24.5%). These differences did not meet statistical significance due to the sample size. Deaths in the DCL group all occurred in those who underwent delayed anastomosis; deaths in the DSP group occurred in 14 ostomy patients and 13 anastomosis patients, said Dr. Garcia-Garcia of Fundacion Valle del Lili, Cali, Colombia.

Disease severity, as measured by APACHE II scores, was similar in the two groups (mean of about 17 for each group). Septic shock was present in 37% at the time of admission. Mean hospital length of stay and mean intensive care unit length of stay did not differ significantly between the groups, nor did the systemic complication rate, or the rates of multiple organ failure and acute respiratory distress syndrome.

Small-bowel perforation occurred in 77 (42.3%), and colon perforation occurred in 105 (57.7%).

The patients included teens and adults aged 16 years or older (mean of 60.3 years) with severe nontrauma secondary peritonitis (NSPT) who were undergoing bowel resection after enteric perforations between 2003 and 2013. The DSP patients underwent either primary anastomosis or primary ostomy, and the DCL patients underwent segmental bowel resection, temporary abdominal closure, and subsequent delayed anastomosis or deferred ostomy.

DCL is a recognized strategy for managing bowel injuries in trauma patients. It was developed in response to the poor outcomes associated with attempting definitive repair, but evidence regarding the role and timing of anastomosis in DCL in NTSP – a condition associated with high morbidity and a 30% in-hospital mortality rate – is lacking, Dr. Garcia-Garcia said, noting that the current findings suggest it is the preferred approach.

“When a definite surgical repair is chosen, there is a 50/50 chance of performing anastomosis or ostomy. However, when a damage control abbreviated laparotomy is performed, there is a high bowel reconstruction success rate of about 80%. Therefore, damage control abbreviated laparotomy is a reliable and safe option in critically ill nontrauma secondary peritonitis patients. At the end of the day it’s your choice: Would you rather leave your patient with an ostomy or tube, or would you give your patient a chance of successful reconstruction without an ostomy?” she said.

Dr. Garcia-Garcia reported having no disclosures.

sworcester@frontlinemedcom.com

LAS VEGAS – Damage control laparotomy is a safe and reliable approach to the surgical management of patients with severe nontrauma secondary peritonitis who require bowel resection, according a review of 182 cases.

For example, the deferred ostomy rate was 16.7% among 72 patients who underwent damage control laparotomy (DCL), which was significantly lower than the primary ostomy rate of 53.6% in 110 patients who underwent a definitive surgical procedure (DSP), Dr. Maria P. Garcia-Garcia reported at the annual meeting of the American Association for the Surgery of Trauma.

Ryan McVay/Thinkstock

Further, the fistula rate was lower among 60 DCL patients who underwent delayed anastomosis, compared with 51 DSP patients who underwent primary anastomosis (26.7% vs. 37.2%), and the mortality rate was lower in the DCL vs. DSP patients (16.7% vs. 24.5%). These differences did not meet statistical significance due to the sample size. Deaths in the DCL group all occurred in those who underwent delayed anastomosis; deaths in the DSP group occurred in 14 ostomy patients and 13 anastomosis patients, said Dr. Garcia-Garcia of Fundacion Valle del Lili, Cali, Colombia.

Disease severity, as measured by APACHE II scores, was similar in the two groups (mean of about 17 for each group). Septic shock was present in 37% at the time of admission. Mean hospital length of stay and mean intensive care unit length of stay did not differ significantly between the groups, nor did the systemic complication rate, or the rates of multiple organ failure and acute respiratory distress syndrome.

Small-bowel perforation occurred in 77 (42.3%), and colon perforation occurred in 105 (57.7%).

The patients included teens and adults aged 16 years or older (mean of 60.3 years) with severe nontrauma secondary peritonitis (NSPT) who were undergoing bowel resection after enteric perforations between 2003 and 2013. The DSP patients underwent either primary anastomosis or primary ostomy, and the DCL patients underwent segmental bowel resection, temporary abdominal closure, and subsequent delayed anastomosis or deferred ostomy.

DCL is a recognized strategy for managing bowel injuries in trauma patients. It was developed in response to the poor outcomes associated with attempting definitive repair, but evidence regarding the role and timing of anastomosis in DCL in NTSP – a condition associated with high morbidity and a 30% in-hospital mortality rate – is lacking, Dr. Garcia-Garcia said, noting that the current findings suggest it is the preferred approach.

“When a definite surgical repair is chosen, there is a 50/50 chance of performing anastomosis or ostomy. However, when a damage control abbreviated laparotomy is performed, there is a high bowel reconstruction success rate of about 80%. Therefore, damage control abbreviated laparotomy is a reliable and safe option in critically ill nontrauma secondary peritonitis patients. At the end of the day it’s your choice: Would you rather leave your patient with an ostomy or tube, or would you give your patient a chance of successful reconstruction without an ostomy?” she said.

Dr. Garcia-Garcia reported having no disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Adding ibrutinib to bendamustine and rituximab improved outcomes without significantly reducing safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the randomized, placebo-controlled, phase III HELIOS trial.

Efficacy results from the double-blind HELIOS trial, as reported by Dr. Asher Alban Chanan-Khan at the 2015 meeting of the American Society of Clinical Oncology, showed that adding ibrutinib to bendamustine and rituximab (BR) significantly extended progression-free survival, compared with BR plus placebo, in patients with CLL/SLL; the risk of progression and death was reduced by 80%.

The current findings, reported by Dr. Chanan-Khan at the American Society of Hematology Meeting on Hematologic Malignancies, demonstrate that this improvement was achieved without sacrificing safety, and they characterize the management of adverse events.

In 578 patients with active chronic CLL/SLL following at least one prior line of systemic therapy who were randomized to receive 420 mg of ibrutinib plus BR or placebo plus BR for six cycles, exposure was 14.7 months and 12.8 months, respectively. Infection rates were similar in the two groups, but exposure-adjusted analysis showed an overall lower infection rate in the ibrutinib group, compared with the placebo group (10.3/100 vs. 11.2/100 patient months), and the rates of grade 3 or higher infections was similar in the groups, said Dr. Chanan-Khan of the Mayo Clinic, Jacksonville, Fla.

The rates of all-grade and grade 3/4 anemia were 22.3% and 3.5%, respectively, in the ibrutinib group, and 28.9% and 8.0%, respectively, in the BR group. The ibrutinib patients also required fewer transfusions – most often red blood cell transfusions (23% vs. 29% in the BR group).This may have been a reflection of restoration of the hematopoietic system in the ibrutinib group, said Dr. Chanan-Khan.

Grade 3/4 neutropenia was similar in the groups (53.7% and 50.5%), but fewer patients discontinued treatment due to treatment-related neutropenia with ibrutinib (1% vs. 2.8%), he noted.

Thrombocytopenia occurred slightly more often in the ibrutinib group (30.7% vs. 24%), but grade 3/4 events occurred in 15% of patients in each group.

Atrial fibrillation (AF) occurred in a small number of patients, but was observed more often with ibrutinib (7.3% vs. 2.8% overall, and 2.8% vs. 0.7% for grade 3/4 AF). Only seven patients required dose interruption – for a median duration of 7 days – to manage AF.

“No dose reductions were required,” said Dr. Chanan-Khan, adding that four patients, all with grade 3/4 AF and all in the ibrutinib group, discontinued therapy because of AF.

“We then analyzed our data to identify potential risk factors for predisposition to AF ... no one baseline risk factor could be identified as causative. However, most patients who developed AF had a known risk factor,” he said.

He added that among those with a prior history of AF, 28% on the ibrutinib arm, and only 9% on the placebo arm, developed AF.

Baseline cardiac comorbidities also were found to have no effect on progression-free survival in either arm.

“We therefore concluded that the risk of AF is low at around 5%, it does not impact progression-free survival, prior history of AF is not a contraindication in the absence of any great freak event, ibrutinib dose interruption or reduction is not warranted, and you should treat CLL patients first for CLL and manage AF second,” he said.

Another important factor that often impacts clinical decision making is the use of anticoagulants or antiplatelet agents and the bleeding risk with ibrutinib, he said, noting that more than 40% of patients in the ibrutinib arm were using such agents.

“We did not see any impact on the progression-free survival outcomes on either of the arms in patients who were on anticoagulant or antiplatelet therapy,” he said.

Bleeding occurred in 31% and 14.6% of patients in the ibrutinib and placebo groups, respectively, and most cases involved grade 1 bruises and contusions. Only four patients discontinued therapy because of bleeding.

The rates of grade 3/4 major bleeding and major hemorrhage events were low in both groups, at less than 4%, and two patients discontinued therapy because of major bleeding. Two patients in the ibrutinib arm died because of major bleeding, including one who had a large preexisting abdominal aortic aneurysm, and one who experienced a large postsurgical intestinal perforation.

“Overall, these data support the use of ibrutinib in patients on concurrent anticoagulant or antiplatelet therapy, with no significantly increased major risk of bleeding with ibrutinib vs. placebo, and most bleeding events being grade 1 in nature,” said Dr. Chanan-Khan.

The rate of treatment-related lymphocytosis – a known pharmacodynamic effect of ibrutinib – occurred in 7% and 5.9% of the ibrutinib and placebo group patients, and most cases resolved within 2 weeks.

Based on the results of the 2014 phase III RESONATE trial and others looking at ibrutinib as a single-agent treatment for CLL, the agent is considered a new standard of care in patients with previously treated CLL/SLL. HELIOS was the first study to investigate ibrutinib in combination with BR.

“Considering the significant improvement in progression-free survival and overall survival, ibrutinib has a strong overall risk-benefit profile,” Dr. Chanan-Khan concluded.

The HELIOS study was sponsored by Janssen Pharmaceuticals. Dr. Chanan-Khan reported having no disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Adding ibrutinib to bendamustine and rituximab improved outcomes without significantly reducing safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the randomized, placebo-controlled, phase III HELIOS trial.

Efficacy results from the double-blind HELIOS trial, as reported by Dr. Asher Alban Chanan-Khan at the 2015 meeting of the American Society of Clinical Oncology, showed that adding ibrutinib to bendamustine and rituximab (BR) significantly extended progression-free survival, compared with BR plus placebo, in patients with CLL/SLL; the risk of progression and death was reduced by 80%.

The current findings, reported by Dr. Chanan-Khan at the American Society of Hematology Meeting on Hematologic Malignancies, demonstrate that this improvement was achieved without sacrificing safety, and they characterize the management of adverse events.

In 578 patients with active chronic CLL/SLL following at least one prior line of systemic therapy who were randomized to receive 420 mg of ibrutinib plus BR or placebo plus BR for six cycles, exposure was 14.7 months and 12.8 months, respectively. Infection rates were similar in the two groups, but exposure-adjusted analysis showed an overall lower infection rate in the ibrutinib group, compared with the placebo group (10.3/100 vs. 11.2/100 patient months), and the rates of grade 3 or higher infections was similar in the groups, said Dr. Chanan-Khan of the Mayo Clinic, Jacksonville, Fla.

The rates of all-grade and grade 3/4 anemia were 22.3% and 3.5%, respectively, in the ibrutinib group, and 28.9% and 8.0%, respectively, in the BR group. The ibrutinib patients also required fewer transfusions – most often red blood cell transfusions (23% vs. 29% in the BR group).This may have been a reflection of restoration of the hematopoietic system in the ibrutinib group, said Dr. Chanan-Khan.

Grade 3/4 neutropenia was similar in the groups (53.7% and 50.5%), but fewer patients discontinued treatment due to treatment-related neutropenia with ibrutinib (1% vs. 2.8%), he noted.

Thrombocytopenia occurred slightly more often in the ibrutinib group (30.7% vs. 24%), but grade 3/4 events occurred in 15% of patients in each group.

Atrial fibrillation (AF) occurred in a small number of patients, but was observed more often with ibrutinib (7.3% vs. 2.8% overall, and 2.8% vs. 0.7% for grade 3/4 AF). Only seven patients required dose interruption – for a median duration of 7 days – to manage AF.

“No dose reductions were required,” said Dr. Chanan-Khan, adding that four patients, all with grade 3/4 AF and all in the ibrutinib group, discontinued therapy because of AF.

“We then analyzed our data to identify potential risk factors for predisposition to AF ... no one baseline risk factor could be identified as causative. However, most patients who developed AF had a known risk factor,” he said.

He added that among those with a prior history of AF, 28% on the ibrutinib arm, and only 9% on the placebo arm, developed AF.

Baseline cardiac comorbidities also were found to have no effect on progression-free survival in either arm.

“We therefore concluded that the risk of AF is low at around 5%, it does not impact progression-free survival, prior history of AF is not a contraindication in the absence of any great freak event, ibrutinib dose interruption or reduction is not warranted, and you should treat CLL patients first for CLL and manage AF second,” he said.

Another important factor that often impacts clinical decision making is the use of anticoagulants or antiplatelet agents and the bleeding risk with ibrutinib, he said, noting that more than 40% of patients in the ibrutinib arm were using such agents.

“We did not see any impact on the progression-free survival outcomes on either of the arms in patients who were on anticoagulant or antiplatelet therapy,” he said.

Bleeding occurred in 31% and 14.6% of patients in the ibrutinib and placebo groups, respectively, and most cases involved grade 1 bruises and contusions. Only four patients discontinued therapy because of bleeding.

The rates of grade 3/4 major bleeding and major hemorrhage events were low in both groups, at less than 4%, and two patients discontinued therapy because of major bleeding. Two patients in the ibrutinib arm died because of major bleeding, including one who had a large preexisting abdominal aortic aneurysm, and one who experienced a large postsurgical intestinal perforation.

“Overall, these data support the use of ibrutinib in patients on concurrent anticoagulant or antiplatelet therapy, with no significantly increased major risk of bleeding with ibrutinib vs. placebo, and most bleeding events being grade 1 in nature,” said Dr. Chanan-Khan.

The rate of treatment-related lymphocytosis – a known pharmacodynamic effect of ibrutinib – occurred in 7% and 5.9% of the ibrutinib and placebo group patients, and most cases resolved within 2 weeks.

Based on the results of the 2014 phase III RESONATE trial and others looking at ibrutinib as a single-agent treatment for CLL, the agent is considered a new standard of care in patients with previously treated CLL/SLL. HELIOS was the first study to investigate ibrutinib in combination with BR.

“Considering the significant improvement in progression-free survival and overall survival, ibrutinib has a strong overall risk-benefit profile,” Dr. Chanan-Khan concluded.

The HELIOS study was sponsored by Janssen Pharmaceuticals. Dr. Chanan-Khan reported having no disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Adding ibrutinib to bendamustine and rituximab improved outcomes without significantly reducing safety in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the randomized, placebo-controlled, phase III HELIOS trial.

Efficacy results from the double-blind HELIOS trial, as reported by Dr. Asher Alban Chanan-Khan at the 2015 meeting of the American Society of Clinical Oncology, showed that adding ibrutinib to bendamustine and rituximab (BR) significantly extended progression-free survival, compared with BR plus placebo, in patients with CLL/SLL; the risk of progression and death was reduced by 80%.

The current findings, reported by Dr. Chanan-Khan at the American Society of Hematology Meeting on Hematologic Malignancies, demonstrate that this improvement was achieved without sacrificing safety, and they characterize the management of adverse events.

In 578 patients with active chronic CLL/SLL following at least one prior line of systemic therapy who were randomized to receive 420 mg of ibrutinib plus BR or placebo plus BR for six cycles, exposure was 14.7 months and 12.8 months, respectively. Infection rates were similar in the two groups, but exposure-adjusted analysis showed an overall lower infection rate in the ibrutinib group, compared with the placebo group (10.3/100 vs. 11.2/100 patient months), and the rates of grade 3 or higher infections was similar in the groups, said Dr. Chanan-Khan of the Mayo Clinic, Jacksonville, Fla.

The rates of all-grade and grade 3/4 anemia were 22.3% and 3.5%, respectively, in the ibrutinib group, and 28.9% and 8.0%, respectively, in the BR group. The ibrutinib patients also required fewer transfusions – most often red blood cell transfusions (23% vs. 29% in the BR group).This may have been a reflection of restoration of the hematopoietic system in the ibrutinib group, said Dr. Chanan-Khan.

Grade 3/4 neutropenia was similar in the groups (53.7% and 50.5%), but fewer patients discontinued treatment due to treatment-related neutropenia with ibrutinib (1% vs. 2.8%), he noted.

Thrombocytopenia occurred slightly more often in the ibrutinib group (30.7% vs. 24%), but grade 3/4 events occurred in 15% of patients in each group.

Atrial fibrillation (AF) occurred in a small number of patients, but was observed more often with ibrutinib (7.3% vs. 2.8% overall, and 2.8% vs. 0.7% for grade 3/4 AF). Only seven patients required dose interruption – for a median duration of 7 days – to manage AF.

“No dose reductions were required,” said Dr. Chanan-Khan, adding that four patients, all with grade 3/4 AF and all in the ibrutinib group, discontinued therapy because of AF.

“We then analyzed our data to identify potential risk factors for predisposition to AF ... no one baseline risk factor could be identified as causative. However, most patients who developed AF had a known risk factor,” he said.

He added that among those with a prior history of AF, 28% on the ibrutinib arm, and only 9% on the placebo arm, developed AF.

Baseline cardiac comorbidities also were found to have no effect on progression-free survival in either arm.

“We therefore concluded that the risk of AF is low at around 5%, it does not impact progression-free survival, prior history of AF is not a contraindication in the absence of any great freak event, ibrutinib dose interruption or reduction is not warranted, and you should treat CLL patients first for CLL and manage AF second,” he said.

Another important factor that often impacts clinical decision making is the use of anticoagulants or antiplatelet agents and the bleeding risk with ibrutinib, he said, noting that more than 40% of patients in the ibrutinib arm were using such agents.

“We did not see any impact on the progression-free survival outcomes on either of the arms in patients who were on anticoagulant or antiplatelet therapy,” he said.

Bleeding occurred in 31% and 14.6% of patients in the ibrutinib and placebo groups, respectively, and most cases involved grade 1 bruises and contusions. Only four patients discontinued therapy because of bleeding.

The rates of grade 3/4 major bleeding and major hemorrhage events were low in both groups, at less than 4%, and two patients discontinued therapy because of major bleeding. Two patients in the ibrutinib arm died because of major bleeding, including one who had a large preexisting abdominal aortic aneurysm, and one who experienced a large postsurgical intestinal perforation.

“Overall, these data support the use of ibrutinib in patients on concurrent anticoagulant or antiplatelet therapy, with no significantly increased major risk of bleeding with ibrutinib vs. placebo, and most bleeding events being grade 1 in nature,” said Dr. Chanan-Khan.

The rate of treatment-related lymphocytosis – a known pharmacodynamic effect of ibrutinib – occurred in 7% and 5.9% of the ibrutinib and placebo group patients, and most cases resolved within 2 weeks.

Based on the results of the 2014 phase III RESONATE trial and others looking at ibrutinib as a single-agent treatment for CLL, the agent is considered a new standard of care in patients with previously treated CLL/SLL. HELIOS was the first study to investigate ibrutinib in combination with BR.

“Considering the significant improvement in progression-free survival and overall survival, ibrutinib has a strong overall risk-benefit profile,” Dr. Chanan-Khan concluded.

The HELIOS study was sponsored by Janssen Pharmaceuticals. Dr. Chanan-Khan reported having no disclosures.

sworcester@frontlinemedcom.com

LAS VEGAS – Choice of damage control resuscitation – plasma-platelet-red blood cell ratio of either 1:1:1 or 1:1:2 – did not affect whether severely injured patients required an emergency laparotomy, nor did it affect time to laparotomy or survival following laparotomy, according to findings from the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial.

“We were unable to detect significant effects of damage control resuscitation on the frequency and time to emergency laparotomy, outcomes, disposition at 30 days, or main endpoint survival,” said Dr. Vicente J. Undurraga Perl of the Oregon Health and Science University, Portland. The lack of a difference between the treatment groups with respect to emergency laparotomy and 30-day survival may be a result of the low overall mortality of 23% and to the study being underpowered to detect a difference between the groups.

The PROPPR trial demonstrated that damage control resuscitation, defined as “a massive transfusion strategy targeting a balanced delivery of plasma-platelet-RBC in a ratio of 1:1:1,” allows earlier achievement of hemostasis in a greater number of severely injured patients than does a 1:1:2 ratio. A corresponding reduction in deaths because of exsanguination was observed in the study subjects, who were enrolled from 12 level-1 trauma centers in North America, where they presented with severe injuries.

Of 680 patients who had severe injuries and were predicted to require massive transfusions, 613 underwent a surgical procedure and 397 underwent a laparotomy. Of the latter, 346 were emergency laparotomies. Of those who received damage control resuscitation using the 1:1:1 ratio, 52% underwent emergency laparotomy (defined as laparotomy within 90 minutes of arrival at a trauma center). Of those who received the 1:1:2 ratio, 50% underwent emergency laparotomy. The difference between the groups was not statistically significant, Dr. Perl reported at the annual meeting of the American Association for the Surgery of Trauma.

The median time to laparotomy was 28 minutes in both groups, and the proportions of patients who survived to 3 hours, 6 hours, 24 hours, and 30 days also were similar in the two groups. For example, 88% and 85% of those in the 1:1:1 and 1:1:2 groups, respectively, survived to 24 hours; 82% and 77%, respectively, survived to 30 days, he said.

There was no overall difference in mortality between the groups (hazard ratio, 0.78), nor was there a difference in survival by study site, he noted.

Dr. Perl reported having no disclosures.

sworcester@frontlinemedcom.com

LAS VEGAS – Choice of damage control resuscitation – plasma-platelet-red blood cell ratio of either 1:1:1 or 1:1:2 – did not affect whether severely injured patients required an emergency laparotomy, nor did it affect time to laparotomy or survival following laparotomy, according to findings from the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial.

“We were unable to detect significant effects of damage control resuscitation on the frequency and time to emergency laparotomy, outcomes, disposition at 30 days, or main endpoint survival,” said Dr. Vicente J. Undurraga Perl of the Oregon Health and Science University, Portland. The lack of a difference between the treatment groups with respect to emergency laparotomy and 30-day survival may be a result of the low overall mortality of 23% and to the study being underpowered to detect a difference between the groups.

The PROPPR trial demonstrated that damage control resuscitation, defined as “a massive transfusion strategy targeting a balanced delivery of plasma-platelet-RBC in a ratio of 1:1:1,” allows earlier achievement of hemostasis in a greater number of severely injured patients than does a 1:1:2 ratio. A corresponding reduction in deaths because of exsanguination was observed in the study subjects, who were enrolled from 12 level-1 trauma centers in North America, where they presented with severe injuries.

Of 680 patients who had severe injuries and were predicted to require massive transfusions, 613 underwent a surgical procedure and 397 underwent a laparotomy. Of the latter, 346 were emergency laparotomies. Of those who received damage control resuscitation using the 1:1:1 ratio, 52% underwent emergency laparotomy (defined as laparotomy within 90 minutes of arrival at a trauma center). Of those who received the 1:1:2 ratio, 50% underwent emergency laparotomy. The difference between the groups was not statistically significant, Dr. Perl reported at the annual meeting of the American Association for the Surgery of Trauma.

The median time to laparotomy was 28 minutes in both groups, and the proportions of patients who survived to 3 hours, 6 hours, 24 hours, and 30 days also were similar in the two groups. For example, 88% and 85% of those in the 1:1:1 and 1:1:2 groups, respectively, survived to 24 hours; 82% and 77%, respectively, survived to 30 days, he said.

There was no overall difference in mortality between the groups (hazard ratio, 0.78), nor was there a difference in survival by study site, he noted.

Dr. Perl reported having no disclosures.

sworcester@frontlinemedcom.com

LAS VEGAS – Choice of damage control resuscitation – plasma-platelet-red blood cell ratio of either 1:1:1 or 1:1:2 – did not affect whether severely injured patients required an emergency laparotomy, nor did it affect time to laparotomy or survival following laparotomy, according to findings from the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial.

“We were unable to detect significant effects of damage control resuscitation on the frequency and time to emergency laparotomy, outcomes, disposition at 30 days, or main endpoint survival,” said Dr. Vicente J. Undurraga Perl of the Oregon Health and Science University, Portland. The lack of a difference between the treatment groups with respect to emergency laparotomy and 30-day survival may be a result of the low overall mortality of 23% and to the study being underpowered to detect a difference between the groups.

The PROPPR trial demonstrated that damage control resuscitation, defined as “a massive transfusion strategy targeting a balanced delivery of plasma-platelet-RBC in a ratio of 1:1:1,” allows earlier achievement of hemostasis in a greater number of severely injured patients than does a 1:1:2 ratio. A corresponding reduction in deaths because of exsanguination was observed in the study subjects, who were enrolled from 12 level-1 trauma centers in North America, where they presented with severe injuries.

Of 680 patients who had severe injuries and were predicted to require massive transfusions, 613 underwent a surgical procedure and 397 underwent a laparotomy. Of the latter, 346 were emergency laparotomies. Of those who received damage control resuscitation using the 1:1:1 ratio, 52% underwent emergency laparotomy (defined as laparotomy within 90 minutes of arrival at a trauma center). Of those who received the 1:1:2 ratio, 50% underwent emergency laparotomy. The difference between the groups was not statistically significant, Dr. Perl reported at the annual meeting of the American Association for the Surgery of Trauma.

The median time to laparotomy was 28 minutes in both groups, and the proportions of patients who survived to 3 hours, 6 hours, 24 hours, and 30 days also were similar in the two groups. For example, 88% and 85% of those in the 1:1:1 and 1:1:2 groups, respectively, survived to 24 hours; 82% and 77%, respectively, survived to 30 days, he said.

There was no overall difference in mortality between the groups (hazard ratio, 0.78), nor was there a difference in survival by study site, he noted.

Dr. Perl reported having no disclosures.

sworcester@frontlinemedcom.com