PET/CT scanner

BALTIMORE—Post-treatment PET/CT scans may be necessary for some patients with non-Hodgkin lymphoma (NHL), according to a presentation at the 2015 SNMMI Annual Meeting.

“[T]he role of post-treatment PET/CT has been controversial,” said Mehdi Taghipour, MD, of Johns Hopkins University in Baltimore, Maryland.

“Our study proves that 39% of follow-up PET/CT scans added clinical value, which represents a significant improvement in NHL patient care.”

Dr Taghipour presented the details of this study at the meeting as abstract 599.

He and his colleagues had examined 560 PET/CT scans from 204 patients. Imaging was performed 6 months or more after the patient completed primary therapy.

The researchers assessed the value of follow-up PET/CT by conducting statistical analyses to determine changes in patient management and evaluated the accuracy of these scans compared to either histopathology or an additional 6-month follow-up.

Results showed that the sensitivity of PET/CT for detecting relapsed NHL was 95.1%, and the specificity was 90.5%. Positive and negative predictive values were 84.5% and 97.1%, respectively.

The overall accuracy of follow-up PET/CT with the common imaging agent fluorodeoxyglucose (FDG) was 92.1%.

Follow-up PET/CT led to changes in patient management in 17% of cases, and new treatments were initiated after 15.7% of scans. More than 69% of scans were performed without prior clinical suspicion of recurrence, and 30.7% of scans were ordered because of suspected disease.

More than 22% of follow-up scans showed suspected disease when there was no clinical suspicion for disease recurrence, and the presence of disease was ruled out in 17.4% of scans where the treating physician had suspected recurrence prior to the scan.

PET/CT scanner

BALTIMORE—Post-treatment PET/CT scans may be necessary for some patients with non-Hodgkin lymphoma (NHL), according to a presentation at the 2015 SNMMI Annual Meeting.

“[T]he role of post-treatment PET/CT has been controversial,” said Mehdi Taghipour, MD, of Johns Hopkins University in Baltimore, Maryland.

“Our study proves that 39% of follow-up PET/CT scans added clinical value, which represents a significant improvement in NHL patient care.”

Dr Taghipour presented the details of this study at the meeting as abstract 599.

He and his colleagues had examined 560 PET/CT scans from 204 patients. Imaging was performed 6 months or more after the patient completed primary therapy.

The researchers assessed the value of follow-up PET/CT by conducting statistical analyses to determine changes in patient management and evaluated the accuracy of these scans compared to either histopathology or an additional 6-month follow-up.

Results showed that the sensitivity of PET/CT for detecting relapsed NHL was 95.1%, and the specificity was 90.5%. Positive and negative predictive values were 84.5% and 97.1%, respectively.

The overall accuracy of follow-up PET/CT with the common imaging agent fluorodeoxyglucose (FDG) was 92.1%.

Follow-up PET/CT led to changes in patient management in 17% of cases, and new treatments were initiated after 15.7% of scans. More than 69% of scans were performed without prior clinical suspicion of recurrence, and 30.7% of scans were ordered because of suspected disease.

More than 22% of follow-up scans showed suspected disease when there was no clinical suspicion for disease recurrence, and the presence of disease was ruled out in 17.4% of scans where the treating physician had suspected recurrence prior to the scan.

PET/CT scanner

BALTIMORE—Post-treatment PET/CT scans may be necessary for some patients with non-Hodgkin lymphoma (NHL), according to a presentation at the 2015 SNMMI Annual Meeting.

“[T]he role of post-treatment PET/CT has been controversial,” said Mehdi Taghipour, MD, of Johns Hopkins University in Baltimore, Maryland.

“Our study proves that 39% of follow-up PET/CT scans added clinical value, which represents a significant improvement in NHL patient care.”

Dr Taghipour presented the details of this study at the meeting as abstract 599.

He and his colleagues had examined 560 PET/CT scans from 204 patients. Imaging was performed 6 months or more after the patient completed primary therapy.

The researchers assessed the value of follow-up PET/CT by conducting statistical analyses to determine changes in patient management and evaluated the accuracy of these scans compared to either histopathology or an additional 6-month follow-up.

Results showed that the sensitivity of PET/CT for detecting relapsed NHL was 95.1%, and the specificity was 90.5%. Positive and negative predictive values were 84.5% and 97.1%, respectively.

The overall accuracy of follow-up PET/CT with the common imaging agent fluorodeoxyglucose (FDG) was 92.1%.

Follow-up PET/CT led to changes in patient management in 17% of cases, and new treatments were initiated after 15.7% of scans. More than 69% of scans were performed without prior clinical suspicion of recurrence, and 30.7% of scans were ordered because of suspected disease.

More than 22% of follow-up scans showed suspected disease when there was no clinical suspicion for disease recurrence, and the presence of disease was ruled out in 17.4% of scans where the treating physician had suspected recurrence prior to the scan.

Attendees at ASCO 2015

© ASCO/Scott Morgan

CHICAGO—A dual inhibitor of FLT3 and Axl may produce more durable responses than other FLT3 inhibitors and improve survival in patients with FLT3-positive, relapsed or refractory acute myeloid leukemia (AML), according to a speaker at the 2015 ASCO Annual Meeting.

The FLT3/Axl inhibitor, ASP2215, has not been compared against other FLT3 inhibitors directly, and the data presented were from a phase 1/2 study.

However, the speaker said ASP2215 provided “potent and sustained” inhibition of FLT3 and produced an overall response rate (ORR) of 52% among FLT3-positive patients.

The median duration of response for these patients was 18 weeks, and their median overall survival was about 27 weeks.

Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, presented these results at ASCO as abstract 7003.*

“We’ve been studying FLT3 inhibitors for a number of years now,” Dr Levis began, “and we think they show significant clinical promise, [but] they also have problems.”

He noted that some of these drugs haven’t been particularly safe or well-tolerated. They can cause gastrointestinal toxicity, hand-foot syndrome, QT prolongation, and myelosuppression.

However, the most intriguing problem with FLT3 inhibitors, according to Dr Levis, is the emergence of resistance-conferring point mutations observed in studies of some of the newer drugs, such as sorafenib and quizartinib.

“So in that context, here we have ASP2215,” Dr Levis said. “This is a type 1 FLT3 tyrosine kinase inhibitor, and, as such, it has activity against not only wild-type and ITD-mutated FLT3 but also against those resistance-conferring point mutations typically found in the activation loop at the so-called gatekeeper residue (F691L).”

With this in mind, he and his colleagues conducted a phase 1/2 trial of ASP2215. The study was sponsored by Astellas Pharma Global Development, Inc., the company developing ASP2215.

The trial was open to patients with relapsed or refractory AML, irrespective of their FLT3 mutation status. The researchers’ goal was to identify a safe, tolerable dose of ASP2215 that fully inhibited FLT3.

The team used a standard 3+3 design, with dose levels ranging from 20 mg to 450 mg once daily. They expanded every cohort until they reached a dose-limiting toxicity.

In all, the trial enrolled 198 patients, 24 in the dose-escalation cohorts and 174 in the dose-expansion cohorts. The patients’ median age was 62 (range, 21-90), and 53.1% were male.

Nearly 66% of patients had FLT3 mutations, 29.4% were FLT3-negative, and 5.2% had unknown FLT3 status. About 35% of patients had received 1 prior line of therapy, 26.3% had 2, 33.5% had 3 or more, and 5.7% had an unknown number of prior therapies.

Safety results

In the 194 patients who were evaluable for safety, treatment-emergent adverse events included diarrhea (13.4%), fatigue (12.4%), AST increase (11.3%), ALT increase (9.3%), thrombocytopenia (7.7%), anemia (7.2%), peripheral edema (7.2%), constipation (6.7%), nausea (6.7%), dizziness (6.2%), vomiting (5.7%), and dysgeusia (5.2%).

Serious adverse events included febrile neutropenia (27.3%), sepsis (11.9%), disease progression (10.3%), pneumonia (8.8%), hypotension (5.7%), and respiratory failure (5.7%).

“The kinds of side effects we saw were typical for a relapsed/refractory AML population,” Dr Levis said. “Nothing really stood out. Any trial of relapsed/refractory AML is going to have febrile neutropenia and sepsis, and those were our dominant, serious adverse events. There was no real safety signal here that was unique to the drug, we felt.”

The researchers said the maximum-tolerated dose of ASP2215 was 300 mg, as 2 patients who received the 450 mg dose experienced dose-limiting toxicities. One was grade 3 diarrhea, and the other was grade 3 AST elevation.

Response and survival

Among the 127 patients who were FLT3-positive, the ORR was 52% (n=66). The complete response (CR) rate was 6.3% (n=8). The composite CR rate, which includes CRs with incomplete hematologic recovery (CRi) and incomplete platelet recovery (CRp), was 40.9% (n=52). And the partial response (PR) rate was 11% (n=14).

“As we scale up the dose, the PRs shift on over to CRis, and the dominant response is, in fact, a complete response with incomplete count recovery,” Dr Levis said. “The categories where we had the largest number of responses were the 120 mg and 200 mg categories. We didn’t really have enough patients in the 300 mg category to comment on it. ”

For the FLT3-positive patients, the median duration of response was 126 days.

“The duration of response really stood out here,” Dr Levis said. “It’s over 4 months. That is something we really didn’t see with the other drugs, and I suspect that is a reflection of the suppression of the outgrowth of these resistance mutations.”

Unfortunately, FLT3-wild-type patients did not fare as well. The ORR among these patients was 8.8%. None of the patients achieved a CR, 3 had a composite CR (5.3%), and 2 had a PR (3.5%).

Among the FLT3-positive patients, the median overall survival was about 27 weeks. It was 128 days in the 20 mg dose cohort (n=13), 105.5 days in the 40 mg cohort (n=8), 201 days in the 80 mg cohort (n=12), 199 days in the 120 mg cohort (n=40), and 161 days in the 200 mg cohort (n=45). Dr Levis did not present survival data for the 300 mg or 450 mg cohorts, which included 7 and 2 patients, respectively.

“[Relapsed/refractory AML] is a population that has a median survival of about 3 months with conventional therapy, at least by historical publications,” Dr Levis noted. “If you look at survival in this trial, patients treated at the FLT3-inhibitory doses [had a] greater than 6-month median survival.”

He added that studies of ASP2215 in combination with other agents are ongoing in patients with newly diagnosed AML. And phase 3 trials of ASP2215 at the 120 mg dose, with the option of scaling up to 200 mg, are planned.

*Information in the abstract differs from that presented at the meeting.

Attendees at ASCO 2015

© ASCO/Scott Morgan

CHICAGO—A dual inhibitor of FLT3 and Axl may produce more durable responses than other FLT3 inhibitors and improve survival in patients with FLT3-positive, relapsed or refractory acute myeloid leukemia (AML), according to a speaker at the 2015 ASCO Annual Meeting.

The FLT3/Axl inhibitor, ASP2215, has not been compared against other FLT3 inhibitors directly, and the data presented were from a phase 1/2 study.

However, the speaker said ASP2215 provided “potent and sustained” inhibition of FLT3 and produced an overall response rate (ORR) of 52% among FLT3-positive patients.

The median duration of response for these patients was 18 weeks, and their median overall survival was about 27 weeks.

Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, presented these results at ASCO as abstract 7003.*

“We’ve been studying FLT3 inhibitors for a number of years now,” Dr Levis began, “and we think they show significant clinical promise, [but] they also have problems.”

He noted that some of these drugs haven’t been particularly safe or well-tolerated. They can cause gastrointestinal toxicity, hand-foot syndrome, QT prolongation, and myelosuppression.

However, the most intriguing problem with FLT3 inhibitors, according to Dr Levis, is the emergence of resistance-conferring point mutations observed in studies of some of the newer drugs, such as sorafenib and quizartinib.

“So in that context, here we have ASP2215,” Dr Levis said. “This is a type 1 FLT3 tyrosine kinase inhibitor, and, as such, it has activity against not only wild-type and ITD-mutated FLT3 but also against those resistance-conferring point mutations typically found in the activation loop at the so-called gatekeeper residue (F691L).”

With this in mind, he and his colleagues conducted a phase 1/2 trial of ASP2215. The study was sponsored by Astellas Pharma Global Development, Inc., the company developing ASP2215.

The trial was open to patients with relapsed or refractory AML, irrespective of their FLT3 mutation status. The researchers’ goal was to identify a safe, tolerable dose of ASP2215 that fully inhibited FLT3.

The team used a standard 3+3 design, with dose levels ranging from 20 mg to 450 mg once daily. They expanded every cohort until they reached a dose-limiting toxicity.

In all, the trial enrolled 198 patients, 24 in the dose-escalation cohorts and 174 in the dose-expansion cohorts. The patients’ median age was 62 (range, 21-90), and 53.1% were male.

Nearly 66% of patients had FLT3 mutations, 29.4% were FLT3-negative, and 5.2% had unknown FLT3 status. About 35% of patients had received 1 prior line of therapy, 26.3% had 2, 33.5% had 3 or more, and 5.7% had an unknown number of prior therapies.

Safety results

In the 194 patients who were evaluable for safety, treatment-emergent adverse events included diarrhea (13.4%), fatigue (12.4%), AST increase (11.3%), ALT increase (9.3%), thrombocytopenia (7.7%), anemia (7.2%), peripheral edema (7.2%), constipation (6.7%), nausea (6.7%), dizziness (6.2%), vomiting (5.7%), and dysgeusia (5.2%).

Serious adverse events included febrile neutropenia (27.3%), sepsis (11.9%), disease progression (10.3%), pneumonia (8.8%), hypotension (5.7%), and respiratory failure (5.7%).

“The kinds of side effects we saw were typical for a relapsed/refractory AML population,” Dr Levis said. “Nothing really stood out. Any trial of relapsed/refractory AML is going to have febrile neutropenia and sepsis, and those were our dominant, serious adverse events. There was no real safety signal here that was unique to the drug, we felt.”

The researchers said the maximum-tolerated dose of ASP2215 was 300 mg, as 2 patients who received the 450 mg dose experienced dose-limiting toxicities. One was grade 3 diarrhea, and the other was grade 3 AST elevation.

Response and survival

Among the 127 patients who were FLT3-positive, the ORR was 52% (n=66). The complete response (CR) rate was 6.3% (n=8). The composite CR rate, which includes CRs with incomplete hematologic recovery (CRi) and incomplete platelet recovery (CRp), was 40.9% (n=52). And the partial response (PR) rate was 11% (n=14).

“As we scale up the dose, the PRs shift on over to CRis, and the dominant response is, in fact, a complete response with incomplete count recovery,” Dr Levis said. “The categories where we had the largest number of responses were the 120 mg and 200 mg categories. We didn’t really have enough patients in the 300 mg category to comment on it. ”

For the FLT3-positive patients, the median duration of response was 126 days.

“The duration of response really stood out here,” Dr Levis said. “It’s over 4 months. That is something we really didn’t see with the other drugs, and I suspect that is a reflection of the suppression of the outgrowth of these resistance mutations.”

Unfortunately, FLT3-wild-type patients did not fare as well. The ORR among these patients was 8.8%. None of the patients achieved a CR, 3 had a composite CR (5.3%), and 2 had a PR (3.5%).

Among the FLT3-positive patients, the median overall survival was about 27 weeks. It was 128 days in the 20 mg dose cohort (n=13), 105.5 days in the 40 mg cohort (n=8), 201 days in the 80 mg cohort (n=12), 199 days in the 120 mg cohort (n=40), and 161 days in the 200 mg cohort (n=45). Dr Levis did not present survival data for the 300 mg or 450 mg cohorts, which included 7 and 2 patients, respectively.

“[Relapsed/refractory AML] is a population that has a median survival of about 3 months with conventional therapy, at least by historical publications,” Dr Levis noted. “If you look at survival in this trial, patients treated at the FLT3-inhibitory doses [had a] greater than 6-month median survival.”

He added that studies of ASP2215 in combination with other agents are ongoing in patients with newly diagnosed AML. And phase 3 trials of ASP2215 at the 120 mg dose, with the option of scaling up to 200 mg, are planned.

*Information in the abstract differs from that presented at the meeting.

Attendees at ASCO 2015

© ASCO/Scott Morgan

CHICAGO—A dual inhibitor of FLT3 and Axl may produce more durable responses than other FLT3 inhibitors and improve survival in patients with FLT3-positive, relapsed or refractory acute myeloid leukemia (AML), according to a speaker at the 2015 ASCO Annual Meeting.

The FLT3/Axl inhibitor, ASP2215, has not been compared against other FLT3 inhibitors directly, and the data presented were from a phase 1/2 study.

However, the speaker said ASP2215 provided “potent and sustained” inhibition of FLT3 and produced an overall response rate (ORR) of 52% among FLT3-positive patients.

The median duration of response for these patients was 18 weeks, and their median overall survival was about 27 weeks.

Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland, presented these results at ASCO as abstract 7003.*

“We’ve been studying FLT3 inhibitors for a number of years now,” Dr Levis began, “and we think they show significant clinical promise, [but] they also have problems.”

He noted that some of these drugs haven’t been particularly safe or well-tolerated. They can cause gastrointestinal toxicity, hand-foot syndrome, QT prolongation, and myelosuppression.

However, the most intriguing problem with FLT3 inhibitors, according to Dr Levis, is the emergence of resistance-conferring point mutations observed in studies of some of the newer drugs, such as sorafenib and quizartinib.

“So in that context, here we have ASP2215,” Dr Levis said. “This is a type 1 FLT3 tyrosine kinase inhibitor, and, as such, it has activity against not only wild-type and ITD-mutated FLT3 but also against those resistance-conferring point mutations typically found in the activation loop at the so-called gatekeeper residue (F691L).”

With this in mind, he and his colleagues conducted a phase 1/2 trial of ASP2215. The study was sponsored by Astellas Pharma Global Development, Inc., the company developing ASP2215.

The trial was open to patients with relapsed or refractory AML, irrespective of their FLT3 mutation status. The researchers’ goal was to identify a safe, tolerable dose of ASP2215 that fully inhibited FLT3.

The team used a standard 3+3 design, with dose levels ranging from 20 mg to 450 mg once daily. They expanded every cohort until they reached a dose-limiting toxicity.

In all, the trial enrolled 198 patients, 24 in the dose-escalation cohorts and 174 in the dose-expansion cohorts. The patients’ median age was 62 (range, 21-90), and 53.1% were male.

Nearly 66% of patients had FLT3 mutations, 29.4% were FLT3-negative, and 5.2% had unknown FLT3 status. About 35% of patients had received 1 prior line of therapy, 26.3% had 2, 33.5% had 3 or more, and 5.7% had an unknown number of prior therapies.

Safety results

In the 194 patients who were evaluable for safety, treatment-emergent adverse events included diarrhea (13.4%), fatigue (12.4%), AST increase (11.3%), ALT increase (9.3%), thrombocytopenia (7.7%), anemia (7.2%), peripheral edema (7.2%), constipation (6.7%), nausea (6.7%), dizziness (6.2%), vomiting (5.7%), and dysgeusia (5.2%).

Serious adverse events included febrile neutropenia (27.3%), sepsis (11.9%), disease progression (10.3%), pneumonia (8.8%), hypotension (5.7%), and respiratory failure (5.7%).

“The kinds of side effects we saw were typical for a relapsed/refractory AML population,” Dr Levis said. “Nothing really stood out. Any trial of relapsed/refractory AML is going to have febrile neutropenia and sepsis, and those were our dominant, serious adverse events. There was no real safety signal here that was unique to the drug, we felt.”

The researchers said the maximum-tolerated dose of ASP2215 was 300 mg, as 2 patients who received the 450 mg dose experienced dose-limiting toxicities. One was grade 3 diarrhea, and the other was grade 3 AST elevation.

Response and survival

Among the 127 patients who were FLT3-positive, the ORR was 52% (n=66). The complete response (CR) rate was 6.3% (n=8). The composite CR rate, which includes CRs with incomplete hematologic recovery (CRi) and incomplete platelet recovery (CRp), was 40.9% (n=52). And the partial response (PR) rate was 11% (n=14).

“As we scale up the dose, the PRs shift on over to CRis, and the dominant response is, in fact, a complete response with incomplete count recovery,” Dr Levis said. “The categories where we had the largest number of responses were the 120 mg and 200 mg categories. We didn’t really have enough patients in the 300 mg category to comment on it. ”

For the FLT3-positive patients, the median duration of response was 126 days.

“The duration of response really stood out here,” Dr Levis said. “It’s over 4 months. That is something we really didn’t see with the other drugs, and I suspect that is a reflection of the suppression of the outgrowth of these resistance mutations.”

Unfortunately, FLT3-wild-type patients did not fare as well. The ORR among these patients was 8.8%. None of the patients achieved a CR, 3 had a composite CR (5.3%), and 2 had a PR (3.5%).

Among the FLT3-positive patients, the median overall survival was about 27 weeks. It was 128 days in the 20 mg dose cohort (n=13), 105.5 days in the 40 mg cohort (n=8), 201 days in the 80 mg cohort (n=12), 199 days in the 120 mg cohort (n=40), and 161 days in the 200 mg cohort (n=45). Dr Levis did not present survival data for the 300 mg or 450 mg cohorts, which included 7 and 2 patients, respectively.

“[Relapsed/refractory AML] is a population that has a median survival of about 3 months with conventional therapy, at least by historical publications,” Dr Levis noted. “If you look at survival in this trial, patients treated at the FLT3-inhibitory doses [had a] greater than 6-month median survival.”

He added that studies of ASP2215 in combination with other agents are ongoing in patients with newly diagnosed AML. And phase 3 trials of ASP2215 at the 120 mg dose, with the option of scaling up to 200 mg, are planned.

*Information in the abstract differs from that presented at the meeting.

Amir Toor, MD

Photo courtesy of VCU

Massey Cancer Center

Results of a retrospective study suggest lymphocyte recovery is associated with outcomes after allogeneic hematopoietic stem cell transplant (HSCT).

Researchers found that, after transplant, lymphocyte recovery occurred in 1 of 3 general patterns.

And these patterns were associated with the rate of survival, relapse, and graft-vs-host disease (GVHD), as well as the need for further donor immune cell infusions to treat the patients’ disease.

Amir Toor, MD, of VCU Massey Cancer Center in Richmond, Virginia, and his colleagues reported these findings in Biology of Blood & Marrow Transplantation.

The team had examined lymphocyte recovery and clinical outcome data from a phase 2 trial (NCT00709592) of 41 patients who received an HSCT from a related or unrelated donor.

As part of the trial protocol, the patients underwent low-dose radiation therapy and received 1 of 2 different doses of anti-thymocyte globulin as GVHD prophylaxis.

The researchers found that, after transplant, lymphocyte recovery followed 1 of 3 general patterns that correlated with patient outcomes.

“We began considering lymphocyte reconstitution following stem cell transplantation as similar to population growth models,” Dr Toor explained. “So we graphed the lymphocyte counts of our patients at various times following their transplant as a logistic function and observed distinct patterns that correlated with clinical outcomes.”

Patients in group A experienced fast, early lymphoid expansion, culminating in a high absolute lymphoid count (ALC) within 2 months of HSCT. Group B experienced a slower, but steady, lymphoid expansion that peaked much later than group A with a lower ALC. Group C experienced very poor lymphocyte recovery that demonstrated an early, but brief, lymphoid expansion with a very low ALC.

Group B had the best survival rate—86%—compared to 67% in group A and 30% in group C. Relapse rates between groups A and B were similar, at 33% and 29%, respectively, while group C experienced a 90% relapse rate.

GVHD occurred in 67% of patients in group A, 43% in group B, and 10% in group C. And adoptive immunotherapy with donor cell infusions was required for 13% of patients in group A, 21% in group B, and 70% in group C.

“Our goal is to use this data to develop models that can predict complications from stem cell transplantation,” Dr Toor said. “Then, we may be able to intervene at key points in time with appropriate clinical treatments that will make the most positive impact on patients’ outcomes.”

Amir Toor, MD

Photo courtesy of VCU

Massey Cancer Center

Results of a retrospective study suggest lymphocyte recovery is associated with outcomes after allogeneic hematopoietic stem cell transplant (HSCT).

Researchers found that, after transplant, lymphocyte recovery occurred in 1 of 3 general patterns.

And these patterns were associated with the rate of survival, relapse, and graft-vs-host disease (GVHD), as well as the need for further donor immune cell infusions to treat the patients’ disease.

Amir Toor, MD, of VCU Massey Cancer Center in Richmond, Virginia, and his colleagues reported these findings in Biology of Blood & Marrow Transplantation.

The team had examined lymphocyte recovery and clinical outcome data from a phase 2 trial (NCT00709592) of 41 patients who received an HSCT from a related or unrelated donor.

As part of the trial protocol, the patients underwent low-dose radiation therapy and received 1 of 2 different doses of anti-thymocyte globulin as GVHD prophylaxis.

The researchers found that, after transplant, lymphocyte recovery followed 1 of 3 general patterns that correlated with patient outcomes.

“We began considering lymphocyte reconstitution following stem cell transplantation as similar to population growth models,” Dr Toor explained. “So we graphed the lymphocyte counts of our patients at various times following their transplant as a logistic function and observed distinct patterns that correlated with clinical outcomes.”

Patients in group A experienced fast, early lymphoid expansion, culminating in a high absolute lymphoid count (ALC) within 2 months of HSCT. Group B experienced a slower, but steady, lymphoid expansion that peaked much later than group A with a lower ALC. Group C experienced very poor lymphocyte recovery that demonstrated an early, but brief, lymphoid expansion with a very low ALC.

Group B had the best survival rate—86%—compared to 67% in group A and 30% in group C. Relapse rates between groups A and B were similar, at 33% and 29%, respectively, while group C experienced a 90% relapse rate.

GVHD occurred in 67% of patients in group A, 43% in group B, and 10% in group C. And adoptive immunotherapy with donor cell infusions was required for 13% of patients in group A, 21% in group B, and 70% in group C.

“Our goal is to use this data to develop models that can predict complications from stem cell transplantation,” Dr Toor said. “Then, we may be able to intervene at key points in time with appropriate clinical treatments that will make the most positive impact on patients’ outcomes.”

Amir Toor, MD

Photo courtesy of VCU

Massey Cancer Center

Results of a retrospective study suggest lymphocyte recovery is associated with outcomes after allogeneic hematopoietic stem cell transplant (HSCT).

Researchers found that, after transplant, lymphocyte recovery occurred in 1 of 3 general patterns.

And these patterns were associated with the rate of survival, relapse, and graft-vs-host disease (GVHD), as well as the need for further donor immune cell infusions to treat the patients’ disease.

Amir Toor, MD, of VCU Massey Cancer Center in Richmond, Virginia, and his colleagues reported these findings in Biology of Blood & Marrow Transplantation.

The team had examined lymphocyte recovery and clinical outcome data from a phase 2 trial (NCT00709592) of 41 patients who received an HSCT from a related or unrelated donor.

As part of the trial protocol, the patients underwent low-dose radiation therapy and received 1 of 2 different doses of anti-thymocyte globulin as GVHD prophylaxis.

The researchers found that, after transplant, lymphocyte recovery followed 1 of 3 general patterns that correlated with patient outcomes.

“We began considering lymphocyte reconstitution following stem cell transplantation as similar to population growth models,” Dr Toor explained. “So we graphed the lymphocyte counts of our patients at various times following their transplant as a logistic function and observed distinct patterns that correlated with clinical outcomes.”

Patients in group A experienced fast, early lymphoid expansion, culminating in a high absolute lymphoid count (ALC) within 2 months of HSCT. Group B experienced a slower, but steady, lymphoid expansion that peaked much later than group A with a lower ALC. Group C experienced very poor lymphocyte recovery that demonstrated an early, but brief, lymphoid expansion with a very low ALC.

Group B had the best survival rate—86%—compared to 67% in group A and 30% in group C. Relapse rates between groups A and B were similar, at 33% and 29%, respectively, while group C experienced a 90% relapse rate.

GVHD occurred in 67% of patients in group A, 43% in group B, and 10% in group C. And adoptive immunotherapy with donor cell infusions was required for 13% of patients in group A, 21% in group B, and 70% in group C.

“Our goal is to use this data to develop models that can predict complications from stem cell transplantation,” Dr Toor said. “Then, we may be able to intervene at key points in time with appropriate clinical treatments that will make the most positive impact on patients’ outcomes.”

ROBERT FOGERTY, MD, MPH, a hospitalist and assistant professor of medicine at Yale University, talks about how his own bout with cancer as a college senior heading to medical school helped influence his I-CARE education initiative, which introduces cost awareness into internal medicine residency programs.

ROBERT FOGERTY, MD, MPH, a hospitalist and assistant professor of medicine at Yale University, talks about how his own bout with cancer as a college senior heading to medical school helped influence his I-CARE education initiative, which introduces cost awareness into internal medicine residency programs.

ROBERT FOGERTY, MD, MPH, a hospitalist and assistant professor of medicine at Yale University, talks about how his own bout with cancer as a college senior heading to medical school helped influence his I-CARE education initiative, which introduces cost awareness into internal medicine residency programs.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

CHRISTOPHER MORIATES, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco, talks about the change in focus and priorities needed for medicine to make progress in waste-reduction efforts.

CHRISTOPHER MORIATES, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco, talks about the change in focus and priorities needed for medicine to make progress in waste-reduction efforts.

CHRISTOPHER MORIATES, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco, talks about the change in focus and priorities needed for medicine to make progress in waste-reduction efforts.

VLADIMIR N. CADET, MPH, associate with the Applied Solutions Group at ECRI Institute in Plymouth Meeting, Pa., discusses why it can be challenging for hospitals to reduce alarm fatigue and provides strategies to address this growing problem.

VLADIMIR N. CADET, MPH, associate with the Applied Solutions Group at ECRI Institute in Plymouth Meeting, Pa., discusses why it can be challenging for hospitals to reduce alarm fatigue and provides strategies to address this growing problem.

VLADIMIR N. CADET, MPH, associate with the Applied Solutions Group at ECRI Institute in Plymouth Meeting, Pa., discusses why it can be challenging for hospitals to reduce alarm fatigue and provides strategies to address this growing problem.

For Robert Fogerty, MD, MPH, it’s more than just a story. It’s a nightmare that he only narrowly avoided.

Now a hospitalist at Yale University School of Medicine in New Haven, Conn., Dr. Fogerty was an economics major in his senior year of college when he was diagnosed with metastatic testicular cancer. Early in the course of his treatment, amid multiple rounds of chemotherapy and before a major surgery, his insurance company informed him that his benefits had been exhausted. Even with family resources, the remaining bills would have been crippling. Luckily, he went to college in Massachusetts, where a state law allowed him to enroll in an individual insurance plan by exempting him from the normal pre-existing condition exclusion. Two years later, he got his life back in order and enrolled in medical school.

“What stuck with me is, yes, I was sick, and yes, I lost all my hair, and yes, I went to my final exams bald with my nausea medicine and my steroids in my pocket and all of those things,” he says. “But after that was all gone, after my hair grew back, and I had my last chemo and my surgery, and I was really starting to get my life back on track, the financial implications of that disease were still there. The financial impact of my illness outlasted the pathological impact of my illness, and the financial burdens could easily have been just as life-altering as a permanent disability.”

Although he was “unbelievably lucky” to escape with manageable medical bills, Dr. Fogerty says, other patients haven’t been as fortunate. That lesson is why he identifies so much with his patients. It’s why he posted his own story to the Costs of Care website, which stresses the importance of cost awareness in healthcare. And it’s why he has committed himself to helping other medical students and residents “remove the blinders” to understand healthcare’s often devastating financial impact.

“When I was going through my residency, I learned a lot about low sodium, and I learned a lot about bloodstream infections and what to do when someone can’t breathe and how to do a skin exam, and all of these things,” Dr. Fogerty says. “But all of these other components that were so devastating to me as a patient weren’t really a main portion of the education that we’re providing tomorrow’s doctors. I thought that was an opportunity to really change things."

By combining his clinical and economics expertise, Dr. Fogerty helped to develop a program called the Interactive Cost-Awareness Resident Exercise, or I-CARE. Launched in 2011, I-CARE seeks to make the abstract problem of healthcare costs—including unnecessary ones—more accessible to trainees. The concept is deceptively simple: Residents compete to see who can reach the correct diagnosis for a given case using the fewest possible resources.

By talking through each case, both trainees and faculty can discuss concepts like waste prevention and financial stewardship in a safe environment. Giving young doctors that “basic set of vocabulary,” Dr. Fogerty says, may help them engage in real decisions later on about a group or health system’s financial pressures and obligations.

The program has since spread to other medical centers, and what began as a cost-awareness exercise has blossomed into a broader discussion about minimizing the cost and burden to patients while maximizing safety and good medicine. TH

For Robert Fogerty, MD, MPH, it’s more than just a story. It’s a nightmare that he only narrowly avoided.

Now a hospitalist at Yale University School of Medicine in New Haven, Conn., Dr. Fogerty was an economics major in his senior year of college when he was diagnosed with metastatic testicular cancer. Early in the course of his treatment, amid multiple rounds of chemotherapy and before a major surgery, his insurance company informed him that his benefits had been exhausted. Even with family resources, the remaining bills would have been crippling. Luckily, he went to college in Massachusetts, where a state law allowed him to enroll in an individual insurance plan by exempting him from the normal pre-existing condition exclusion. Two years later, he got his life back in order and enrolled in medical school.

“What stuck with me is, yes, I was sick, and yes, I lost all my hair, and yes, I went to my final exams bald with my nausea medicine and my steroids in my pocket and all of those things,” he says. “But after that was all gone, after my hair grew back, and I had my last chemo and my surgery, and I was really starting to get my life back on track, the financial implications of that disease were still there. The financial impact of my illness outlasted the pathological impact of my illness, and the financial burdens could easily have been just as life-altering as a permanent disability.”

Although he was “unbelievably lucky” to escape with manageable medical bills, Dr. Fogerty says, other patients haven’t been as fortunate. That lesson is why he identifies so much with his patients. It’s why he posted his own story to the Costs of Care website, which stresses the importance of cost awareness in healthcare. And it’s why he has committed himself to helping other medical students and residents “remove the blinders” to understand healthcare’s often devastating financial impact.

“When I was going through my residency, I learned a lot about low sodium, and I learned a lot about bloodstream infections and what to do when someone can’t breathe and how to do a skin exam, and all of these things,” Dr. Fogerty says. “But all of these other components that were so devastating to me as a patient weren’t really a main portion of the education that we’re providing tomorrow’s doctors. I thought that was an opportunity to really change things."

By combining his clinical and economics expertise, Dr. Fogerty helped to develop a program called the Interactive Cost-Awareness Resident Exercise, or I-CARE. Launched in 2011, I-CARE seeks to make the abstract problem of healthcare costs—including unnecessary ones—more accessible to trainees. The concept is deceptively simple: Residents compete to see who can reach the correct diagnosis for a given case using the fewest possible resources.

By talking through each case, both trainees and faculty can discuss concepts like waste prevention and financial stewardship in a safe environment. Giving young doctors that “basic set of vocabulary,” Dr. Fogerty says, may help them engage in real decisions later on about a group or health system’s financial pressures and obligations.

The program has since spread to other medical centers, and what began as a cost-awareness exercise has blossomed into a broader discussion about minimizing the cost and burden to patients while maximizing safety and good medicine. TH

For Robert Fogerty, MD, MPH, it’s more than just a story. It’s a nightmare that he only narrowly avoided.

Now a hospitalist at Yale University School of Medicine in New Haven, Conn., Dr. Fogerty was an economics major in his senior year of college when he was diagnosed with metastatic testicular cancer. Early in the course of his treatment, amid multiple rounds of chemotherapy and before a major surgery, his insurance company informed him that his benefits had been exhausted. Even with family resources, the remaining bills would have been crippling. Luckily, he went to college in Massachusetts, where a state law allowed him to enroll in an individual insurance plan by exempting him from the normal pre-existing condition exclusion. Two years later, he got his life back in order and enrolled in medical school.

“What stuck with me is, yes, I was sick, and yes, I lost all my hair, and yes, I went to my final exams bald with my nausea medicine and my steroids in my pocket and all of those things,” he says. “But after that was all gone, after my hair grew back, and I had my last chemo and my surgery, and I was really starting to get my life back on track, the financial implications of that disease were still there. The financial impact of my illness outlasted the pathological impact of my illness, and the financial burdens could easily have been just as life-altering as a permanent disability.”

Although he was “unbelievably lucky” to escape with manageable medical bills, Dr. Fogerty says, other patients haven’t been as fortunate. That lesson is why he identifies so much with his patients. It’s why he posted his own story to the Costs of Care website, which stresses the importance of cost awareness in healthcare. And it’s why he has committed himself to helping other medical students and residents “remove the blinders” to understand healthcare’s often devastating financial impact.

“When I was going through my residency, I learned a lot about low sodium, and I learned a lot about bloodstream infections and what to do when someone can’t breathe and how to do a skin exam, and all of these things,” Dr. Fogerty says. “But all of these other components that were so devastating to me as a patient weren’t really a main portion of the education that we’re providing tomorrow’s doctors. I thought that was an opportunity to really change things."

By combining his clinical and economics expertise, Dr. Fogerty helped to develop a program called the Interactive Cost-Awareness Resident Exercise, or I-CARE. Launched in 2011, I-CARE seeks to make the abstract problem of healthcare costs—including unnecessary ones—more accessible to trainees. The concept is deceptively simple: Residents compete to see who can reach the correct diagnosis for a given case using the fewest possible resources.

By talking through each case, both trainees and faculty can discuss concepts like waste prevention and financial stewardship in a safe environment. Giving young doctors that “basic set of vocabulary,” Dr. Fogerty says, may help them engage in real decisions later on about a group or health system’s financial pressures and obligations.

The program has since spread to other medical centers, and what began as a cost-awareness exercise has blossomed into a broader discussion about minimizing the cost and burden to patients while maximizing safety and good medicine. TH

As the hospital medicine specialty matures in the U.S., HM is establishing itself globally. Two American hospitalists who have moved to Doha, Qatar to build a hospital medicine program at Hamid General Hospital talk about their experiences, how they decided to practice overseas, and what they see as an opportunity for HM globally.

As the hospital medicine specialty matures in the U.S., HM is establishing itself globally. Two American hospitalists who have moved to Doha, Qatar to build a hospital medicine program at Hamid General Hospital talk about their experiences, how they decided to practice overseas, and what they see as an opportunity for HM globally.

As the hospital medicine specialty matures in the U.S., HM is establishing itself globally. Two American hospitalists who have moved to Doha, Qatar to build a hospital medicine program at Hamid General Hospital talk about their experiences, how they decided to practice overseas, and what they see as an opportunity for HM globally.