Lymphoma & Plasma Cell Disorders

SAN DIEGO – Stretching out the delivery of rituximab significantly improved overall and event-free survival among older patients with poor-prognosis diffuse large B-cell lymphoma, German investigators reported.

Patients older than 60 years who had diffuse large B-cell lymphoma (DLBCL) were treated with the CHOP regimen and rituximab (Rituxan) on days 4 and 1 before CHOP and at increasing intervals thereafter, in the SMARTE-R-CHOP-14 trial.

Those with poor-prognosis disease had an overall survival rate of 80% at 37 months, compared with 67% for similar patients treated with CHOP and biweekly rituximab in an earlier trial (P = .034), reported Dr. Michael Pfreundschuh on behalf of his colleagues in the German High-Grade Non-Hodgkin's Lymphoma Study Group.

Event-free survival rates among poor-prognosis patients (defined as those with an International Prognostic Index [IPI] score higher than 2) were also significantly higher with the extended rituximab–dosing schedule, dubbed SMARTE-R-CHOP-14, at 67% vs. 54% for patients who received biweekly rituximab in the previous RICOVER-60 trial (P = .030).

"SMARTE-R-CHOP 14 has achieved by far the best results reported to date for elderly patients with poor prognosis," said Dr. Pfreundschuh of Saarland University in Homburg, Germany, at the annual meeting of the American Society of Hematology (ASH).

Giving rituximab every 3 weeks after 2 pre-CHOP doses maintains serum levels of rituximab over a longer period than when it is given every other week, he said.

Patients with good- or moderate-prognosis disease (defined as an IPI of 1 or 2) also had numerically better event-free and overall survival rates, compared with patients treated with biweekly rituximab, he noted, but the differences were not significant.

Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 14 days (CHOP-14) had been shown to be superior to CHOP given every 21 days (CHOP-21), the same could not be said when rituximab was added (R-CHOP-14 vs. R-CHOP-21). Presentations at ASH in 2009 and at the American Society of Clinical Oncology annual meeting in 2011 suggested that biweekly rituximab dosing was suboptimal, Dr. Freundschuh said.

In the SMARTE-R-CHOP-14 study, Dr. Pfreundschuh and colleagues treated 190 patients with DLBCL with six cycles of CHOP-14. combined with eight cycles of rituximab 375 mg/m². The first three rituximab cycles were given in a dose-dense fashion on days 1 and 4 before CHOP, followed by infusions on days 10, 29, 57, 99, 155, and 239. Patients also received prophylaxis against infections with levofloxacin, acyclovir, and cotrimoxazole. One patient did not give informed consent for the trial, and was not included in the final analysis.

In the RICOVER-60 trial that was used for comparison, patients received six cycles of CHOP plus rituximab given on days 1, 15, 29, 43, 57, 71, 85, and 99. The baseline characteristics of patients were similar between the trials, except that significantly more patients in SMARTE-R-CHOP-14 had high-risk disease (P = .015).

Complete response rates overall were not significantly different (85% in SMARTE-R and 78% in RICOVER-60). Among patients with IPI scores less than 2, the respective rates were 90% and 84%, also not significantly different. Among patients with an IPI greater than 2, however, the complete response rate in SMARTE-R-CHOP-14 was 81%, compared with 68% in RICOVER-60 (P = .035).

Overall survival did not differ significantly between the trials, at 84% in SMARTE-R and 78% in RICOVER. When patients stratified by risk were considered, there were no between-trial differences for low-risk patients.

Overall event-free survival was 71% at 37 months’ median follow-up in SMARTE-R, and 66% at 34 months in RICOVER; this difference was not significant, nor was the difference between the trials among patients with low-risk disease.

"The pharmacokinetics of eight biweekly applications of rituximab are adequate for elderly patients with good prognosis, meaning patients with IP1 1 or 2, or low tumor burden diffuse large B-cell lymphoma, but not for higher tumor loads," Dr. Pfreundschuh said.

The investigators are exploring the SMARTE-R treatment strategy in a prospective trial, labeled "OPTIMAL Greater Than 60."

The trial was supported by Deutsche Krebshilfe and Roche. Dr. Pfreundschuh disclosed serving on a Roche board of directors or advisory committee, and receiving research funding from that company and from Amgen.

SAN DIEGO – Stretching out the delivery of rituximab significantly improved overall and event-free survival among older patients with poor-prognosis diffuse large B-cell lymphoma, German investigators reported.

Patients older than 60 years who had diffuse large B-cell lymphoma (DLBCL) were treated with the CHOP regimen and rituximab (Rituxan) on days 4 and 1 before CHOP and at increasing intervals thereafter, in the SMARTE-R-CHOP-14 trial.

Those with poor-prognosis disease had an overall survival rate of 80% at 37 months, compared with 67% for similar patients treated with CHOP and biweekly rituximab in an earlier trial (P = .034), reported Dr. Michael Pfreundschuh on behalf of his colleagues in the German High-Grade Non-Hodgkin's Lymphoma Study Group.

Event-free survival rates among poor-prognosis patients (defined as those with an International Prognostic Index [IPI] score higher than 2) were also significantly higher with the extended rituximab–dosing schedule, dubbed SMARTE-R-CHOP-14, at 67% vs. 54% for patients who received biweekly rituximab in the previous RICOVER-60 trial (P = .030).

"SMARTE-R-CHOP 14 has achieved by far the best results reported to date for elderly patients with poor prognosis," said Dr. Pfreundschuh of Saarland University in Homburg, Germany, at the annual meeting of the American Society of Hematology (ASH).

Giving rituximab every 3 weeks after 2 pre-CHOP doses maintains serum levels of rituximab over a longer period than when it is given every other week, he said.

Patients with good- or moderate-prognosis disease (defined as an IPI of 1 or 2) also had numerically better event-free and overall survival rates, compared with patients treated with biweekly rituximab, he noted, but the differences were not significant.

Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 14 days (CHOP-14) had been shown to be superior to CHOP given every 21 days (CHOP-21), the same could not be said when rituximab was added (R-CHOP-14 vs. R-CHOP-21). Presentations at ASH in 2009 and at the American Society of Clinical Oncology annual meeting in 2011 suggested that biweekly rituximab dosing was suboptimal, Dr. Freundschuh said.

In the SMARTE-R-CHOP-14 study, Dr. Pfreundschuh and colleagues treated 190 patients with DLBCL with six cycles of CHOP-14. combined with eight cycles of rituximab 375 mg/m². The first three rituximab cycles were given in a dose-dense fashion on days 1 and 4 before CHOP, followed by infusions on days 10, 29, 57, 99, 155, and 239. Patients also received prophylaxis against infections with levofloxacin, acyclovir, and cotrimoxazole. One patient did not give informed consent for the trial, and was not included in the final analysis.

In the RICOVER-60 trial that was used for comparison, patients received six cycles of CHOP plus rituximab given on days 1, 15, 29, 43, 57, 71, 85, and 99. The baseline characteristics of patients were similar between the trials, except that significantly more patients in SMARTE-R-CHOP-14 had high-risk disease (P = .015).

Complete response rates overall were not significantly different (85% in SMARTE-R and 78% in RICOVER-60). Among patients with IPI scores less than 2, the respective rates were 90% and 84%, also not significantly different. Among patients with an IPI greater than 2, however, the complete response rate in SMARTE-R-CHOP-14 was 81%, compared with 68% in RICOVER-60 (P = .035).

Overall survival did not differ significantly between the trials, at 84% in SMARTE-R and 78% in RICOVER. When patients stratified by risk were considered, there were no between-trial differences for low-risk patients.

Overall event-free survival was 71% at 37 months’ median follow-up in SMARTE-R, and 66% at 34 months in RICOVER; this difference was not significant, nor was the difference between the trials among patients with low-risk disease.

"The pharmacokinetics of eight biweekly applications of rituximab are adequate for elderly patients with good prognosis, meaning patients with IP1 1 or 2, or low tumor burden diffuse large B-cell lymphoma, but not for higher tumor loads," Dr. Pfreundschuh said.

The investigators are exploring the SMARTE-R treatment strategy in a prospective trial, labeled "OPTIMAL Greater Than 60."

The trial was supported by Deutsche Krebshilfe and Roche. Dr. Pfreundschuh disclosed serving on a Roche board of directors or advisory committee, and receiving research funding from that company and from Amgen.

SAN DIEGO – Stretching out the delivery of rituximab significantly improved overall and event-free survival among older patients with poor-prognosis diffuse large B-cell lymphoma, German investigators reported.

Patients older than 60 years who had diffuse large B-cell lymphoma (DLBCL) were treated with the CHOP regimen and rituximab (Rituxan) on days 4 and 1 before CHOP and at increasing intervals thereafter, in the SMARTE-R-CHOP-14 trial.

Those with poor-prognosis disease had an overall survival rate of 80% at 37 months, compared with 67% for similar patients treated with CHOP and biweekly rituximab in an earlier trial (P = .034), reported Dr. Michael Pfreundschuh on behalf of his colleagues in the German High-Grade Non-Hodgkin's Lymphoma Study Group.

Event-free survival rates among poor-prognosis patients (defined as those with an International Prognostic Index [IPI] score higher than 2) were also significantly higher with the extended rituximab–dosing schedule, dubbed SMARTE-R-CHOP-14, at 67% vs. 54% for patients who received biweekly rituximab in the previous RICOVER-60 trial (P = .030).

"SMARTE-R-CHOP 14 has achieved by far the best results reported to date for elderly patients with poor prognosis," said Dr. Pfreundschuh of Saarland University in Homburg, Germany, at the annual meeting of the American Society of Hematology (ASH).

Giving rituximab every 3 weeks after 2 pre-CHOP doses maintains serum levels of rituximab over a longer period than when it is given every other week, he said.

Patients with good- or moderate-prognosis disease (defined as an IPI of 1 or 2) also had numerically better event-free and overall survival rates, compared with patients treated with biweekly rituximab, he noted, but the differences were not significant.

Although CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 14 days (CHOP-14) had been shown to be superior to CHOP given every 21 days (CHOP-21), the same could not be said when rituximab was added (R-CHOP-14 vs. R-CHOP-21). Presentations at ASH in 2009 and at the American Society of Clinical Oncology annual meeting in 2011 suggested that biweekly rituximab dosing was suboptimal, Dr. Freundschuh said.

In the SMARTE-R-CHOP-14 study, Dr. Pfreundschuh and colleagues treated 190 patients with DLBCL with six cycles of CHOP-14. combined with eight cycles of rituximab 375 mg/m². The first three rituximab cycles were given in a dose-dense fashion on days 1 and 4 before CHOP, followed by infusions on days 10, 29, 57, 99, 155, and 239. Patients also received prophylaxis against infections with levofloxacin, acyclovir, and cotrimoxazole. One patient did not give informed consent for the trial, and was not included in the final analysis.

In the RICOVER-60 trial that was used for comparison, patients received six cycles of CHOP plus rituximab given on days 1, 15, 29, 43, 57, 71, 85, and 99. The baseline characteristics of patients were similar between the trials, except that significantly more patients in SMARTE-R-CHOP-14 had high-risk disease (P = .015).

Complete response rates overall were not significantly different (85% in SMARTE-R and 78% in RICOVER-60). Among patients with IPI scores less than 2, the respective rates were 90% and 84%, also not significantly different. Among patients with an IPI greater than 2, however, the complete response rate in SMARTE-R-CHOP-14 was 81%, compared with 68% in RICOVER-60 (P = .035).

Overall survival did not differ significantly between the trials, at 84% in SMARTE-R and 78% in RICOVER. When patients stratified by risk were considered, there were no between-trial differences for low-risk patients.

Overall event-free survival was 71% at 37 months’ median follow-up in SMARTE-R, and 66% at 34 months in RICOVER; this difference was not significant, nor was the difference between the trials among patients with low-risk disease.

"The pharmacokinetics of eight biweekly applications of rituximab are adequate for elderly patients with good prognosis, meaning patients with IP1 1 or 2, or low tumor burden diffuse large B-cell lymphoma, but not for higher tumor loads," Dr. Pfreundschuh said.

The investigators are exploring the SMARTE-R treatment strategy in a prospective trial, labeled "OPTIMAL Greater Than 60."

The trial was supported by Deutsche Krebshilfe and Roche. Dr. Pfreundschuh disclosed serving on a Roche board of directors or advisory committee, and receiving research funding from that company and from Amgen.

Hodgkin lymphoma represents one of the major successes of modern oncology. Several decades ago, it was fatal in most patients. With the development of the combination therapy mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), many patients were cured of this disease. However, the regimen was associated with an unacceptable risk of acute toxicities, infertility, and secondary malignancies.1 Several subsequent studies established adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) as the standard treatment because of its greater efficacy and less toxicity compared with MOPP.2 As a result, about 90% of patients with limited-stage disease are now cured, as are 60% of those with advanced disease. Newer regimens such as bleomycin, etoposide, adriamycin, cyclophosphamide, prednisone, and procarbazine (BEACOPP) seem to prolong time to treatment failure, but with considerably greater toxicity,3 and with no clear improvement in overall survival. A minority of patients who are either refractory to initial treatment or who subsequently relapse can be cured with such modalities as stem-cell transplantation. However, few effective options are available for the remainder of patients...

*For a PDF of the full article, click in the link to the left of this article.

(See Community Translations, “Bretuximab vedotin in Hodgkin lymphoma and systemic anaplastic large-cell lymphoma”)

Hodgkin lymphoma represents one of the major successes of modern oncology. Several decades ago, it was fatal in most patients. With the development of the combination therapy mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), many patients were cured of this disease. However, the regimen was associated with an unacceptable risk of acute toxicities, infertility, and secondary malignancies.1 Several subsequent studies established adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) as the standard treatment because of its greater efficacy and less toxicity compared with MOPP.2 As a result, about 90% of patients with limited-stage disease are now cured, as are 60% of those with advanced disease. Newer regimens such as bleomycin, etoposide, adriamycin, cyclophosphamide, prednisone, and procarbazine (BEACOPP) seem to prolong time to treatment failure, but with considerably greater toxicity,3 and with no clear improvement in overall survival. A minority of patients who are either refractory to initial treatment or who subsequently relapse can be cured with such modalities as stem-cell transplantation. However, few effective options are available for the remainder of patients...

*For a PDF of the full article, click in the link to the left of this article.

(See Community Translations, “Bretuximab vedotin in Hodgkin lymphoma and systemic anaplastic large-cell lymphoma”)

Hodgkin lymphoma represents one of the major successes of modern oncology. Several decades ago, it was fatal in most patients. With the development of the combination therapy mechlorethamine, vincristine, prednisone, and procarbazine (MOPP), many patients were cured of this disease. However, the regimen was associated with an unacceptable risk of acute toxicities, infertility, and secondary malignancies.1 Several subsequent studies established adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) as the standard treatment because of its greater efficacy and less toxicity compared with MOPP.2 As a result, about 90% of patients with limited-stage disease are now cured, as are 60% of those with advanced disease. Newer regimens such as bleomycin, etoposide, adriamycin, cyclophosphamide, prednisone, and procarbazine (BEACOPP) seem to prolong time to treatment failure, but with considerably greater toxicity,3 and with no clear improvement in overall survival. A minority of patients who are either refractory to initial treatment or who subsequently relapse can be cured with such modalities as stem-cell transplantation. However, few effective options are available for the remainder of patients...

*For a PDF of the full article, click in the link to the left of this article.

(See Community Translations, “Bretuximab vedotin in Hodgkin lymphoma and systemic anaplastic large-cell lymphoma”)

SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.

The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.

These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.

"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.

There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.

She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.

The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.

Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.

In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.

The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.

She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.

The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.

In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.

"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.

Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.

The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.

SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.

The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.

These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.

"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.

There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.

She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.

The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.

Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.

In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.

The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.

She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.

The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.

In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.

"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.

Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.

The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.

SAN DIEGO – Adolescents and young adults with Hodgkin’s lymphoma can have high response rates and durable remissions under protocols developed for children, with potentially lower long-term toxicities than those commonly seen with adult-oriented regimens, said investigators at the annual meeting of the American Society of Hematology.

The 15- to 20-year-olds with Hodgkin’s lymphoma who were treated under two similar Children’s Oncology Group protocols had a 5-year event-free survival rate of 85.9%, compared with 87.0% for patients younger than 15 years. The 10-year rate was 77.3% in the older patients and 83.8% in the younger group (P = .515), reported Dr. Karen S. Fernandez of the pediatrics department at the University of Illinois, Peoria.

These 5-year event-free survival results are comparable to outcomes of other studies in which adolescents and young adults were treated with adult cooperative-group protocols. Moreover, the cumulative doses of alkylators, anthracyclines, and etoposide used are below thresholds usually associated with significant long-term toxicities, Dr. Fernandez noted.

"Based on this data, we favor the use of pediatric-focused therapy with dose-limited regimens for adolescents and young adults with Hodgkin’s lymphoma in whom decreasing long-term effects is important to improve quality of life, particularly for adolescents with advanced stages," she said.

There is no widely accepted standard of treatment for adolescents and young adults with Hodgkin’s lymphoma, in part because different centers variously treat teens with adult or pediatric protocols, and published data specifically regarding the treatment of adolescents and young adults with Hodgkin’s lymphoma are scarce, Dr. Fernandez said.

She and her colleagues in the Children’s Oncology Group tried to find a balance between maximum possible cure rates and reduced long-term effects by conducting a retrospective analysis comparing children younger than 15 years with adolescents and young adults aged 15-20 years, in the Children’s Oncology Group protocols P9425 and P9426.

The P9425 study looked at the ABVE-PC regimen (doxorubicin [Adriamycin], bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide in dose-dense application) in patients with advanced-stage Hodgkin’s lymphoma. P9426 evaluated the ABVE regimen (the same combination, also dose-dense but without prednisone or cyclophosphamide) in patients with low-stage Hodgkin’s lymphoma.

Patients with an early response in P9425 received 21 Gy of radiation after three cycles of ABVE-PC spaced 21 days apart; patients with a slow response received the same radiation dose after five cycles.

In the P9426 protocol, patients with early responses received 25 Gy after two cycles, while all others received the same radiation dose after four cycles of ABVE. Patients in both protocols received dexrazoxane at the investigators’ discretion.

The cumulative chemotherapy doses delivered in the ABVE and ABVE-PC regimens in these trials were significantly lower than those delivered in other trials of patients with standard or high- to intermediate-risk Hodgkin’s disease, including the BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], prednisone, and procarbazine), COPP-ABVD (the same drugs as BEACOPP plus vinblastine and dacarbazine), and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

When Dr. Fernandez and her colleagues conducted a Cox regression analysis of patients in the combined studies, they found that neither sex, histologic subtypes, nor tumor staging was predictive of outcomes.

She noted that the study was limited by the retrospective design and the small number of adolescents in each group (104 in P9425 and 99 in P9426). Another limitation was the fact that neither study was designed to distinguish between children and adolescents/young adults, she said.

The investigators plan to collaborate with adult oncology groups to standardize treatment of adolescents and young adults, Dr. Fernandez concluded.

In the question and response session following the presentation, Dr. Jonathan Friedberg, chief of hematology/oncology at the University of Rochester (N.Y.), noted that the toxicities associated with therapy are not all drug related.

"Your pediatric group seems to be very focused on decreasing the doses of chemotherapy in an effort to mediate late toxicity, but I think most people would accept that radiation is probably the big driver of late toxicity, and it appears that in these regimens you’re giving radiation to patients with advanced-stage Hodgkin’s," commented Dr. Friedberg, who moderated the session but was not involved in the study.

Dr. Fernandez acknowledged that all patients in the P9425 and P9426 protocols received radiation, but added that the group is currently conducting trials in which radiation will be given based on patient responses determined by PET scans following the first cycle of chemotherapy.

The study was supported by the Children’s Oncology Group. Dr. Fernandez reported that she had no relevant conflicts of interest. Dr. Friedberg reported being a consultant to or receiving honoraria from Genentech, Astellas, Lilly, Trubion, Seattle Genetics, and Cephalon.

SAN DIEGO – The risk of a secondary malignancy doubled in patients with newly diagnosed multiple myeloma treated with melphalan plus thalidomide or lenalidomide in a retrospective, pooled analysis of 2,283 patients.

Incidence rates per 100 persons per year of follow-up were 0.95 with high-dose melphalan (Alkeran) followed by lenalidomide (Revlimid) maintenance and 1.05 with melphalan and thalidomide. In comparison, rates were 0.40 with cyclophosphamide, lenalidomide, and dexamethasone and 0.42 with melphalan and no immunomodulatory drugs, Dr. Antonio Palumbo reported at the annual meeting of the American Society of Hematology (ASH).

At 4 years of follow-up, second cancers were diagnosed in 48 (2.1%) of the 2,283 patients enrolled in nine experimental trials of the European Myeloma Network. There was consistent evidence of an increase in late events over time.

"I do not want to underestimate the issue," Dr. Palumbo said. "There is a signal, but the first conclusion is caution. When you come to 48 cancers versus 2,200 patients, by chance many things may happen."

He noted that the risk of multiple myeloma progression is between 10 and 15 times higher than the diagnosis of a second cancer, and suggested that the emphasis on second cancers may be overshadowing the risk of death due to toxic effects and infections.

Of the 48 secondary cancers, 8 of the 10 hematologic malignancies and 8 of the 38 solid tumors were fatal. In contrast, there were 124 toxic deaths (8.6%) and 49 infective deaths (3.4%) among 1,435 patients given the combination of melphalan-prednisone-thalidomide or bortezomib (Velcade)-melphalan-prednisone, said Dr. Palumbo, chief of the myeloma unit at the University of Torino (Italy).

"We take it for granted that with chemo we have some toxic effects," he said in an interview. "We should increase our alert of our combinations, and not focus solely on the second cancers."

Session co-moderator Dr. Meral Beksac, with Ankara (Turkey) University, said the Italian data suggest caution and greater vigilance regarding routine cancer screenings among multiple myeloma patients, but would not change her treatment approach.

"Dr. Palumbo has shown very beautifully that the benefits you achieve in terms of the long-term myeloma effect outweigh the risk of secondary malignancies," she said in an interview. "Personally, I think we must plan to avoid alkylating agents when we now have these better agents."

Preliminary data from three trials showing a fourfold increase in secondary cancers in multiple myeloma patients treated with lenalidomide as maintenance therapy or in combination with melphalan prompted investigations into the safety of lenalidomide in the United States and Europe in 2011.

The European Medicines Agency concluded in September that the benefits of lenalidomide continue to outweigh the risks within the approved setting of relapsed multiple myeloma, but recommended that a warning be added on the risk of second cancers. The U.S. Food and Drug Administration review is ongoing, and includes the risk for thalidomide, since lenalidomide is an analogue of thalidomide.

Although the development of acute myeloid leukemia (AML) following multiple myeloma was observed decades ago, the underlying mechanisms remain unclear. Swedish researchers recently reported that the risk of AML and myelodysplastic syndromes is 11.5-fold higher in multiple myeloma patients than in the general population, even before the introduction of novel agents (Blood 2011;118:4086-92). In addition, the risk of AML/MDS was eightfold higher in patients with monoclonal gammopathy of undetermined significance (MGUS), even though none of the MGUS patients developed multiple myeloma, according to session co-moderator Dr. Sigurdur Y. Kristinsson, who was a coauthor of the Swedish study.

"Even those people that never develop the disease have an increased risk of AML and MDS, so it shows that it’s not only the treatment that we’re giving, but it’s also an inherent susceptibility," Dr. Kristinsson, with the Karolinska Hospital and Institute in Stockholm, said in an interview.

Work is ongoing to identify multiple myeloma patients at an increased risk of second cancers, thereby allowing clinicians to tailor therapy to reduce risks. A separate poster presentation at the ASH meeting reported that higher risk of second cancers was associated with older age, male sex, and radiation and/or surgery among roughly 29,250 multiple myeloma patients in the Surveillance, Epidemiology, and End Results (SEER) database.

Subgroup analysis of the pooled Italian data did not identify specific subgroups at greater risk, Dr. Palumbo said. The incidence rate was higher at 1.13 per 100 person-years for patients given melphalan-lenalidomide vs. 0.76 per 100 person-years for patients treated with autologous stem cell transplantation and lenalidomide (median age 68 years vs. 59 years, respectively).

Speaking on behalf of the investigators, Dr. Palumbo reported employment with, serving as a consultant and on the speakers bureau of, having equity ownership in, and receiving research funding, patent royalties, and honoraria from Celgene, maker of lenalidomide. Dr. Beksac reported honoraria and speakers bureau activity with Celgene and Janssen Cilag. Dr. Kristinsson reported no conflicts of interest.

SAN DIEGO – The risk of a secondary malignancy doubled in patients with newly diagnosed multiple myeloma treated with melphalan plus thalidomide or lenalidomide in a retrospective, pooled analysis of 2,283 patients.

Incidence rates per 100 persons per year of follow-up were 0.95 with high-dose melphalan (Alkeran) followed by lenalidomide (Revlimid) maintenance and 1.05 with melphalan and thalidomide. In comparison, rates were 0.40 with cyclophosphamide, lenalidomide, and dexamethasone and 0.42 with melphalan and no immunomodulatory drugs, Dr. Antonio Palumbo reported at the annual meeting of the American Society of Hematology (ASH).

At 4 years of follow-up, second cancers were diagnosed in 48 (2.1%) of the 2,283 patients enrolled in nine experimental trials of the European Myeloma Network. There was consistent evidence of an increase in late events over time.

"I do not want to underestimate the issue," Dr. Palumbo said. "There is a signal, but the first conclusion is caution. When you come to 48 cancers versus 2,200 patients, by chance many things may happen."

He noted that the risk of multiple myeloma progression is between 10 and 15 times higher than the diagnosis of a second cancer, and suggested that the emphasis on second cancers may be overshadowing the risk of death due to toxic effects and infections.

Of the 48 secondary cancers, 8 of the 10 hematologic malignancies and 8 of the 38 solid tumors were fatal. In contrast, there were 124 toxic deaths (8.6%) and 49 infective deaths (3.4%) among 1,435 patients given the combination of melphalan-prednisone-thalidomide or bortezomib (Velcade)-melphalan-prednisone, said Dr. Palumbo, chief of the myeloma unit at the University of Torino (Italy).

"We take it for granted that with chemo we have some toxic effects," he said in an interview. "We should increase our alert of our combinations, and not focus solely on the second cancers."

Session co-moderator Dr. Meral Beksac, with Ankara (Turkey) University, said the Italian data suggest caution and greater vigilance regarding routine cancer screenings among multiple myeloma patients, but would not change her treatment approach.

"Dr. Palumbo has shown very beautifully that the benefits you achieve in terms of the long-term myeloma effect outweigh the risk of secondary malignancies," she said in an interview. "Personally, I think we must plan to avoid alkylating agents when we now have these better agents."

Preliminary data from three trials showing a fourfold increase in secondary cancers in multiple myeloma patients treated with lenalidomide as maintenance therapy or in combination with melphalan prompted investigations into the safety of lenalidomide in the United States and Europe in 2011.

The European Medicines Agency concluded in September that the benefits of lenalidomide continue to outweigh the risks within the approved setting of relapsed multiple myeloma, but recommended that a warning be added on the risk of second cancers. The U.S. Food and Drug Administration review is ongoing, and includes the risk for thalidomide, since lenalidomide is an analogue of thalidomide.

Although the development of acute myeloid leukemia (AML) following multiple myeloma was observed decades ago, the underlying mechanisms remain unclear. Swedish researchers recently reported that the risk of AML and myelodysplastic syndromes is 11.5-fold higher in multiple myeloma patients than in the general population, even before the introduction of novel agents (Blood 2011;118:4086-92). In addition, the risk of AML/MDS was eightfold higher in patients with monoclonal gammopathy of undetermined significance (MGUS), even though none of the MGUS patients developed multiple myeloma, according to session co-moderator Dr. Sigurdur Y. Kristinsson, who was a coauthor of the Swedish study.

"Even those people that never develop the disease have an increased risk of AML and MDS, so it shows that it’s not only the treatment that we’re giving, but it’s also an inherent susceptibility," Dr. Kristinsson, with the Karolinska Hospital and Institute in Stockholm, said in an interview.

Work is ongoing to identify multiple myeloma patients at an increased risk of second cancers, thereby allowing clinicians to tailor therapy to reduce risks. A separate poster presentation at the ASH meeting reported that higher risk of second cancers was associated with older age, male sex, and radiation and/or surgery among roughly 29,250 multiple myeloma patients in the Surveillance, Epidemiology, and End Results (SEER) database.

Subgroup analysis of the pooled Italian data did not identify specific subgroups at greater risk, Dr. Palumbo said. The incidence rate was higher at 1.13 per 100 person-years for patients given melphalan-lenalidomide vs. 0.76 per 100 person-years for patients treated with autologous stem cell transplantation and lenalidomide (median age 68 years vs. 59 years, respectively).

Speaking on behalf of the investigators, Dr. Palumbo reported employment with, serving as a consultant and on the speakers bureau of, having equity ownership in, and receiving research funding, patent royalties, and honoraria from Celgene, maker of lenalidomide. Dr. Beksac reported honoraria and speakers bureau activity with Celgene and Janssen Cilag. Dr. Kristinsson reported no conflicts of interest.

SAN DIEGO – The risk of a secondary malignancy doubled in patients with newly diagnosed multiple myeloma treated with melphalan plus thalidomide or lenalidomide in a retrospective, pooled analysis of 2,283 patients.

Incidence rates per 100 persons per year of follow-up were 0.95 with high-dose melphalan (Alkeran) followed by lenalidomide (Revlimid) maintenance and 1.05 with melphalan and thalidomide. In comparison, rates were 0.40 with cyclophosphamide, lenalidomide, and dexamethasone and 0.42 with melphalan and no immunomodulatory drugs, Dr. Antonio Palumbo reported at the annual meeting of the American Society of Hematology (ASH).

At 4 years of follow-up, second cancers were diagnosed in 48 (2.1%) of the 2,283 patients enrolled in nine experimental trials of the European Myeloma Network. There was consistent evidence of an increase in late events over time.

"I do not want to underestimate the issue," Dr. Palumbo said. "There is a signal, but the first conclusion is caution. When you come to 48 cancers versus 2,200 patients, by chance many things may happen."

He noted that the risk of multiple myeloma progression is between 10 and 15 times higher than the diagnosis of a second cancer, and suggested that the emphasis on second cancers may be overshadowing the risk of death due to toxic effects and infections.

Of the 48 secondary cancers, 8 of the 10 hematologic malignancies and 8 of the 38 solid tumors were fatal. In contrast, there were 124 toxic deaths (8.6%) and 49 infective deaths (3.4%) among 1,435 patients given the combination of melphalan-prednisone-thalidomide or bortezomib (Velcade)-melphalan-prednisone, said Dr. Palumbo, chief of the myeloma unit at the University of Torino (Italy).

"We take it for granted that with chemo we have some toxic effects," he said in an interview. "We should increase our alert of our combinations, and not focus solely on the second cancers."

Session co-moderator Dr. Meral Beksac, with Ankara (Turkey) University, said the Italian data suggest caution and greater vigilance regarding routine cancer screenings among multiple myeloma patients, but would not change her treatment approach.

"Dr. Palumbo has shown very beautifully that the benefits you achieve in terms of the long-term myeloma effect outweigh the risk of secondary malignancies," she said in an interview. "Personally, I think we must plan to avoid alkylating agents when we now have these better agents."

Preliminary data from three trials showing a fourfold increase in secondary cancers in multiple myeloma patients treated with lenalidomide as maintenance therapy or in combination with melphalan prompted investigations into the safety of lenalidomide in the United States and Europe in 2011.

The European Medicines Agency concluded in September that the benefits of lenalidomide continue to outweigh the risks within the approved setting of relapsed multiple myeloma, but recommended that a warning be added on the risk of second cancers. The U.S. Food and Drug Administration review is ongoing, and includes the risk for thalidomide, since lenalidomide is an analogue of thalidomide.

Although the development of acute myeloid leukemia (AML) following multiple myeloma was observed decades ago, the underlying mechanisms remain unclear. Swedish researchers recently reported that the risk of AML and myelodysplastic syndromes is 11.5-fold higher in multiple myeloma patients than in the general population, even before the introduction of novel agents (Blood 2011;118:4086-92). In addition, the risk of AML/MDS was eightfold higher in patients with monoclonal gammopathy of undetermined significance (MGUS), even though none of the MGUS patients developed multiple myeloma, according to session co-moderator Dr. Sigurdur Y. Kristinsson, who was a coauthor of the Swedish study.

"Even those people that never develop the disease have an increased risk of AML and MDS, so it shows that it’s not only the treatment that we’re giving, but it’s also an inherent susceptibility," Dr. Kristinsson, with the Karolinska Hospital and Institute in Stockholm, said in an interview.

Work is ongoing to identify multiple myeloma patients at an increased risk of second cancers, thereby allowing clinicians to tailor therapy to reduce risks. A separate poster presentation at the ASH meeting reported that higher risk of second cancers was associated with older age, male sex, and radiation and/or surgery among roughly 29,250 multiple myeloma patients in the Surveillance, Epidemiology, and End Results (SEER) database.

Subgroup analysis of the pooled Italian data did not identify specific subgroups at greater risk, Dr. Palumbo said. The incidence rate was higher at 1.13 per 100 person-years for patients given melphalan-lenalidomide vs. 0.76 per 100 person-years for patients treated with autologous stem cell transplantation and lenalidomide (median age 68 years vs. 59 years, respectively).

Speaking on behalf of the investigators, Dr. Palumbo reported employment with, serving as a consultant and on the speakers bureau of, having equity ownership in, and receiving research funding, patent royalties, and honoraria from Celgene, maker of lenalidomide. Dr. Beksac reported honoraria and speakers bureau activity with Celgene and Janssen Cilag. Dr. Kristinsson reported no conflicts of interest.

SAN DIEGO – More than 40% of patients with sickle cell disease return for acute care within 14 days following an emergency department treat-and-release visit, with young adults and those with public insurance having the highest rates of return.

Those are key findings from a large analysis of data from the 2005 and 2006 State Emergency Department Databases and State Inpatient Databases managed by the Healthcare Cost and Utilization Project, a federal, state, and industry partnership sponsored by the Agency for Healthcare Research and Quality.

"Patients with sickle cell disease who are discharged from the hospital have higher rates of rehospitalization than [patients with] almost any other chronic disease," lead study author Dr. David C. Brousseau said at the annual meeting of the American Society of Hematology. "Because of the high rate of rehospitalizations, many hospitals have been developing programs to decrease rehospitalization rates for sickle cell disease. This effort is primarily driven by two factors: the recent federal emphasis on rehospitalizations, and a desire to improve care, with the belief that rehospitalizations represent a deficiency in care quality, or at least an opportunity to improve care."

Previous studies have shown that about half of ED visits made by patients with sickle cell disease result in inpatient hospitalization, he continued, "yet little emphasis has been placed on what happens after an ED treat-and-release visit."

Dr. Brousseau and his associates conducted a retrospective cohort study of all sickle cell disease–related ED visits and hospitalizations during 2005 and 2006 in the states of Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee. "One-third of patients with sickle cell disease in the United States reside in these eight states," said Dr. Brousseau, of the pediatrics department at the Medical College of Wisconsin and an emergency medicine specialist at Children’s Hospital of Wisconsin, Milwaukee.

The researchers hypothesized that patients with sickle cell disease who were treated and released from an ED would have high rates of 14-day return visits to both the ED and an inpatient unit. A 14-day window was chosen "to more accurately reflect a time period ... where a revisit would not be due to a new crisis," he said.

During the 2-year study period, 12,109 people with sickle cell disease made 39,775 index ED visits. The 14-day return visit rate was 42.1%, "meaning that 42.1% of all ED treat-and-release visits were followed within 14 days by a return visit to either the ED or the inpatient unit," Dr. Brousseau said. A higher proportion of the return visits were to the ED than to the inpatient unit (25.4% vs. 16.7%, respectively).

Analysis of data by patient age and insurance provider revealed that the highest proportion of return visits within 14 days was made by patients aged 18-30 years (49%) and by those who carried public insurance (46.5%).

The 7-day return rate was 31.6%. Of these, 18.6% were to the ED and 13% were to the inpatient unit.

The 14-day revisit rate to the same hospital was 31.2%. Children were more likely than adults to make return visits to the same hospital (84.3% vs. 72.7%, respectively).

"We conclude that an ED treat-and-release visit should serve as a trigger to focus enhanced outpatient care to prevent subsequent inpatient visits and to improve patient care," Dr. Brousseau said.

Dr. Brousseau said he had no relevant financial disclosures.

SAN DIEGO – More than 40% of patients with sickle cell disease return for acute care within 14 days following an emergency department treat-and-release visit, with young adults and those with public insurance having the highest rates of return.

Those are key findings from a large analysis of data from the 2005 and 2006 State Emergency Department Databases and State Inpatient Databases managed by the Healthcare Cost and Utilization Project, a federal, state, and industry partnership sponsored by the Agency for Healthcare Research and Quality.

"Patients with sickle cell disease who are discharged from the hospital have higher rates of rehospitalization than [patients with] almost any other chronic disease," lead study author Dr. David C. Brousseau said at the annual meeting of the American Society of Hematology. "Because of the high rate of rehospitalizations, many hospitals have been developing programs to decrease rehospitalization rates for sickle cell disease. This effort is primarily driven by two factors: the recent federal emphasis on rehospitalizations, and a desire to improve care, with the belief that rehospitalizations represent a deficiency in care quality, or at least an opportunity to improve care."

Previous studies have shown that about half of ED visits made by patients with sickle cell disease result in inpatient hospitalization, he continued, "yet little emphasis has been placed on what happens after an ED treat-and-release visit."

Dr. Brousseau and his associates conducted a retrospective cohort study of all sickle cell disease–related ED visits and hospitalizations during 2005 and 2006 in the states of Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee. "One-third of patients with sickle cell disease in the United States reside in these eight states," said Dr. Brousseau, of the pediatrics department at the Medical College of Wisconsin and an emergency medicine specialist at Children’s Hospital of Wisconsin, Milwaukee.

The researchers hypothesized that patients with sickle cell disease who were treated and released from an ED would have high rates of 14-day return visits to both the ED and an inpatient unit. A 14-day window was chosen "to more accurately reflect a time period ... where a revisit would not be due to a new crisis," he said.

During the 2-year study period, 12,109 people with sickle cell disease made 39,775 index ED visits. The 14-day return visit rate was 42.1%, "meaning that 42.1% of all ED treat-and-release visits were followed within 14 days by a return visit to either the ED or the inpatient unit," Dr. Brousseau said. A higher proportion of the return visits were to the ED than to the inpatient unit (25.4% vs. 16.7%, respectively).

Analysis of data by patient age and insurance provider revealed that the highest proportion of return visits within 14 days was made by patients aged 18-30 years (49%) and by those who carried public insurance (46.5%).

The 7-day return rate was 31.6%. Of these, 18.6% were to the ED and 13% were to the inpatient unit.

The 14-day revisit rate to the same hospital was 31.2%. Children were more likely than adults to make return visits to the same hospital (84.3% vs. 72.7%, respectively).

"We conclude that an ED treat-and-release visit should serve as a trigger to focus enhanced outpatient care to prevent subsequent inpatient visits and to improve patient care," Dr. Brousseau said.

Dr. Brousseau said he had no relevant financial disclosures.

SAN DIEGO – More than 40% of patients with sickle cell disease return for acute care within 14 days following an emergency department treat-and-release visit, with young adults and those with public insurance having the highest rates of return.

Those are key findings from a large analysis of data from the 2005 and 2006 State Emergency Department Databases and State Inpatient Databases managed by the Healthcare Cost and Utilization Project, a federal, state, and industry partnership sponsored by the Agency for Healthcare Research and Quality.

"Patients with sickle cell disease who are discharged from the hospital have higher rates of rehospitalization than [patients with] almost any other chronic disease," lead study author Dr. David C. Brousseau said at the annual meeting of the American Society of Hematology. "Because of the high rate of rehospitalizations, many hospitals have been developing programs to decrease rehospitalization rates for sickle cell disease. This effort is primarily driven by two factors: the recent federal emphasis on rehospitalizations, and a desire to improve care, with the belief that rehospitalizations represent a deficiency in care quality, or at least an opportunity to improve care."

Previous studies have shown that about half of ED visits made by patients with sickle cell disease result in inpatient hospitalization, he continued, "yet little emphasis has been placed on what happens after an ED treat-and-release visit."

Dr. Brousseau and his associates conducted a retrospective cohort study of all sickle cell disease–related ED visits and hospitalizations during 2005 and 2006 in the states of Arizona, California, Florida, Massachusetts, Missouri, New York, South Carolina, and Tennessee. "One-third of patients with sickle cell disease in the United States reside in these eight states," said Dr. Brousseau, of the pediatrics department at the Medical College of Wisconsin and an emergency medicine specialist at Children’s Hospital of Wisconsin, Milwaukee.

The researchers hypothesized that patients with sickle cell disease who were treated and released from an ED would have high rates of 14-day return visits to both the ED and an inpatient unit. A 14-day window was chosen "to more accurately reflect a time period ... where a revisit would not be due to a new crisis," he said.

During the 2-year study period, 12,109 people with sickle cell disease made 39,775 index ED visits. The 14-day return visit rate was 42.1%, "meaning that 42.1% of all ED treat-and-release visits were followed within 14 days by a return visit to either the ED or the inpatient unit," Dr. Brousseau said. A higher proportion of the return visits were to the ED than to the inpatient unit (25.4% vs. 16.7%, respectively).

Analysis of data by patient age and insurance provider revealed that the highest proportion of return visits within 14 days was made by patients aged 18-30 years (49%) and by those who carried public insurance (46.5%).

The 7-day return rate was 31.6%. Of these, 18.6% were to the ED and 13% were to the inpatient unit.

The 14-day revisit rate to the same hospital was 31.2%. Children were more likely than adults to make return visits to the same hospital (84.3% vs. 72.7%, respectively).

"We conclude that an ED treat-and-release visit should serve as a trigger to focus enhanced outpatient care to prevent subsequent inpatient visits and to improve patient care," Dr. Brousseau said.

Dr. Brousseau said he had no relevant financial disclosures.

SAN DIEGO – Even before it has earned a name, the novel targeted agent designated PCI-32765 is earning an impressive reputation, first for its mettle against chronic lymphocytic leukemia, and now for its potent action against relapsed or refractory mantle cell lymphoma in early clinical data, reported investigators at the annual meeting of the American Society of Hematology.

Preliminary results of a phase II trial of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, show that the agent induced complete responses in 16% of 51 patients with relapsed/refractory mantle cell lymphoma (MCL) and partial responses in 53%, for a combined overall response rate of 69%, said Dr. Luhua (Michael) Wang from the division of lymphoma and myeloma at the University of Texas M.D. Anderson Cancer Center in Houston.

"We think, as a single oral agent in the relapse setting of mantle cell lymphoma, this is a high response rate so far. The efficacy is also observed in patients with bulky disease, and also in refractive disease. Most importantly, the efficacy is independent, so far, from the MIPI [MCL International Prognostic Index] score," he said.

Patients with a high-risk MIPI score had a 75% response rate, the same as that for patients with a low-risk score; intermediate-risk patients had a 65% response rate.

An additional 18% of patients overall had stable disease; only 14% experienced disease progression.

In an earlier presentation at the ASH meeting, Dr. Susan O’Brien, also from M.D. Anderson, reported that PCI-32765 was associated with an overall response rate of 70% at 10.2 months’ follow-up in patients with relapsed/refractory CLL.

In the mantle cell lymphoma study, the BTK-inhibitor induced good responses both in patients who had previously been treated with the proteasome inhibitor bortezomib (Velcade), with rates of 15% for complete responses and 50% for partial responses, and in those who were bortezomib naive, with a 16% complete response rate and 55% partial response rate.

"People are very interested in this agent," commented Dr. Mitchell R. Smith from the Fox Chase Cancer Center in Philadelphia, in an interview.

"It looks very active, but we don’t know a lot about long-term effects and how long responses will last. But when you think about hitting specific pathways, that’s our goal in treating these diseases. This hits a specific pathway, does it well, and there have been responses in many B-cell disorders," he said. Dr. Smith comoderated the session at which the data were presented, but was not involved in the study.

PCI-32765 is an oral inhibitor of BTK, an essential element of the B-cell antigen receptor-signaling pathway. It blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion, and has been shown in in vitro studies to block pERK, pJNK, and NF-kappaB pathways in MCL cell lines.

The trial, designated PCYC-1104-CA, is a multicenter open-label phase II study of PCI-32765 in 68 patients. Dr. Wang presented data from an efficacy analysis of 51 patients who had at least one post-baseline tumor assessment. The patients were divided into two groups: bortezomib-exposed (27 patients) and bortezomib naive (41 patients, 34 of whom had never received bortezomib, and 7 who had received less than 2 cycles).

The patients were treated with 560 mg PCI-32765 daily until disease progression.

Median time on study was 3.7 months among all patients. At the most recent follow-up, 71% of bortezomib-naive and 70% of bortezomib-exposed patients were still on study. Discontinuations were primarily for disease progression, and there was one on-study death, a patient who had previously received bortezomib.

Non-hematologic adverse events were generally mild, with the only grade 4 toxicity being abdominal pain in about 2% of patients.

Grade 3 neutropenia occurred in 2% overall of 61 patients available for a safety analysis, and grade 4 neutropenia was seen 3%. Grade 3 febrile neutropenia, anemia, and thrombocytopenias were each seen in 3% of patients (no grade 4), and grade 4 pancytopenia was seen in 2%.

The investigators saw a 57% overall response rate in patients with bulky disease, 67% in those with refractory disease, 77% among those who had received fewer than 3 prior lines of therapy, and 57% among those who had received 3 or more. In addition, the overall response rate was 71% in patients who had received high-intensity prior therapy, and 65% in those who had received standard-dose therapy.

Additional follow-up will be required before the investigators can determine duration of response and progression-free survival, and more clinical trials with PCI-32765 are in the planning stages, Dr. Wang said.

Pharmacyclics sponsored the study. Dr. Wang disclosed consulting, having equity ownership in, and receiving research funding from, Pharmacyclics. He also disclosed relationships with Celgene, Millennium, Novartis, and Onyx. Dr. Smith disclosed board membership and receiving research funding from Cephalon, and being on the speakers bureau for Celgene, Genentech, Spectrum, and Allos.

SAN DIEGO – Even before it has earned a name, the novel targeted agent designated PCI-32765 is earning an impressive reputation, first for its mettle against chronic lymphocytic leukemia, and now for its potent action against relapsed or refractory mantle cell lymphoma in early clinical data, reported investigators at the annual meeting of the American Society of Hematology.

Preliminary results of a phase II trial of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, show that the agent induced complete responses in 16% of 51 patients with relapsed/refractory mantle cell lymphoma (MCL) and partial responses in 53%, for a combined overall response rate of 69%, said Dr. Luhua (Michael) Wang from the division of lymphoma and myeloma at the University of Texas M.D. Anderson Cancer Center in Houston.

"We think, as a single oral agent in the relapse setting of mantle cell lymphoma, this is a high response rate so far. The efficacy is also observed in patients with bulky disease, and also in refractive disease. Most importantly, the efficacy is independent, so far, from the MIPI [MCL International Prognostic Index] score," he said.

Patients with a high-risk MIPI score had a 75% response rate, the same as that for patients with a low-risk score; intermediate-risk patients had a 65% response rate.

An additional 18% of patients overall had stable disease; only 14% experienced disease progression.

In an earlier presentation at the ASH meeting, Dr. Susan O’Brien, also from M.D. Anderson, reported that PCI-32765 was associated with an overall response rate of 70% at 10.2 months’ follow-up in patients with relapsed/refractory CLL.

In the mantle cell lymphoma study, the BTK-inhibitor induced good responses both in patients who had previously been treated with the proteasome inhibitor bortezomib (Velcade), with rates of 15% for complete responses and 50% for partial responses, and in those who were bortezomib naive, with a 16% complete response rate and 55% partial response rate.

"People are very interested in this agent," commented Dr. Mitchell R. Smith from the Fox Chase Cancer Center in Philadelphia, in an interview.

"It looks very active, but we don’t know a lot about long-term effects and how long responses will last. But when you think about hitting specific pathways, that’s our goal in treating these diseases. This hits a specific pathway, does it well, and there have been responses in many B-cell disorders," he said. Dr. Smith comoderated the session at which the data were presented, but was not involved in the study.

PCI-32765 is an oral inhibitor of BTK, an essential element of the B-cell antigen receptor-signaling pathway. It blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion, and has been shown in in vitro studies to block pERK, pJNK, and NF-kappaB pathways in MCL cell lines.

The trial, designated PCYC-1104-CA, is a multicenter open-label phase II study of PCI-32765 in 68 patients. Dr. Wang presented data from an efficacy analysis of 51 patients who had at least one post-baseline tumor assessment. The patients were divided into two groups: bortezomib-exposed (27 patients) and bortezomib naive (41 patients, 34 of whom had never received bortezomib, and 7 who had received less than 2 cycles).

The patients were treated with 560 mg PCI-32765 daily until disease progression.

Median time on study was 3.7 months among all patients. At the most recent follow-up, 71% of bortezomib-naive and 70% of bortezomib-exposed patients were still on study. Discontinuations were primarily for disease progression, and there was one on-study death, a patient who had previously received bortezomib.

Non-hematologic adverse events were generally mild, with the only grade 4 toxicity being abdominal pain in about 2% of patients.

Grade 3 neutropenia occurred in 2% overall of 61 patients available for a safety analysis, and grade 4 neutropenia was seen 3%. Grade 3 febrile neutropenia, anemia, and thrombocytopenias were each seen in 3% of patients (no grade 4), and grade 4 pancytopenia was seen in 2%.

The investigators saw a 57% overall response rate in patients with bulky disease, 67% in those with refractory disease, 77% among those who had received fewer than 3 prior lines of therapy, and 57% among those who had received 3 or more. In addition, the overall response rate was 71% in patients who had received high-intensity prior therapy, and 65% in those who had received standard-dose therapy.

Additional follow-up will be required before the investigators can determine duration of response and progression-free survival, and more clinical trials with PCI-32765 are in the planning stages, Dr. Wang said.

Pharmacyclics sponsored the study. Dr. Wang disclosed consulting, having equity ownership in, and receiving research funding from, Pharmacyclics. He also disclosed relationships with Celgene, Millennium, Novartis, and Onyx. Dr. Smith disclosed board membership and receiving research funding from Cephalon, and being on the speakers bureau for Celgene, Genentech, Spectrum, and Allos.

SAN DIEGO – Even before it has earned a name, the novel targeted agent designated PCI-32765 is earning an impressive reputation, first for its mettle against chronic lymphocytic leukemia, and now for its potent action against relapsed or refractory mantle cell lymphoma in early clinical data, reported investigators at the annual meeting of the American Society of Hematology.

Preliminary results of a phase II trial of PCI-32765, an inhibitor of Bruton’s tyrosine kinase (BTK) expressed in several hematologic malignancies, show that the agent induced complete responses in 16% of 51 patients with relapsed/refractory mantle cell lymphoma (MCL) and partial responses in 53%, for a combined overall response rate of 69%, said Dr. Luhua (Michael) Wang from the division of lymphoma and myeloma at the University of Texas M.D. Anderson Cancer Center in Houston.

"We think, as a single oral agent in the relapse setting of mantle cell lymphoma, this is a high response rate so far. The efficacy is also observed in patients with bulky disease, and also in refractive disease. Most importantly, the efficacy is independent, so far, from the MIPI [MCL International Prognostic Index] score," he said.

Patients with a high-risk MIPI score had a 75% response rate, the same as that for patients with a low-risk score; intermediate-risk patients had a 65% response rate.

An additional 18% of patients overall had stable disease; only 14% experienced disease progression.

In an earlier presentation at the ASH meeting, Dr. Susan O’Brien, also from M.D. Anderson, reported that PCI-32765 was associated with an overall response rate of 70% at 10.2 months’ follow-up in patients with relapsed/refractory CLL.

In the mantle cell lymphoma study, the BTK-inhibitor induced good responses both in patients who had previously been treated with the proteasome inhibitor bortezomib (Velcade), with rates of 15% for complete responses and 50% for partial responses, and in those who were bortezomib naive, with a 16% complete response rate and 55% partial response rate.

"People are very interested in this agent," commented Dr. Mitchell R. Smith from the Fox Chase Cancer Center in Philadelphia, in an interview.

"It looks very active, but we don’t know a lot about long-term effects and how long responses will last. But when you think about hitting specific pathways, that’s our goal in treating these diseases. This hits a specific pathway, does it well, and there have been responses in many B-cell disorders," he said. Dr. Smith comoderated the session at which the data were presented, but was not involved in the study.

PCI-32765 is an oral inhibitor of BTK, an essential element of the B-cell antigen receptor-signaling pathway. It blocks receptor signaling and induces apoptosis, as well as mantle cell migration and adhesion, and has been shown in in vitro studies to block pERK, pJNK, and NF-kappaB pathways in MCL cell lines.

The trial, designated PCYC-1104-CA, is a multicenter open-label phase II study of PCI-32765 in 68 patients. Dr. Wang presented data from an efficacy analysis of 51 patients who had at least one post-baseline tumor assessment. The patients were divided into two groups: bortezomib-exposed (27 patients) and bortezomib naive (41 patients, 34 of whom had never received bortezomib, and 7 who had received less than 2 cycles).

The patients were treated with 560 mg PCI-32765 daily until disease progression.

Median time on study was 3.7 months among all patients. At the most recent follow-up, 71% of bortezomib-naive and 70% of bortezomib-exposed patients were still on study. Discontinuations were primarily for disease progression, and there was one on-study death, a patient who had previously received bortezomib.

Non-hematologic adverse events were generally mild, with the only grade 4 toxicity being abdominal pain in about 2% of patients.

Grade 3 neutropenia occurred in 2% overall of 61 patients available for a safety analysis, and grade 4 neutropenia was seen 3%. Grade 3 febrile neutropenia, anemia, and thrombocytopenias were each seen in 3% of patients (no grade 4), and grade 4 pancytopenia was seen in 2%.

The investigators saw a 57% overall response rate in patients with bulky disease, 67% in those with refractory disease, 77% among those who had received fewer than 3 prior lines of therapy, and 57% among those who had received 3 or more. In addition, the overall response rate was 71% in patients who had received high-intensity prior therapy, and 65% in those who had received standard-dose therapy.

Additional follow-up will be required before the investigators can determine duration of response and progression-free survival, and more clinical trials with PCI-32765 are in the planning stages, Dr. Wang said.

Pharmacyclics sponsored the study. Dr. Wang disclosed consulting, having equity ownership in, and receiving research funding from, Pharmacyclics. He also disclosed relationships with Celgene, Millennium, Novartis, and Onyx. Dr. Smith disclosed board membership and receiving research funding from Cephalon, and being on the speakers bureau for Celgene, Genentech, Spectrum, and Allos.

LAS VEGAS – Although certain characteristics of lymphomatoid papulosis appear be associated with progression to lymphoma, the majority of patients will have a benign course of disease.

The recurrent papulonodular skin eruption lymphomatoid papulosis (LyP) can be a confusing dermatologic entity because it appears malignant histologically, but it usually follows a clinically benign and indolent course (Arch. Dermatol. 1968;97:23-30). And even the 10%-20% of patients who do progress to lymphoma tend to have less aggressive disease, said Dr. Lawrence E. Gibson, professor of dermatology at the Mayo Clinic in Rochester, Minn. The reasons for this disconnect are not yet known.

"Patients with LyP look like lymphoma under the microscope but have clinically indolent cutaneous disease. ... It is an example of a very important clinical-pathological relationship that really needs to be made to help us understand how to treat patients better," he said.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas."

To identify which LyP patients are more likely to progress to lymphoma, Dr. Gibson, Dr. Rokea A. el-Azhary, Dr. Aieska de Souza, and their associates conducted a retrospective analysis of 123 patients seen at the Mayo Clinic between 1991 and 2008. The patients were followed for a mean of 4 years (range, 2 months to 14 years). The 65 males and 58 females had a mean age of 47 years (range, 1-83 years), and a mean of 14 lesions (range, 1-100). Most (88%) of the lesions were papules, with a reported mean duration of 5.5 weeks. Pruritis was present in 38% and scar formation in 58%, the researchers reported (J. Am. Acad. Dermatol. 2011 [doi:10.1016/j.jaad.2011.07.012]).

Hematologic malignancies were present in 17 patients (14%). Of those, 10 were cutaneous lymphomas – 8 mycosis fungoides (MF) and 2 anaplastic large-cell lymphomas (ALCL). Hodgkin lymphoma was present in three patients (including the two with ALCL), multiple myeloma or monoclonal gammopathy in three, and myelodysplastic syndrome in one.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas. They certainly don’t have cytotoxic lymphomas. And if they have lymphoma, they usually have MF. I think that’s somewhat reassuring to us. And for the most part, most of the patients don’t have anything. They have a normal life," Dr. Gibson said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

Of 97 LyP patients for whom original biopsy slides were available, the majority (69) had World Health Organization/European Organization for Research and Treatment of Cancer histologic classification type A, including 35 with immunophenotypic subtype CD8 and 34 with subtype CD4. Another 13 patients had type B lesions (8 CD4, 5 CD8), and 6 had type C, all of which were CD4. The other 9 patients had more than one histologic type (A, B, or C), and/or more than one immunophenotypic subtype (CD4 or CD8). They were designated mixed type.

Clinically, there were no distinguishing features among the subtypes. This finding contrasts with some previous reports that the CD8 subtype might predispose to worse disease outcome (Am. J. Pathol. 1999;155:483-92).

"Our findings indicated that the LyP subtype CD8 does not signify more aggressive disease, a poor prognosis, or an association with malignancy," Dr. Gibson and his colleagues wrote.

Hematologic malignancies were present in 5 of the 9 mixed-type patients (55.5%), compared with 4 of the 34 with A/CD4 (12%), 4 of the 35 A/CD8 (11.5%), 1 of the 8 B/CD4 patients (12.5%), and 1 of the 5 B/CD8 patients (20%). (Two of the 17 malignancies were excluded from analysis because original slides were not available.) The odds ratio for malignancy for the patients with mixed-type LyP versus all other types was a statistically significant 4.33 (P = .03).

In a molecular genetics substudy of 84 LyP lesions from 76 patients, 42 (50%) were positive for clonal T-cell receptor gene rearrangement (TCRGR), 34 (40%) were negative, and 8 (10%) showed equivocal results or had insufficient DNA for analysis. Among the LyP patients who had a hematologic malignancy, 9 of 11 (82%) had positive TCRGR, compared with 30 of 68 (44%) LyP patients without malignancy. That association was also significant, with an odds ratio of 5.7 (P = .02), noted the investigators.

"A positive T-cell receptor gene rearrangement or having more than one type of LyP may have a higher risk of progression to lymphoma, but the evidence is not hard and fast. ... The take-home message is most of these patients do just fine," Dr. Gibson said.

Dr. Gibson stated that he had no relevant financial disclosures or conflicts of interest. SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Although certain characteristics of lymphomatoid papulosis appear be associated with progression to lymphoma, the majority of patients will have a benign course of disease.

The recurrent papulonodular skin eruption lymphomatoid papulosis (LyP) can be a confusing dermatologic entity because it appears malignant histologically, but it usually follows a clinically benign and indolent course (Arch. Dermatol. 1968;97:23-30). And even the 10%-20% of patients who do progress to lymphoma tend to have less aggressive disease, said Dr. Lawrence E. Gibson, professor of dermatology at the Mayo Clinic in Rochester, Minn. The reasons for this disconnect are not yet known.

"Patients with LyP look like lymphoma under the microscope but have clinically indolent cutaneous disease. ... It is an example of a very important clinical-pathological relationship that really needs to be made to help us understand how to treat patients better," he said.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas."

To identify which LyP patients are more likely to progress to lymphoma, Dr. Gibson, Dr. Rokea A. el-Azhary, Dr. Aieska de Souza, and their associates conducted a retrospective analysis of 123 patients seen at the Mayo Clinic between 1991 and 2008. The patients were followed for a mean of 4 years (range, 2 months to 14 years). The 65 males and 58 females had a mean age of 47 years (range, 1-83 years), and a mean of 14 lesions (range, 1-100). Most (88%) of the lesions were papules, with a reported mean duration of 5.5 weeks. Pruritis was present in 38% and scar formation in 58%, the researchers reported (J. Am. Acad. Dermatol. 2011 [doi:10.1016/j.jaad.2011.07.012]).

Hematologic malignancies were present in 17 patients (14%). Of those, 10 were cutaneous lymphomas – 8 mycosis fungoides (MF) and 2 anaplastic large-cell lymphomas (ALCL). Hodgkin lymphoma was present in three patients (including the two with ALCL), multiple myeloma or monoclonal gammopathy in three, and myelodysplastic syndrome in one.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas. They certainly don’t have cytotoxic lymphomas. And if they have lymphoma, they usually have MF. I think that’s somewhat reassuring to us. And for the most part, most of the patients don’t have anything. They have a normal life," Dr. Gibson said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

Of 97 LyP patients for whom original biopsy slides were available, the majority (69) had World Health Organization/European Organization for Research and Treatment of Cancer histologic classification type A, including 35 with immunophenotypic subtype CD8 and 34 with subtype CD4. Another 13 patients had type B lesions (8 CD4, 5 CD8), and 6 had type C, all of which were CD4. The other 9 patients had more than one histologic type (A, B, or C), and/or more than one immunophenotypic subtype (CD4 or CD8). They were designated mixed type.

Clinically, there were no distinguishing features among the subtypes. This finding contrasts with some previous reports that the CD8 subtype might predispose to worse disease outcome (Am. J. Pathol. 1999;155:483-92).

"Our findings indicated that the LyP subtype CD8 does not signify more aggressive disease, a poor prognosis, or an association with malignancy," Dr. Gibson and his colleagues wrote.

Hematologic malignancies were present in 5 of the 9 mixed-type patients (55.5%), compared with 4 of the 34 with A/CD4 (12%), 4 of the 35 A/CD8 (11.5%), 1 of the 8 B/CD4 patients (12.5%), and 1 of the 5 B/CD8 patients (20%). (Two of the 17 malignancies were excluded from analysis because original slides were not available.) The odds ratio for malignancy for the patients with mixed-type LyP versus all other types was a statistically significant 4.33 (P = .03).

In a molecular genetics substudy of 84 LyP lesions from 76 patients, 42 (50%) were positive for clonal T-cell receptor gene rearrangement (TCRGR), 34 (40%) were negative, and 8 (10%) showed equivocal results or had insufficient DNA for analysis. Among the LyP patients who had a hematologic malignancy, 9 of 11 (82%) had positive TCRGR, compared with 30 of 68 (44%) LyP patients without malignancy. That association was also significant, with an odds ratio of 5.7 (P = .02), noted the investigators.

"A positive T-cell receptor gene rearrangement or having more than one type of LyP may have a higher risk of progression to lymphoma, but the evidence is not hard and fast. ... The take-home message is most of these patients do just fine," Dr. Gibson said.

Dr. Gibson stated that he had no relevant financial disclosures or conflicts of interest. SDEF and this news organization are owned by Elsevier.

LAS VEGAS – Although certain characteristics of lymphomatoid papulosis appear be associated with progression to lymphoma, the majority of patients will have a benign course of disease.

The recurrent papulonodular skin eruption lymphomatoid papulosis (LyP) can be a confusing dermatologic entity because it appears malignant histologically, but it usually follows a clinically benign and indolent course (Arch. Dermatol. 1968;97:23-30). And even the 10%-20% of patients who do progress to lymphoma tend to have less aggressive disease, said Dr. Lawrence E. Gibson, professor of dermatology at the Mayo Clinic in Rochester, Minn. The reasons for this disconnect are not yet known.

"Patients with LyP look like lymphoma under the microscope but have clinically indolent cutaneous disease. ... It is an example of a very important clinical-pathological relationship that really needs to be made to help us understand how to treat patients better," he said.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas."

To identify which LyP patients are more likely to progress to lymphoma, Dr. Gibson, Dr. Rokea A. el-Azhary, Dr. Aieska de Souza, and their associates conducted a retrospective analysis of 123 patients seen at the Mayo Clinic between 1991 and 2008. The patients were followed for a mean of 4 years (range, 2 months to 14 years). The 65 males and 58 females had a mean age of 47 years (range, 1-83 years), and a mean of 14 lesions (range, 1-100). Most (88%) of the lesions were papules, with a reported mean duration of 5.5 weeks. Pruritis was present in 38% and scar formation in 58%, the researchers reported (J. Am. Acad. Dermatol. 2011 [doi:10.1016/j.jaad.2011.07.012]).

Hematologic malignancies were present in 17 patients (14%). Of those, 10 were cutaneous lymphomas – 8 mycosis fungoides (MF) and 2 anaplastic large-cell lymphomas (ALCL). Hodgkin lymphoma was present in three patients (including the two with ALCL), multiple myeloma or monoclonal gammopathy in three, and myelodysplastic syndrome in one.

"The bottom line is most of our patients who have LyP do not go on to have aggressive lymphomas. They certainly don’t have cytotoxic lymphomas. And if they have lymphoma, they usually have MF. I think that’s somewhat reassuring to us. And for the most part, most of the patients don’t have anything. They have a normal life," Dr. Gibson said at the seminar sponsored by Skin Disease Education Foundation (SDEF).

Of 97 LyP patients for whom original biopsy slides were available, the majority (69) had World Health Organization/European Organization for Research and Treatment of Cancer histologic classification type A, including 35 with immunophenotypic subtype CD8 and 34 with subtype CD4. Another 13 patients had type B lesions (8 CD4, 5 CD8), and 6 had type C, all of which were CD4. The other 9 patients had more than one histologic type (A, B, or C), and/or more than one immunophenotypic subtype (CD4 or CD8). They were designated mixed type.

Clinically, there were no distinguishing features among the subtypes. This finding contrasts with some previous reports that the CD8 subtype might predispose to worse disease outcome (Am. J. Pathol. 1999;155:483-92).

"Our findings indicated that the LyP subtype CD8 does not signify more aggressive disease, a poor prognosis, or an association with malignancy," Dr. Gibson and his colleagues wrote.

Hematologic malignancies were present in 5 of the 9 mixed-type patients (55.5%), compared with 4 of the 34 with A/CD4 (12%), 4 of the 35 A/CD8 (11.5%), 1 of the 8 B/CD4 patients (12.5%), and 1 of the 5 B/CD8 patients (20%). (Two of the 17 malignancies were excluded from analysis because original slides were not available.) The odds ratio for malignancy for the patients with mixed-type LyP versus all other types was a statistically significant 4.33 (P = .03).

In a molecular genetics substudy of 84 LyP lesions from 76 patients, 42 (50%) were positive for clonal T-cell receptor gene rearrangement (TCRGR), 34 (40%) were negative, and 8 (10%) showed equivocal results or had insufficient DNA for analysis. Among the LyP patients who had a hematologic malignancy, 9 of 11 (82%) had positive TCRGR, compared with 30 of 68 (44%) LyP patients without malignancy. That association was also significant, with an odds ratio of 5.7 (P = .02), noted the investigators.

"A positive T-cell receptor gene rearrangement or having more than one type of LyP may have a higher risk of progression to lymphoma, but the evidence is not hard and fast. ... The take-home message is most of these patients do just fine," Dr. Gibson said.

Dr. Gibson stated that he had no relevant financial disclosures or conflicts of interest. SDEF and this news organization are owned by Elsevier.