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Survival improves for AYAs with leukemia and lymphoma
New research suggests adolescents and young adults (AYAs) with leukemias and lymphomas are living longer than such patients did 2 decades ago.
However, their survival still lags behind survival in children. It even lags behind survival in older adults in the case of acute myeloblastic leukemia (AML).
Investigators reported these findings online August 24 ahead of the November 1 print edition of Cancer.
Dianne Pulte, MD, of the University of Medicine and Dentistry of New Jersey, and colleagues analyzed data from the Surveillance, Epidemiology and End Results (SEER) database to determine survival rates of young people with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), AML, and chronic myelocytic leukemia (CML).
They compared data from 1981–1985 with data from 2001–2005.
The investigators found that survival had improved significantly in each of the 5 malignancies. For AYAs with Hodgkin’s lymphoma, 10-year survival increased from 80.4% to 93.4%. For those with NHL, it increased from 55.6% to 76.2%; for those with ALL, from 30.5% to 52.1%; for those with AML, from 15.2% to 45.1%; and for those with CML, from 0% to 74.5%.
They analyzed the data further and found that the survival rate for young people with the lymphomas or CML had improved steadily over the 2 decades. And the survival rate was stable for patients with the acute leukemias during the late 1990s and early 21st century.
However, they found that survival in AYAs is still not as good as the survival rate for children with these hematologic malignancies, with the exception of patients with Hodgkin lymphoma. And survival in AYAs with AML lags behind survival in older adults.
The investigators acknowledge that improving survival rates for the AYA population is a major challenge. Dr Pulte suggests that “more research into how to treat these diseases and how to make sure that all patients have access to the best treatment is needed.” 
New research suggests adolescents and young adults (AYAs) with leukemias and lymphomas are living longer than such patients did 2 decades ago.
However, their survival still lags behind survival in children. It even lags behind survival in older adults in the case of acute myeloblastic leukemia (AML).
Investigators reported these findings online August 24 ahead of the November 1 print edition of Cancer.
Dianne Pulte, MD, of the University of Medicine and Dentistry of New Jersey, and colleagues analyzed data from the Surveillance, Epidemiology and End Results (SEER) database to determine survival rates of young people with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), AML, and chronic myelocytic leukemia (CML).
They compared data from 1981–1985 with data from 2001–2005.
The investigators found that survival had improved significantly in each of the 5 malignancies. For AYAs with Hodgkin’s lymphoma, 10-year survival increased from 80.4% to 93.4%. For those with NHL, it increased from 55.6% to 76.2%; for those with ALL, from 30.5% to 52.1%; for those with AML, from 15.2% to 45.1%; and for those with CML, from 0% to 74.5%.
They analyzed the data further and found that the survival rate for young people with the lymphomas or CML had improved steadily over the 2 decades. And the survival rate was stable for patients with the acute leukemias during the late 1990s and early 21st century.
However, they found that survival in AYAs is still not as good as the survival rate for children with these hematologic malignancies, with the exception of patients with Hodgkin lymphoma. And survival in AYAs with AML lags behind survival in older adults.
The investigators acknowledge that improving survival rates for the AYA population is a major challenge. Dr Pulte suggests that “more research into how to treat these diseases and how to make sure that all patients have access to the best treatment is needed.”
New research suggests adolescents and young adults (AYAs) with leukemias and lymphomas are living longer than such patients did 2 decades ago.
However, their survival still lags behind survival in children. It even lags behind survival in older adults in the case of acute myeloblastic leukemia (AML).
Investigators reported these findings online August 24 ahead of the November 1 print edition of Cancer.
Dianne Pulte, MD, of the University of Medicine and Dentistry of New Jersey, and colleagues analyzed data from the Surveillance, Epidemiology and End Results (SEER) database to determine survival rates of young people with Hodgkin lymphoma, non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), AML, and chronic myelocytic leukemia (CML).
They compared data from 1981–1985 with data from 2001–2005.
The investigators found that survival had improved significantly in each of the 5 malignancies. For AYAs with Hodgkin’s lymphoma, 10-year survival increased from 80.4% to 93.4%. For those with NHL, it increased from 55.6% to 76.2%; for those with ALL, from 30.5% to 52.1%; for those with AML, from 15.2% to 45.1%; and for those with CML, from 0% to 74.5%.
They analyzed the data further and found that the survival rate for young people with the lymphomas or CML had improved steadily over the 2 decades. And the survival rate was stable for patients with the acute leukemias during the late 1990s and early 21st century.
However, they found that survival in AYAs is still not as good as the survival rate for children with these hematologic malignancies, with the exception of patients with Hodgkin lymphoma. And survival in AYAs with AML lags behind survival in older adults.
The investigators acknowledge that improving survival rates for the AYA population is a major challenge. Dr Pulte suggests that “more research into how to treat these diseases and how to make sure that all patients have access to the best treatment is needed.”
Lymphoma and Biologics
Dr. Joel Gelfand discusses research concerning the use of biologics and lymphoma risk. Kerri Wachter of the Global Medical News Network (GMNN) reports from the American Academy of Dermatology's Academy 2009 meeting in Boston.
Dr. Joel Gelfand discusses research concerning the use of biologics and lymphoma risk. Kerri Wachter of the Global Medical News Network (GMNN) reports from the American Academy of Dermatology's Academy 2009 meeting in Boston.
Dr. Joel Gelfand discusses research concerning the use of biologics and lymphoma risk. Kerri Wachter of the Global Medical News Network (GMNN) reports from the American Academy of Dermatology's Academy 2009 meeting in Boston.
Potential cause of R-CHOP failure ruled out
Researchers say they have come one step closer to determining the cause of R-CHOP failure in diffuse large B-cell lymphoma (DLBCL) by ruling out a potential cause.
Randy D. Gascoyne, MD, of the British Columbia Cancer Agency, and colleagues found that CD20 mutations involving the rituximab epitope are not the source of R-CHOP resistance. In fact, the mutations are rare in both de novo and relapsed DLBCL.
The rituximab epitope is located in exon 5 of the MS4A1 gene, so Dr Gascoyne and colleagues sequenced this region in DLBCL samples taken at diagnosis and relapse (1 month after completion of 6 cycles of R-CHOP). The team successfully sequenced 264 diagnostic samples and 15 relapsed samples.
The samples could be considered representative of the DLBCL population in British Columbia because clinical characteristics were similar to those observed in previous studies, according to the researchers. In addition, most of the patients had nodal disease with a minimum of 80% tumor, which was sufficient for detecting mutations.
Only 1 of 264 diagnostic samples showed a CD20 mutation involving the rituximab epitope—a 13 base pair heterozygous deletion at position IVS5(+8) in intron 5. Dr Gascoyne and colleagues were unable to determine if this was a polymorphism or a somatic mutation.
This patient achieved a complete response to R-CHOP and is still in remission more than 2 years after diagnosis. This outcome rules out the possibility of mutation-induced rituximab resistance.
As with the diagnostic samples, only 1 of the relapsed samples showed a CD20 mutation involving the rituximab epitope. This was a heterozygous 4 base pair deletion (TAAT) at nucleotide position 353-356, which predicted for a premature termination at amino acid position 121, well before the critical ANPS binding site.
The researchers were unable to establish whether this mutation was present at diagnosis, but they did determine there were no single nucleotide polymorphisms in exon 5 of the CD20 gene.
The rarity of mutations in the rituximab epitope observed in this study suggests these mutations cannot be responsible for the majority of R-CHOP treatment failures. However, Dr Gascoyne and colleagues said they cannot exclude the possibility that R-CHOP resistance might result from mutations at other sites in MS4A1, as these sites were not evaluated.
These findings appear in the March issue of haematologica. 
Researchers say they have come one step closer to determining the cause of R-CHOP failure in diffuse large B-cell lymphoma (DLBCL) by ruling out a potential cause.
Randy D. Gascoyne, MD, of the British Columbia Cancer Agency, and colleagues found that CD20 mutations involving the rituximab epitope are not the source of R-CHOP resistance. In fact, the mutations are rare in both de novo and relapsed DLBCL.
The rituximab epitope is located in exon 5 of the MS4A1 gene, so Dr Gascoyne and colleagues sequenced this region in DLBCL samples taken at diagnosis and relapse (1 month after completion of 6 cycles of R-CHOP). The team successfully sequenced 264 diagnostic samples and 15 relapsed samples.
The samples could be considered representative of the DLBCL population in British Columbia because clinical characteristics were similar to those observed in previous studies, according to the researchers. In addition, most of the patients had nodal disease with a minimum of 80% tumor, which was sufficient for detecting mutations.
Only 1 of 264 diagnostic samples showed a CD20 mutation involving the rituximab epitope—a 13 base pair heterozygous deletion at position IVS5(+8) in intron 5. Dr Gascoyne and colleagues were unable to determine if this was a polymorphism or a somatic mutation.
This patient achieved a complete response to R-CHOP and is still in remission more than 2 years after diagnosis. This outcome rules out the possibility of mutation-induced rituximab resistance.
As with the diagnostic samples, only 1 of the relapsed samples showed a CD20 mutation involving the rituximab epitope. This was a heterozygous 4 base pair deletion (TAAT) at nucleotide position 353-356, which predicted for a premature termination at amino acid position 121, well before the critical ANPS binding site.
The researchers were unable to establish whether this mutation was present at diagnosis, but they did determine there were no single nucleotide polymorphisms in exon 5 of the CD20 gene.
The rarity of mutations in the rituximab epitope observed in this study suggests these mutations cannot be responsible for the majority of R-CHOP treatment failures. However, Dr Gascoyne and colleagues said they cannot exclude the possibility that R-CHOP resistance might result from mutations at other sites in MS4A1, as these sites were not evaluated.
These findings appear in the March issue of haematologica.
Researchers say they have come one step closer to determining the cause of R-CHOP failure in diffuse large B-cell lymphoma (DLBCL) by ruling out a potential cause.
Randy D. Gascoyne, MD, of the British Columbia Cancer Agency, and colleagues found that CD20 mutations involving the rituximab epitope are not the source of R-CHOP resistance. In fact, the mutations are rare in both de novo and relapsed DLBCL.
The rituximab epitope is located in exon 5 of the MS4A1 gene, so Dr Gascoyne and colleagues sequenced this region in DLBCL samples taken at diagnosis and relapse (1 month after completion of 6 cycles of R-CHOP). The team successfully sequenced 264 diagnostic samples and 15 relapsed samples.
The samples could be considered representative of the DLBCL population in British Columbia because clinical characteristics were similar to those observed in previous studies, according to the researchers. In addition, most of the patients had nodal disease with a minimum of 80% tumor, which was sufficient for detecting mutations.
Only 1 of 264 diagnostic samples showed a CD20 mutation involving the rituximab epitope—a 13 base pair heterozygous deletion at position IVS5(+8) in intron 5. Dr Gascoyne and colleagues were unable to determine if this was a polymorphism or a somatic mutation.
This patient achieved a complete response to R-CHOP and is still in remission more than 2 years after diagnosis. This outcome rules out the possibility of mutation-induced rituximab resistance.
As with the diagnostic samples, only 1 of the relapsed samples showed a CD20 mutation involving the rituximab epitope. This was a heterozygous 4 base pair deletion (TAAT) at nucleotide position 353-356, which predicted for a premature termination at amino acid position 121, well before the critical ANPS binding site.
The researchers were unable to establish whether this mutation was present at diagnosis, but they did determine there were no single nucleotide polymorphisms in exon 5 of the CD20 gene.
The rarity of mutations in the rituximab epitope observed in this study suggests these mutations cannot be responsible for the majority of R-CHOP treatment failures. However, Dr Gascoyne and colleagues said they cannot exclude the possibility that R-CHOP resistance might result from mutations at other sites in MS4A1, as these sites were not evaluated.
These findings appear in the March issue of haematologica.
Novel agent more effective than standard therapy in NHL
Preliminary results of a phase 3 study indicate that pixantrone is more effective than standard chemotherapy in patients with advanced, relapsed, aggressive non-Hodgkin lymphoma (NHL).
The phase 3 EXTEND PIX301 trial enrolled 140 NHL patients from 130 sites in 17 countries. Patients had received 2 or more prior therapies and were sensitive to anthracycline treatment.
They were randomized to receive either pixantrone or another single-agent drug currently used in this patient population and selected by a physician. The trial assessed patients’ complete remission or unconfirmed complete remission rate, overall survival, and progression-free survival.
Twenty percent of patients who received pixantrone achieved either a confirmed or unconfirmed complete remission, compared to 5.7% of patients on standard chemotherapy. Eleven percent of pixantrone patients’ remissions were confirmed, whereas none of the standard chemotherapy remissions were.
The overall response rate was 37.1% with pixantrone and 14.3% for patients on standard chemotherapy. Response rates were determined by an independent assessment panel that was blinded to treatment assignments.
Complete safety information for this study is not yet available. However, the study was monitored on an ongoing basis by an independent Data Safety Monitoring Committee, and no serious concerns were raised. The most common serious toxicities (> 5%) observed in previous trials of pixantrone include grade 3 and 4 neutropenia and febrile neutropenia.
Seventy-four percent of patients enrolled in this study discontinued therapy due to disease progression or death, the majority of which were in the standard chemotherapy control arm.
This study was funded by Cell Therapeutics, Inc., the company developing pixantrone.
Cell Therapeutics says it plans to submit complete study data for presentation at a major scientific conference. The organization also plans to request a pre-New Drug Application meeting with the FDA and expects to begin submission of a rolling New Drug Application to the FDA in early 2009.
Pixantrone is an antitumor agent that contains an aza-anthracenedione molecular structure, which differentiates it from anthracycline chemotherapy agents.
Preliminary results of a phase 3 study indicate that pixantrone is more effective than standard chemotherapy in patients with advanced, relapsed, aggressive non-Hodgkin lymphoma (NHL).
The phase 3 EXTEND PIX301 trial enrolled 140 NHL patients from 130 sites in 17 countries. Patients had received 2 or more prior therapies and were sensitive to anthracycline treatment.
They were randomized to receive either pixantrone or another single-agent drug currently used in this patient population and selected by a physician. The trial assessed patients’ complete remission or unconfirmed complete remission rate, overall survival, and progression-free survival.
Twenty percent of patients who received pixantrone achieved either a confirmed or unconfirmed complete remission, compared to 5.7% of patients on standard chemotherapy. Eleven percent of pixantrone patients’ remissions were confirmed, whereas none of the standard chemotherapy remissions were.
The overall response rate was 37.1% with pixantrone and 14.3% for patients on standard chemotherapy. Response rates were determined by an independent assessment panel that was blinded to treatment assignments.
Complete safety information for this study is not yet available. However, the study was monitored on an ongoing basis by an independent Data Safety Monitoring Committee, and no serious concerns were raised. The most common serious toxicities (> 5%) observed in previous trials of pixantrone include grade 3 and 4 neutropenia and febrile neutropenia.
Seventy-four percent of patients enrolled in this study discontinued therapy due to disease progression or death, the majority of which were in the standard chemotherapy control arm.
This study was funded by Cell Therapeutics, Inc., the company developing pixantrone.
Cell Therapeutics says it plans to submit complete study data for presentation at a major scientific conference. The organization also plans to request a pre-New Drug Application meeting with the FDA and expects to begin submission of a rolling New Drug Application to the FDA in early 2009.
Pixantrone is an antitumor agent that contains an aza-anthracenedione molecular structure, which differentiates it from anthracycline chemotherapy agents.
Preliminary results of a phase 3 study indicate that pixantrone is more effective than standard chemotherapy in patients with advanced, relapsed, aggressive non-Hodgkin lymphoma (NHL).
The phase 3 EXTEND PIX301 trial enrolled 140 NHL patients from 130 sites in 17 countries. Patients had received 2 or more prior therapies and were sensitive to anthracycline treatment.
They were randomized to receive either pixantrone or another single-agent drug currently used in this patient population and selected by a physician. The trial assessed patients’ complete remission or unconfirmed complete remission rate, overall survival, and progression-free survival.
Twenty percent of patients who received pixantrone achieved either a confirmed or unconfirmed complete remission, compared to 5.7% of patients on standard chemotherapy. Eleven percent of pixantrone patients’ remissions were confirmed, whereas none of the standard chemotherapy remissions were.
The overall response rate was 37.1% with pixantrone and 14.3% for patients on standard chemotherapy. Response rates were determined by an independent assessment panel that was blinded to treatment assignments.
Complete safety information for this study is not yet available. However, the study was monitored on an ongoing basis by an independent Data Safety Monitoring Committee, and no serious concerns were raised. The most common serious toxicities (> 5%) observed in previous trials of pixantrone include grade 3 and 4 neutropenia and febrile neutropenia.
Seventy-four percent of patients enrolled in this study discontinued therapy due to disease progression or death, the majority of which were in the standard chemotherapy control arm.
This study was funded by Cell Therapeutics, Inc., the company developing pixantrone.
Cell Therapeutics says it plans to submit complete study data for presentation at a major scientific conference. The organization also plans to request a pre-New Drug Application meeting with the FDA and expects to begin submission of a rolling New Drug Application to the FDA in early 2009.
Pixantrone is an antitumor agent that contains an aza-anthracenedione molecular structure, which differentiates it from anthracycline chemotherapy agents.
Most effective first-line therapy for T-PLL
Washington, DC—Alemtuzumab is the most effective first-line therapy for T-cell prolymphocytic leukemia (T-PLL), according to a presentation at the Peripheral T-cell Lymphoma Forum.
Alemtuzumab is effective when administered alone or in combination with purine analogs, should be administered intravenously as opposed to subcutaneously, and is also effective as a second-line therapy in T-PLL, said Claire Dearden, MD, FRCP, FRCPATH, of The Royal Marsden Hospital.
Dr Dearden also recommended that T-PLL patients be considered for allogeneic stem cell transplant versus autologous stem cell transplant during first remission after alemtuzumab treatment to ensure long-term survival. Once patients relapse, she said, there is no second chance for transplant.
Dr Dearden discussed results she and her colleagues observed in T-PLL patients treated with alemtuzumab in the last 10 years. Some patients were previously untreated, and others underwent chemotherapy prior to receiving alemtuzumab.
In 38 previously treated patients, 62% achieved a complete response (CR). When 16 untreated patients received alemtuzumab intravenously, 88% achieved a CR. In comparison, 11% of patients achieved a CR after subcutaneous administration. This group was rescued with intravenous administration and pentastatin.
These results suggest that alemtuzumab should be administered intravenously rather than subcutaneously to achieve substantial efficacy. The use of intravenous alemtuzumab resulted in survival greater than 2 years.
Dr Dearden also communicated results in 26 T-PLL patients who received stem cell transplant following response to alemtuzumab. Fifteen patients received autograft, and 11 received allograft.
Fifty-five percent of patients who received allograft are still alive, as are 40% of patients who received autograft. Allografted patients also have a lower relapse rate than autografted patients, at 27% vs 53%, respectively. However, the rate of transplant-related mortality is higher in allografted patients, at 27% vs 14%, respectively.
Dr Dearden pointed out that allogeneic stem cell transplant is usually an attractive option. However, because patients with T-PLL tend to belong to an older age group, the procedure often involves a high morbidity and mortality rate.
Dr Dearden also discussed the cytogenetics that uniquely characterize T-PLL. She observed that 75% of cases have the same break point on chromosome 14. These include the inversion (14)(q11q32), the translocation t(14;14)(q11;q32), and the translocation t(X;14)(q28;q11).
Other recurrent changes involve chromosome 8, where 8 translocations have been noted. Significant molecular abnormalities also include the expression of ATM on 11q23, MTCP1 on Xq28, and TCL1a on 14q32.
The oncogene products, most commonly TCL1a, form stabilizing complexes with Akt. They activate Akt by complexing and inducing phosphorylation, downregulating pro-apoptotic control, and ensuring proliferation and survival of the T-PLL cell.
There is also an enrichment of deregulated genes on chromosome 8. NBS1 stimulates the Akt pathway. The gene UPD causes a loss of tumor suppressor gene regulation. ANK-1 is involved in motility and may explain the skin lesions and peritoneal involvement observed in T-PLL.
Dr Dearden suggested that many chromosomal and genetic abnormalities lead to a common upregulation of Akt. Therefore, using Akt or HSP 90 inhibitors may be viable approaches to future treatment.
The Peripheral T-cell Lymphoma Forum took place September 18-20.
Washington, DC—Alemtuzumab is the most effective first-line therapy for T-cell prolymphocytic leukemia (T-PLL), according to a presentation at the Peripheral T-cell Lymphoma Forum.
Alemtuzumab is effective when administered alone or in combination with purine analogs, should be administered intravenously as opposed to subcutaneously, and is also effective as a second-line therapy in T-PLL, said Claire Dearden, MD, FRCP, FRCPATH, of The Royal Marsden Hospital.
Dr Dearden also recommended that T-PLL patients be considered for allogeneic stem cell transplant versus autologous stem cell transplant during first remission after alemtuzumab treatment to ensure long-term survival. Once patients relapse, she said, there is no second chance for transplant.
Dr Dearden discussed results she and her colleagues observed in T-PLL patients treated with alemtuzumab in the last 10 years. Some patients were previously untreated, and others underwent chemotherapy prior to receiving alemtuzumab.
In 38 previously treated patients, 62% achieved a complete response (CR). When 16 untreated patients received alemtuzumab intravenously, 88% achieved a CR. In comparison, 11% of patients achieved a CR after subcutaneous administration. This group was rescued with intravenous administration and pentastatin.
These results suggest that alemtuzumab should be administered intravenously rather than subcutaneously to achieve substantial efficacy. The use of intravenous alemtuzumab resulted in survival greater than 2 years.
Dr Dearden also communicated results in 26 T-PLL patients who received stem cell transplant following response to alemtuzumab. Fifteen patients received autograft, and 11 received allograft.
Fifty-five percent of patients who received allograft are still alive, as are 40% of patients who received autograft. Allografted patients also have a lower relapse rate than autografted patients, at 27% vs 53%, respectively. However, the rate of transplant-related mortality is higher in allografted patients, at 27% vs 14%, respectively.
Dr Dearden pointed out that allogeneic stem cell transplant is usually an attractive option. However, because patients with T-PLL tend to belong to an older age group, the procedure often involves a high morbidity and mortality rate.
Dr Dearden also discussed the cytogenetics that uniquely characterize T-PLL. She observed that 75% of cases have the same break point on chromosome 14. These include the inversion (14)(q11q32), the translocation t(14;14)(q11;q32), and the translocation t(X;14)(q28;q11).
Other recurrent changes involve chromosome 8, where 8 translocations have been noted. Significant molecular abnormalities also include the expression of ATM on 11q23, MTCP1 on Xq28, and TCL1a on 14q32.
The oncogene products, most commonly TCL1a, form stabilizing complexes with Akt. They activate Akt by complexing and inducing phosphorylation, downregulating pro-apoptotic control, and ensuring proliferation and survival of the T-PLL cell.
There is also an enrichment of deregulated genes on chromosome 8. NBS1 stimulates the Akt pathway. The gene UPD causes a loss of tumor suppressor gene regulation. ANK-1 is involved in motility and may explain the skin lesions and peritoneal involvement observed in T-PLL.
Dr Dearden suggested that many chromosomal and genetic abnormalities lead to a common upregulation of Akt. Therefore, using Akt or HSP 90 inhibitors may be viable approaches to future treatment.
The Peripheral T-cell Lymphoma Forum took place September 18-20.
Washington, DC—Alemtuzumab is the most effective first-line therapy for T-cell prolymphocytic leukemia (T-PLL), according to a presentation at the Peripheral T-cell Lymphoma Forum.
Alemtuzumab is effective when administered alone or in combination with purine analogs, should be administered intravenously as opposed to subcutaneously, and is also effective as a second-line therapy in T-PLL, said Claire Dearden, MD, FRCP, FRCPATH, of The Royal Marsden Hospital.
Dr Dearden also recommended that T-PLL patients be considered for allogeneic stem cell transplant versus autologous stem cell transplant during first remission after alemtuzumab treatment to ensure long-term survival. Once patients relapse, she said, there is no second chance for transplant.
Dr Dearden discussed results she and her colleagues observed in T-PLL patients treated with alemtuzumab in the last 10 years. Some patients were previously untreated, and others underwent chemotherapy prior to receiving alemtuzumab.
In 38 previously treated patients, 62% achieved a complete response (CR). When 16 untreated patients received alemtuzumab intravenously, 88% achieved a CR. In comparison, 11% of patients achieved a CR after subcutaneous administration. This group was rescued with intravenous administration and pentastatin.
These results suggest that alemtuzumab should be administered intravenously rather than subcutaneously to achieve substantial efficacy. The use of intravenous alemtuzumab resulted in survival greater than 2 years.
Dr Dearden also communicated results in 26 T-PLL patients who received stem cell transplant following response to alemtuzumab. Fifteen patients received autograft, and 11 received allograft.
Fifty-five percent of patients who received allograft are still alive, as are 40% of patients who received autograft. Allografted patients also have a lower relapse rate than autografted patients, at 27% vs 53%, respectively. However, the rate of transplant-related mortality is higher in allografted patients, at 27% vs 14%, respectively.
Dr Dearden pointed out that allogeneic stem cell transplant is usually an attractive option. However, because patients with T-PLL tend to belong to an older age group, the procedure often involves a high morbidity and mortality rate.
Dr Dearden also discussed the cytogenetics that uniquely characterize T-PLL. She observed that 75% of cases have the same break point on chromosome 14. These include the inversion (14)(q11q32), the translocation t(14;14)(q11;q32), and the translocation t(X;14)(q28;q11).
Other recurrent changes involve chromosome 8, where 8 translocations have been noted. Significant molecular abnormalities also include the expression of ATM on 11q23, MTCP1 on Xq28, and TCL1a on 14q32.
The oncogene products, most commonly TCL1a, form stabilizing complexes with Akt. They activate Akt by complexing and inducing phosphorylation, downregulating pro-apoptotic control, and ensuring proliferation and survival of the T-PLL cell.
There is also an enrichment of deregulated genes on chromosome 8. NBS1 stimulates the Akt pathway. The gene UPD causes a loss of tumor suppressor gene regulation. ANK-1 is involved in motility and may explain the skin lesions and peritoneal involvement observed in T-PLL.
Dr Dearden suggested that many chromosomal and genetic abnormalities lead to a common upregulation of Akt. Therefore, using Akt or HSP 90 inhibitors may be viable approaches to future treatment.
The Peripheral T-cell Lymphoma Forum took place September 18-20.