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Consolidation treatment for ALL—which is best?
Newsdesk
Consolidation treatment for ALL—which is best? Allogeneic stem-cell treatment (SCT) does not produce a better outcome than autologous SCT or chemotherapy in children in complete remission of very-high-risk acute lymphoblastic leukaemia (VHR-ALL), according to a study in J Clin Oncol 2007; 25: 16–24. In a randomised trial Jose-Maria Ribera (Institut Catala d’OncologiaHospital Universitari Germans Trias i Pujol, Barcelona, Spain) and colleagues attempted to establish the optimum postremission treatment for children with VHR-ALL by comparing the outcomes of allogeneic and autologous SCT and chemotherapy. The authors report that intensification of consolidation has not improved the outcome of children with VHR-ALL and that in these patients the role of allogeneic stem-cell transplantation in first remission has not been well defined. 106 children with VHR-ALL were recruited and given induction treat-
ment with five drugs followed by intensification with three cycles of chemotherapy. Of the 100 children in complete remission, 24, who had an HLA-identical family donor, were assigned to allogeneic SCT, and the remaining 76 were randomly assigned to either autologous SCT (n=38) or delayed intensification followed by maintenance chemotherapy for up to 2 years in complete remisson (n=38). By an intention-to-treat analysis, no significant difference was seen between the donor and nodonor groups for disease-free survival (DFS; 45% [95% CI, 27–65%] vs 45% [37–55%], respectively) or for overall survival (OS; 48% [30–67%] vs 51% [43–61%]). The same was true for the comparison of autologous SCT with chemotherapy (DFS: 44% [29–60%] vs 46% [32–62%], respectively; OS: 45% [31–62%] vs 57% [43–73%], respectively).
These results suggest that allogeneic SCT does not produce a better outcome for children with VHR-ALL than does autologous SCT or chemotherapy. However, Adriana Balduzzi (Clinica Pediatrica dell’Universita degli Studi di Milano Bicocca, Milan, Italy) cautions that: “the lack of any advantage, reported within this cohort, of allogenic transplantation is not consistent with previous reports, in particular with [another trial] reporting 357 patients, whose outcome was significantly affected by donor availability”. Goran Gustafsson (Childhood Cancer Research Unit, Karolinska Institute, Sweden) adds, “the number of patients in the different groups is low, especially in the allogeneic arm”. Although the conclusion might be correct, he feels that this study does not provide the evidence needed because of the small study size and low power.
Angela Paolino
Risk of sarcoma increased in survivors of retinoblastoma Survivors of hereditary retinoblastoma have an increased risk of developing soft-tissue sarcomas several decades after their original diagnosis, according to a new study (J Natl Cancer Inst 2007; 99: 24–31). The risk for six subtypes of softtissue sarcoma was assessed in a cohort of 963 1-year survivors of
Retinoblastoma treatment may lead to sarcomas
104
hereditary retinoblastoma diagnosed from 1914–1984: 69 soft-tissue sarcomas were identified in 68 patients (standardised incidence ratio [SIR] compared with population data 184 [95% CI 143–233]). The most common subtype was leiomyosarcoma (SIR 390 [247–585]). 78% of leiomyosarcomas were seen over 30 years after the original retinoblastoma diagnosis. Most sarcomas identified were in patients who had received radiotherapy for retinoblastoma, but 18 were outside the radiation field. The cumulative risk for any sarcoma 50 years after radiotherapy for retinoblastoma was 13·1% (9·7–17·0%). These findings suggest patients with germline RB1 mutations have a genetic pre-disposition to developing sarcoma. “Soft tissue sarcomas are attributed to a mutation in RB1 and to the radiation treatment that most patients with retinoblastoma were given up to
80 years ago. The risks of soft tissue sarcoma in this study result from treatments used decades ago”, says lead author, Ruth Kleinerman (National Cancer Institute, Rockville, MD, USA). “The fact that survivors of hereditary retinoblastoma have an increased incidence of cancer, especially osteosarcoma, has been known for many years. However, the striking incidence of softtissue sarcomas, especially leiomyosarcoma, is less well appreciated”, says Ian Judson (Institute of Cancer Research, Surrey, UK). Survivors of retinoblastoma, especially those who were treated with radiotherapy, “need to be advised to take new lumps or persistent pain very seriously”, concludes Judson. “A robust referral pathway needs to be put in place such that any suspicious lesions are investigated promptly and appropriately”, he adds.
Hannah Cumber http://oncology.thelancet.com Vol 8 February 2007
Consolidation treatment for ALL—which is best? Allogeneic stem-cell treatment (SCT) does not produce a better outcome than autologous SCT or chemotherapy in children in complete remission of very-high-risk acute lymphoblastic leukaemia (VHR-ALL), according to a study in J Clin Oncol 2007; 25: 16–24. In a randomised trial Jose-Maria Ribera (Institut Catala d’OncologiaHospital Universitari Germans Trias i Pujol, Barcelona, Spain) and colleagues attempted to establish the optimum postremission treatment for children with VHR-ALL by comparing the outcomes of allogeneic and autologous SCT and chemotherapy. The authors report that intensification of consolidation has not improved the outcome of children with VHR-ALL and that in these patients the role of allogeneic stem-cell transplantation in first remission has not been well defined. 106 children with VHR-ALL were recruited and given induction treat-
ment with five drugs followed by intensification with three cycles of chemotherapy. Of the 100 children in complete remission, 24, who had an HLA-identical family donor, were assigned to allogeneic SCT, and the remaining 76 were randomly assigned to either autologous SCT (n=38) or delayed intensification followed by maintenance chemotherapy for up to 2 years in complete remisson (n=38). By an intention-to-treat analysis, no significant difference was seen between the donor and nodonor groups for disease-free survival (DFS; 45% [95% CI, 27–65%] vs 45% [37–55%], respectively) or for overall survival (OS; 48% [30–67%] vs 51% [43–61%]). The same was true for the comparison of autologous SCT with chemotherapy (DFS: 44% [29–60%] vs 46% [32–62%], respectively; OS: 45% [31–62%] vs 57% [43–73%], respectively).
These results suggest that allogeneic SCT does not produce a better outcome for children with VHR-ALL than does autologous SCT or chemotherapy. However, Adriana Balduzzi (Clinica Pediatrica dell’Universita degli Studi di Milano Bicocca, Milan, Italy) cautions that: “the lack of any advantage, reported within this cohort, of allogenic transplantation is not consistent with previous reports, in particular with [another trial] reporting 357 patients, whose outcome was significantly affected by donor availability”. Goran Gustafsson (Childhood Cancer Research Unit, Karolinska Institute, Sweden) adds, “the number of patients in the different groups is low, especially in the allogeneic arm”. Although the conclusion might be correct, he feels that this study does not provide the evidence needed because of the small study size and low power.
Angela Paolino
Risk of sarcoma increased in survivors of retinoblastoma Survivors of hereditary retinoblastoma have an increased risk of developing soft-tissue sarcomas several decades after their original diagnosis, according to a new study (J Natl Cancer Inst 2007; 99: 24–31). The risk for six subtypes of softtissue sarcoma was assessed in a cohort of 963 1-year survivors of
Retinoblastoma treatment may lead to sarcomas
104
hereditary retinoblastoma diagnosed from 1914–1984: 69 soft-tissue sarcomas were identified in 68 patients (standardised incidence ratio [SIR] compared with population data 184 [95% CI 143–233]). The most common subtype was leiomyosarcoma (SIR 390 [247–585]). 78% of leiomyosarcomas were seen over 30 years after the original retinoblastoma diagnosis. Most sarcomas identified were in patients who had received radiotherapy for retinoblastoma, but 18 were outside the radiation field. The cumulative risk for any sarcoma 50 years after radiotherapy for retinoblastoma was 13·1% (9·7–17·0%). These findings suggest patients with germline RB1 mutations have a genetic pre-disposition to developing sarcoma. “Soft tissue sarcomas are attributed to a mutation in RB1 and to the radiation treatment that most patients with retinoblastoma were given up to
80 years ago. The risks of soft tissue sarcoma in this study result from treatments used decades ago”, says lead author, Ruth Kleinerman (National Cancer Institute, Rockville, MD, USA). “The fact that survivors of hereditary retinoblastoma have an increased incidence of cancer, especially osteosarcoma, has been known for many years. However, the striking incidence of softtissue sarcomas, especially leiomyosarcoma, is less well appreciated”, says Ian Judson (Institute of Cancer Research, Surrey, UK). Survivors of retinoblastoma, especially those who were treated with radiotherapy, “need to be advised to take new lumps or persistent pain very seriously”, concludes Judson. “A robust referral pathway needs to be put in place such that any suspicious lesions are investigated promptly and appropriately”, he adds.
Hannah Cumber http://oncology.thelancet.com Vol 8 February 2007