- Email: [email protected]
High leukaemia cure rate in Down's syndrome explained
Newsdesk
Lights on for patients with skin cancer
© Michael Abbey/Science Photo Library
Children with skin cancer have been successfully treated with 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). Three children with basalcell carcinoma (BCC) or basiloid follicular hamartoma covering 12–25% of body-surface area were treated with ALA cream and light from a dye laser and filtered tungsten-halogen lamp, leading to 85–98% overall clearance.
Basal-cell carcinoma can be treated with topical cream and photodynamic therapy
“The outcomes were very much better than would have been obtained from therapeutic alternatives. The children had durable responses without problems from scarring, loss of function or change in appearance, or the stress of multiple extensive surgical procedures”, says lead investigator Allan Oseroff, Roswell Park Cancer Institute, Buffalo, NY, USA, who believes that this is the first time that wide-area ALA-PDT has been used in children. Alexandr Itkin, Scripps Clinic, San Diego, CA, USA, says: “Despite the fact that this is an observational study of only three patients, the high number of tumours treated provides strong evidence for broad area PDT of multiple BCC.” Itkin emphasises the cosmetic results of the treatment, because it avoids the mutilating sideeffects of conventional surgery. He adds, “Broad-area treatment makes good sense because it allows clinicians
to address existing and subclinical tumours not yet visible to the naked eye”. Oseroff agrees: “One of the most interesting findings is the lack of new BCC in subsequent years. This could result from destruction of microscopic subclinical lesions or induction of an anticarcinoma immune response”. ALA-PDT should also be used for adults. “Wide area PDT has been very successful in treating adults with almost confluent in-situ squamouscell carcinomas (SCC) and actinic keratoses on the lower legs, resulting from sun damage”, says Oseroff. “Also, we are just finishing a large study of ALA-PDT in 126 adults with BCC and in-situ SCC. For 4–6 h ALA application, the complete response rate for single treatment of superficial lesions was 90–96% and more than 80% for nodular carcinomas.”
Cathel Kerr
High leukaemia cure rate in Down’s syndrome explained Researchers report that children with Down’s syndrome who develop acute megakaryocytic leukaemia (AMkL) respond well to chemotherapy based on cytosine arabinoside (ara-C) because of characteristic mutations in the haemopoietic transcription factor GATA1. “These mutations reduce the expression of cytidine deaminase, an enzyme that normally inactivates araC”, explains senior researcher Jeffrey Taub (Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA). About 10% of children with Down’s syndrome have transient myeloproliferative disorder, an accumulation of immature megakaryocytes in the blood and elsewhere. The disorder often spontaneously regresses— indeed, only 1–10% of cases are routinely diagnosed but 20–30% of these cases develop AMkL in early childhood. Mutations in the GATA1 134
gene are present in leukaemic blasts from most children with AMkL and could be the initiating mutation for this unusual leukaemia. Taub and his colleagues now report that these GATA1 mutations, which produce a truncated version of the transcription factor, also have a beneficial effect. Children with Down’s syndrome are known to have a far better survival rate after ara-C treatment than do those without Down’s syndrome who have other forms of acute myeloid leukaemia. The investigators now show that this difference relates to the GATA1 mutations identified in AMkL. Their data indicate that GATA1 mutations reduce the expression of cytidine deaminase in AMkL blast cells, which makes the cells hypersensitive to ara-C (J Natl Cancer Inst 2005: 97: 226–31). “This study provides tremendous insights into the unique sensitivity of
AMkL blasts from Down’s syndrome children to ara-C”, comments John Crispino (University of Chicago, IL, USA), adding that the absence of GATA1 mutations partly explains the lack of hypersensitivity to ara-C in non-Down’s syndrome acute myeloid leukaemia . “These results support the idea that children with Down’s syndrome can be safely treated with lower doses of ara-C”, he notes, “but cannot be translated to other forms of leukaemia because GATA1 is not mutated in these”. Taub agrees that his results are mainly relevant to children with Down’s syndrome and AMkL. But he adds, “knowing that GATA1 mutations make cells very sensitive to ara-C may be something that can be exploited in other forms of leukaemia”.
Jane Bradbury http://oncology.thelancet.com Vol 6 March 2005
Lights on for patients with skin cancer
© Michael Abbey/Science Photo Library
Children with skin cancer have been successfully treated with 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). Three children with basalcell carcinoma (BCC) or basiloid follicular hamartoma covering 12–25% of body-surface area were treated with ALA cream and light from a dye laser and filtered tungsten-halogen lamp, leading to 85–98% overall clearance.
Basal-cell carcinoma can be treated with topical cream and photodynamic therapy
“The outcomes were very much better than would have been obtained from therapeutic alternatives. The children had durable responses without problems from scarring, loss of function or change in appearance, or the stress of multiple extensive surgical procedures”, says lead investigator Allan Oseroff, Roswell Park Cancer Institute, Buffalo, NY, USA, who believes that this is the first time that wide-area ALA-PDT has been used in children. Alexandr Itkin, Scripps Clinic, San Diego, CA, USA, says: “Despite the fact that this is an observational study of only three patients, the high number of tumours treated provides strong evidence for broad area PDT of multiple BCC.” Itkin emphasises the cosmetic results of the treatment, because it avoids the mutilating sideeffects of conventional surgery. He adds, “Broad-area treatment makes good sense because it allows clinicians
to address existing and subclinical tumours not yet visible to the naked eye”. Oseroff agrees: “One of the most interesting findings is the lack of new BCC in subsequent years. This could result from destruction of microscopic subclinical lesions or induction of an anticarcinoma immune response”. ALA-PDT should also be used for adults. “Wide area PDT has been very successful in treating adults with almost confluent in-situ squamouscell carcinomas (SCC) and actinic keratoses on the lower legs, resulting from sun damage”, says Oseroff. “Also, we are just finishing a large study of ALA-PDT in 126 adults with BCC and in-situ SCC. For 4–6 h ALA application, the complete response rate for single treatment of superficial lesions was 90–96% and more than 80% for nodular carcinomas.”
Cathel Kerr
High leukaemia cure rate in Down’s syndrome explained Researchers report that children with Down’s syndrome who develop acute megakaryocytic leukaemia (AMkL) respond well to chemotherapy based on cytosine arabinoside (ara-C) because of characteristic mutations in the haemopoietic transcription factor GATA1. “These mutations reduce the expression of cytidine deaminase, an enzyme that normally inactivates araC”, explains senior researcher Jeffrey Taub (Children’s Hospital of Michigan, Wayne State University School of Medicine, Detroit, MI, USA). About 10% of children with Down’s syndrome have transient myeloproliferative disorder, an accumulation of immature megakaryocytes in the blood and elsewhere. The disorder often spontaneously regresses— indeed, only 1–10% of cases are routinely diagnosed but 20–30% of these cases develop AMkL in early childhood. Mutations in the GATA1 134
gene are present in leukaemic blasts from most children with AMkL and could be the initiating mutation for this unusual leukaemia. Taub and his colleagues now report that these GATA1 mutations, which produce a truncated version of the transcription factor, also have a beneficial effect. Children with Down’s syndrome are known to have a far better survival rate after ara-C treatment than do those without Down’s syndrome who have other forms of acute myeloid leukaemia. The investigators now show that this difference relates to the GATA1 mutations identified in AMkL. Their data indicate that GATA1 mutations reduce the expression of cytidine deaminase in AMkL blast cells, which makes the cells hypersensitive to ara-C (J Natl Cancer Inst 2005: 97: 226–31). “This study provides tremendous insights into the unique sensitivity of
AMkL blasts from Down’s syndrome children to ara-C”, comments John Crispino (University of Chicago, IL, USA), adding that the absence of GATA1 mutations partly explains the lack of hypersensitivity to ara-C in non-Down’s syndrome acute myeloid leukaemia . “These results support the idea that children with Down’s syndrome can be safely treated with lower doses of ara-C”, he notes, “but cannot be translated to other forms of leukaemia because GATA1 is not mutated in these”. Taub agrees that his results are mainly relevant to children with Down’s syndrome and AMkL. But he adds, “knowing that GATA1 mutations make cells very sensitive to ara-C may be something that can be exploited in other forms of leukaemia”.
Jane Bradbury http://oncology.thelancet.com Vol 6 March 2005