Malignancies in Down syndrome.

Down Syndrome (DS) is associated with an increased incidence of malignancies, especially leukaemias. We came across 8 DS children presenting with malignancies and having trisomy 21 as the sole cytogenetic abnormality. Of these 8 DS cases, 4 presented with acute lymphocytic leukaemia, 2 with acute myeloid leukaemia and one case each with Hodgkin's disease and Wilms' tumour. There are contradictory reports regarding the distribution of myeloid versus lymphoid malignancies in DS children and their response to therapy. The exact mechanism by which patients with DS are predisposed to develop malignancies is unclear. However, presence of the extra chromosome no. 21 is presumed to disrupt the genetic balance which increases generalized susceptibility to genetic and environmental trauma. Furthermore, an increased methotrexate toxicity observed in these patients should also be taken into consideration in designing treatment for DS children with malignancies.

Bone marrow transplantation.

Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph' chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are achieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recommendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.

Oncogenes: present status.

Oncogenes are genes associated with causation of cancer. They were originally associated with the ability of retroviruses to cause tumors in animals. These viral oncogenes (V-onc) have their cellular counterparts (C-onc) called Proto oncogenes. Function of Proto oncogenes is to maintain cellular growth and development. Activation of these proto-oncogenes can occur due to mutation which leads to uncontrolled cell growth. The Proto oncogenes can be grouped into different categories based on their protein products, i.e. protein kinases, growth factors, growth factor receptors, and DNA binding proteins. There are also genes that normally suppress malignant transformation and these are called anti oncogenes. Loss of their suppressor activity leads to unimpeded growth. Oncogene abnormalities are seen in pediatric leukemias, lymphomas, and various solid tumors. Anti oncogenes are associated with retinoblastoma (Rb gene), Wilms' tumor, rhabdomyosarcoma and neuroblastoma, etc. Identification of these abnormalities have diagnostic, prognostic and therapeutic implications. The utility of oncogenes in classification of human cancer and monitoring cancer therapy is quite clear, but the future of these for therapeutic interventions remains uncertain. Role of c-abl oncogene in chronic myeloid leukemia (CML), bcl-2, in lymphomas, N-myc in neuroblastomas and retinoblastoma (Rb) gene in retinoblastomas is well understood and used in designing proper therapeutic approaches. Since oncogenes also control normal cellular function, their use for therapy may be limited by the amount of damage to normal cells. Their maximum therapeutic benefit may be realized only when used in combination with other modalities.