We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.

The extent of development of digital adhesive toe-pads in sympatric species of microhylid frogs, Cophixalus and Sphenophryne, correlates with the degree of arboreality exhibited by the species. The same basic structures and cell types are found in the toe-pads of these microhylid frogs as are found in other arboreal and semi- arboreal frogs of many diverse evolutionary lineages. A variety of types of cell surface, with unknown functional significance but potential systematic use, are found on the feet of these frogs. Allometric increase in adhesive-pad area in larger species is by widening of the toe-pad, as opposed to acquisition of accessory pads as in some hylid tree frogs.

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Figure 2IgH and Ig rearrangement analysis at diagnosis and relapses. Genomic DNA from diagnosis and relapses was subjected to PCR analysis using the FR1c-5Ј and JHc-3Ј IgH-specific primers and using the IRSS-5Ј and Kde-3Ј Ig-specific primers. Both IgH and Igspecific PCR products were spotted in duplicate on to the nylon membrane and hybridized with the patient-specific probe. Mononuclear cells (MNC) from a healthy volunteer donor served as a control. Dotblot results for IgH and Ig are shown in a and b, respectively. because the same IgH chain rearrangement was already present at the onset, while chain gene deletion was detectable at relapse only.This case underlines the important role of comparative studies, mainly at the molecular level, between disease patterns at diagnosis and relapse, as potential means yielding valuable insights into the mechanism of leukemic recurrence. Therapy-related T cell lymphoblastic lymphoma with t(11;19)(q23;p13) and MLL gene rearrangement TO THE EDITORDuring the past several decades, advances in the treatment of childhood cancers have resulted in increased survival of pediatric cancer patients. This is in large part due to the use of aggressive chemotherapy regimens, radiation therapy or a combination of both. However, along with the benefits of increased survival. It has become Correspondence: PD Aplan at his current address: