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With the advances in the therapy of childhood cancers over the past 30 years, many children who are now cured of their cancer are moving into adulthood. These patients have, in many cases, been exposed to multiple therapeutic modalities (chemotherapy, radiation, and/or surgery), and in recent years have experienced more and more intensive therapies. Potential late sequelae can involve almost any organ system, but can be predicted, in part, by the chemotherapy or radiation that individuals may have received. These complications may be categorized by their timing relative to the discontinuation of therapy: early (under 5 years), intermediate (5-20 years), or very late (over 20 years). Four potential late sequelae are reviewed (thyroid, cataracts, renal, and osteoporosis), and recommendations are made for screening of at risk individuals for these long-term complications. The need for long-term follow-up of this unique group of individuals is critical as we attempt to completely define the risks and benefits of our therapeutic efforts.

In recent years there has been a significant improvement in the survival rate of children with malignant solid tumors. With Wilms' tumor, the survival rate has risen to 80%, but a subset of these patients with unfavorable histologies and therefore a higher rate of relapse need a different strategy. For those patients with soft tissue sarcoma, brain tumors, and bone tumors the combination of preoperative chemotherapy, surgery, and radiotherapy followed by maintenance multiagent chemotherapy has resulted in a survival rate of 45% to 70%. In the case of neuroblastoma, a similar aggressive approach has not resulted in an improved survival. A different approach that uses screening of infants by urinary testing for VMA and HVA to detect earlier and potentially less malignant tumors has begun in Japan and North America in the hope that preclinical detection will reduce mortality.

Clinical research has by and large been responsible for the success achieved in treating pediatric cancer during the last 20 years. An important milestone has recently been reached with the passing of the halfway mark in the goal of curing all childhood cancer. It is important to re-evaluate our priorities and set future goals. The large multi-institutional cooperative groups have been the mainstay of past successes and should as their major goal continue work towards improvements in survival, particularly for those malignancies which continue to have a poor prognosis. The second priority should be the identification of potential long-term effects of childhood cancer and the effects associated with therapy. Concomitant with improvements in the cure rate it is our responsibility to ensure that cured patients can have the opportunity to enjoy productive, useful and happy lives. The third priority is to foster research of pilot clinical research to serve as a source of ideas to be used for future Phase III clinical trials. Moreover, increased efforts should be directed towards aspects of preventive oncology which requires increased knowledge regarding the etiology of childhood cancers.

The clinical and pathologic findings of four patients with Chediak-Higashi syndrome in the accelerated phase were studied in order to clarify the nature of this enigmatic process. Fever, lymphadenopathy, hepatosplenomegaly, and cytopenias were present in every patient. All cases demonstrated extensive parenchymal infiltrates in many organs composed of benign-appearing histiocytes manifesting hemophagocytosis accompanied by lymphocytes and plasma cells. Studies in one patient suggested a viral etiology with the findings of a low blood lymphocyte OKT4 to OKT8 ratio, acquired loss of lymphocyte response to mitogens, the presence of Epstein-Barr virus genome in the mononuclear cells of lymph node, blood, and bone marrow, and possible clinical responses to acyclovir. It is concluded that the accelerated phase of Chediak-Higashi syndrome may be the clinicopathologic expression of the virus-associated hemophagocytic syndrome.

Of 395 male pediatric patients with previously untreated acute lymphoblastic leukemia, 20 (5%) exhibited testicular infiltration prior to or concurrent with their first bone marrow relapse. Fourteen occurred as an isolated relapse and six occurred concomitant with bone marrow and/or central nervous system relapse. Nine of the 20 relapses were in patients who had discontinued therapy after completing three years of continuous complete remission. Factors found to be independently associated with an increased risk of testicular relapse during maintained remission included pretreatment lymphadenopathy, and to a lesser extent, initial hemoglobin level and initial platelet count. Pretreatment splenomegaly and lymphadenopathy appear to imply an increased risk of testicular relapse for those patients who have their maintenance therapy discontinued. Time from testicular relapse to bone marrow relapse or death was significantly shorter for patients with testicular involvement while receiving chemotherapy when compared to patients with testicular relapse after discontinuing therapy. In those patients achieving three years of continuous complete remission, subsequent testicular relapse occurred significantly more often in patients who discontinued therapy than a similar group who continued therapy. In a group of 76 males who received presymptomatic gonadal radiation immediately after achieving an initial marrow remission, protection appears to have been provided against the manifestation of testicular leukemia during maintained remission.

Sudden cerebrovascular insults occurred during or immediately following remission induction therapy in 4 children with acute lymphoblastic leukemia. In 3, cerebral infarction was due to thrombosis. In the fourth, an intracerebral hematoma developed representing either frank hemorrhaging or a hemorrhagic infarction. None of the patients had central nervous system leukemia or extreme leukocytosis at the time of diagnosis. Symptoms were obtundation, hemiparesis, seizures, and headache. The induction chemotherapy included L-asparaginase which causes deficiencies of antithrombin, plasminogen, fibrinogen, and factors IX and XI. These hemostatic abnormalities may explain the thromboses and bleeding observed in these children.