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Since 1947, we have treated 19 children with neuroblastoma whose first symptoms were paralysis or weakness of an extremity, and/or incontinence due to tumor in the spinal canal. In 18 patients, the spine tumor was part of a dumbbell tumor which was present in the adjacent paravertebral area and in one, no extra-spinal tumor was found. Aggressive treatment was employed for all. In 17 children, the intraspinal tumor was treated by laminectomy and irradiation with and without chemotherapy. Radiation and chemotherapy were used for two. The extraspinal tumor was excised totally in six and partially in six. All 12 children received postoperative radiation and chemotherapy. In 6 children, the extraspinal tumor was treated only with radiation and chemotherapy. Nine of 19 children are alive without evidence of neuroblastoma. Thirteen patients showed either partial (6) or full (7) neurologic recovery. Survival was related to the child's age at diagnosis and the extent of disease. While 8 of 9 children under 1 yr of age survived, only 1 of 10 children over 1 yr survived. None of the 5 children with Stage IV disease at diagnosis could be saved. The degree and frequency of neurologic recovery were greatest in children whose neurologic symptoms had been present the shortest times and were equal among those who survived and those who died. The outlook for children who become paralyzed by neuroblastoma is not hopeless; therapy aimed at saving life or neurologic function is both worthwhile and rewarding.

Adrenal cortical carcinoma is a rare neoplasm in infancy. Most cases present with Cushing’s syndrome, hirsuitism, precocious puberty, or rarely inappropriate ADH secretion. Associated congenital anomalies and concurrent central nervous system and hepatic tumors have also been documented. Occasionally, the tumor may be non-functioning. Three cases have been seen at the M.D. Anderson Hospital and Tumor Institute with a variety of presentations and outcome.

Brain metastasis is uncommon in osteosarcoma, but this may be changing with prolonged patient survival in the modern chemotherapy era. We present 5 patients with brain metastases out of 39 with lung metastasis (13%) in a total of 87 osteosarcoma patients. The clinical manifestations of brain metastases were catastrophic: massive hemorrhage in 2 and status epilepticus in 3. Metastases were single or multiple, and some were osteoblastic. Surgical intervention in 2 cases resulted in dramatic, though transient, clinical improvement. We advocate periodic neuroradiology screening in osteosarcoma patients with lung metastases, for early detection of brain involvement.

The response to intraarterial cis-diamminedichloroplatinum II (CDP) chemotherapy was evaluated by computed tomography (CT) in 33 patients with pathologically proved osteosarcoma of the long or flat bones. Twenty-one of the 33 patients had a CT scan before chemotherapy was started. In the other 12 patients, a CT scan was obtained after at least two courses of treatment, and additional studies were performed during the course of therapy. In those patients responding to treatment, the posttherapy scan revealed a remarkable decrease or complete disappearance of the associated soft-tissue mass and clear reestablishment of the fat planes between the muscle bundles that had been obscured. There was sharp definition of the peripheral margins of the calcified healing neoplasm, and the calcification in the healing tumor could be differentiated easily from that of the original bone neoplasm. The findings of CT were compared with those of conventional studies and pathologic results. CT was more accurate than conventional studies in detecting healing process and diagnosis of remission.

The clinical and microbiologic characteristics of 29 episodes of sepsis caused by Acinetobacter calcoaceticus were reviewed in 25 children with underlying malignancies. Of the 29 episodes of sepsis with this organism 28 occurred from 1980 through 1984, compared with 1 episode from 1973 to 1979. Risk of infection was associated with the presence of intravascular cannulae, osteosarcoma and recent administration of antitumor chemotherapy. There was no association with neutropenia, malnutrition or focal infection. Of 28 organisms for which the biotypes were known, 14 (50%) were var. lwoffi and 14 (50%) were var. anitratus; 11 episodes (38%) were part of a polymicrobial bacteremia. All patients responded favorably to antimicrobial therapy.

Transcatheter intra-arterial infusion of chemotherapeutic agents for osteosarcomas and embolization of inoperable giant cell tumors of the axial skeleton have become essential components in patient management [1–13].

Of 43 testicular tumors in children seen at the Children’s Hospital Medical Center and Sidney Farber Cancer Institute 33 were malignant. These tumors occurred primarily in young children. Any solid scrotal mass in an infant must be considered malignant until proved otherwise. Primary emphasis is placed on the 20 cases of embryonal cell carcinoma. Of9 patients who underwent only orchiectomy 5 have died, whereas all 11 patients who received combination therapy have survived. We recommend radical inguinal orchiectomy, extended unilateral retroperitoneal lymphadenectomy and adjuvant chemotherapy in repeated courses for 2 years. Radiotherapy is withheld if the lymphadenectomy is negative.

During the past decade, major advances have been reported in the treatment of osteosarcoma [1–9]. These derive principally from the application of chemotherapy in the management of the primary tumor, as an adjuvant to prevent pulmonary metastases, and in multidisciplinary strategies to eradicate established disease. These developments, however, have not been without controversy [10–13]. The latter emerged principally from a comparison of the results of the new investigations with historical controls. This communication will outline the impact of chemotherapy in osteosarcoma and examine the controversial issues.

Rhabdomyosarcomas of the head and neck may spread by diffuse local invasion, resulting in erosion of the base of the skull with possible extension to the leptomeninges, brain, and cranial nerves, as well as invasion of the ventricular system with possible intradural, extramedullary metastases anywhere along the neuraxis. Meningeal spread of tumor is difficult to eradicate, and nearly all patients reviewed died soon after meningeal disease was evident. Patients with erosion of the base of the skull or abnormal cranial nerve findings seem to have a risk of seeding the meninges with tumor. The clinical evolution of this pattern of metastatic spread is reviewed, diagnostic studies are recommended, and therapeutic considerations are discussed. Tentative treatment guidelines are also offered.

Chemotherapy and ionizing radiation currently in use as anticancer agents may adversely affect normal tissues and developing organs. Long-term complications may only become manifest many years later. These considerations are particularly important in view of the improved survival and projected normal life expectancies which are being anticipated for patients with malignant conditions. The major sequelae attributed to treatment with anticancer agents are outlined.

High-dose methotrexate (V-MTX-CF) and adriamycin (ADR) were utilized as adjuvant and definitive treatment in osteogenic sarcoma. Three regimens have been investigated: 1. V-MTX-CF administered at 3-weekly intervals for 18-24 months (12 patients). 2. V-MTX-CF + ADR (day 7) administered at 4-weekly intervals following the 3-weekly schedule for 18 months (22 patients). 3. Three 4-weekly V-MTX-CF consolidating courses at the beginning, middle and end of a 12 month period with V-MTX-CF interposed between courses (25 patients). Actuarial analysis reveals that over 60% of patients are free of disease for 4+ to 72+ months. This contrasts with past experience when only 20% were cured. Additional patients were rendered free of disease by multidisciplinary treatment. Pre-operative chemotherapy administered to selected patients for limb preservation caused variable degrees of tumor destruction.

Cytocidal activity of a drug is dependent on both drug dosage and duration of exposure. In contrast to the 'conventional" 6-h infusion and in an attempto to improve its efficacy, the high-dose methotrexate therapeutic regimen was given over a 24-h period with 10% of the dose administered in the first hour. Citrovorum factor was initiated at hour 24 and continued for 72 h. Treatment was administered every 2-3 weeks. 57 infusions were performed in twelve patients aged 7-20 years (six with osteogenic sarcoma and six with acute lymphoblastic leukemia). Determinations of serum methotrexate levels revealed that the levels were dependent on the dose. Levels assayed at 24 h revealed the following results: 4.4 +/- 1.4 x 10(-5) molar with 4.5 g/m(2), 2.04 +/- 0.34 x 10(-4) molar with 7.5 g/m(2) and 4.59 +/- 0.80 x 10(-4) molar with 12.5 g/m(2). Major toxicity was myelosuppression in 12 of 57 patients. There were no responses. The study demonstrates that 24-h infusions of high-dose methotrexate can be tolerated every 2-3 weeks in patients without bone marrow involvement and levels of at least 10(-4) molar can be maintained during the infusion.

Three major factors that have contributed to recent major improvements in survival figures in childhood cancers are a better understanding of the mode of action of chemotherapeutic agents, their more intensive and prolonged use, and the steady introduction of new drugs and protocols. The long-term administration of such medicines can become increasingly difficult as the limited supply of veins is exhausted by repeated injections of corrosive thrombogenic substances causing progressive discomfort to the patient, family, and physician and increasing the risk of either termination of therapy or tissue-threatening extravasations. To minimize or obviate these hazards, we have performed vascular access procedures in 74 children and in infants weighing less than 10 kg. These techniques have been borrowed from the repertoire of the transplant surgeon and have been upgraded to meet the special needs of patients who require repeated venipuncture for blood drawing, drug injection, and blood products administration, especially during periods of profound aplasia when infection is an everpresent threat. The operation of choice is a loop fistula from saphenous vein to superficial femoral artery. Bovine carotid artery and umbilical vein loops have been employed when the first procedure cannot be performed. When immediate access has been required, femoral-femoral shunts have been constructed and have proved entirely serviceable for periods of over 1 yr. Saphenous fistulas have the advantages of not requiring external connections, of using solely autogenous material, of high flow rates to rapidly dilute chemicals, and of lasting for at least as long as 3 yr. No infections and only two faifures have occurred in the series; in both instances a synthetic material was employed. Such accesses provide another surgical modality to help make easier and more successful the care and life of the child with malignancy. The particular choice of operation is mandated by the individual case.

Multidisciplinary treatment for childhood urologic cancer has resulted in improved survival. However, the sucessful results may be marred by the appearance of therapy-related sequelae. Thus, radiation therapy has produced spine deformities (kyphosis and scoliosis), ovarian failure, renal disease and abnormalities in the skin, subcutaneous tissue, and muscle. Successful treatment of pulmonary metastases has been associated with abnormalities in pulmonary physiology and chest wall deformities. Chemotherapy-related complications include hemorrhagic cystitis and possible gonadal failure. If exenteration for bladder or prostate cancer is required, the sequelae are immediately apparent and include ureterosigmoidostomy, colostomy, or iliostomy. Oncogenic sequelae comprise benign and malignant neoplasms, and many of them appear to be radiation induced. Recognition of these sequelae has lead to changes in therapy to reduce or prevent their occurrence. However, despite innovative changes, long-term survivors still appear to be a risk for the development of late complications. The importance of continued surveillance is stressed.

• A patient with acute oliguric uric acid nephropathy was treated with hemodialysis. Recovery in this disorder is based on treatment of both the uremic state and the intrarenal crystal obstruction. Hemodialysis with high uric acid clearance is much more efficient than other forms of therapy in this disorder. ( Am J Dis Child 129:956-958, 1975)

Temporary neurologic abnormalities were detected in 9 of 60 patients undergoing treatment with high-dose methotrexate and citrovorum factor rescue (MTX-CF) for osteosarcoma. The incidence of abnormalities and abnormalities themselves were more severe than previously reported. This was attributed to an increased dose and more frequent administration of MTX-CF. In view of the transient nature of the abnormalities, a biochemical cause is implicated, and the mechanisms by which it may occur are discussed.

Osteogenic sarcoma has been shown to be responsive to adriamycin (ADR) and vincristine-high-dose methotrexate with citrovorum factor "rescue" (VCR-MTX-CF). Both regimens have produced responses in patients with established disease. These experiences prompted utilization of these forms of chemotherapy in adjuvant programs. The VCR-MTX-CF regimen was also utilized in combination with radiation therapy to treat patients with inoperable tumors and those with presumed residual microscopic tumor in the lungs or elsewhere following surgical resection. More recently, chemotherapy was utilized in pre-treatment programs to facilitate local en bloc resection and insertion of internal prostheses to achieve useful functioning limbs. The evolution of these programs at the Sidney Farber Cancer Institute from January 1971, is documented and the results are updated to June 1976.

In an effort to achieve high concentrations and prolonged exposure times, high-dose methotrexate (MTX) was administered by the intra-arterial route over 6 hours at a dose of 12.5 g/m2 to nine patients with osteosarcoma. This was followed by citrovorum factor (CF) rescue, which was initiated 12 hours after completion of the infusion (MTX-CF). The regimen achieved high local concentrations over a finite period. No toxicity was encountered. Treatment was administered at weekly intervals, during which intravenous MTX-CF was interposed if facilities for intra-arterial administration were not available. However, despite increases in local venous concentrations and exposure times, only four of nine patients (44%) responded. This is similar to responses achieved with 7.5 g/m2 (48%) with CF initiated 2 hours after completion of the infusion. Higher MTX doses, intra-arterial administration, and prolongation of cytotoxic exposure time did not confer a therapeutic advantage as opposed to "conventional" intravenous high doses.

A syndrome of fever, lethargy, irritability and rash occurred in patients undergoing surgery, irradiation and chemotherapy for Wilms' tumor. The incidence, course and severity of these findings are described. Potential etiologic factors are analyzed and a hypothesis advanced.

A patient with telangiectatic osteosarcoma of the proximal fibula while receiving adjuvant chemotherapy, developed pulmonary and, later, mesenteric metastases. The pulmonary metastases were resected and the mesenteric metastasis was eradicated with surgery and intra-arterial cis-diamminedichloroplatinum II. This represents an additional example of an alteration in the clinical pattern of metastases induced by chemotherapy and the ability to achieve cure with a multidisciplinary approach.

Adjuvant chemotherapy comprising Adriamycin (ADM) and Methotrexate (MTX) with Citrovorum Factor (CF) was administered on a randomization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor. One group received high dose MTX (regimen I) and the other moderate dose MTX (regimen II). In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery. All patients were free of metastasis at the beginning of therapy. The efficacy of therapy was determined by recording the percentage of continuously disease-free patients. This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only. The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group. Over the ensuing 27-66 months, 31 of 56 patients (55%) treated with regimen I and 25 of 50 (50%) treated with regimen II were disease-free. The overall disease-free survival in both regimens was 53%. This is similar to the 132 patients treated with previous adjuvant chemotherapy protocols (45-50%). However, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients (12%) treated contemporaneously with surgery only (P less than 0.0005). Survival in the latter is similar to that of historical control patients. These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy. These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious.

Optimum treatment for osteogenic sarcoma involves a rapid definitive attack upon the primary tumor and systemic treatment to destroy pulmonary metastases [2, 4, 5, 6, 10, 11, 13, 14, 16]. Traditionally, the first objective is attempted by amputation, although radiation therapy has also been employed [1]. The latter, however, has not met with universal approval since osteogenic sarcoma is generally considered a radioresistant tumor, and retention of an uninhibited source of metastases is contrary to sound principles of cancer management. Not infrequently, tumor growth after irradiation required amputation for palliation [9].

Between July 1976 and December 1981, 46 patients seen at the Dana Farber Cancer Institute and the Children’s Hospital (DFCI/TCH) who met the criteria of being less than 30 years of age, without evidence of metastatic disease by plain chest radiograph, bone scan, and whole lung or computed tomography, were entered into this study. Detailed discussions relative to the merits and safety of limb salvage (LS) surgery were carried out in each case felt by the surgeon (HGW) to be a candidate for LS. Criteria for LS were: proximal humeral primaries if the brachial artery was univolved, midfemur lesions if the distal growth plate could be safely spared, distal femur or proximal fibular lesions if sufficient linear growth had been achieved, and lesions in an expendable bone (e.g., fibula). In all cases, a minimum of a wide margin was attempted. The chemotherapy regimen included vincristine (2 mg/m2), methotrexate (7.5 gm/m2) with leucovorin rescue, and doxorubicin (75 mg/m2) to a total of 450 mg/m2. All operative reports and staging studies were reviewed and the operative procedures classified as marginal, wide, or radical. Survival median curves were estimated by the method of Kaplan and Meier. Sixty-one patients who met the eligibility requirements for this study and were treated at the DFCI/TCH between 1948 and 1972 served as historical controls.

Two clinically silent renal metastatic lesions from primary osteogenic sarcoma were first detected on radionuclide bone scan. A needle biopsy performed under the guidance of abdominal ultrasonography confirmed the diagnosis. Prior to nephrectomy, further definition of the metastatic lesion was attained using enhanced computed tomography. A review of the English literature revealed only six previous cases of metastatic osteosarcoma detected in the kidney prior to autopsy.

Genetic effects of cancer in childhood were examined among offspring of patients enrolled in the tumor registries of the Sidney Farber Cancer Institute and the Kansas University Medical Center. For 146 patients, 84 women and 62 men, 293 pregnancies were reported after cessation of treatment of diverse neoplasms. The outcomes of 286 completed pregnancies were as follows: 242 live births (1 set of twins), 1 stillbirth, 25 spontaneous abortions, and 19 therapeutic abortions. Seven live-born infants died during the first 2 years of life, a frequency in accord with expectation. Two offspring have developed cancer. One girl and her father had bilateral hereditary retinoblastoma. A second girl developed acute myelocytic leukemia; her mother had received radiotherapy during childhood for a brain tumor. Compared with their cousins and with published figures for the general population, the study progeny had no excess of congenital anomalies or other diseases. Chromosome and immunoglobulin studies of a few offspring did not reveal damage from preconception exposure to cancer chemotherapy and radiotherapy. Findings indicated that large collaborative studies are needed to monitor the offspring of childhood cancer survivors for inherited traits associated with the parental tumors and for mutagenic effects of therapy, particularly intense multimodality treatments.

The therapeutic efficacy of intra-arterial cis-Diamminedichloroplatinum-II on the primary tumor was assessed in relationship to survival. Patients with a combined complete and partial response (over 60% necrosis) had a 64% metastases-free survival, and those with no response (under 60% necrosis) a 34% survival.

A follow-up study was made of two independent series of 1,807 and 425 children who were alive five years after diagnosis of a malignant neoplasm. Over the subsequent 20 years (5 to 24 years after initial diagnosis), actuarial survival rates for the cohorts were 83% and 79%, respectively, compared to 97% for matched control subjects in the general population (P less than 0.01). Cure was achieved in a large majority of the 5-year relapse-free survivors of cancer in this study.

Biological reconstruction of an extremity was performed in seven children undergoing treatment with chemotherapy and tumor resection for osteosarcoma. An allograft was utilized in six patients and an autograft in one. One patient had a local recurrence at 6 months and was treated by hemipelvectomy. Healing at the distal site of the autograft was present prior to the operation. Among the remaining six patients, union occurred in 11 of 12 potential sites of osteosynthesis. Two patients required secondary procedures. All patients have remained free of pulmonary metastases. The patient treated with an autograft developed a secondary (? metastatic) osteosarcoma in the allograft and at other bony sites. Biological reconstruction deserves further investigation as a means of accomplishing limb salvage.

High-dose methotrexate with citrovorum factor "rescue" (MTX-CF) produced an apparent complete response of the primary tumor in three patients with osteosarcoma. The response was sustained with MTX-CF, intra-arterial cis-diamminedichloroplatinum II (CDP) and Adriamycin (doxorubicin) for 18 months. Treatment was then electively discontinued. Local recurrence occurred in two patients, 6 and 4 months later, respectively. MTX-CF was reinstated and a complete response was again achieved in one patient. This has been maintained for 15+ months with MTX-CF and intra-arterial CDP administered for 13 of the 15+ months. Reinduction with MTX-CF failed in the second relapsed patient but an apparent remission was again achieved with radiation and intra-arterial CDP. This has been maintained with intravenous CDP, cyclophosphamide and phenylalanine mustard for 14+ months. A complete response in the primary tumor was still present in the nonrelapsed patient, 42 months from diagnosis. All patients have remained free of pulmonary metastases, 40+ to 42+ months from diagnosis.

The clinical and morphologic features of 18 patients with paratesticular rhabdomyosarcoma are reviewed. Although medical attention was sought frequently within 2 months the lesion was mistaken initially for other more common scrotal conditions in more than a third of the patients, delaying a correct diagnosis for 3 weeks to 4 months. Half of the patients had retroperitoneal lymph node metastases. However, with multimodal therapy 61 per cent remain free of disease at a median of 6 years from diagnosis.

Fifty-six patients with osteosarcoma were studied to determine the onset of pulmonary and bone metastases. While pulmonary metastases were always detected prior to bone metastases in the era before adjuvant chemotherapy, in this study of patients on adjuvant therapy 16% of patients with metastases showed osseous metastases prior to or without pulmonary metastases.

The potential neuropsychological effects of treatment were investigated in 124 childhood cancer patients. Children were classified into groups on the basis of treatment modality and treatment status. All patients received systemic chemotherapy. Other treatment modalities included intrathecal chemotherapy and intrathecal chemotherapy plus central nervous system radiation therapy. Treatment status was determined by whether children were newly diagnosed patients in active treatment or long-term survivors of cancer. This classification resulted in five groups; group 1 (n = 29)—children with newly diagnosed disease who were receiving intrathecal chemotherapy; group 2 (n = 21)—children with newly diagnosed disease who were receiving systemic chemotherapy without central nervous system treatment; group 3 (n = 24)—long-term survivors who had received intrathecal chemotherapy; group 4 (n = 25)—long—term survivors who had received intrathecal chemotherapy plus cranial radiotherapy; and group 5 (n = 25)—long—term survivors who had received systemic chemotherapy only (no specific central nervous system treatment). Groups were compared by using multivariate analysis of variance on sets of neuropsychological test variables that represent major cognitive domains. Results of comparisons indicated significant group differences for most dependent-variable sets. Follow-up pairwise comparisons showed that the group of long-term survivors who had received intrathecal chemotherapy plus cranial radiotherapy consistently obtained lower test scores than the other four groups. These findings are consistent with results of previous studies, thus indicating that intrathecal chemotherapy plus cranial radiotherapy is associated with significant effects on neuropsychological performance. Comparisons among newly diagnosed and long-term groups of patients who did not receive cranial radiotherapy yielded null results on measures of higher-order cognitive functions. However, significant group differences were observed on measures of fine-motor and visual-motor skills; newly diagnosed groups obtained lower scores than the nonirradiated long-term survivor groups. Findings were attributed to chemotherapy-induced peripheral neuropathy that differentially affected the newly diagnosed groups. ( J Child Neurol 1988;3:53-62).

Intraarterial infusion of cis-platinum was evaluated in 14 patients with primary osteosarcoma because the method delivers a higher dose to the neoplasm without increasing systemic toxicity. The tumor response was evaluated by clinical examination, conventional radiography, angiography, and histopathologic examination. Eight (57%) of the 14 patients responded. Among the eight responders, four patients with medullary osteosarcoma of the extremities were treated by limb salvage operation followed by insertion of an endoprosthesis to preserve limb function. The responders are all alive with a median follow-up period of 17.5 months; six of them have no evaluable disease. The six failures died of disease after median survival of 6.5 months. Intraarterial cis-platinum infusion proved to be an effective approach in treating osteosarcoma and created the opportunity for limb salvage.

Renal insufficiency due to hyperuricaemia (uric acid nephropathy) has been observed as a complication of leukaemia and lymphoma (Rieselbach, Bentzel, Cotclave, Frei and Freireich, 1964; Barry, Hunter, Davis and Crosby, 1967; Gold and Fritz, 1957; Greenbaum and Stone, 1959). It is caused by an increase in nucleoprotein catabolism and may occur spontaneously or be precipitated or exacerbated by chemotherapeutic agents and radiation therapy. It is an important cause of renal failure usually manifesting with oliguria or anuria. In this report hyperuricaemia in a patient with leukaemia was associated with abnormal nephrograms. D.M., a 12-year-old white female with acute myelogenous leukaemia, was admitted to the Children's Hospital Medical Center following several days of vomiting and abdominal pain. She had experienced several episodes of blood-stained urine during this time. The diagnosis of acute myelogenous leukaemia had been established two years prior to admission; several remissions had been achieved bu...

Three cases are reported to describe further our experience with antitumor chemotherapeutic agents, administered either during or following irradiation to the liver in children. The scan defect that has occurred acutely and the peripheral blood cell count depression make us believe that these agents are toxic to liver which is irradiated in whole or in part; further, that the unirradiated segment may be adversely affected by these agents since it is in a sensitive state of compensatory hypertrophy; and that such defects can occur suddenly after the completion of irradiation when certain chemotherapeutic agents are administered within 6 months of the completion of irradiation.

A two dosage therapeutic regimen of L-asparaginase was investigated to determine the differences in the production of abnormal reactions and remission induction in pediatric patients with leukemia. Among 35 patients, 17 were randomized to receive 200 I.U./kg daily for 2 weeks and 18, 5,000 I.U./kg twice weekly for 2 weeks. Of the 17 children on the daily schedule there were nine complete remissions and one improved marrow; among the 18 children in the twice-weekly schedule there were nine complete remissions, two partial remissions, and two improved marrows. The median duration of remission in each group was 9 weeks. Hypocellular marrows were noted in each regimen. Anaphylactoid reactions occurred only in the twice-weekly schedule. In the latter, one patient developed pancreatitis and another hyperglycemia not related to pancreatitis. Greater aberrations in the blood ammonia and serum amylase were noted in the twice-weekly regimen. A high intermittent dose schedule, while permitting less frequent clinic visits, increases the risk of side effects without adding to the beneficial effects of the drug.

A patient with Wilms' tumor and pulmonary metastases (successfully treated with radiotherapy and chemotherapy) subsequently developed a cerebral metastasis. This was treated by surgical excision, radiotherapy, and the continued use of chemotherapy. The patient is living and free of disease five years after craniotomy. Cerebral metastases from Wilms' tumor should not be considered incurable.

Dr. Pochedly is to be congratulated on his efforts to present to the "pediatrician, general practitioner as well as the clinical hematologist" a monograph devoted exclusively to childhood leukemia. The text is arranged in logical sequence commencing with types of acute leukemia in childhood (chapter I) and congenital leukemia (chapter II). Chapters III through VII deal with the signs and symptoms, complications and metabolic and immunologic abnormalities. Diseases which simulate leukemia are discussed in chapter VIII, while the remaining four chapters are devoted to treatment and to chronic granulocytic leukemia of childhood.

We indicated that the cause of hypoglycemia was not entirely resolved. Certainly, among the possibilities we cited, an abnormality in glucose metabolism due to reduced liver glucose-6-phosphatase should also be considered. We regret its omission. Indeed, all causes of hypoglycemia should receive consideration. We were most impressed with the leukemic infiltration of the organs and tissues noted at autopsy. Report by other workers suggesting that this could be an etiological factor1-3 and particularly the correlation between a reduction in the size of the spleen and an increase in blood sugar,4 prompted us to infer that the leukemic mass probably played a major role in the pathogenesis.

PANNICULITIS of the subcutaneous tissue may follow the withdrawal of large doses of corticosteroids.1 2 3 4 5 6 It may be confused with leukemic infiltrations of the skin. Case Report Acute undifferentiated leukemia was established in a 6 1/2-year-old boy. Therapy comprised methotrexate and prednisone. Partial bone-marrow remission was achieved, and the dosage of prednisone was tapered, with methotrexate continued as maintenance therapy. The total dose of prednisone administered was 1350 mg. Forty-three days after withdrawal of corticosteroids 2 painful, enlarging nodules developed in the right thigh. Repeat bone-marrow examination demonstrated relapse, and the lesions were considered to be leukemic infiltrates. Therapy was altered . . .

Cancer Diagnosis in Children is a review of the diagnostic work-up which the author claims will be of interest to the general physician, paramedical personnel, students, and anyone concerned with child health. The text is presented in readable style, culminating in an extremely useful appendix (Chapter 7) . This provides a concise resume of the information presented in the previous six chapters. It adds to the quality of the book which could have been further enhanced by the inclusion of an index, which I found sadly lacking.

Long-term reproductive and gonadal steroid potential has been investigated in 10 female patients (pts) who were treated for a variety of abdominal malignancies before puberty. All pts presented with complaints of primary amenorrhea and lack of development of secondary sexual characteristics while off therapy and free of extant disease for 1-23 years. Evaluation consisted of assessment of pubertal development according to Tanner and by double antibody radioimmunoassay of serum gonadotropins according to Odell. All pts demonstrated significantly elevated serum gonadotropins indicative of ovarian failure: 24 mIU/ml to 85 mIU/ml LH and 78 mIU/ml to 156 mIU/ml FSH, with FSH consistently elevated above LH. The pts had been treated with between 1790-5500 rad to the abdomen and/or pelvis in fractionated doses as well as one or a combination of chemotherapeutic agents including vincristine, methotrexate, cyclophosphamide, actinomycin D or chlorambucil. Improved long-term survivorship from prepubertal malignancies necessitates consideration of future ovarian steroidal and reproductive function in therapeutic regimes. Evaluation of other pts to attempt to separate the effects of radio- and chemotherapy on gonadal function, as well as assessment of the effects of replacement estrogen therapies is planned. (Supported by Grant CA82002.)