bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐dose chemotherapy and blood stem cell autografts for children with first relapsed acute lymphoblastic leukemia: A pilot study of the children's cancer and leukemia study group of Japan (CCLSG)
Authors: Takaue Yoichi , Watanabe Arata , Murakami Tatsuo , Watanabe Tsutomu , Kawano Yoshifumi , Kuroda Yasuhiro , Matsushita Takeji , Kikuta Atsushi , Kosaka Yoshiyuki , Kudo Toru , Shimizu Hiroyuki , Koizumi Shoichi , Fujimoto Takeo
Published: February 2007

This study was performed to determine the value of high‐dose chemotherapy and peripheral blood stem cell autografts (PBSCT) in the treatment of children with first relapsed acute lymphoblastic leukemia (ALL). Eighteen children underwent PBSCT during the second complete remission (CR) and had a minimum 10 month follow‐up. The median age of the patients was 11 yr (range, 2–17 yr). Fifteen patients received the “MCVAC” regimen, one received high‐dose MCNU + busulfan therapy, one received high‐dose melphalan + VP‐16, and one received melphalan + carboplatin + cytosine arabinoside + MCNU. None of these regimens included total body irradiation. Eight patients developed recurrence of the disease at 1 to 19 mo (median, 3 mo) after PBSCT. Patients in whom the first relapse occurred sooner, that is, within 16 mo of initial therapy, tended to have a better survival rate than those who developed relapse after 30 mo (six of seven survived versus four of 11; not significant). Although the preliminary data provided little conclusive information, it did suggest that incorporation of PBSCT in the salvage protocol of relapsed childhood ALL can be justified. © 1994 Wiley‐Liss, Inc.
Neuropsychological evaluation of children with intracranial tumors: Impact of treatment modalities
Authors: García‐Pérez A. , Sierrasesumaga L. , Narbona‐García J. , Calvo‐Manuel F. , Aguirre‐Ventalló M.
Published: February 2007

Antineoplastic treatment has a deleterious effect on intellectual functions, which is mainly attributable to radiotherapy. With the object of determining the neuropsychological disturbances associated with brain irradiation in the child, and to try to differentiate them from the effects caused by the other types of treatment (surgical and chemotherapy) as well as from the effects of the tumor itself, a cross‐sectional study was carried out in 25 survivors of medial edge intracranial tumors. In order to monitor the effect of systemic chemotherapy on the cognitive functions, and the effect of prolonged absence from school, two control groups were formed, one made up of subjects treated with chemotherapy for extracranial tumors, and the other of patients with nonmalignant chronic disease. Neuropsychological functions were measured using the Spanish version of the Wechsler scale, as well as the following tests: Spreen‐Benton, ITPA and TALE scales, Yuste Memory Test, Thurstone Attention Test, and the Rey Complex Figure.

In addition to a progressive decline found in the full scale intelligence quotient in children irradiated for intracranial tumors, variance analysis showed that these patients deteriorate mainly in visual attention and memory, but also significantly in verbal fluency and in the Performance Intelligence Quotient and all its subtests, when compared to the control groups. Visual attention and the Wechsler Picture Arrangement and Block Designs, were the tests whose decline correlated with the total radiation administered. The article relates this specific neuropsychological injury with the total brain irradiation dose but also with the structures located in the cone‐down fields of irradiation to boost regions in the middle edge intracranial content. © 1994 Wiley‐Liss, Inc.
Hormonal treatment in pregnancy: A possible risk factor for neuroblastoma
Authors: Mandel M. , Toren A. , Rechavi G. , Dor J. , Ben‐Bassat I. , Neumann Y.
Published: February 2007

In the last 4 years, 24 cases of neuroblastoma were treated in the Pediatric Hematology‐Oncology Unit at the Chaim Sheba Medical Center, 8 of whom were under 1 year of age. Four of them were the product of a pregnancy‐induced or preserved by gonadotropins, clomiphene citrate, or progestational hormones. These drugs are known to produce a higher than normal level of estradiol or progestrone in the early stages of pregnancy. Our observation led to the hypothesis that high levels of progestational hormones given during pregnancy are a risk factor for neuroblastoma in infancy. © 1994 Wiley‐Liss, Inc.
Low grade malignant hemangioendothelioma of bone: A disease potentially curable with radiotherapy
Authors: Welles Laurie , Dorfman Howard , Valentine Edward S. , Wiernik Peter H.
Published: February 2007

This is a case of a young woman with a low grade malignant hemangioendothelioma of bone, who is considered cured after more than 8 years of follow‐up post radiotherapy. This patient demonstrates that, despite the characteristic multifocality of this rare tumor, treatment with radiotherapy alone can be curative. © 1994 Wiley‐Liss, Inc.
Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: A randomized study
Authors: Risseeuw‐Appel Inge M. , Dekker Ina , Hop Wim C. J. , Hählen Karel
Published: February 2007

A randomized study was done in twenty newly diagnosed children with acute lymphoblastic leukemia. Ten children were treated with Escherichia coli L‐asparaginase, and ten with Erwinia chrysanthemi L‐asparaginase. L‐asparaginase (ASP) treatment started halfway during ALL‐induction treatment with vincristine, prednisone, daunorubicine and intrathecal methotrexate.

The mean activated partial thromboplastin time (APTT) level in all children demonstrated a significant fall (P < 0.001) from 28.25 sec at diagnosis to 23.0 sec at the start of ASP treatment. In this same time interval, the mean fibrinogen level declined markedly from 3 g/l to 1.2 g/l (P < 0.001), probably due to prednisone therapy. The APTT stayed shortened during ASP therapy, whereas the hypofibrinogenemia recovered significantly faster in the Erwinia group (P ⩽ 0.01). Factors (F) II, V, VII and X stayed within the normal range, while F VIII and F IX were elevated. During the entire period of induction therapy, the ATIII activity remained within the normal range in both treatment groups. The protein C values, however, demonstrated a steady decline from 140% at start of ASP treatment to a mean of 81% and 93%, respectively, at the end of the ASP therapy in the E. coli and Erwinia group. Five of the ten children treated with E. coli ASP demonstrated protein C levels below 70% at the end of ASP therapy, opposed to none of the Erwinia treated patients (P = 0.03).

We suggest that the effect of ASP resulting in decreased coagulationfactor synthesis is in part counterbalanced by the effect of prednisone on the coagulation system, when ASP is administered at the end of ALL induction treatment. The overall effect of ASP either of E. coli or of Erwinia on the hemorrhagic system reveals a slight imbalance towards thrombosis, mainly because of a gradual decrease in protein C activity. This imbalance is less pronounced in the Erwinia group. © 1994 Wiley‐Liss, Inc.
Ocular sequelae of multimodal therapy of hematologic malignancies in children
Authors: Pakisch B. , Langmann G. , Langmann A. , Slavc I. , Poier E. , Urban C. , Poschauko J. , Lackner H. , Knoblauch S. , Leitner H. , Dornbusch H. J. , Stücklschweiger G. , Raith J. , Hackl A.
Published: February 2007

We retrospectively analyzed the ocular findings after polychemotherapy including intrathecal methotrexate, systemic corticosteroids, and prophylactic cranial irradiation in children with acute lymphoblastic leukemia (n = 16) and non‐Hodgkin's lymphoma (n = 2). After a median surveillance time of 4.1 years, asymptomatic ocular abnormalities were observed in 83% of the patients: 7/18 had a decreased tear formation, 5/17 had an opacity of the vitreous body, and 13/18 had an opacity of the lens. It was not possible to determine retrospectively which therapy caused a particular effect. A comparison of the 2 irradiation techniques (with and without blocking of the lacrimal glands) showed that in 5/7 children who developed a reduced eye secretion, the lacrimal glands are within the treatment volume. Therefore, the reduced eye secretion is most likely radiation‐induced. Whereas the opacities of the vitreous body were caused by thrombopenia and bleeding during the course of disease, corticoid therapy might have contributed to the lens opacities. © 1994 Wiley‐Liss, Inc.
Treatment of advanced stage diffuse, small non‐cleaved cell lymphoma in childhood: Further experience with total therapy B
Authors: Griffin Timothy C. , Bowman W. Paul , Winick Naomi J. , Buchanan George R.
Published: February 2007

Prior to the development of intensive treatments for patients with advanced stage B‐cell non‐Hodgkin's lymphoma (B‐NHL), the prognosis for such patients was dismal. A minority of patients attained long‐term, disease‐free survival. Since 1981, we have treated 28 children with advanced stage B‐NHL with an intensive chemotherapeutic protocol, Total Therapy B. This regimen employs cycles of fractionated high‐dose cyclophosphamide, doxorubicin, and vincristine alternating with sequential infusions of high‐dose methotrexate and escalating doses of cytarabine, in addition to intensive intrathecal therapy. The planned duration of therapy is approximately 6 months. Two patients had B‐cell acute lymphoblastic leukemia and 26 had stage III B‐NHL; none had CNS involvement. The median age was 7 years. All 28 patients achieved complete remission (CR). Both patients with B‐ALL and 21 of 26 with stage III B‐NHL remain in CR, with a median follow‐up of 51 months. Treatment failures included 3 patients with recurrent or progressive disease, 1 toxic death in CR, and 1 patient who developed a secondary mediastinal T‐cell lymphoblastic lymphoma 4 1/2 years after the diagnosis of B‐NHL. The 2‐ and 5‐year event‐free survival rates were 85.7 ± 6.6% (SE) and 79.6 ± 8.5%, respectively. Total Therapy B is a highly effective therapy for children with advanced stage B‐NHL without CNS involvement. © 1994 Wiley‐Liss, Inc.
Carboplatin and VP 16 in medulloblastoma: A phase II study of the French Society of Pediatric Oncology (sfop)
Authors: Gentet Jean Claude , Doz François , Bouffet Eric , Plantaz Dominique , Roché Henri , Tron Philippe , Kalifa Chantal , Mazingue Françhise , Sariban Eric , Chastagner Pascal , Bernard Jean‐Louis , Brunat‐Mentigny Maud , Raybaud Claude , Zucker Jean‐Michel
Published: February 2007

The purpose of this study is to evaluate the antitumor activity of combination carboplatin and etoposide in measurable medulloblastoma. From January '89 to January '92, 26 patients with medulloblastoma were included in a multicentric phase II study of 2 courses of carboplatin 160 mg/m2/d day 1 to day 5 and VP16 100 mg/m2/d day 1 to day 5. Median age was 10 years (19 months‐14.5 years). First treatment was surgery alone in 1 patient, surgery + radiotherapy in 4 patients, surgery + chemotherapy in 2 patients less than 3 years old, surgery + radiotherapy + chemotherapy in 19 patients (“8 drugs in 1 day” based:17, SIOP I:1, SIOP II:1). Previous treatment included cisplatin (20 cases), carboplatin (1 case), and VP16 (7 cases). Measurable disease was evaluated by CT scan, MRI or myelogram and CSF. Response rate (RR) was 72 ± 10%:8 complete responses (CR), 10 partial responses (PR), 1 objective effect (OE), 6 progressive disease (PD), 1 non‐evaluable. Thirty‐six courses were evaluated for toxicity. Median duration of WHO grade 4 neutropenia was 8 days (0–23). One patient died at day 18 after the first course because of diffuse haemorrhage during septic aplasia. Five other non‐life‐threatening septicemias were recorded. Median number of platelet transfusions was 1 (0–4). One child who had achieved a PR after two courses died from CNS bleeding after the third course. This drug combination achieves a high response rate in childhood medulloblastoma. Severe toxicity has been mainly encountered in previously heavily treated patients. Tolerance may be acceptable in newly diagnosed children, but careful hematological follow‐up and platelet transfusional support are definitely mandatory. © 1994 Wiley‐Liss, Inc.
Disseminated nonlymphoblastic lymphoma of childhood: A childrens cancer group study, CCG‐552
Authors: Finlay Jonathan L. , Anderson James R. , Cecalupo Anthony J. , Hutchinson Raymond J. , Kadin Marshall E. , Kjeldsberg Carl R. , Provisor Arthur J. , Woods William G. , Meadows Anna T.
Published: February 2007

(1) Purpose: To assess the efficacy of a chemotherapy‐only regimen in pediatric patients with disseminated nonlymphoblastic lymphoma and acute B‐cell leukemia (B‐ALL).

(2) Patients and Methods: Sixty‐eight eligible patients with previously untreated disseminated non‐lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty‐five patients had small non‐cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty‐seven were stage III, six were stage IV, and 15 had B‐ALL; 13 had central nervous system (CNS) involvement.

(3) Results: Four year event‐free survival (EFS) was 53% (SE ± 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki‐1‐positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients.

(4) Conclusions: Advanced stage SNCCL requires better CNS‐directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease‐free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy‐only strategies. DLCL patients do not need intensive CNS‐directed chemotherapy. © 1994 Wiley‐Liss, Inc.
High‐dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma
Authors: Kremens Bernhard , Klingebiel Thomas , Herrmann Friedrich , Bender‐Götze Christine , Burdach Stefan , Ebell Wolfram , Friedrich Wolfgang , Koscielniak Ewa , Schmid Hansjörg , Siegert Wolfgang , Suttorp Meinolf , Schaefer Ulrich W. , Berthold Frank
Published: February 2007

Twenty‐six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty‐two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression‐free after 16–56 months.

These results are essentially not different from a single‐center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue. © 1994 Wiley‐Liss, Inc.
Epstein‐barr virus (EBV) latent membrane protein (LMP) in tumor cells of Hodgkin's disease in pediatric patients
Authors: Preciado María Victoria , De Matteo Elena , Diez Blanca , Grinstein Saúl
Published: February 2007

Twenty‐nine out of 31 consecutive pediatric patients with Hodgkin's disease treated at our hospital from 1988 to 1992 were studied. The selection criterion was the availability of sufficient formalin‐fixed, paraffin‐embedded tissue for analysis. Patient age ranged from 3 to 15 years with a median age of 7 years. Lymph node biopsies were examined for the presence of Epstein‐Barr virus (EBV)‐encoded latent membrane protein (LMP) in malignant cells by peroxidase immunolabeling. LMP positivity was present in 10/15 (67%) of mixed cellularity, 1/6 (17%) of lymphocyte predominance, 0/7 (0%) of nodular sclerosis, and 1/1 (100%) of lymphocyte depletion. Positive cases by age range were: 10/12 (83%) for 3–6 years and 2/17 (11%) for 7–15 years. The association between EBV and Hodgkin's disease in children appeared to be more frequent in patients with mixed cellularity and those in the 3–6 age range, though examples of EBV‐positive tumors were found in other histologic subtypes, stages and ages. Findings indicate that Hodgkin's disease in children is at least as strongly linked to EBV as in adults. Furthermore, we suggest that the EBV is associated with a subgroup of patients which can be defined on the basis of the age at diagnosis. © 1995 Wiley‐Liss, Inc.
High‐dose epirubicin and r‐met‐hu G‐CSF (Filgrastim) in the treatment of patients with advanced breast cancer: A hellenic cooperative oncology group study
Authors: Fountzilas George , Skarlos Demosthenis , Katsohis Constantine , Pavlidis Nicholas , Giannakakis Theodoros , Bafaloukos Dimitrios , Fahantidis Epaminondas , Klouvas George , Beer Mario , Kosmidis Paris
Published: February 2007

The delivery of high‐dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G‐CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 μg/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0–16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19–49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r‐met‐hu G‐CSF allows the administration of high‐dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life. © 1995 Wiley‐Liss, Inc.
Isolated CNS metastasis as the first site of recurrence in a child with germ cell tumor of the mediastinum
Authors: Berkow Roger L. , Kelly David R.
Published: February 2007

We describe a 2‐year‐old black female who was previously in complete remission from a stage 4 mediastinal germ cell tumor (stage 4 because of a single pulmonary parenchymal lesion). She presented with headaches, obtundation, and brain herniation, and suffered sudden death 12 months after completing high‐dose chemotherapy. Autopsy revealed a large intraventricular lesion with mixed germ cell tumor elements, but no other evidence of malignancy was found. This case represents the first report of isolated CNS metastasis of malignant germ cell tumor in a child in apparent remission without evidence of advanced or recurrent disease in other sites. It is possible that the aggressive chemotherapy used resulted in a change in the natural history of this disorder. © 1995 Wiley‐Liss, Inc.
Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: Leukemic cell procoagulant activity is not responsible for the hypercoagulable state
Authors: Bilgrami Syed , Greenberg Bernard R. , Weinstein Ralph E. , Hair Gregory A. , Rickles Frederick R.
Published: February 2007

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well‐known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre‐B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients. © 1995 Wiley‐Liss, Inc.
Consecutive glioblastoma and B cell non‐Hodgkin's lymphoma in a young child with von recklinghausen's neurofibromatosis
Authors: Uyttebroeck Anne , Legius Eric , Brock Penelope , Van De Casseye Willy , Casaer Paul , Van Daele Maria Casteels
Published: February 2007

A young child with neurofibromatosis type 1 (NF1) is reported who developed two primary malignancies: a glioblastoma, followed 6 months later by an abdominal B cell non‐Hodgkin's lymphoma. The child is now 4.5 years off treatment and disease free, but has developed progressive and severe psychomotor retardation as sequelae. The NF1 gene is known to act as a tumor suppressor gene. The possible mechanisms leading to the occurrence of a second primary tumor in this child are discussed. © 1995 Wiley‐Liss, Inc.
Intrauterine monoclonal origin of neonatal concordant acute lymphoblastic leukemia in monozygotic twins
Authors: Mahmoud Hazem H. , Ridge Susan A. , Behm Frederick G. , Pui Ching‐Hon , Ford Anthony M. , Raimondi Susana C. , Greaves Melvin F.
Published: February 2007

We report detailed immunological, cytogenetic and molecular evidence for complete identity of the leukemic cell populations in monozygotic female twins with concordant leukemia diagnosed at two months of age. Both infants had early pre‐B acute lymphoblastic leukemia with the (11;19)(q23;p13) chromosomal translocation. A common clonal origin of leukemia in these infants was suggested by the finding of identical oligoclonal heavy chain immunoglobulin gene rearrangements. Leukemic cell DNA was examined for 11q23 rearrangements by Southern blotting and restriction fragments of identical size were found in the two cases, in contrast to the diversity of rearrangements observed in other unrelated and nontwinned control infants with t(11;19)(q23;p13). Similar restriction fragments were absent in blood mononuclear DNA from both parents, liver tissue from one twin and remission bone marrow of the other, indicating that the 11q23 rearrangement was acquired and not inherited as a chromosomal abnormality or polymorphism. These findings provide a definitive evidence for intrauterine single cell origin, with twin to twin transmission, of concordant leukemia in this infant twin pair. © 1995 Wiley‐Liss, Inc.
Wilms' tumor: A rational use of preoperative imaging
Authors: Ditchfield Michael R. , De Campo John F. , Waters Keith D. , Nolan Terrance M.
Published: February 2007

Objective—To determine whether a preoperative imaging protocol relying predominantly on a chest X‐ray film (CXR) and ultrasound in patients with Wilms' tumor is adequate for patient management and to determine the frequency more sophisticated imaging, in particular, computed tomography (CT), is required. Design and setting—Historical cohort study at a tertiary pediatric hospital. Subjects—60 consecutive patients with Wilms' tumor treated at our institution between 1980 and 1990. Main outcome measure—The preoperative imaging was recorded and 2‐ and 4‐year survival were compared with the National Wilms' Tumor Study. Results—100% of patients had a preoperative CXR, 95% abdominal ultrasound, 5% abdominal CT, 13% chest CT, 47% abdominal X‐ray, 2% aortography, 5% cavography, and 35% intravenous urography. The overall 2‐ and 4‐year survivals of 92% and 90%, respectively, did not statistically differ from the National Wilms' Tumor Study 2‐ and 4‐year survivals of 94% and 91%. Conclusions—A preoperative imaging protocol relying predominantly on a CXR and abdominal ultrasound does not reduce survival. Other more sophisticated imaging, in particular, CT, is not required in the majority of cases and is warranted only when a CXR or ultrasound is unable to resolve relevant management problems. © 1995 Wiley‐Liss, Inc.
Juvenile chronic myelocytic leukemia—report of 10 cases
Authors: Arya Laxman S. , Bhatia Poonam , Jain Yogesh , Chaudhary Ved P. , Verma Ishwar C. , Chinnappan D. , Pati Har Prasad
Published: February 2007

Ten children (five boys and five girls) with juvenile chronic myelocytic leukemia were seen over a period of 12 years (1980–1991) at the All India Institute of Medical Sciences, New Delhi. With the exception of one who was aged 4.5 years, all children were below 4 years of age (mean age 20.4 months). The presenting features included fever, bleeding secondary to thrombocytopenia, marked hepatosplenomegaly, and skin rash. The striking hematological features were anemia, thrombocytopenia, peripheral blood monocytosis, and normoblastemia. There was no significant myeloid proliferation in the bone marrow aspirate (mean M:E = 5:1), while erythroid proliferation was prominent along with monocytosis (mean 11.2%). Fetal hemoglobin was raised in 8 of the 10 patients (mean 14.1%). Long‐term survival was poor, with maximum survival being 18 months in one case. New modalities of management of this rare entity are discussed. © 1995 Wiley‐Liss, Inc.
Papillary thyroid cancer with pulmonary metastases beginning in childhood: Clinical course over three decades
Authors: Vassilopoulou‐Sellin Rena , Libshitz Herman I. , Haynie Thomas P.
Published: February 2007

We present a case of childhood papillary thyroid cancer with persistent but stable pulmonary metastases for over three decades in order to highlight the natural history and clinical features of this unusual disease entity. A nine‐year‐old girl had thyroidectomy and cervical lymph node dissection followed by neck irradiation for invasive papillary thyroid cancer. Diffuse pulmonary metastases were present at the time of diagnosis and were treated with radioactive iodine 10 and 30 years later; both the chest radiographs and the patient remained stable throughout. This case illustrates the potential indolence of thyroid cancer when it presents during childhood. © 1995 Wiley‐Liss, Inc.
Rhabdoid tumor of the kidney with humoral hypercalcemia and parathyroid hormone‐related protein production
Authors: Papadakis Vassilios , Vlachopapadopoulou Elphis‐Athina , Levine Lenore
Published: February 2007

This is a report of a 7‐month‐old infant with malignant rhabdoid tumor of the kidney (RTK). The patient (pt) demonstrated clinical and biochemical evidence of humoral hypercalcemia of malignancy (HHM). The hypercalcemia responded promptly to calcitonin treatment and tumor removal. Despite aggressive surgery and chemotherapy, the patient expired four months after diagnosis. The primary tumor displayed adenylate cyclase‐stimulating activity (ACSA) indicating the production of parathyroid hormone‐related protein (PTHrP) by the primary tumor. This is the first report of ACSA documented in a pt with RTK. © 1995 Wiley‐Liss, Inc.
Letter to the editor: “Thoughts from SIOP 1993: Randomised trials of bone marrow transplantation in paediatric malignancy?”
Authors: Shaw Peter J.
Published: February 2007

Having recently returned from the very successful SIOP meeting in San Francisco, several different thoughts expressed at the meeting lead me to the conclusion that we should be considering initiating a randomised trial of autologous Bone Marrow Transplant (ABMT) in patients with a “good,” not a bad, prognosis.
Developing a measure of health outcomes in survivors of childhood cancer: A review of the issues
Authors: Jenney Meriel E. M. , Kane Robert L. , Lurie Nicole
Published: February 2007

The success of treatment for childhood cancer has prompted greater attention to issues of quality of life for the survivors. Work on health‐related quality of life has proceeded faster for adults than for children. This paper reviews the results of such work for adults and points to the potential for applications in children. Specific problems in adapting measures and in interpreting the results in the context of a child's development are discussed. An approach to the assessment of the health‐related quality of life for survivors of childhood cancer is proposed. © 1995 Wi1ey‐Liss Inc.
Pharmacokinetics of HD‐MTX in infants, children, and adolescents with non‐B acute lymphoblastic leukemia
Authors: Donelli Maria Grazia , Zucchetti Massimo , Robatto Lantonella , Perlangeli Vittoria , D'Incalci Maurizio , Masera Giuseppe , Rossi Mario R.
Published: February 2007

A retrospective pharmacokinetic analysis was done of methotrexate serum levels after high‐dose treatment (HD‐MTX, four cycles at two‐week intervals of 5 g/sq.1m. over 24 h i.v.) in children with non‐B acute lymphoblastic leukemia (ALL) with the specific aim of seeking differences in patients of different ages, including infants under one year.

A total of 122 children (seven infants aged 3 months‐1 year, 26 children aged 1–3 years, 68 children aged 3–10 years and 21 adolescents aged 10–15 years) with normal liver and renal function, receiving consolidation therapy at the Pediatric Clinic of Monza between May 1988 and April 1992, were enrolled in this study. MTX was given as an intravenous infusion in 24 h and serum concentrations were measured up to at least 72 h after the start of infusion by an enzyme immunoassay (TDX Abbot, Dallas, TX) in order to modulate folinic acid rescue.

Pharmacokinetic analysis of MTX levels according to a two‐compartment open model indicated that, compared to all children up to 10 years old, in adolescents older than 10 years the drug reached higher concentrations in serum and was cleared at a lower rate. Steady‐state levels and AUC were from 60% higher to more than double and the total clearance of the compound, expressed either per square meter surface area or per kg body weight, in each cycle was significantly lower in adolescents >10 years of age, sometimes being only one‐third of the clearance in infants (0.2 vs. 0.6 1/h/kg and 6.6 vs. 10.7 1/h/sq.m). The relationship between each age and systemic clearance was highly significant as measured by regression analysis. Methotrexate systemic clearance progressively decreased as a function of age. Subsequent treatments did not induce changes in MTX pharmacokinetics.

These data suggest that the better tolerance of HD‐MTX in children may have a pharmacokinetic basis. The faster elimination of MTX in infants, who usually show the worst prognosis, suggests that full doses could be safely used in order to maximize the antileukemic effect without a high risk of toxicity. © 1995 Wiley‐Liss, Inc.
Juvenile chronic myelogenous leukemia: In vitro characterization before and after allogeneic bone marrow transplantation
Authors: Zecca Marco , Rosti Vittorio , Pinto Luciano , Comoli Patrizia , Carrà Anna Maria , Prete Luisella , Bonetti Federico , Pedrazzoli Paolo , Locatelli Franco , Cazzola Mario
Published: February 2007

In previously published studies on patients with juvenile chronic myelogenous leukemia (JCML), excessive proliferation of malignant monocyte‐macrophage elements and impaired growth of normal hematopoietic progenitors were demonstrated. A selective hypersentivity of granulocytemachrophage progenitors (CFU‐GM) to granulocyte‐macrophage colony stimulating factor (GM‐CSF) seems to represent the main pathogenetic mechanism. Allogeneic bone marrow transplantation (BMT) has been demonstrated to be the only curative strategy for patients with JCML. In this study, we evaluated the growth of peripheral blood hematopoietic progenitors in semisolid cultures in two children with JCML before and after allogeneic BMT. Serum levels of GM‐CSF, interleukin‐1 (JCIL‐1) and tumor necrosis factor‐α (TNF‐α) were also assessed. IL‐1‐β, GM‐CSF and TNF‐α serum levels of the patients before and after BMT did not differ significantly from those obtained in 45 healthy controls. After marrow transplant, the engraftment of donor hematopoietic stem cell was associated with the disappearance of both pretransplant GM‐CSF hypersensitivity and CFU‐GM spontaneous growth. The inhibitory effect on the growth of normal hematopoietic progenitors also resolved. This confirms that the substitution of the pathological hematopoietic progenitors represents the basis for the curvative effect of allogeneic BMT in the treatment of JCML, abolishing both the excessive responsiveness of JCML progenitor cells even to very low concentrations of GM‐CSF and the growth‐inhibitory effect on normal hematopoiesis. © 1995 Wiley‐Liss, Inc.
Cardiac tamponade as the initial manifestation of primary pericardial mesothelioma
Authors: Stein Moshe , Neuman Avivit , Dale Janet , Drumea Keren , Ben‐Itzhak Ofer , Bar‐Shalom Rachel , Goldscher Dorit , Haim Nissim
Published: February 2007

Although cardiac tamponade is a known complication of malignancy, it is rarely the initial manifestation. We report a 46‐year‐old male who presented with malignant cardiac tamponade 6 months prior to the definitive diagnosis of primary pericardial mesothelioma. A thorough literature search has not revealed a similar care. © 1995 Wi1ey‐Liss Inc.
Lung function and exercise capacity in survivors of childhood leukaemia
Authors: Jenney Meriel E. M. , Faragher E. Brian , Jones Patricia H. Morris , Woodcock Ashley
Published: February 2007

The survival from acute lymphoblastic leukaemia in childhood is now approximately 60–70%, and from acute myeloid leukaemia, up to 50%. However, there is little information on the effects of intensive chemotherapy and radiotherapy used in the treatment of these conditions on lung function and exercise capacity in the long term.

Seventy survivors of acute leukaemia from one centre in the UK were studied. Measurements of lung volumes, spirometry and transfer factor were made. Each child also performed a standard, symptom‐limited maximal exercise test on a cycle ergometer. Predictive equations for indices of lung function and exercise tolerance were calculated from 146 age‐ and sex‐matched control subjects. The results of the survivors of leukaemia were compared to these.

There was a significant reduction of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and transfer for carbon monoxide (DLCO;P< 0.05 for each measurement), in the survivors of leukaemia when compared to the control subjects. In addition, there was a mild but significant reduction of both maximal and submaximal indices of exercise capacity in the leukaemic group. A multivariate analysis was carried out to identify those variables acting independently to reduce lung volumes. For FEV1, FVC and TLC, these were craniospinal irradiation, cyclophosphamide and chest complications during treatment. For a reduction in DLCO, the significant factors were administration of anthracyclines, craniospinal irradiation and bone marrow transplantation.

Survivors of acute leukemia have impaired pulmonary function and exercise capacity. Long‐term cardiopulmonary follow‐up may be necessary and new regimens devised which reduce long‐term toxicity without compromising survival rates. © 1995 Wi1ey‐Liss Inc.
Intracranial large vessel vasculopathy and anaplastic meningioma 19 years after cranial irradiation for acute lymphoblastic leukaemia
Authors: Foreman Nicholas K. , Laitt Roger D. , Chambers E. Joanna , Duncan Andrew W. , Cummins Brian H.
Published: February 2007

A child was diagnosed in 1969 as having acute lymphoblastic leukaemia (ALL) and received chemotherapy. On bone marrow relapse in 1973, he was treated with cranial irradiation (20 Gy) in addition to chemotherapy. He continues in complete remission 19 years after his relapse. At age 25 years, he presented with headaches and left hemiparesis. Computerised tomograph demonstrated a large, enhancing right‐sided intracranial tumour. Angiography was performed and showed the right internal carotid artery was occluded. Most of the right hemisphere was supplied from the external carotid via the middle meningeal artery. The left posterior cerebral artery and the left anterior cerebral artery were absent presumably as a result of radiation‐induced arteritis. A resection of an anaplastic meningioma arising from the right sphenoidal ridge was achieved. There was a rapid improvement in function and he returned to work. Vasculopathy of the large intracranial arteries has been described after high dose radiation. It may occur as in this case after moderate dose radiation. There is a correlation with meningioma. There is a possibility that large artery vasculopathy will be present in a proportion of patients irradiated for ALL. The long lag time between irradiation and the development of meningioma may mean that, as survivors of childhood ALL enter their third decade since cure, this tumour may be seen increasingly. © 1995 Wi1ey‐Liss Inc.
Incidence of Bone Marrow Involvement in Ewing's Sarcoma: Value of Extensive Investigation of the Bone Marrow
Authors: Oberlin Odile , Bayle Chantal , Hartmann Olivier , Terrier‐Lacombe Marie José , Lemerle Jean
Published: February 2007

Purpose: Bone marrow (BM) status is a critical matter when intensified chemotherapy with bone marrow rescue is proposed to improve the survival of patients with poor prognosis Ewing's sarcoma (ES): metastatic or relapsing disease. A systematic bone marrow investigation was performed in all the patients with newly diagnosed ES or relapsing ES to assess their BM status. Patients and Methods: From January 1985 to February 1989, 59 untreated patients and five patients at the time of relapse had a bone marrow investigation under general anesthesia: two BM biopsies and two BM aspirates until May 1986, then two BM biopsies and 10 BM aspirates. The classical method of smearing each BM aspirate was compared to cytocentrifugation of the pool of BM samples after gradient density separation.

Results: The BM was involved in 13 of 59 untreated patients. BM was the single site of metastatic spread in only one patient but was involved in 52% of the patients with metastatic disease at other sites. This involvement was focal in several patients and frequent discrepancies were noted between the aspirates and biopsies at the various sites explored. The number of positive cases of BM involvement discovered by the two methods is somewhat limited. However preliminary results indicate a superior rate of positive smears with the pool technique which did however fail to detect involvement in some cases.

Conclusions: The present study indicates that 1) BM involvement is a frequent event in metastatic ES (52%); 2) is often multifocal and therefore requires extensive BM investigation; and 3) further investigation of the pool technique to facilitate the BM screening is warranted. © 1995 Wi1ey‐Liss, Inc.
Male Gonadal Function After Chemotherapy in Survivors of Childhood Malignancy
Authors: Mustieles Carmen , Muñoz Arturo , Alonso Milagros , Ros Purificación , Yturriaga Rafael , Maldonado Soledad , Otheo Enrique , Barrio Raquel
Published: February 2007

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise.

We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males.

The mean age of the patients at the time of the study was 18.2 ± 3.6 years (range 13.8–29.0), and when given chemotherapy treatment was 10.2 ± 3.0 years (range 6–16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0–16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted. © 1995 Wi1ey‐Liss, Inc.
Combination Chemotherapy With Vinblastine, Bleomycin, Cisplatin, and Etoposide (VBPE) in Children With Primary Intracranial Germ Cell Tumors
Authors: Chang Te‐Kau , Wong Tai Tong , Hwang Betau
Published: February 2007

We have treated 13 children with primary intracranial germ cell tumors with the combination of vinblastine, bleomycin, cisplatin, and etoposide, the so‐called VBPE regimen in the past seven years at one institution. The clinical diagnosis of these children were: three germinomas, seven non‐germinomatous germ cell tumors, and three recurrent non‐germinomatous germ cell tumors without previous chemotherapy. Of this group, three germinomas and three non‐germinomatous germ cell tumors were treated primarily with VBPE plus radiotherapy. All of them responded completely, and were free of tumor. Primary VBPE regimen without radiotherapy was used in another four non‐germinomatous germ cell tumors. After six courses of VBPE regimen, only one of the four patients achieved complete response for 30 months. VBPE regimen was used as salvage chemotherapy in three recurrent non‐germinomatous germ cell tumors without previous chemotherapy. After six courses of VBPE regimen, two had complete response for 58+ months and 78+ months respectively. We concluded that in newly‐diagnosed intracranial non‐germinomatous germ cell tumors, the combination of chemotherapy VBPE regimen and radiotherapy led to good results. Primary chemotherapy with VBPE alone was not adequate for the treatment of non‐germinomatous germ cell tumors. However, VBPE regimen might be one of the salvage therapies for recurrent germ cell tumors without chemotherapy before relapse. © 1995 Wi1ey‐Liss, Inc.
Neuroblastoma IV‐S Followed by Extra‐Adrenal Pheochromocytoma 15 Years Later
Authors: López‐Andreu Juan A. , Castel Victoria , Verdeguer Amparo , Muro M. Dolores , Esquembre Carlos , Ferrís Josep
Published: February 2007

Common origin of sympathoblasts and pheochromoblasts from the neural crest cells is generally accepted. Neuroblastoma and pheochromocytoma result from an abnormal proliferation of these committed cells. They are included in the group of neuroendocrine neoplasms, formerly named Apudomas. Previous reports of mixed tumours of neuroblastoma and pheochromocytoma, and ganglioneuroma and pheochromocytoma, support this hypothesis.

A case of extra‐adrenal pheochromocytoma in an adolescent who 15 years before was successfully treated for a stage IV‐S neuroblastoma without evidence of primitive tu mour is reported. Two hypothesis are formulated: (1) the second neoplasm may have arisen from the unlocated primitive tumour, probably silent evolution could be due to its maturation into ganglioneuroma‐pheochromocytoma; (2) taken into account a common origin of both neoplasms, the patient may have a genetic predisposition to develop neuroendocrine tumours. Whatever the mechanism, second neoplasms, as the case reported, late relapses, and late toxic effects may justify long follow‐up of neuroblastoma survivors. © 1995 Wi1ey‐Liss, Inc.
Granisetron as antiemetic therapy in children with cancer
Authors: Craft A. W. , Price L. , Eden O. B. , Shaw P. , Campbell R. , Pierce D. M. , Murdoch R. , Upward J.
Published: February 2007

The safety and efficacy of the new 5HT‐3 antagonist granisetron as an antiemetic in children with cancer was evaluated in 40 children at a single dose of 40 μg/kg. No adverse affects attributable to the granisetron were noted. The overall major and complete response rate was 82.5% and this was highest in the younger children. Only 2 patients showed no response. Pharmacokinetic studies showed associations between some pharmacokinetic parameters and age which were no longer apparent after normalisation for body weight.

Granisetron is an effective and very well tolerated antiemetic and appears to be an important addition to the supportive care available for children with cancer. © 1995 Wiley‐Liss, Inc.
Variation in the use of ondansetron as an antiemetic drug in children treated with chemotherapy
Authors: Ninane Jacques , Ozkaynak M. Fevzi , Kurtin Paul , Siegel Stuart E.
Published: February 2007

Selective 5‐HT3 receptor antagonists such as ondansetron are potent antiemetics for chemotherapy‐induced emesis. Ondansetron has been shown to be highly effective in preventing nausea and vomiting in children treated with chemotherapy and/or radiotherapy. However, its high cost may limit its application. A “physician profile” provided by the hospital pharmacy and a questionnaire survey conducted amongst the attending physicians of the hematology/oncology division of a Children's hospital showed wide variation in ondansetron use. This variation was evident for both the indications of use and the schedule of administration. Moreover, 80% of the physicians were not aware of the actual cost of ondansetron. In order to reduce this variation, which may affect the quality of care and increase costs unnecessarily, guidelines have been developed for the use of antiemetic drugs in pediatric oncology patients at this institution. © 1995 Wiley‐Liss, Inc.