bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of myelodysplastic syndromes with low‐dose oral 6‐thioguanine
Authors: Spitzer Thomas R. , Lazarus Hillard M. , Crum Edward D. , Weisman Russell
Published: February 2007

Several cytotoxic agents when used in vitro in very low concentrations have been shown to induce differentiation of leukemic cells. We treated 18 patients with myelodysplastic syndromes with low‐dose oral 6‐thioguanine (6‐TG; 20 to 60 mg daily). Four patients demonstrated significant improvement in peripheral blood counts. An additional three patients had significant reductions in the percentage of leukemic myeloblasts in the marrow without a corresponding improvement in peripheral counts. With the exception of a fall in the peripheral neutrophil count in four patients requiring dose reductions, no toxicity was observed. Low‐dose oral 6‐TG gives a response rate in myelodysplastic syndromes similar to that of parenteral agents such as cytosine arabinoside. Given the ease of administration and lack of toxicity, oral 6‐TG may be a useful treatment modality for these syndromes either alone or in combination with other differentiation‐enhancing agents.
Phase II trial of 4′‐deoxydoxorubicin (DxDx) in non‐small cell lung cancer: A cancer and leukemia group B trial
Authors: Ringenberg Q. Scott , Perry Michael C. , Propert Kathleen J. , Modeas Caron , Hirsh Vera , Weiss Raymond B. , Richards Frederick , Graziano Stephen , Green Mark
Published: February 2007

Eighty‐seven patients with histologically or cytologically proven non‐small‐cell carcinoma of the lung were treated with 4′‐deoxydoxo‐rubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large‐cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P < 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4′‐Deoxydoxorubicin had little activity in non‐small‐cell lung cancer at the dose used in this study.
Congenital anomalies associated with rhabdomyosarcoma: An autopsy study of 115 cases. A report from the intergroup rhabdomyosarcoma study committee (representing the children's cancer study group, the pediatric oncology group, the United Kingdom children's cancer study group, and the pediatric intergroup statistical center)
Authors: Ruymann Frederick B. , Maddux Helen R. , Ragab Abdel , Soule Edward H. , Palmer Nigel , Beltangady Mohan , Gehan Edmund A. , Newton William A.
Published: February 2007

Congenital anomalies were identified in 37 of 115 (32%) children and adolescents autop‐sied with rhabdomyosarcoma. An analysis of sex, age, site, and histology of cases with or without congenital anomalies showed no significant differences. Of the 45 identified anomalies, 14 were considered major and 31 minor. The distribution of the anomalies by system included central nervous (9), genitourinary (10), gastrointestinal (13), and cardiovascular systems (4). Ten patients had complex or miscellaneous anomalies. There was one child with each of the following: Rubinstein‐Taybi syndrome, neurofibromatosis, single horseshoe kidney, hemihypertrophy, and Arnold‐Chiari malformation. Aniridia was not noted in any case of rhabdomyosarcoma. Individuals with rhabdomyosarcoma have an increased incidence of genitourinary anomalies similar to that in Wilms' tumor. Recent molecular genetic investigations have suggeted that rhabdomyosarcoma, Wilms' tumor, and he‐patoblastoma share a common pathogenetic mechanism involving chromosome 11. The uniquely increased association of central nervous system anomalies with rhabdomyosarcoma and absence of aniridia would support a different gene locus operative on chromosome 11 for individuals with rhabdomyosarcoma compared to Wilms' tumor. Extensive epidemiologic studies now in progress in patients with rhabdomyosarcoma should provide the incidence of congenital anomalies and potential linkage with prenatal events.
Possible association of human growth hormone treatment with an occurrence of acute myeloblastic leukemia with an inversion of chromosome 3 in a child of pituitary dwarfism
Authors: Endo Machiko , Kaneko Yasuhiko , Shikano Takaaki , Minami Hideki , Chino Jun‐Ichi
Published: February 2007

An 11–yr‐old girl, who had been treated with human growth hormone (h‐GH) for 31 months, developed acute myeloblastic leukemia with an inv(3)(q21q26). Since CH has been suggested to influence the genesis of leukemia, and the inversion 3 has been reported only in adult leukemia patients, the GH treatment may have caused the development of leukemia or accelerated the proliferation of the leukemia cells.
Childhood hepatic mesenchymoma: Successful treatment with surgery and multiple‐agent chemotherapy
Authors: Ware Russell , Friedman Henry S. , Filston Howard C. , Chaffee Sara , Kurtzberg Joanne , Kinney Thomas R. , Falletta John M.
Published: February 2007

Malignant undifferentiated sarcoma (mesenchymoma) of the liver is a rare tumor of childhood, with fewer than 100 cases reported in the literature. The overall prognosis for patients with this malignancy is poor. In this report, two children with hepatic mesenchymoma underwent surgical excision followed by 2 years of adjuvant chemotherapy. Rotating cycles of cisplatinum, vincristine/doxorubicin, vincristine/cyclophosphamide, and vincristine/actinomycin D were given with minimal toxicity. Both patients are alive, with no evidence of disease at least 5 years from diagnosis. Previous reports of treatment are reviewed.
Prognostic factors in 281 children with nonmetastatic rhabdomyosarcoma (RMS) at diagnosis
Authors: Rodary C. , Rey A. , Olive D. , Flamant F. , Quintana E. , Brunat‐Mentigny M. , Otten J. , Voute P. A.
Published: February 2007

Pretreatment characteristics of 281 children with nonmetastatic rhabdomyosarcoma, included in the registry of the International Society of Pediatric Oncology (SIOP) between January 1975 and December 1983, were examined to study the children's prognosis. The multivariate statistical method (Cox regression model) was used for each of two end‐points: survival time and disease‐free time.

The three most important predictors for survival time were primary site (p < .001), clinical stage (p = .009), and sex (p = .020). The best results involved paratesticular and orbital primary sites, regardless of the clinical stage; males fared slightly better than females. These same three factors were also significant predictors for disease‐free time.
Malignant disease in the mothers of children with Ewing's tumour
Authors: Hartley A. L. , Birch J. M. , Marsden H. B. , Harris M. , Blair V.
Published: February 2007

Previous research has shown that mothers of children with soft tissue sarcoma, osteosarcoma, and chondrosarcoma are at excess risk of developing breast cancer. The occurrence of malignant disease in the mothers of a population‐based series of children with Ewing's sarcoma was investigated in order to determine whether these mothers were at excess risk of cancer and of breast cancer in particular. Sixty‐one mothers were traced; there were two cases of breast cancer and two other registrable neoplasms. Risk of malignancy in the mothers was not in excess of expectation.
Effectiveness of attenuated chemotherapy in myelodysplastic syndromes: A preliminary report
Authors: Owens Michael R. , Bennett John M.
Published: February 2007

A small group of elderly male patients received attenuated doses of daunomycin, cytosine arabinoside (Ara‐C), and 6‐thioguanine for treatment of myelodysplastic syndrome (MDS). Three patients had refractory anemia with excess blasts (RAEB), and two had chronic myelomonocytic leukemia (CMMoL). All five patients had developed severe transfusion requirements for platelets and red blood cells before therapy was begun. One patient developed necrosis of the cecum and expired 19 days after therapy, but the other four all showed substantial benefit from treatment. Three of those patients received multiple courses of chemotherapy which led to improvement in peripheral blood counts in each case. Duration of responses as noted by improvement in peripheral blood counts compared to pretreatment levels ranged from 1.5 to 9 months. Despite considerable improvement in peripheral blood parameters, some of the abnormal morphologic features of MDS persisted after each course of chemotherapy. These results obtained with attenuated chemotherapy schedules in a small group of patients are sufficiently encouraging to warrant an expanded phase II trial, which is under way at the University of Rochester Cancer Center.
Preliminary experience with chemotherapy in advanced salivary gland neoplasms
Authors: Belani Chandra P. , Eisenberger Mario A. , Gray William C.
Published: February 2007

Eight patients with advanced incurable salivary gland carcinoma were treated with the combination of cyclophosphamide, doxorubicin, and cisplatin (CAP). There were three clinical complete responses and two excellent partial responses. One of the three nonresponders had symptomatic improvement without any response in the measurable disease sites. Side effects were acceptable. All patients had moderate nausea and some degree of vomiting, which were adequately controlled by antiemetics. These results are preliminary but when considered with other reported trials using the same combination suggest an active treatment program for advanced neoplasms of the salivary glands.
Reproductive problems and birth defects in survivors of Wilms' tumor and their relatives
Authors: Byrne Julianne , Mulvihill John J. , Connelly Roger R. , Austin Donald A. , Holmes Grace E. , Holmes Frederick F. , Latourette Howard B. , Meigs J. Wister , Strong Louise C. , Myers Max H.
Published: February 2007

In a retrospective cohort study of 47 Wilms' tumor survivors and their 77 sibling controls, female survivors had a fourfold excess risk (risk ratio, 4.1; 95% confidence interval, 1.7‐10.1) for any adverse livebirth outcome, including birth defects, compared with their sibling controls. Wives of male survivors had no apparent excess risk for problem pregnancies. The families had a number of severe reproductive problems and major birth defects, such as primary amenorrhea in two survivors, bicornuate uterus in two survivors and one control, and mental retardation in one male survivor and a male control. The son of a female survivor died after bilateral Wilms' tumors. Birth defects in the offspring of female survivors are compatible either with intrauterine constraint, possibly due to radiation‐induced fibrosis or with the complex of malformations associated with Wilms' tumor. Female survivors of Wilms' tumor appear to be at increased risk for a variety of reproductive problems, from sterility to fetal loss, early delivery, and birth defects in offspring. Furthermore, relatives of survivors of Wilms' tumor may be at risk of having associated birth defects, with clinically significant consequences.
Male reproductive function in long‐term survivors of childhood cancer
Authors: Jaffe Norman , Sullivan Margaret P. , Ried Hubert , Boren Hallie , Marshall Robert , Meistrich Marvin , Maor Moshe , Cunha Miguel Da
Published: February 2007

We evaluated reproductive function in 27 male long‐term survivors of childhood cancer treated during the prepubertal and pubertal period. Sperm samples were obtained from 23 patients; four who refused to provide specimens indicated that they had fathered normal healthy children. Thirteen patients were 12 years old or younger at the time of diagnosis and initiation of therapy. Chemotherapy was calculated according to the cumulative amount of drug administered and correlated with the surface area. Sterility was associated with large doses of single alkylating agents or reduced doses administered with other agents in combination regimens. It was noted in boys treated in both the prepubertal and pubertal period. Sterility was also observed in patients who received testicular radiation alone or in combination with chemotherapy. However, it was not an inevitable consequence in all patients, despite treatment with similar or identical regimens. Fertility potential could not be predicted by clinical examination (testicular size) or gonadotrophin and testosterone values. The results were compared to published reports of treatmentinduced sterility in adult males. Additional investigations are required to establish more accurate correlations of dosage with reproductive potential.
Pneumonia carcinomatosa from small cell undifferentiated carcinoma of the lung presenting as “reverse radiation pneumonitis”
Authors: Adelstein David J. , Padhya Tushar , Tomashefski Joseph F. , Park Chanho
Published: February 2007

We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term “reverse radiation pneumonitis” is applied in view of the striking non segmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be added to the differential diagnosis of radio‐graphic peripheral pulmonary infiltrates.
Measles and rubella antibody status in previously vaccinated children with cancer
Authors: Feldman Sandor , Gigliotti Francis , Bockhold Carol , Naegele Robert
Published: February 2007

Measles and rubella antibody status were determined by ELISA for 115 previously vaccinated children with cancer. Seventy subjects were receiving chemotherapy, and 45 had successfully completed treatment for their malignancy. Overall, 18% of the subjects were seronegative for measles antibody and 8% for rubella antibody. Only 3% of patients lacked both. In general, seronegative individuals were over age 10 years. Subjects born before 1976 were significantly more likely to be seronegative to measles, 29% vs. 11% (P = 0.02) and to rubella, 16% vs. 4% (P = 0.03) than those born afterwards. Antibody status showed no apparent relationship to the duration of anticancer therapy. Stored serum samples were available for nine seronegative subjects, of whom five were initially seropositive and then lost antibody during or after the completion of anticancer therapy. Our observations suggest that cancer and its associated therapy interfere with antibody production. In view of the increasing survival rates for childhood cancers, additional studies are needed to assess the immune status of these subjects for all vaccine‐preventable infections. Pending the outcome of further studies, we suggest that long‐term survivors, particularly those born before 1976, or known to be vaccinated at less than 13 months of age, be tested after the completion of therapy for antibody to measles and rubella (and mumps). Also, immune serum globulin should be considered for any previously immunized patient with a close exposure to an active case of measles.
VP‐16 + adriamycin vs. Adriamycin alone in advanced adenocarcinoma of the breast, phase II, a randomized trial: A southwest oncology group study
Authors: Vaughn Clarence B. , Green Stephanie J. , O'Bryan Robert , Reed Melvin , Grozea Petre N. , Fletcher William S. , Green J. Benjamin , Metch Barbara , Oishi Noboru
Published: February 2007

One hundred twenty‐two patients with advanced adenocarcinoma of the breast were randomized to receive adriamycin (AD) alone or a combination of VP‐16 plus lower dose adriamycin (VAD). The patients were stratified to good and poor risk. The starting dose (day 1) of AD was 60 mg/m2 for good risk and 45 mg/m2 for poor risk. The starting dose of the VAD combination for the good‐risk patient was VP‐16, 75 mg/m2 daily × 5 plus adriamycin 35 mg/m2.

The poor‐risk dose for VAD was VP‐16, 50 mg/m2 daily × 5 plus adriamycin, 30 mg/m2 on day 1. The total dose of AD was 450 mg/m2 on both arms. The patients who were on the VAD arm continued on VP‐16 maintenance. Both arms were repeated every 21 days. There were 54 evaluable patients on the adriamycinarm and 52 evaluable patients on the VAD arm. Both arms were similar with regard to age, menopausal status, performance status, and prior hormonal therapy. More hematologic toxicity was seen in the adriamycin arm. Complete responses were observed on both arms, three (5%) with adriamycin and three (5%) with combination. Eleven (19%) and ten (18%) partial responses were observed with the adriamycin and VP‐16 plus adriamycin, respectively. AD produced more stable disease than VAD (41% vs. 29%). Complete responses were seen only in the good‐risk patients. Time to progression was delayed on the combination arm (P = 0.02). The survival in both arms was similar. The addition of VP‐16 to adriamycin does not offer an important clinical advantage.
Deoxycoformycin treatment for childhood T‐cell acute lymphoblastic leukemia early in second remission: A pediatric oncology group study
Authors: Winick Naomi , Buchanan George R. , Murphy Sharon B. , Yu Alice , Boyett James
Published: February 2007

2‐Deoxycoformycin (DCF) was added to an intensive Pediatric Oncology Group protocol ( 8303) for children with T‐cell acute lymphoblastic leukemia or T‐cell lymphoblastic lymphoma in first relapse. Twenty‐seven patients received one or more courses of DCF at 15 mg/m2/day as a 3‐day continuous infusion immediately after achieving a second remission with a four‐drug reinduction regimen. Renal and neuromuscular toxicities were frequent and occasionally severe despite the provision of a source of adenosine deaminase by means of a packed red cell transfusion 1 day following the infusion of DCF. Hepatic toxicity, manifested by transaminase elevations, accompanied 62% of the courses. The median duration of the second complete re mission was 4 months (range 2‐16+ months) with only two of the 27 patients still in remission at 13 + and 16 + months. Plasma concentrations of deoxyadenosine (dAdo) and the ratio of red cell deoxyadenosine triphosphate to adenosine triphosphate (dATP:ATP) were measured prior to the DCF infusion and on day 4. A dATP:ATP ratio of 1.0 or greater was seen in two patients with acute renal failure. There was no apparent correlation between toxicity or response and the plasma dAdo concentrations. DCF administered according to this dose and schedule was excessively toxic and did not appreciably prolong the duration of the second complete remission in children with T‐cell lymphoblastic malignancies.
Chemotherapy‐associated eccrine hidradenitis: Neutrophilic eccrine hidradenitis reevaluated: The role of neutrophilic infiltration
Authors: Greenbaum Barbara H. , Heymann Warren R. , Reid Cheryl S. , Travis Susan F. , Donaldson Milton H.
Published: February 2007

Two cases of chemotherapy‐associated eccrine hidradenitis are presented. Previous cases have been labeled “neutrophilic eccrine hidradenitis” (NEH). Both cases reported herein involve neutropenic patients and are notable for the absence of neutrophils on histologic examination. Oncologists need to be aware of this newly described process, and this rash must be added to the differential diagnosis of the neutropenic oncology patient. The role of neutrophils in this disorder is discussed, and a new term, “chemotherapy‐associated eccrine hidradenitis,” is suggested for this unusual process.
Treatment of refractory lymphoma with methotrexate, VM‐26 (teniposide), procarbazine, and dexamethasone: Cancer and leukemia group B study 7902
Authors: Lachant Neil A. , Anderson James , Ginsberg Sandra J. , Cooper M. Robert , Hurd David D. , Bloomfield Clara D. , Gottlieb Arlan J.
Published: February 2007

Seventy‐eight individuals previously treated with chemotherapy for nonHodgkin's lymphoma were enrolled in a phase II pilot study employing methotrexate 100 mg/M2 iv (day 1), calcium leucovorin 10 mg/M2 iv and/or po q6h (days 2–4), VM‐26 (teniposide) 100 mg/M2 iv (days 2 and 9), procarbazine 100 mg/M2 po (days 2–15), and dexamethasone 15 mg/M2po (days 2–8) (MV26PD). Thirty percent of the 78 patients treated had a response to therapy (8% complete, 22% partial). Twenty‐four percent of patients with diffuse histiocytic (large cell) lymphoma had a response (12% complete, 12% partial). The estimated failure‐free survival was 41% at 3 months and the median survial (death from any cause) was 4.5 months for the entire cohort. Two individuals, including one individual with diffuse histiocytic lymphoma, remain in a complete response for over 900 days. Significant hematologic toxicity and infectious complications were seen in this heavily pretreated group of patients. MV26PD represents an active combination of agents for the treatment of non‐Hodgkin's lymphoma. The optimal dosing for MV26PD remains to be determined.
Procarbazine hypersensitivity manifested as a fixed drug eruption
Authors: Giguere Jeffrey K. , Douglas Danny M. , Lupton George P. , Baker James R. , Weiss Raymond B.
Published: February 2007

A case of a previously unrecognized form of hypersensitivity to procarbazine characterized by a nonpigmented fixed drug eruption is reported. Despite skin testing, association of the skin lesion to procarbazine could be determined only by drug rechallenge. Various aspects of procarbazine hypersensitivity reactions as well as the pathogenesis and importance of the fixed drug eruption are discussed.
Long‐term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus
Authors: Adelstein David J. , Sharan Vishwa M. , Snow Norman J. , Carter Susan G. , Horrigan Terrence P. , Hines John D.
Published: February 2007

Seven patients with locally far‐advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5‐fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor‐prognosis subset of patients with esophageal cancer.
Langerhans' cell histiocytosis (Histiocytosis X): Experience at the children's hospital of philadelphia, 1970–1984
Authors: Raney R. Beverly , D'Angio Giulio J.
Published: February 2007

Sixty‐four patients with biopsy‐proven Langerhans' cell histiocytosis (LCH, formerly designated as histiocytosis X) were managed at the Children's Hospital of Philadelphia from 1970 through 1984. Their median age was 3 yr (range, 0.1–22 yr). Thirty‐three patients had localized lesions affecting a bone (27) or soft‐tissue region (6). Twenty‐two patients had multifocal disease affecting bones (17) or soft, nonosseöüs tissues (5). None of these patients had evidence of dysfunction of liver or lungs, and none had abnormal peripheral blood cell counts. The remaining nine patients had multifocal LCH plus dysfunction of liver or lungs (6) or abnormal blood counts (3). Treatment consisted primarily of surgical excision for patients with localized lesions and of drug therapy with or without irradiation and surgery for those with multifocal disease. Recurrence was infrequent (7%) in those with localized LCH, and all survived. Recurrence was frequent (74%) in those with multifocal LCH but without organ dysfunction or abnormal blood counts, but 21 of the 22 survived. By contrast, only three of the nine patients with organ dysfunction or abnormal blood counts survived. Thus organ dysfunction and abnormal blood counts at diagnosis emerged as the major adverse prognostic factors in children with LCH.
Rhabdomyosarcoma, presenting as disseminated malignancy from an unknown primary site: A retrospective study of ten pediatric cases
Authors: Etcubanas Erlinda , Peiper Stephen , Stass Sanford , Green Alexander
Published: February 2007

From 1962–1984, ten children were referred to St. Jude Children's Hospital with a metastatic poorly differentiated malignancy; extensive diagnostic workup had failed to disclose the site of the primary tumor. Multiple skeletal metastases as well as bone marrow involvement were common findings. Erythrocytes were detected in the cytoplasm of tumor cells in several cases, and cytochemical stains confirmed that these phagocytic cells did not have features of mononuclear phagocytes. Establishing a pathologic diagnosis in these cases was difficult, and most special studies including cytochemistry and electron microscopy were not helpful in elucidating the diagnosis. A diagnosis of rhabdomyosarcoma was made at presentation in six cases. In the remaining cases, the diagnosis of rhabdomyosarcoma was subsequently made after rebiopsy of new tumor masses during thecourse of the illness, by ultrastructural examination of a cell line derived from the tumor or at postmortem examination. Based on initial symptoms, clinical features, and postmortem findings, the primary tumor sites were assumed to be in the middle ear, paravertebral area, base of skull, retrobulbar space, chest wall, and retropancreatic area. In four patients the disease was confined to bone marrow, lymph nodes, and meninges so that a primary site could not be assigned. The approach to pediatric patients presenting with disseminated malignancy from an occult primary site should consist of an aggressive pursuit of a specific diagnosis and establishment of a primary site to better direct therapy, particularly for those children whose tumors may be responsive to specific therapy.
Enhanced cis‐platinum ototoxicity in children with brain tumours who have received simultaneous or prior cranial irradiation
Authors: Walker D. A. , Pillow J. , Waters K. D. , Keir E.
Published: February 2007

We report on four children who received cis‐platinum simultaneously with, or in one case 10 months after, cranial irradiation and experienced exaggerated ototoxicity affecting all audible frequencies. The hearing loss was severe, affecting the critical areas for speech perception, and necessitated the provision of bilateral hearing aids. The audiograms of these patients are shown and compared to those of four children who had received cis‐platinum as part of their treatment for neuroblastoma but without cranial irradiation. The precipitation of the exaggerated hearing loss with the administration of cis‐platinum in one patient 10 months after finishing cranial irradiation suggests that care should be taken in the timing of cis‐platinum administration in relation to concurrent or previous cranial irradiation.
Combination versus sequential single‐agent chemotherapy in the treatment of patients with advanced non‐small cell lung cancer
Authors: Niell Harvey B. , Griffin John P. , Hunter Robert F. , Meredith Charlotte A. , Somes Grant
Published: February 2007

We have carried out a randomized phase Ill study in 105 patients with advanced non‐small cell lung cancer, comparing a fourdrug cisplatin‐mitomycin‐based combination chemotherapy regimen to sequential single‐agent therapy. The combination chemotherapy regimen consisted of mitomycin C (10 mg/m2), vinblastine (5 mg/m2), methotrexate (40 mg/m2), and cisplatin (40 mg/m2) given every 28 days. Sequential single‐agent chemotherapy consisted of mitomycin C (10 mg/m2) monthly until progression followed by vinblastine (5 mg/m2) every 2 weeks until progression followed by methotrexate (40 mg/m2) weekly until relapse. Patients failing either regimen were followed with supportive care. The objective response rate for the sequential single‐agent therapy was 19% versus 25% for the combination chemotherapy group (P> .5). The median survival for the single‐agent group was 166 days and 191 days for the combination chemotherapy group. Overall survival was not statistically different between the two groups (P> .5). Leucopenia, anemia, and prolonged anorexia with nausea and vomiting were more common in the combination chemotherapy group compared to the single‐agent group. This study failed to demonstrate a sufficient therapeutic benefit in the face of the added toxicity for the combination chemotherapy regimen compared to sequential singleagent therapy.
Phase II trial of amsacrine in patients with multiple myeloma
Authors: Greipp Philip R. , Coleman Morton , Anderson Keaven , McIntyre O. Ross
Published: February 2007

Seventy‐four previously treated patients with multiple myeloma were treated with Amsacrine (m‐AMSA) 120 mg/m2 every 3 weeks. A good response was observed in two patients (3%), and improvement was seen in three patients (4%). Severe toxicity was observed in 33% of patients who received three or more courses of treatment. This dose and schedule of m‐AMSA in multiple myeloma is usually ineffective.
Similar chromosomal patterns and lack of N‐myc gene amplification in localized and IV‐S stage neuroblastomas in infants
Authors: Hayashi Yasuhide , Inaba Toshiya , Hanada Ryoji , Yamada Masao , Nakagome Yasuo , Yamamoto Keiko
Published: February 2007

Chromosome analysis was performed on 33 neuroblastomas in infants. Near triploid chromosome abnormalities (range, 60 to 77) were found in 29 patients with localized and IV‐S stage neuroblastoma, and hyperdiploidy (range, 50 to 56) in 3 patients with localized neuroblastoma. No marker chromosome 1, homogeneously staining region (HSR), or double minutes (DMS) was observed in these patients, all of which have been previously reported in advanced neuroblastomas. N‐myc gene amplification was not detected in any of these patients. All the patients were completely free of disease 4–45 months after diagnosis. Only one patient with stage IV neuroblastoma had a marker chromosome 1 (mode 46) and N‐myc gene amplification and relapsed. Five patients with IV‐S neuroblastoma lacking N‐myc gene amplification had near triploid chromosomal abnormalities similar to those seen in localized neuroblastoma in infants. We consider that, cytogenetically, localized and IV‐S neuroblastoma may be within the same disease category and different from advanced neuroblastoma.
Selection of a management strategy for pediatric brainstem tumors
Authors: Halperin Edward C. , Wehn Stanley M. , Scott Janice W. , Djang William , Oakes W. Jerry , Friedman Henry S.
Published: February 2007

Brainstem tumors arise in portions of the rhombencephalon and mesencephalon. Some authorities include diencephalic tumors in this group. We have reviewed our clinical experience of 69 children (<21 years of age) with brainstem tumors evaluated and treated at Duke University Medical Center (DUMC) from 1960 to 1986. There were 19 patients with group I tumors (thalamus, third ventricle region, or midbrain) and 50 with group II tumors (pons, medulla oblongata). The common presenting signs and symptoms were ataxia, headache, motor loss, and cranial nerve palsies. The most commonly employed diagnostic imaging studies were air examinations and CT. Preradiotherapy confirmation of malignancy was obtained in five group I patients (astrocytoma, 4; germinoma, 1) and 8 group II patients (astrocytoma, 3; anaplastic astrocytoma, 2; glioblastoma multiforme, 3). All patients received radiotherapy.

The 5‐year survival rate for the entire population was 40%. The survival rate for group I patients was significantly better than that observed for group II patients. In the 50 group II patients neither patient sex nor age nor presence of cranial nerve palsies nor pretreatment CT scan findings nor field size influenced survival. A long duration of symptoms positively influenced survival. The vast majority of tumor recurrences were within the radiation field. Half of the patients had either stable or improved Karnofsky status 6 months following completion of irradiation.

The management strategy for childhood brainstem tumors is discussed.
Radio‐iodobenzylguanidine scintigraphy of neuroblastoma: Conflicting results, when compared with standard investigations
Authors: Schmiegelow Kjeld , Siimes Martti A. , Agertoft Lone , Berglund Gunilla , Storm‐Mathisen Ingebjørg , Andreassen Michael , Salmi Toivo T. , Nygård Randi , Wiebe Thomas , Kreuger Anders , Hayder Salah
Published: February 2007

Seventy‐one patients with neuroblastoma (NB) and 25 patients with other neoplastic or nonneoplastic diseases were studied with MIBG scintigraphy. Sensitivity and specificity at diagnosis were 94% and 88%, respectively. Of 52 patients with NB studied during follow‐up, 14 had on one or several occasions conflicting results, when the findings at MIBG scintigraphy were compared to standard investigations (SI: CT scan, bone scan, x‐ray, and ultrasound). The correlation of MIBG scintigraphy and SI to clinical outcome were in these 14 patients not significantly different. Adding VMA‐excretion measurements did not significantly improve the predictive value of MIBG scintigraphy or SI. Patients with tumor‐suspected lesions only at MIBG scintigraphy should be followed closely and the nature of the lesions should be explored through biopsy.
Treatment and prognosis of metastatic carcinoma of unknown primary: Analysis of 100 patients
Authors: Alberts A. S. , Falkson G. , Falkson H. C. , van der Merwe M. P.
Published: February 2007

One hundred patients with metastatic carcinoma of unknown primary were analyzed to assess the importance of prognostic factors on survival. Patients were treated with cytostatic combinations, single drugs, or symptomatic care only. Response in the treatment groups ranged from 10% to 33%. The median survival of all patients was 124 days. In a univariate analysis good performance status, the presence of lymph node metastases, and the absence of liver metastases favorably influenced survival. In a Cox proportional hazards model, good performance status contributed significantly to a better survival. In addition there was a trend for female patients, patients with lymph node metastases, and patients without liver metastases to survive longer. These patient subsets deserve optimal treatment despite the dismal prognosis of this disease.
Prognostic significance of auer rods in childhood acute myelogenous leukemia: Results of the studies AML‐BFM‐78 and −83
Authors: Ritter Jörg , Vormoor Josef , Creutzig Ursula , Schellong Günther
Published: February 2007

The prognostic significance of Auer rods in predicting response rate and remission duration was investigated in 257 patients of the two West German acute myelogenous leukemia (AML) studies BFM‐78 and ‐83. Auer rods were found in 129 children (50%) in the initial bone marrow smear. The incidence was higher in myeloid subtypes M1 (63%) and M2 (78%) compared with subtypes M4 (47%) and M5 (5%) with monocytic differentiation. In both studies, the remission rate was significantly higher in patients with Auer rods (P= 0.01), and in the study AML‐BFM‐83 a significantly longer remission duration was evaluated for Auer rodpositive patients (P= 0.007). In the M1 type, Auer rods were of high prognostic significance regarding both the induction success (P= 0.003) and the remission duration (P= 0.004), whereas no significant differences between Auer rodpositive and ‐negative patients in other subtypes were found. Occurrence of Auer rods was independent of hyperleukocytosis, the most powerful prognostic parameter in the studies AML‐BFM‐78 and ‐83, whereas absence of Auer rods was associated with the AML risk group M5. In the M1 type, Auer rod‐negative leukemias appeared to represent cases of poorly differentiated AML. Auer rods were therefore useful in differentiating between patients with a poor and a more favorable prognosis, particularly in the M1 type.
Liposarcoma of hepatic hilum in childhood: Report of a case and review of the literature
Authors: Soares F. A. , Landell G. A. Magnani , Peres L. C. , Oliveira M. A. , Vicente Y. A. M. V. A. , Tone L. G.
Published: February 2007

Liposarcoma in childhood has seldom been documented. The rare occurrence of this tumor has resulted in a lack of information about its natural history, prognosis, and management. The differential diagnosis with lipoblastomatosis is obligatory. A 2 year 4 month‐old white male child presented at the Hospital das Clinicas of Medical School of Ribeirão Preto, University of São Paulo, with fever, jaundice, and coluria secondary to a tumoral mass of the hepatic hilum causing obstruction of the biliary tree. Histologic and immunohistochemical study at autopsy disclosed a liposarcoma. A literature review found 64 other reported cases. Special attention was given to age, sex, anatomic localization, and histologic aspects of the literature cases. Liposarcoma involving the hepatic hilum and causing obstruction of the biliary tree in childhood was not previously reported in the literature.
Bone marrow transplantation in childhood leukemia using reverse isolation techniques
Authors: Ogden Angela Kent , Steuber C. Philip , Mahoney Donald H. , Fernbach Donald J.
Published: February 2007

Between 1979 and 1986, 29 pediatric patients underwent bone marrow transplantation at Texas Children's Hospital using routine reverse isolation. Laminar air flow rooms, prophylactic antibiotics, and gut sterilization were not utilized. The diagnoses included acute lymphocytic leukemia (ALL) (16 patients), acute nonlymphocytic leukemia (ANLL) (10 patients), and chronic myelogenous leulemia (CML) (three patients). All patients had fever during hospitalization. There were 11 episodes of bacteremia in seven patients giving a bacteremia rate of 37.9%. Moderate‐to‐severe (grade II–IV) acute graft‐versus‐host disease (GVHD) was seen in eight patients (27.6%). The incidence of infection and GVHD during the first 100 days post‐transplantation is comparable to published reports from centers utilizing rigid isolation and sterilization of the gut. It is suggested that bone marrow transplantation may be done using standard reverse isolation techniques without increasing the morbidity or mortality of the procedure.
Undifferentiated acute leukemia and lineage infidelity (difficulties in classification and management)
Authors: Delaat Cynthia A. , Files Beatrice , Harris Richard E. , Neudorf Steven , Lampkin Beatrice C.
Published: February 2007

The acute leukemias have been considered to represent a clonal expansion of a malignant transformed hematopoietic progenitor cell with adherence to either the myeloid or lymphoid lineage—“lineage fidelity.” Lineage fidelity has been challenged by the demonstration of lineage switching or mixed‐lineage leukemias. We describe a 7 year old male who presented with undifferentiated acute leukemia and nasopharyngeal and cervical masses. His blasts had the morphologic appearance of myeloblasts (FAB M1) and were positive solely for the myeloid antigen CD15. He entered a complete remission (CR) with acute nonlymphocytic leukemia therapy. At first relapse he had evidence of mixed‐lineage leukemia with B‐cell lymphoid and myeloid phenotypes. He again relapsed from a second CR with Burkitt‐cell leukemia. Cytogenetic findings showed a consistent 14q+,17p+ abnormality in the blasts and nasopharyngeal mass. The t(8;14) associated with Burkitt's lymphoma was found in the mass tissue only following passage in the nude mouse.

Our patient demonstrates that limitations still exist in our ability to classify acute leukemia. That leukemic transformation occurred in a multipotential progenitor cell leading to undifferentiated leukemia at diagnosis and/or that chemotherapy can influence the genetic programs of leukemic cells leading to the evidence of mixed‐lineage leukemia and lineage switching is supported.
Systemic administration of radionuclides in neuroblastoma as planned radiotherapeutic intervention
Authors: Lashford L. S. , Clarke J. , Kemshead J. T.
Published: February 2007

Targeted radiotherapy, using systemically administered radionuclides, is an exciting proposition for the treatment of disseminated disease. In neuroblastoma, two groups of compounds have been developed as radiation delivery systems: monoclonal antibodies, exemplified by UJ13A, and the small‐molecular‐weight radio‐pharmaceutical meta‐Iodobenzylguanidene (mIBG).
Rhabdomyosarcoma with heterologous cartilage of the uterine cervix: A clinicopathologic and immunohistochemical study of an aggressive neoplasm in a young female
Authors: Perrone Theresa , Carson Linda F. , Dehner Louis P.
Published: February 2007

This report concerns a 20‐year‐old female who had a F.I.G.O. stage I rhabdomyosarcoma (sarcoma botryoides) of the cervix with a predominant embryonal pattern and heterologous cartilage that pursued an aggressive course despite surgery and chemotherapy. The patient had a pelvic recurrence, developed pulmonary metastases 15 months after diagnosis, and died 6 months later. Despite some previously published favorable prognostic assessments about this unique variant of cervical rhabdomyosarcoma, our limited experience would interject a note of caution, especially in the presence of a focal alveolar pattern and invasion of lymphatics in the cervix.
Prognostic factors for patients with diffuse large cell or immunoblastic non‐Hodgkin's lymphomas: Experience of the non‐Hodgkin's lymphoma pathologic classification project
Authors: Simon Richard , Durrleman Sylvain , Hoppe Richard T. , Bonadonna Gianni , Bloomfield Clara D. , Rudders Richard A. , Cheson Bruce D. , Berard Costan W.
Published: February 2007

Prognostic factors for long‐term survival of 312 patients with diffuse large cell or immunoblastic non‐Hodgkin's lymphoma are presented based on analysis of the multi‐institution clinicopathologic study sponsored by the National Cancer Institute. At the time of analysis, 75% of the patients had died and the median follow‐up for patients still alive was 11 years. The distribution of Ann Arbor stages was 21% stage 1, 32% stage 11, 17% stage III, and 30% stage IV. Factors of prognostic significance for survival included age, stage, histologic subtype, presence of B symptoms, size of the largest lesion, number of extra‐lymphoid organs involved, and extent of lymphatic involvement. Recursive partitioning analysis suggested a prognostic classification system based on stage, age, size of the largest lesion, and presence of mediastinal involvement. Stage I patient <50 years of age had a 10 year survival rate of 65% compared to 36% for older stage I patients. Stage II patients <65 years old without bulky lesions or mediastinal involvement had a 10 year survival rate of 45% compared to 10% for the poorer risk stage II patients. Although statistically significant prognostic factors were identified for the stage III/IV patients, they were not strong discriminants of 5–10 year survival rate. Because of the correlation among potential prognostic factors, there is no uniquely best classification system. Reasons for discrepancies among reported prognostic factor analyses are discussed, and a prognostic grouping that synthesizes our results with those of others is proposed.
Radiation therapy in the management of langerhans cell histiocytosis
Authors: Selch Michael T. , Parker Robert G.
Published: February 2007

Twenty‐two patients with Langerhans cell histiocytosis (LCH) were managed in the UCLA Department of Radiation Oncology from 1974 to 1987. Their median age was 17 years (range 1–42 years) and median followup 4.5 years (range 1–13 years). Fourteen patients had disease localized to a bone (13) or a soft tissue (one). Eight patients had LCH involving multiple bones (3) or soft tissues plus bones (5). Nine of 10 patients less than 19 years old had disease confined to bone(s) compared to 7 of 12 older patients. Fifty‐six sites of LCH (40 bone, 16 soft tissue) were irradiated. Pediatric patients received therapy to 15 sites (14 bone, 1 soft tissue) and adults 41 sites (26 bone, 15 soft tissue). Median dose for bone lesions was 900 cGy (range 600–1,500) and for soft tissue 1,500 cGy (range 600–2,600). Local control was achieved in 46 of 56 sites (82%). Control rates for bone and soft tissue lesions were 35 of 40 (88%) and 11 of 16 (69%), respectively. Fifteen of 15 sites in pediatric patients were controlled compared to 29 of 41 (72%) in adults. Ten sites (18%) recurred 10 months to 4 years after irradiation. Recurrences were in‐field and noted only in adults with involvement of multiple soft tissues plus bones. All recurrent soft tissue lesions had been treated with orthovoltage. Five patients developed new foci of LCH subsequent to irradiation. Four of these patients had disease involving soft tissues and bones. One patient with progressive LCH initially presented with a single bone lesion. The acute and chronic effects of radiation therapy were minimal. One patient suffered transient enlargement of adenopathy. An elevated serum TSH level was detected 9 years after irradiation of a cervical vertebra in another patient.
Epidemiological and familial aspects of hepatoblastoma
Authors: Hartley A. L. , Birch J. M. , Kelsey A. M. , Jones P. H. Morris , Harris M. , Blair V.
Published: February 2007

Data on the 20 cases of hepatoblastoma registered with the Manchester Children's Tumour Registry between 1954 and 1988 are presented. The cases represent about 0.6% of childhood malignancies and show a male: female ratio of 2.3:1. Age at presentation was almost always under 2 1/2 years. Cancer rates in close relatives were not significantly different from those expected. One family was confirmed as having Gardner syndrome, but the presence of other syndromes e.g., Beckwith‐Wiedemann, could not be reliably detected in this retrospective series. The need to take an extensive pedigree and for clinical examination of other family members at the time of the child's diagnosis is emphasized.
Neuropsychologic and ct examinations in leukemic patients surviving 10 or more years
Authors: Schuler D. , Bakos M. , Borsi J. , Gacsály I. , Kálmánchey R. , Kardos G. , Koós R. , Nagy C. S. , Révész T. , Somló P. , Gebauer E.
Published: February 2007

Long‐term survivors of childhood leukemia were studied to determine their neuropsychologic status. All had had cranial irradiation 10 or more years before. The results were

1. The IQ and academic performance of 56 cured leukemic patients show no significant difference from the normal population.

2. More exact neuropsychological tests (attention, reaction time, visual‐motor coordination, memory) reveal important deficits.

3. The frequency of CT aberrations in 33 study patients was 45% and showed no correlation with either the IQ or other neuropsychological results.
Familial phaeochromocytoma: Successful treatment with 131I‐MIBG
Authors: Goncalves Eduardo , Ninane Jacques , Wese François‐Xavier , Leonet Jacqueline , Piret Louis , Cornu Guy , De Meyer Roger
Published: February 2007

We report the case of a family in which the mother died of hypertensive encephalopathy following the relapse of a phaeochromocytoma. Two of her children are still alive. Both children had malignant phaeochromocytomas that have been treated by surgery and 131I‐MIBG. The first child presented with phaeochromocytoma of the right suprarenal gland at the age of 7 years. Surgery was performed. At the age of 14 years, he developed a tumour of the left suprarenal gland and two pulmonary metastases demonstrated by 131‐MIBG. The three tumours were removed, but new lesions occurred. The boy then was treated with 200 mCi (7,400 MBq) of 131‐MIBG given twice, and is now free of disease more than 2 years after treatment. His sister presented at the age of 12 years with phaeochromocytoma of the left suprarenal gland, the only lesion recognized by 131I‐MIBG. The tumour was removed, but 5 months later, she developed phaeochromocytoma in the right suprarenal gland. She was treated with 200 mCi (7,400 MBq) of 131I‐MIBG and surgery was performed 6 months later. Histology of the suprarenal gland could not demonstrate the persistence of phaeochromocytoma cells. The child is now free of disease more than 2 years after treatment.