Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors

Background:An update of results from the High Risk Protocol ofthe Meta-EICESS Study, conducted at the Pediatric Stem-Cell Transplant Centersof Düsseldorf and Vienna. In order to evaluate a possible therapeuticbenefit after allogeneic SCT in patients with advanced Ewing tumors (AET), wecompared outcome after autologous and allogeneic stem-cell transplantation(SCT). Patients and methods:We analyzed 36 patients treated with themyeloablative Hyper-ME protocol (hyperfractionated total body irradiation,melphalan, etoposide ± carboplatin) between November 1986 and December1994. Minimal follow-up for all patients was five years. All patientsunderwent remission induction chemotherapy and local treatment beforemyeloablative therapy. Seventeen of thirty-six patients had multifocal primaryEwing's tumor, eighteen of thirty-six had early, multiple or multifocalrelapse, one of thirty-six patients had unifocal late relapse. Twenty-six ofthirty-six were treated with autologous and ten of thirty-six with allogeneichematopoetic stem cells. We analyzed the following risk factors, that couldpossibly influence the event-free survival (EFS): number of involved bones,degree of remission at time of SCT, type of graft, indication for SCT, bonemarrow infiltration, bone with concomitant lung disease, age at time ofdiagnosis, pelvic involvement, involved compartment radiation,histopathological diagnosis. Results:EFS for the 36 patients was 0.24 (0.21) ± 0.07.Eighteen of thirty-six patients suffered relapse or died of disease, nine ofthirty-six died of treatment related toxicity (DOC). Nine of thirty-sixpatients are alive in CR. Age 17 years at initial diagnosis (P< 0.005) significantly deteriorated outcome. According to the type ofgraft, EFS was 0.25 ± 0.08 after autologous and 0.20 ± 0.13after allogeneic SCT. Incidence of DOC was more than twice as high afterallogeneic (40%) compared to autologous (19%) SCT, even thoughthe difference did not reach significance (P = 0.08, Fisher's exacttest). Conclusions:Because of the rather short observation period,secondary malignant neoplasm (SMN) may complicate the future clinical courseof some of our patients who are currently viewed as event-free survivors. EFSin AET is not improved by allogeneic SCT due to a higher complication rate.The patient group was to small to analyze for a possiblegraft-versus-tumor effect.     

Statement by members of the Ponte di Legno group on the right of children with leukemia to have full access to essential treatment for acute lymphoblastic leukemia.

During the panel discussion in the Sixth International ChildhoodAcute Lymphoblastic Leukemia (ALL) meeting of the Ponte di LegnoWorking Group, held in San Diego in December 2003, it was apparentthat recent improvements in treatment have further paradoxicallywidened the gap of inequality between children living in resource-richcountries and those in low-income countries. The representativesfrom 15 leading study groups and institutions decided to issuea statement [1] to lobby international and national agenciesto provide the necessary drugs at affordable cost throughoutthe world for children with ALL or other highly curable cancer.We wish to draw a wider readership and support     

Neuroblastoma mass screening in late infancy: insights into the biology of neuroblastic tumors.

PURPOSE: Neuroblastoma screening in early infancy has detected predominantly "favorable" tumors. We postponed screening to an age between 7 and 12 months to test whether this shift of screening age might influence the detection rate of genetically/clinically unfavorable tumors. PATIENTS AND METHODS: In a 10-year period, 313,860 infants were screened by analysis of urine catecholamines. When a neuroblastoma was diagnosed, at least two different areas from every tumor were analyzed for genetic features (MYCN amplification, 1p status, ploidy). Furthermore, neuroblastoma incidence and mortality of the screened group and the cohort of 572,483 children not participating in the screening program were compared. RESULTS: Forty-six neuroblastomas were detected by mass screening. In 17 tumors (37%) at least one of the biologic features was "unfavorable." In 10 of 17 patients, one or more of these alterations were only focally present (tumor heterogeneity). In the screened cohort, neuroblastoma incidence was significantly higher when compared with unscreened children (18.2 v 11.2/100,000 births), while there was a trend towards lower incidence of stage 4 over 1 year (2.2 v 3.8). Mortality was not significantly different (0.96 v 1.57). CONCLUSION: In contrast to other neuroblastoma screening programs, more than one-third of patients were found with unfavorable genetic markers in our study. The high proportion of focal alterations suggests that biologically young neuroblastomas may consist of genetically favorable and unfavorable parts/areas/clones. We conclude that at least one-third of neuroblastomas detected by screening in late infancy are anticipated cases. This, however, does not result in significantly reduced mortality.     

Akute Pankreatitis Seltene Komplikation bei primärem Hyperparathyroidismus (pHPT)

Background. Primary hyperparathyroidism (pHPT) in childhood and adolescence is a rare disease. Therefore diagnosis often is delayed. Methods. We report on a 13 year old boy, who sufferd from nausea, abdominal pain and weight loss for 9 months. We diagnosed an adenoma of the parathyroid gland and an acute pancreatitis in the course of a hypercalcemic crisis. Results. After stabilizing the patient, the adenoma was removed surgically. No problems occured after the surgical treatment. Within 3 months the boy regained his original weight. Conclusion. Symptoms like nausea, abdominal pain, cephalea, hypertonia, anorexia and renal stones could be a hint for pHPT. The coincidence of pHPT and pancreatitis is extremely rare. According to references in the literatur this association is most likely related to elevated calcium levels due to advanced pHPT.     

Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.

PURPOSE: Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone. PATIENTS AND METHODS: We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models. RESULTS: On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies. CONCLUSION: Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.     

Endocrine function after antineoplastic therapy in 22 children with acute lymphoblastic leukaemia.

In 22 children who were in complete remission after acute lymphoblastic leukaemia endocrinological investigations were performed 5-12 weeks after cessation of therapy. The children had received central nervous system irradiation (tele-Co60, 850-1800 rad), and long term, aggressive cytostatic drug therapy during 21 to 36 months. Growth hormone, TSH, thyroxine, LH, FSH, cortisol secretion, and urinary concentrating capacity were found to be normal, with a few exceptions where borderline results were obtained.     

Manifestations of graft-versus-host disease following allogenic bone marrow transplantation.

Sixty-seven patients undergoing allogenic bone marrow transplantation (BMT) were examined before and at regular intervals for up to 87 months (1-87 months, mean 18) after transplantation. Within a period of 1-39 months, 14 of these patients died (11 male, 3 female; age at BMT 16-46y). Five of these patients died within the first 100 days. They showed no eye involvement; three patients had intraretinal hemorrhage, in one case of squamous blepharitis and filiform keratitis developed during chronic graft-versus-host disease (GVHD). In contrast, 22 of 53 (41.5%) surviving patients (30 male, 23 female; age at BMT 1-47y) were found to have ocular involvement. Before BMT only two cases of retinal hemorrhage and central chorioretinal scars each were detected. During the stage of acute GVHD (up to day 100), nine patients were free of ocular manifestations. However, 16 of the 20 patients with chronic GVHD showed ocular involvement; 14 (70%) had reduced tearflow, ten had severe keratoconjunctivitis sicca, four suffered from sterile corneal ulcerations. Bilateral cataracts were detected in 11 patients, nine of whom only had minimal posterior subcapsular opacification, possibly resulting from highdose steroid medication. One additional case presented with bilateral multifocal recurrent chorioretinitis and panuveitis. The fundus lesions appeared some months after BMT (before cyclosporin-A treatment started) and recurred during systemic treatment. All patients undergoing allogenic BMT, especially when treated for severe chronic GVHD, require regular ocular observation to avoid complications such as keratoconjunctivitis sicca at an early stage, as late complications are often severe and hardly amenable to conservative or surgical treatment.     

The TCCS—A short measure to evaluate treatment-related coping and compliance in hospitalised childhood cancer patients and their primary caregivers

Goals This report describes the development and validation of a short rating system to assess treatment-related coping and compliance (TCC) in childhood cancer patients and their primary caregivers.Patients and methods The initial system contained 21 items referring to supportive parenting style of the caregiver, treatment-related attitudes and behaviour of both caregiver and child, communicative skills of the child and relationships with the health care team. This questionnaire was completed independently by a nurse, a nursery-school teacher, a psychologist and a physician who are all working full time at the oncology unit. The sample under study included 111 patients aged 3–18 years who were on treatment, as well as their caregivers (in most cases the mother).Results Using defined rules for item reduction, the questionnaire was reduced to 14 items, of which seven were referring to the TCC of the child and seven to the TCC of the caregiver. Cronbachs alpha coefficients ranged from 0.81 to 0.91 across the different assessments, indicating high internal consistency reliability. There was moderate to high agreement amongst observers (intra-class correlation coefficients ranged between 0.50 and 0.68). Construct validity was confirmed by a significant association between a global rating of TCC and the instruments summary scores in the four assessments.Conclusions Our system may be used for clinical trials and clinical monitoring. Further testing of psychometric properties is recommended.