Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank  < .001). The OES did not differ significantly between the two treatment groups (plogrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.

Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG).

INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Malignancy and chemotherapy induced haemophagocytic lymphohistiocytosis in children and adolescents-a single centre experience of 20 years.

Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1.3-18.0, median 10.1 years; malignancy induced n = 2; chemotherapy induced n = 20). Patients with acute myeloblastic leukaemia (AML) developed HLH significantly more often than patients with acute lymphoblastic leukaemia (ALL) (10/55, 18.2% vs. 6/148, 4.1%, p = 0.0021). As possible viral triggers, we detected BKV (53.8% of the tested patients), HHV-6 (33.3%), EBV (27.8%), CMV (23.5%), ADV (16.7%) and PVB19 (16.7%) significantly more frequently than in haemato-/oncologic patients without HLH. Despite lacking evidence of concurrent bacterial infection, C-reactive protein (CRP) and procalcitotnin (PCT) were elevated in 94.7 and 77.7% of the patients, respectively. Ferritin and sIL2R were markedly elevated in all patients. HLH-associated mortality significantly (p = 0.0276) decreased from 66.6% (1995-2004) to 6.25% (2005-2014), suggesting improved diagnostic and therapeutic management. Awareness of HLH is important, and fever refractory to antibiotics should prompt to consider this diagnosis. Elevated ferritin and sIL2R seem to be good markers, while inflammatory markers like CRP and PCT are not useful to discriminate viral triggered HLH from severe bacterial infection. Re-/activation of several viruses may play a role as possible trigger.

Successful Unrelated Stem Cell Transplantation in an Infant With Congenital Acute Myelogenous Leukemia FAB M5 Showing Massive Cutaneous Infiltrations--A Challenging Multidisciplinary Approach.

The multidisciplinary management of a male neonate presenting with congenital acute myelogenous leukemia of monoblastic phenotype is reported using conventional chemotherapy, high dose conditioning, and matched unrelated donor stem cell transplantation. These therapies were combined to add a graft versus leukemia effect to the treatment. Although chimerism studies showed a decrease of donor white blood cells, T-cells remained stable of allogeneic origin. We hypothesize that a continuous graft versus leukemia effect results in minimal residual disease negativity for now more than 18 months since stem cell transplantation.

Sirolimus for the treatment of children with various complicated vascular anomalies.

Vascular anomalies include a heterogeneous group of disorders that are categorized as vascular tumors or vascular malformations. Treatment options include resection, embolization, laser therapy, and sclerotherapy or medical treatment such as propranolol, steroids, interferon, and cytostatic chemotherapy. Mammalian target of rapamycin seems to play a key role in the signal pathway of angiogenesis and subsequently in the development of vascular anomalies. Recently, the successful use of sirolimus has been reported in children with lymphatic malformations and kaposiform hemangioendotheliomas. We report on six patients with different vascular anomalies (kaposiform hemangioendothelioma n = 2, combined lymphatico-venous malformation n = 2, pulmonary lymphangiectasia n = 1, and orbital lymphatic malformation n = 1) who were treated with peroral sirolimus. Three of the children initially presented with a Kasabach-Merrit phenomenon. Median duration of treatment was 10 months; two children are still on treatment. Three children each achieved complete and partial remission. Kasabach-Merrit phenomenon resolved within 1 month in all patients. Treatment with sirolimus was tolerated well; only mild reversible leukopenia was observed. CONCLUSION: Sirolimus proved to be effective in children with complicated lymphatic or lymphatico-venous malformations and kaposiform hemangioendotheliomas. Treatment was tolerated well with acceptable side effects. The optimum length of treatment and possible long-term side effects have to be evaluated. WHAT IS KNOWN: • Vascular anomalies including vascular tumors and vascular malformations may lead to life-threatening conditions.• Some patients are refractory to established treatment and/or are not available for local invasive procedures. WHAT IS NEW: • We reviewed the literature focusing treatment of vascular anomalies inc hildren and adolescents.• Our data support recent studies that sirolimus is an effective treatment option in patients with complicated vascular tumors andmalformations

Amphotericin B transfer to CSF following intravenous administration of liposomal amphotericin B.

OBJECTIVES: Although amphotericin B (AmB) and its lipid formulations are used for the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF after intravenous administration of liposomal amphotericin B (LAmB) are not well characterized. PATIENTS AND METHODS: From 14 paediatric haemato-oncological patients (aged 0.4-19.5 years, median 7.6 years), we obtained 30 CSF samples by means of routine punctures (performed for intrathecal treatment of the underlying diseases) at different timepoints after the prophylactic intravenous infusion of LAmB (AmBisome, 3 mg/kg/day). Concurrent serum samples were obtained to calculate the transfer rates. An HPLC method was used for AmB detection. RESULTS: CSF levels of AmB 1-100 h after the intravenous infusion of LAmB were between 10 and 120 ng/mL, except in one case with a level of 529 ng/mL. Concurrent serum levels were about 1000-fold higher, ranging between 3 and 75 µg/mL. CSF levels did not show a clear time-dependent concentration profile, but remained at a steady-state for longer than 48 h after infusion. The transfer rate ranged from 0.02% to 0.92% (median 0.13%) and correlated significantly (r=0.801, P<0.001) with increasing time after infusion. CONCLUSIONS: After the intravenous administration of LAmB, AmB CSF levels were low, confirming published animal data. CSF levels remained at a steady-state level for longer than 48 h. As indicated by published post mortem data, higher levels in brain tissue, which would be necessary for the successful treatment of CNS infections, might be possible.

Short-term intravenous fish-oil emulsions in pediatric oncologic patients--effect on liver parameters.

Pediatric oncologic patients often need parenteral nutrition (PN) during chemotherapy. Long-term use of soybean-based lipid emulsions is associated with progressive liver disease and cholestasis, whereas fish-oil based emulsions have anticholestatic effects. We studied the potentially hepato-protective effects of short-term use of SMOF lipids in children undergoing chemotherapy. Fifteen pediatric oncologic patients treated with SMOF lipids were retrospectively analyzed in respect to bilirubin and liver parameters and compared to matched-controls who had received soybean-based fat emulsions. For statistics the time-points baseline, Day 14 of PN (PN14), and post (Day+7) were chosen. None of the study patients developed cholestasis. Within the SMOF-lipid group there were no differences in the laboratory parameters between baseline, PN14, and post. In the control group, gamma glutamyltransferase (γGT) levels increased during PN (baseline vs. PN14, 26.43 vs. 63.00 U/l, P < 0.05). Lactate dehydrogenase (LDH) levels showed a significantly different behavior in the 2 groups: In the SMOF lipids group, LDH decreased whereas it increased in the controls (-32.75 U/l vs. + 29.57 U/l, P < 0.05). An advantage of fish oil-based fat emulsions can be shown even after short-term PN. In children undergoing chemotherapy the use of soybean-based fat emulsions but not SMOF lipids led to increased γGT levels.

Paley's multiplier method does not accurately predict adult height in children with bone sarcoma.

BACKGROUND: The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy. QUESTIONS/PURPOSES: We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients. METHODS: Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores). RESULTS: Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma. CONCLUSIONS: Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.

Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler syndrome.

For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 × 10(6) CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of α-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a "tailored" number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H.

Age- and gender-related differences in teicoplanin levels in paediatric patients.

OBJECTIVES: Teicoplanin is a glycopeptide antibiotic active against Gram-positive bacteria, including methicillin-resistant staphylococci. While teicoplanin trough levels (TTLs) >10 mg/L are commonly considered appropriate, levels >20 mg/L are aimed for in the treatment of severe infections. Due to toxicity, it is recommended to avoid levels >60 mg/L. PATIENTS AND METHODS: In our institution, the initial dosing schedule of teicoplanin (10-15 mg/kg every 12 h for three loading doses and every 24 h thereafter) is adapted according to TTLs analysed by a fluorescence polarization immunoassay on treatment days 2 to 4. Teicoplanin peak levels (TPLs) are analysed in selected cases 30 min after the end of infusion. In a retrospective analysis we evaluated 1357 TTLs and 333 TPLs from 410 treatment episodes from 2005 to 2011. RESULTS: Initial TTLs were <10 mg/L in 14.1% and <20 mg/L in 72.6% of episodes. Toddlers had significantly lower TTLs, with a 2-fold and 2.5-fold increased risk of having levels <10 mg/L (24.6%) and <20 mg/L (82.6%), respectively. For the entire cohort, follow-up TTLs were less likely to be <10 mg/L and more likely to be >20 mg/L when compared with initial TTLs (P < 0.001, each). Adolescent girls had significantly higher initial TPLs (P = 0.001) and significantly higher follow-up TTLs (P = 0.016) than adolescent boys. In parallel, adolescent girls had initial TPLs >60 mg/L significantly more frequently (P = 0.012) and follow-up TTLs <10 mg/L significantly less frequently (P = 0.005). CONCLUSIONS: More tailored dosing regimens with higher loading doses, especially for toddlers, should be considered. While further pharmacokinetic data in paediatric patients are pending, therapeutic drug monitoring is mandatory.

Add-on-therapy with bevacizumab in children and adolescents with poor prognosis non-CNS solid tumors.

Bevacizumab is increasingly being used in adult patients with cancer and children with central nervous system (CNS) tumors. Little, however, is known about the efficacy, risks, and benefits of bevacizumab administration in non-CNS tumors of childhood. The aim of the present study was to report on bevacizumab administered as add-on-therapy for poor prognosis non-CNS solid tumors of childhood and adolescence, including a prospective evaluation of side effects of bevacizumab. Seven patients (female: n = 5; median age, 14.5 years) with relapsed (n = 4) or primary metastatic (n = 3) solid non-CNS tumors received bevacizumab at 5-10 mg/kg body weight intravenously every 2-3 weeks. Assessment of cardiac function, thyroid hormone levels, urine analysis, and radiographic responses were carried out every 3 months. The median time of bevacizumab treatment was 10 (range, 5-17) months. Patients received a median of 16 (range, 10-38) bevacizumab infusions. With a median follow-up of 25 (range, 13-38) months, five patients relapsed after 7-25 months and three of them died. Two patients are still in complete remission for 31 and 32 months, respectively. Fraction shortening decreased in two patients. Bevacizumab was associated with new-onset increase in basal thyroid-stimulating hormone (n = 3), mild proteinuria/hematuria (n = 5), intermittent hypertension (n = 2), hypertension requiring antihypertensive medication (n = 3), and epistaxis (n = 2). In two patients, therapy with bevacizumab was terminated because of side effects. Selected patients with relapsed or primary metastatic solid non-CNS tumors of childhood and adolescence might benefit from add-on-therapy with bevacizumab. Although the side effects were usually mild, cardiac monitoring seems to be essential during and after the administration of bevacizumab.

Alternative donor HSCT in refractory acquired aplastic anemia - prevention of graft rejection and graft versus host disease by immunoablative conditioning and graft manipulation.

Early alternative donor HSCT is a potentially curative therapeutic option for patients with AAA not responding to IST. Seven patients (median age at diagnosis, 11 yr) with refractory AAA without a MSD underwent HSCT from matched unrelated (n = 6) or haploidentical (n = 1) donors. Conditioning regimens included CY (n = 7), muromonab-CD3/ATG (n = 7), TT (n = 6), FLU (n = 5), and TLI (n = 2). Grafts were either CD34 purified and/or CD3/19 depleted and contained a median of 10.17 × 10(6) /kg CD34 and 5.5 × 10(4) /kg CD3 cells. All patients engrafted rapidly. Median time to leukocyte engraftment was 10 days. With a median follow-up of 26 (range, 11-153) months, six patients are alive and well with complete donor hematopoiesis. One heavily pretreated patient developed GVHD grade III and died from progressive renal failure (resulting from microangiopathic hemolytic anemia) and disseminated aspergillosis. Early alternative donor HSCT can help to avoid complications from prolonged IST and presumably improve survival of patients with refractory AAA. Administration of high doses of CD34 purified and/or CD3/19 depleted stem cells following novel immunoablative conditioning may prevent graft rejection and GVHD. However, a long interval from diagnosis to HSCT seems to be associated with poor outcome.

Bone marrow necrosis in a girl with Hodgkin's disease.

Bone marrow necrosis (BMN) is a rare finding in children with malignancy occurring most commonly in children with acute lymphoblastic leukemia. This article describes the first case of a girl who developed BMN during treatment for Hodgkin's disease. During the second cycle of chemotherapy, she experienced sudden profound bone pain in the lumbosacral region associated with elevated levels of lactate dehydrogenase (LDH), fibrin degradation products (D-Dimer), and alkaline phosphatase as well as pancytopenia and leukoerythroblastosis. MRI studies showed multiple confluent areas with low signal intensity and rim contrast enhancement in all vertebral bodies. Bone marrow biopsy revealed focal necrosis within hypocellular bone marrow. The patient responded quickly to symptomatic treatment with analgetics and heparin; however, elevations of LDH and D-Dimer persisted for 1.5 and 8 months, respectively. Clinicians should be aware of this rare condition to establish the diagnosis and to continue oncologic treatment as early as possible.

Survival and late effects in children with stage 4 neuroblastoma.

BACKGROUND: Treatment of metastatic neuroblastoma (NB) demands aggressive oncological therapy, which may cause long-term sequelae in survivors. The aim of this retrospective single center study is to give an overview of survival in children with stage 4 NB and to describe the spectrum of late effects seen in survivors. PROCEDURE: Medical records of 31 patients with stage 4 NB treated between 1984 and 2009, who were included in a follow-up programme, were reviewed for information on tumor, treatment and late effects. RESULTS: Five-year overall survival was 54.3 ± 9% and 5-year event-free survival was 44.9 ± 9%. Patients diagnosed after 1996 had a significantly better survival rate than those diagnosed before (74 ± 11.2% vs. 33.3 ± 12.2%, P = 0.011). In 15 of the 16 survivors (93.8%), numerous late effects were detected. The most common long-term sequelae were renal changes in 10 patients (62.5%) and endocrine disturbances in 9 patients (56.3%), including hypothyroidism with need of substitution in 50%, GH deficiency in 37.5% and hypogonadism in 12.5%. Sensorineural hearing loss occurred in 37.5% of survivors. Further observed late effects were hepatobiliary changes (31.3%), musculoskeletal problems, and pulmonary abnormalities (each 25%), as well as neurologic changes (18.8%), dental defects (12.5%), and unilateral blindness (6.3%). Second neoplasms appeared in 3 patients, 1 of whom died of hepatocellular carcinoma following infection with hepatitis B. CONCLUSIONS: More than 50% of children with stage 4 NB may survive. The high incidence of severe long-term sequelae underlines the importance of careful follow-up in order to detect and treat late effects early enough.

Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.

Successful treatment of progressive cutaneous mastocytosis with imatinib in a 2-year-old boy carrying a somatic KIT mutation.

Cutaneous mastocytosis (CM) in children is a usually benign skin disorder caused by mast cell proliferation. Progressive disease leading to systemic involvement and fatal outcomes has been described. C-kit receptor mutations have been identified as causative for CM, some of which potentially respond to imatinib treatment as described for patients with systemic mastocytosis. We report successful therapy of progressive CM with imatinib in a 23-month-old boy. KIT gene analysis revealed not only a somatic deletion of codon 419 in exon 8 (c.1255_1257delGAC) which responds to imatinib therapy, but also a novel germ line p. Ser840Asn substitution encoded by exon 18 in the c-kit kinase domain. Family history suggests this exchange does not affect receptor function or cause disease. Imatinib therapy was well tolerated, stopped symptoms and disease progression, and appeared to shorten the course of the disease. Imatinib could possibly represent a novel therapeutic option in patients with progressive CM.

Pheochromocytoma in a 2.75-year-old-girl with a germline von Hippel-Lindau mutation Q164R.

Pheochromocytomas are rare tumors of the adrenal gland occurring sporadically or as part of familial cancer syndromes. Here we report on the case of a pheochromocytoma due to the germline missense mutation c.491A>G (Q164R) in exon 3 of the von Hippel-Lindau gene in a girl as young as 2.75 years. Extended analyses of her relatives showed that the mutation occurred de novo in the patient's father who was subsequently diagnosed with bilateral pheochromocytomas and a retinal angioma. To the best of our knowledge, this is the youngest patient presenting with pheochromocytoma so far described in the literature. The same VHL mutation has been reported in a patient who developed a pheochromocytoma at the age of 10 years; therefore, for known VHL Q164R mutation carriers, we suggest screening for pheochromocytoma beginning at 2 years of age.

Peripheral blood stem cell mobilization with pegfilgrastim compared to filgrastim in children and young adults with malignancies.

BACKGROUND: Pegfilgrastim, the long acting agent of rh-GCSF, has been shown to be as effective as Filgrastim in children undergoing cytotoxic chemotherapy by reducing the duration of neutropenia. Recent studies in adults have also shown that Pegfilgrastim is effective to mobilize CD34+ stem cells, resulting in earlier peripheral stem cell collections (PSCC). The aim of the study was to compare the efficacy of Pegfilgrastim with Filgrastim for CD34+ stem cell mobilization in children. PROCEDURE: Three groups of patients were compared: Group 1: six patients with Ewing Sarcoma stimulated with Filgrastim; Group 2: five patients with Ewing Sarcoma, Ependymoma, and Neuroblastoma; Group 3: four patients with relapsed neoplasm. Patients of Group 2 and 3 were stimulated with Pegfilgrastim followed by peripheral stem cell collection. Two patients in Group 3 needed further cytokine stimulation with Filgrastim combined with stem cell factor, Ancestim. RESULTS: In Groups 1-3, a median of 4, 3, and 3 PSCC between day 12-24, 6-13, and 8-30 were performed, yielding a median of 14.2, 24.0, and 10.3 x 10(6) CD34+ stem cells/kg BW, respectively. CONCLUSIONS: Group 2 data show that stem cell mobilization with Pegfilgrastim in children when performed during primary or without previous long lasting chemotherapy seems to produce earlier CD34+ peaks and better CD34+ yields than in Group 1. CD34+ cell mobilization with Pegfilgrastim in Group 3-patients with previous long lasting chemotherapy was possible.

Medulloblastoma in a child with down syndrome: long-term remission with multimodality treatment.

A 4(3/4)-year-old male with Down syndrome (DS) presented with unsteady gait and fatigue. Neuroimaging revealed a cerebellar mass with concomitant obstructive hydrocephalus and additional metastatic lesions. He was successfully treated and is still in complete remission 5 years from diagnosis. The present case illustrates that, although not yet reported, medulloblastoma can also occur in patients with DS.