BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 DELIBERAZIONE 4 agosto 2008, n. 622

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1 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 DELIBERAZIONE 4 agosto 2008, n. 622 Direttive alle Aziende Sanitarie Toscane sull impiego in pediatria dei farmaci fuori dalle indicazioni di registrazione, ai sensi dell art 1, comma 796, lettera Z della legge 296/2006. LA GIUNTA REGIONALE Vista la Legge 8 aprile 1998 n. 94: Conversione in legge, con modificazioni, del Decreto-Legge 17 febbraio 1998, n. 23, recante disposizioni urgenti in materia di sperimentazioni cliniche in campo oncologico e altre misure in materia sanitaria con particolare riferimento all articolo 3; Vista la legge 27 dicembre 2006, n. 296, recante disposizioni per la formazione del bilancio annuale e pluriennale dello Stato (legge finanziaria 2007) ed in particolare l art. 1, comma 796, lettera z), dove si pongono dei limiti all dei farmaci al di fuori delle indicazioni di registrazione, con oneri a carico del SSR; Richiamata la propria deliberazione n. 394 del 26 maggio 2008, con la quale è stata approvata la lista dei medicinali oncologici off-label utilizzati nel trattamento di tumori solidi ed ematologici nell adulto; Ritenuto opportuno predisporre la lista dei farmaci oncologici off-label per pediatrico (Allegato A) e dei farmaci non antitumorali di supporto alla chemioterapia pediatrica (Allegato B); La lista (Allegato A) e la lista (Allegato B) costituite in forma di tabella, definiscono l elenco dei farmaci in commercio in Italia erogabili a carico del SSR nel rispetto dell estensione delle indicazioni riportate negli elenchi medesimi in ordine alfabetico: Nella prima colonna (Nome Composto) sono elencati i farmaci per i quali è stata individuata un estensione delle indicazioni terapeutiche già autorizzate; Nella seconda colonna (Sintesi delle Indicazioni già Autorizzate per l impiego in Pediatria) sono riassunte le indicazioni terapeutiche previste dal provvedimento di autorizzazione all immissione in commercio presenti nella scheda tecnica del farmaco; Nella terza colonna : - dell Allegato A (Estensione delle Indicazioni sulla base della delibera AIFA e di nuove Evidenze Scientifiche) sono elencate sia l estensione delle indicazioni terapeutiche già approvate dalla Commissione AIFA e presente nell elenco dei farmaci off-label oncologici AIFA (carattere corsivo) che l ulteriore estensione proposta dalla Commissione Terapeutica Toscana, sulla base di nuove evidenze scientifiche (carattere grassetto) presenti nella letteratura scientifica internazionale che saranno sottoposte a revisioni periodiche; - dell Allegato B (Estensione delle Indicazioni sulla base di nuove Evidenze Scientifiche) sono elencate le estensioni delle indicazioni terapeutiche sulla base di nuove evidenze scientifiche che saranno sottoposte a revisioni periodiche; Nella quarta colonna (Bibliografia) sono elencate le principali fonti bibliografiche a sostegno dell estensione delle indicazioni; Nella quinta colonna ( Nazionali e Internazionali in ) sono elencate come da Legenda in (Allegato C) le abbreviazioni dei nomi di società scientifiche e protocolli internazionali ; Acquisito il parere favorevole della Commissione Terapeutica Regionale di cui all art. 81 della L.R. n. 40/2005 nella seduta del 16 luglio 2008; A voti unanimi; DELIBERA Per quanto in premessa riportato: di approvare la lista dei farmaci oncologici per pediatrico, utilizzabili per indicazioni diverse da quelle previste dal provvedimento di autorizzazione all immissione in commercio e non comprese negli Allegati 1 e 3 della determinazione AIFA del 29 Maggio 2007 (pubblicata sulla Gazzetta Ufficiale della Repubblica Italiana n 129 del 6 Giugno 2007), per cui è ammesso l utilizzo off-label con oneri a carico del SSR (Allegato A) e dei farmaci non antitumorali di supporto alla chemioterapia pediatrica (Allegato B) completati dalla Legenda (Allegato C); di specificare che gli Allegati (A, B e C) di cui al punto precedente sono parte integrante e sostanziale del presente atto; di precisare che l utilizzo di un farmaco, in una patologia non prevista dal decreto di autorizzazione all immissione in commercio (AIC) del farmaco stesso, e non ricompresa nelle liste di cui ai precedenti punti può essere disposto, con oneri a carico del SSR, da un medico, nel rispetto della normativa vigente, solo se contestualmente alla prescrizione, trasmette una sintetica relazione alla Commissione Terapeutica Regionale (CTR), per il tramite del Settore Farmaceutica Regionale, oltre che alla Direzione Sanitaria della propria azienda, circa l attivazione della terapia avendo cura comunque di specificare la patologia per la quale il farmaco viene impiegato; la CTR valuta, avvalendosi anche di componenti dell Istituto Toscano Tumori e di eventuali ulteriori

2 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 specialisti esperti, le comunicazioni di cui al precedente punto e nel caso in cui ritenga che la letteratura scientifica non supporti l utilizzo off-label richiesto, detto verrà ricompreso in una lista negativa e non potrà essere posto a carico del SSR in tutte le Aziende Sanitarie Toscane, salvo la conclusione delle terapie già attivate; 99 di disporre che mensilmente le Aziende Sanitarie debbano fornire al Settore Farmaceutica della Direzione Generale del Diritto alla Salute e delle Politiche di Solidarietà una rendicontazione dei pazienti trattati, dei medicinali erogati e l onere finanziario sostenuto, nel rispetto della legge sulla privacy. di precisare che le liste (Allegato A e B) di cui sopra restano in vigore sino alla stesura e pubblicazione di eventuali ulteriori aggiornamenti; di precisare che l impiego off-label dei farmaci è da ritenersi, negli specifici casi in cui esso avviene, come sostitutivo di altre terapie farmacologiche concesse a carico del Servizio Sanitario Nazionale e pertanto non comporta oneri aggiuntivi a carico del bilancio regionale; Il presente atto è pubblicato integralmente sul BURT ai sensi dell art. 5 comma 1 lettera e della LR 23/2007 e sulla banca dati degli atti amministrativi della Giunta regionale ai sensi dell art.18 comma 2 della medesima LR 23/2007 Segreteria della Giunta Il Direttore Generale Valerio Pelini SEGUONO ALLEGATI

3 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 ACIDO TRANSRETINOICO ACIDO 13-CIS- RETINOICO Allegato A Farmaci oncologici off-label per pediatrico Nessuna -Neuroblastoma -Nefroblastoma -Leucemia promielocitica acuta Neuroblastoma e Nefroblastoma Adamson PC et al. A phase 2 trial of all-trans-retinoic acid in combination with interferon-alpha2a in children with recurrent neuroblastoma or Wilms tumor: a Pediatric Oncology Branch, NCI and Children's Oncology Group Study. Pediatr Blood Cancer 2007;49: Leucemia promielocitica acuta Dvorak CC et al. Reinduction of relapsed acute promyelocytic leukemia with ATRA and low dose antimetabolite-based chemotherapy. Pediatr Blood Cancer 2007;48: Ortega JJ et al. Treatment with all-trans retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol 2005;23: Nessuna -Neuroblastoma Neuroblastoma Veal G et al. Pharmacokinetics and pharmacogenetics of 13-cis-retinoic acid in children with high risk neuroblastoma. A study of the UK Children s Cancer Study Group. Br J Cancer 2007;96: Reynolds CP et al. Retinoid therapy of high-risk neuroblastoma.cancer Lett 2003;197: AIDA-Prot. (lap0493) GIMEMA AIEOP - NB-AR-01

4 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N ACTINOMICINA-D -Nefroblastoma -Neuroblastoma - Tumori solidi (nel primo anno di vita) - Rabdomiosarcoma - Tumori della famiglia del sarcoma di Ewing - Emangiopericitoma - Carcinoma del rene a cellule chiare - Carcinoma nasofaringeo - Tumori a cellule germinali Tumori solidi (nel primo anno di vita) Orbach D et al. Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee. J Clin Oncol 2005;23: Rabdomiosarcoma Waiterhouse I and Watson A. Optimal management strategies for rhabdomyosarcoma in children. Paediatr Drugs 2007;9: Tumori della famiglia del sarcoma di Ewing Bernstein M et al. Ewing s sarcoma family of tumors: current management. Oncologist 2006;11: Emangiopericitoma Gowans LK et al. Successful treatment of an infant with constitutional chromosomal abnormality and hemangiopericytoma with chemotherapy alone. J Pediatr Hematol Oncol 2007;29: Carcinoma del rene a cellule chiare Varan A et al. Renal cell carcinoma in children: experience of a single center. Nephron Clin Pract 2007;105:58-61 Carcinoma nasofaringeo Küpeli S et al. Treatment results of 84 patients with nasopharyngeal carcinoma in childhood. Pediatr Blood Cancer 2006;46: Tumori a cellule germinali Lo Curto M et al. Mature and immature teratomas: results of the first paediatric Italian study. Pediatr Surg Int 2007;23: AIEOP T.Wilms, EpSSG-RMS & NRSTS, ISG/SSG III - ISG/SSG IV - AIEOP/ ISG 02 (EW- REC) - AIEOP/SICP TREP, 2005

5 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 ALEMTUZUMAB Nessuna -Anemia aplastica grave -Sindromi mielodisplastiche -Trapianto di midollo osseo Anemia aplastica grave e Sindromi mielodisplastiche Rzepecki P et al. Alemtuzumab, fludarabine and melphalan as a conditioning therapy in severe aplastic anemia and hypoplastic myelodysplastic syndrome single center experience. Jpn J Clin Oncol 2006;36:46-49 Trapianto di midollo osseo Benesch M et al. Five-month marrow aplasia in a child with refractory acute myeloid leukaemia: successful management with continuous granulocyte support and reduced intensity conditioning followed by matched unrelated bone marrow transplantation. J Pediatr Hematol Oncol 2005;27: ARSENICO TRIOSSIDO Nessuna -Leucemia acuta promielocitica Leucemia acuta promielocitica Mantadakis E et al. A comprehensive review of acute promyelocytic leukemia in children. Acta Haematol 2008;119:73-82 Fox E et al. Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. Blood 2008;111: Clark JJ et al. Update in childhood acute myeloid leukemia: recent developments in the molecular basis of disease and novel therapies. Curr Opin Hematol 2003;10: ICC APL 01

6 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N BEVACIZUMAB Nessuna -Tumori solidi refrattari -Carcinoma del rene a cellule chiare -Carcinoma del colon-retto BLEOMICINA Nessuna -In associazione negli schemi PEB per i tumori germinali e ABVD nel linfoma di Hodgkin -Tumori del SNC Tumori solidi refrattari Bender JL et al. Phase I trial and pharmacokinetic study of bevacizumab in pediatric patients with refractory solid tumors: a Children's Oncology Group Study. J Clin Oncol 2008;26: Benesch M et al. Compassionate use of bevacizumab (Avastin) in children and young adults with refractory or recurrent solid tumors. Ann Oncol 2008;19: Carcinoma del rene a cellule chiare Joshi DD and Banerjee T. Vascular endothelial growth factor (VEGF) receptor antibody bevacizumab (avastin) induces regression of renal cell carcinoma in an adolescent resulting in residual tumorectomy. Pediatr Blood Cancer 2008;50: Benesch M et al. Compassionate use of bevacizumab (Avastin) in children and young adults with refractory or recurrent solid tumors. Ann Oncol 2008;19: Carcinoma del colon-retto Saab R and Furman WL. Epidemiology and management options for colorectal cancer in children. Paediatr Drugs 2008;10: Tumori del SNC Hukin J et al. Intracystic bleomycin therapy for craniopharyngioma in children: the Canadian experience. Cancer 2007;109: AIEOP LH AIEOP TCG AIEOP/SICP TREP 2005

7 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 BUSULFANO -Policitemia vera -Trombocitopenia essenziale -Condizionamento pretrapianto CARBOPLATINO -Carcinoma dell ovaio dell adolescente/giovane adulta -Neuroblastoma in stadio 4, in associazione a melphalan nei regimi mieloablativi -Sarcomi della famiglia Ewing a cattiva prognosi in associazione a melphalan nei regimi mieloablativi - Leucemia mielomonocitica giovanile - Sindrome di Shwachman-Diamond - Medulloblastoma -Neuroblastoma (stadio 3 e 4) in combinazione con altri citotossici -Tumore di Wilms ad istologia sfavorevole o metastatico in combinazione con altri farmaci -Rabdomiosarcoma localizzato e avanzato -Gliomi a basso ed alto grado -Retinoblastoma localmente avanzato e metastatico Leucemia mielomonocitica giovanile Locatelli F et al. Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial. Blood 2005;105: Sindrome di Shwachman-Diamond Sauer M et al. Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman-Diamond syndrome. Bone Marrow Transplant 2007;9: Medulloblastoma Ridola V et al. High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy. Cancer 2007;110: Sarcomi dei tessuti molli Bernbeck B et al. Serial intense chemotherapy combining topotecan, etoposide, carboplatin and cyclophosphamide (TECC) followed by autologous hematopoietic stem cell support in patients with high risk soft tissue sarcoma (STS). Klin Pediatr 2007;219: Osteosarcoma del Prever AB et al. Long-term survival in high-grade axial osteosarcoma with bone and lung metastases treated with chemotherapy only. J Pediatr Hematol Oncol 2005;27: AIEOP LAM 2002/ NB-AR-01 - SIOP-AIEOP NB Infant - AIEOP LAM REC/01 - AIEOP LLA REC AIEOP ALCL 99 - HLH INTERINFAN 06 - ISG/SSG III ISG/SSG IV - AIEOP/ISG 02 (EW-REC) - EICNHL ( ALCL relapse ) - SIOPEL 3 - SIOPEL 4 - AIEOP T.Wilms NB- AR-01 - SIOP-AIEOP NB Infant - SIOP EUROPE UnresectNB 00 -

8 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N Epatoblastoma a prognosi sfavorevole -Medulloblastoma localizzato in alternativa a cisplatino -Sarcomi dei tessuti molli -Osteosarcoma -Tumori a cellule germinali -Sarcoma di Ewing ad alto rischio Daw NC et al. Metastatic osteosarcoma. Cancer 2006;106: Tumori a cellule germinali Lo Curto M et al. Malignant germ cell tumors in childhood: results of the first Italian cooperative study "TCG 91". Med Pediatr Oncol 2003;41: Sarcoma di Ewing ad alto rischio Burdach S et al. Allogeneic and autologous stem-cell transplantation in advanced Ewing tumors. An update after long-term follow-up from two centers of the European Intergroup study EICESS. Stem-Cell Transplant Programs at Düsseldorf University Medical Center, Germany and St. Anna Kinderspital, Vienna, Austria. Ann Oncol 2000;11: Van Winkle P et al. Ifosfamide, carboplatin and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: the Children's Cancer Group (CCG) experience. Pediatr Blood Cancer 2005;44: Milano GM et al. High histologic and overall response to dose intensification of ifosfamide, carboplatin and etoposide with cyclophosphamide, doxorubicin and vincristine in patients with high-risk Ewing sarcoma family tumors: the Bambino Gesù Children's Hospital experience. Cancer 2006;106: CARMUSTINA Nessuna -Gliomi ad alto grado di malignità Gliomi ad alto grado di malignità Chastagner P et al. Outcome of children treated with preradiation chemotherapy for a high-grade glioma: results of a French Society of Pediatric Oncology (SFOP) Pilot Study. Pediatr Blood Cancer 2007;49: AIEOP/ISG OSTEO REC VHR - AIEOP/ISG 02 (EW -REC) - AIEOP RB 05 - AIEOP SNC <3a - AIEOP /SICP TREP AIEOP TCG HIT-SIOP PNET 4 - SIOP LGG AIEOP SNC 99 - HIT SIOP PNET 4

9 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 CICLOFOSFAMIDE Nessuna -Neuroblastoma -Tumori della famiglia del sarcoma di Ewing -Gliomi a basso grado di malignità -Leucemia linfoblastica acuta -Linfoma di Hodgkin -Linfoma non-hodgkin -Medulloblastoma -Osteosarcoma -Epatoblastoma -Condizionamento pre-trapianto -Rabdomiosarcoma Neuroblastoma Donfrancesco A et al. Prolonged response to oral gefitinib, cyclophosphamide and topotecan in heavily pretreated relapsed stage 4 neuroblastoma: a case report. J Pediatr Hematol Oncol 2007;29: Simon T et al. Topotecan, cyclophosphamide and etoposide (TCE) in the treatment of high-risk neuroblastoma. Results of a phase-ii trial. J Cancer Res Clin Oncol 2007;133: Tumori della famiglia del sarcoma di Ewing Miser JS et al. Treatment of metastatic Ewing sarcoma/ primitive neuroectodermal tumor of bone: evaluation of increasing the dose intensity of chemotherapy-a report from the Children's Oncology Group. Pediatric Blood Cancer 2007;49: Bernstein ML et al. Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study a report from the Children's Oncology Group. J Clin Oncol 2006;24: Gliomi a basso grado di malignità Lee MJ et al. Effectiveness of novel combination chemotherapy, consisting of 5-fluorouracil, vincristine, cyclophosphamide and etoposide, in the treatment of lowgrade gliomas in children. J Neurooncol 2006;80: Leucemia linfoblastica acuta Shah AJ et al. Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation. J Pediatr Hematol Oncol 2004;26: AIEOP LAM 2002/ AIDA-Prot. (lap0493) GIMEMA AIEOP - AIEOP EsPhALL - AIEOP LH EURO LB-02 - AIEOP ALCL 99 - AIEOP/ISG OSTEO REC VHR - ISG/SSG III ISG/SSG IV - AIEOP/ISG 02 (EW -REC) - ISG-AIEOP/ VHR- EW-2 - EpSSG RMS & NRSTS SIOPEL 3 - AIEOP 2 Ependi 03 - SIOP LGG NB-AR-01 - SIOP-AIEOP NB infant -AIEOP Interinfant 99

10 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N Aricò M et al. Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol 2008;26: Linfoma di Hodgkin Krasin MJ et al. Patterns of treatment failure in pediatric and young adult patients with Hodgkin's disease: local disease control with combined-modality therapy. J Clin Oncol 2005;23: Linfoma non-hodgkin Patte C et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non- Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood 2007;109: Medulloblastoma Dhall G et al. Outcome of children less than three years old at diagnosis with non-metastatic medulloblastoma treated with chemotherapy on the "Head Start" I and II protocols. Pediatr Blood Cancer 2008;50: Osteosarcoma Tunn PU and Reichardt P. Chemotherapy for osteosarcoma without high-dose methotrexate: a 12-year follow-up on 53 patients. Onkologie 2007;30: Epatoblastoma Cacciavillano WD et al. Phase II study of high-dose cyclophosphamide in relapsing and/or resistant hepatoblastoma in children: a study from the SIOPEL group. Eur J Cancer 2004;40: INTERINFAN 06 - HLH AIEOP LLA REC AIEOP LAM REC/01

11 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 CISPLATINO Nessuna -Neuroblastoma -Epatoblastoma -Medulloblastoma -Gliomi a basso ed alto grado -Osteosarcoma -Tumori germinali -Linfomi Hodgkin e non-hodgkin recidivanti - Tumori desmoplastici a piccole cellule rotonde -Carcinoma del rene a cellule chiare -Carcinoma corticosurrenalico -Retinoblastoma -Tumore del seno endodermico della Condizionamento pre-trapianto Shah AJ et al. Busulfan and cyclophosphamide as a conditioning regimen for pediatric acute lymphoblastic leukemia patients undergoing bone marrow transplantation. J Pediatr Hematol Oncol 2004;26:91-97 Rabdomiosarcoma Meza JL et al. Analysis of prognostic factors in patients with nonmetastatic rhabdomyosarcoma treated on intergroup rhabdomyosarcoma studies III and IV: the Children's Oncology Group. J Clin Oncol 2006;20: Tumori desmoplastici a piccole cellule rotonde Hayes-Jordan A et al. Continuous hyperthermic peritoneal perfusion for desmoplastic small round cell tumor. J Pediatr Surg 2007;42:29-32 Carcinoma del rene a cellule chiare Varan A et al. Renal cell carcinoma in children: experience of a single center. Nephron Clin Pract 2007;105:58-61 Carcinoma corticosurrenalico Zancanella P et al. Mitotane associated with cisplatin, etoposide and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 2006;28: Retinoblastoma de Aguirre Neto JC et al. Retinoblastoma in children older than 5 years of age. Pediatr Blood Cancer 2007;48: ISG/OSI - AIEOP/ISG/SSG 02 (EW REC) - ISG -AIEOP/VHR- EW-2 - AIEOP/SICP TREP SIOPEL 3 - SIOPEL 4 - AIEOP TCG SIOP LGG HIT-SIOP PNET 4 - AIEOP SNC <3a - NB-AR-01 - SIOP-AIEOP NB Infant

12 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N vagina -Carcinoma nasofaringeo -Tumori ovarici dello stroma gonadico (sex cord-stromal) CITARABINA -Leucemia mieloide acuta e cronica -Leucemia linfoblastica acuta -Linfoma non-hodgkin Tumore del seno endodermico della vagina Terenziani M et al. Endodermal sinus tumor of the vagina. Pediatr Blood Cancer 2007;48: Carcinoma nasofaringeo Küpeli S et al. Treatment results of 84 patients with nasopharyngeal carcinoma in childhood. Pediatr Blood Cancer 2006;46: Tumori ovarici dello stroma gonadico (sex cordstromal) Schneider DT et al. Ovarian sex cord-stromal tumors in children and adolescents. J Reprod Med 2005;50: Leucemia linfoblastica acuta Silverman LB. Acute lymphoblastic leukemia in infancy. Pediatr Blood Cancer 2007;49: Linfoma non-hodgkin Patte C et al. The Société Française d'oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001;97: AIEOP LAM 2002/ AIDA- Prot.(lap0493) GIMEMA AIEOP - AIEOP LLA REC Ph AIEOP LLA R AIEOP LAM REC/ 01 - AIEOP LNH 97 - ICC APL 01 - AIEOP ALCL 99 - EURO LB-02 - LCH-S AIEOP Interinfant 99 - INTERFAN T06

13 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 CITARABINA LIPOSOMIALE Nessuna -Tumori del SNC -Leucemia mieloide acuta -Leucemia linfoblastica acuta Tumori del SNC Lassaletta A et al. Successful treatment of intracranial ependymoma with leptomeningeal spread with systemic chemotherapy and intrathecal liposomal cytarabine in a two-year-old child. J Neurooncol 2007;83: Leucemia mieloide acuta e Leucemia linfoblastica acuta Benesch M and Urban C. Liposomal cytarabine for leukemic and lymphomatous meningitis: recent developments. Expert Opin Pharmacother 2008;9: Benesch M et al. Feasibility and toxicity of intrathecal liposomal cytarabine in 5 children and young adults with refractory neoplastic meningitis. J Pediatr Hematol Oncol 2007;29: CLADRIBINA Nessuna -Istiocitosi a cellule di Langerhans Istiocitosi a cellule di Langerhans Mottl H et al. Treatment of recurrent Langerhans cell histiocytosis in children with 2-chlorodeoxyadenosine. Leuk Lymphoma 2006;47: CLORAMBUCILE Nessuna -Linfoma di Hodgkin Linfoma di Hodgkin Hall GW et al. Outcome of children with nodular lymphocyte predominant Hodgkin lymphoma - a Children's Cancer and Leukaemia Group report-. Br J Haematol 2007;138: Capra M et al. Long-term outcome in children with Hodgkin's lymphoma: the United Kingdom Children's Cancer Study Group HD82 trial. Eur J Cancer 2007;43: AIEOP EsPhALL - LCH -S-2005

14 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N DACARBAZINA Nessuna -Linfoma di Hodgkin -Sarcomi dei tessuti molli DAUNORUBICINA Nessuna -Leucemie e linfomi del bambino recidivanti -Linfoma non-hodgkin -Leucemia linfoblastica acuta -Leucemia mieloide acuta Linfoma di Hodgkin Engert A et al. Two cycles of doxorubicin, bleomycin, vinblastine and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 2007;25: Hsu SC et al. Comparison of treatment outcomes of childhood Hodgkin lymphoma in two US centers and a center in Recife, Brazil. Pediatr Blood Cancer 2007;49: Kung FH et al. POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with stages I, IIA, IIIA1 Hodgkin disease: a report from the Children's Oncology Group. J Pediatr Hematol Oncol 2006;28: Sarcomi dei tessuti molli Pratt CB et al. Treatment of unresectable or metastatic pediatric soft tissue sarcomas with surgery, irradiation and chemotherapy: a Pediatric Oncology Group Study. Med Pediatr Oncol 1998;30: Linfoma non-hodgkin Crosswell HE et al. Successful treatment with modified CHOP-rituximab in pediatric AIDS-related advanced stage Burkitt lymphoma. Pediatr Blood Cancer 2008;50: Leucemia linfoblastica acuta Escherich G et al. Daunomicin induced cell kill with 1- hour versus 24 hours infusion: a randomized comparison in children with newly diagnosed acute lymphoblastic leukaemia. Klin Padiatr 2007;219: AIEOP LH AIEOP EsPhALL - AIEOP Interinfant 99 - INTERINFAN 06 - EURO LB-02 - AIEOP LNH 97

15 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 DOXORUBICINA -Osteosarcoma -Sarcomi dei tessuti molli -Linfoma non-hodgkin -Neuroblastoma -Nefroblastoma -Leucemia linfoblastica acuta -Leucemia mieloide acuta -Sarcoma di Ewing in prima linea o recidivante -Rabdomiosarcoma in prima linea o recidivante -Epatoblastoma in prima linea o recidivante - Tumori della famiglia del sarcoma di Ewing - Tumori del SNC - Emangiopericitoma - Carcinoma surrenalico - Tumori rabdoidi - Retinoblastoma - Istiocitosi a cellule di Langerhans Leucemia mieloide acuta Creutzig U et al. Significance of age in acute myeloid leukemia patients younger than 30 years: a common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A. Cancer 2008;112: Lange BJ et al. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group. Blood 2008;111: Tumori della famiglia del sarcoma di Ewing Castex MP et al. Extraosseous localized Ewing tumors: improved outcome with anthracyclines-the French society of pediatric oncology and international society of pediatric oncology. J Clin Oncol 2007;25: Tumori del SNC Fiorillo A et al. Shunt-related abdominal metastases in an infant with medulloblastoma: long-term remission by systemic chemotherapy and surgery. J Neurooncol 2001;52: Emangiopericitoma Gowans LK et al. Successful treatment of an infant with constitutional chromosomal abnormality and hemangiopericytoma with chemotherapy alone. J Pediatr Hematol Oncol 2007;29: Carcinoma surrenalico Zancanella P et al. Mitotane associated with cisplatin, etoposide and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 2006;28: AIEOP Es Ph ALL - AIEOP ALCL 99 - EURO LB-02 - AIEOP LNH 97 - AIEOP LH ISG/OSI - ISG/SSG III - ISG/SSG IV - AIEOP T.Wilms SIOPEL 3 - SIOPEL 4 - SIOP-AIEOP NB infant - ISG-AIEOP/VHR EW2 - AIEOP RB 05 - AIEOP/SICP

16 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N DOXORUBICINA LIPOSOMIALE Nessuna -Tumori del SNC ad alto grado di malignità -Leucemia linfatica acuta in recidiva -Tumori solidi refrattari EPIRUBICINA Nessuna -Sarcomi dei tessuti molli -Linfoma non-hodgkin -Leucemia linfoblastica acuta Tumori rabdoidi Hosoi H et al. Continuous remission in an infant with chest wall malignant rhabdoid tumor after relapse. J Pediatr Surg 2007;42:9-12 Retinoblastoma Mustafa MM et al. Adjuvant chemotherapy with vincristine, doxorubicin and cyclophosphamide in the treatment of postenucleation high risk retinoblastoma. J Pediatr Hematol Oncol 1999;21: Istiocitosi a cellule di Langerhans Morimoto A et al. Improved outcome in the treatment of pediatric multifocal Langerhans cell histiocytosis: Results from the Japan Langerhans Cell Histiocytosis Study Group-96 protocol study. Cancer 2006;107: Tumori del SNC ad alto grado di malignità Wagner S et al. Pegylate liposomial doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors. J Neurooncol 2008;86: Leucemia linfatica acuta in recidiva Hempel et al. Population pharmacokinetics of liposomal daunorubicin in children. Br J Clin Pharmacol 2003;56: Tumori solidi refrattari Lowe E et al. Phase I trial and pharmacokinetic study of liposomal doxorubicin in children with refractory solid tumors. Proc Ann Meet ASCO 2002;21:1099 Sarcomi dei tessuti molli Stohr W et al. Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study. J Cancer Res Clin Oncol 2006;132:35-40 TREP EpSSG RMS & NRSTS AIEOP Interinfant 99 - AIEOP/ISG 02 (EW- REC) - AIEOP NB rec/ res 00 - SIOP/EUROPE UnresectNB 00 AIEOP LLA Rec 2003

17 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 -Epatoblastoma ed epatocarcinoma -Tumori mesenchimali (nel primo anno di vita) ETOPOSIDE Nessuna -Tumore di Wilms a prognosi sfavorevole e metastatico -Neuroblastoma di grado 3 e 4 -Sarcomi dei tessuti molli alla ricaduta Linfoma non-hodgkin Pocali B et al. Ifosfamide, epirubicin and etoposide (IEV) regimen as salvage and mobilization therapy for refractory or early relapsing patients with aggressive non-hodgkin's lymphoma. Leuk Lymphoma 2004;45: Leucemia linfoblastica acuta Bhutani M et al. Randomized study comparing 4'-epidoxorubicin (epirubicin) versus doxorubicin as a part of induction treatment in adult acute lymphoblastic leukemia. Am J Hematol 2002;71: Eksborg S et al. A comparative pharmacokinetic study of doxorubicin and 4'-epi-doxorubicin in children with acute lymphocytic leukemia using a limited sampling procedure. Anticancer Drugs 2000;11: Epatoblastoma ed epatocarcinoma Casanova M et al. Etoposide, cisplatin, epirubicin chemotherapy in the treatment of pediatric liver tumors. Pediatr Hematol Oncol 2005;22: Tumori mesenchimali (nel primo anno di vita) Orbach D et al. Soft tissue sarcoma or malignant mesenchymal tumors in the first year of life: experience of the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Committee. J Clin Oncol 2005;23: Leucemia linfoblastica acuta Gassas A et al. Comparative outcome of hematopoietic stem cell transplant for pediatric acute lymphoblastic leukaemia following cyclophosphamide and total body irradiation or VP16 and total body irradiation conditioning regimens. Bone Marrow Transplant 2006;38: AIEOP LLA REC Ph HLH AIEOP Interinfant 99 -

18 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N Famiglia dei sarcomi di Ewing -Rabdomiosarcoma recidivante -Osteosarcoma -Gliomi a basso ed alto grado -Ependimomi -Tumori neuroectodermici primitivi cerebrali -Retinoblastoma localmente avanzato o metastatico -Istiocitosi a cellule di Langerhans -Leucemia linfoblastica acuta -Leucemia mieloide acuta -Epatoblastoma -Tumori a cellule germinali -Carcinoma surrenalico -Linfoma di Hodgkin -Linfoma non-hodgkin Leucemia mieloide acuta Styczynski J et al. Fludarabine, treosulfan and etoposide sensitivity and the outcome of hematopoietic stem cell transplantation in childhood acute myeloid leukemia. Anticancer Res 2007;27: Ayas M et al. The outcome of children with acute myeloid leukemia (AML) post-allogeneic stem cell transplantation (SCT) is not improved by the addition of etoposide to the conditioning regimen. Pediatr Blood Cancer 2006;47: Epatoblastoma Casanova M et al. Etoposide, cisplatin, epirubicin chemotherapy in the treatment of pediatric liver tumors. Pediatr Hematol Oncol 2005;22: Häberle B et al. Differentiated treatment protocols for high- and standard-risk hepatoblastoma- an interim report of the German Liver Tumor Study HB99-. Klin Padiatr 2003;215: Tumori a cellule germinali Shinkoda Y et al. Successful treatment of an endodermal sinus tumor of the vagina by chemotherapy alone: a rare case of an infant diagnosed by pathological examination of discharged tumor fragment. Pediatr Hematol Oncol 2006;23: Cushing B et al. Randomized comparison of combination chemotherapy with etoposide, bleomycin and either highdose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study -Pediatric Oncology Group 9049 and Children's Cancer Group J Clin Oncol 2004;22: INTERINFAN 06 - AIEOP ALCL 99 - AIEOP LNH 97 - AIEOP LH AIEOP LAM 2002/ ISG/SSG III - ISG/SSG IV - AIEOP T Wilms AIEOP SNC 99 - AIEOP RB 05 - AIDA Prot.(lap0493 GIMEMA AIEOP) - SIOP LGG AIEOP/ISG 02 (EW-REC) - SIOP-AIEOP NB infant - AIEOP SNC 95-01<3a - AIEOP TCG AIEOP 2 Ependi 03

19 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 FLUDARABINA Nessuna -Leucemia mieloide acuta in recidiva pre-trapianto -Leucemia linfoblastica acuta in recidiva -Anemia di Fanconi -Condizionamento pre-trapianto Carcinoma surrenalico Zancanella P et al. Mitotane associated with cisplatin, etoposide and doxorubicin in advanced childhood adrenocortical carcinoma: mitotane monitoring and tumor regression. J Pediatr Hematol Oncol 2006;28: Linfoma di Hodgkin Landman-Parker J et al. Localized childhood Hodgkin's disease: response-adapted chemotherapy with etoposide, bleomycin, vinblastine and prednisone before low-dose radiation therapy-results of the French Society of Pediatric Oncology Study MDH90. J Clin Oncol 2000;18: Linfoma non-hodgkin Patte C et al. The Société Française d'oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001;97: Leucemia mieloide acuta in recidiva pre-trapianto Styczynski J et al. Fludarabine, treosulfan and etoposide sensitivity and the outcome of hematopoietic stem cell transplantation in childhood acute myeloid leukemia. Anticancer Res 2007;27: Leucemia linfoblastica acuta in recidiva Gutierrez-Aguirre CH et al. Non-myeloablative stem cell transplantation in patients with relapsed acute lymphoblastic leukemia: results of a multicenter study. Bone Marrow Transplant 2007;40: AIEOP/SICP TREP ISG/OSI - AIEOP/ISG OSTEO REC VHR - ISG-AIEOP/VHR- EW-2 - NB-AR-01 - AIEOP LAM REC/01

20 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N FLUOROURACILE Nessuna -Carcinoma nasofaringeo -Tumori maligni del fegato -Carcinoma del rene a cellule chiare Anemia di Fanconi Wagner JE et al. Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia. Blood 2007;109: Condizionamento pre-trapianto Kornguth DG et al. Fludarabine allows dose reduction for total body irradiation in pediatric hematopoietic stem cell transplantation. Int J Radiat Oncol Biol Phys 2007;68: Sauer M et al. Substitution of cyclophosfamide and busulfan by fludarabine, treosulfan and melphalan in a preparation regimen for children and adolescents with Shwachman-Diamond syndrome. Bone Marrow Transplant 2007;39: Sauer M et al. Complete substitution of cyclophosphamide by fludarabine and ATG in a busulfan based preparative regimen for children and adolescents with beta- Thalassemia. Bone Marrow Transplant 2005;36: Carcinoma nasofaringeo Haimi M et al. Nasopharyngeal carcinoma in the pediatric age group: the northern Israel (Rambam) medical center experience, J Pediatr Hematol Oncol 2005;27: Rodriguez-Galindo C et al. Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil and leucovorin for pediatric nasopharingeal carcinoma. Cancer 2005;103: Tumori maligni del fegato Malogolowkin MH et al. Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. J Clin Oncol 2006;24: EICNHL (ALCL-relapse) - SIOP EUROPE Unresect NB 00 - AIEOP LLA Rec AIEOP/SICP TREP 2005

21 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 GEMCITABINA Nessuna -Tumori pediatrici refrattari -Linfoma di Hodgkin -Carcinoma midollare del rene GEMTUZUMAB Nessuna -Leucemia acuta promielocitica refrattaria o recidivante Katzenstein HM et al. Fibrolamellar hepatocellular carcinoma in children and adolescents. Cancer 2003;97: Carcinoma del rene a cellule chiare Varan A et al. Renal cell carcinoma in children: experience of a single center. Nephron Clin Pract 2007;105:58-61 Tumori pediatrici refrattari Fulfaro F et al. Antiblastic drug combinations with ifosfamide: an update. Oncology 2003;65:21-30 Linfoma di Hodgkin Ozkaynak MF and Jayabose S. Gemcitabine and vinorelbine as a salvage regimen for relapse in Hodgkin lymphoma after autologous hematopoietic stem cell transplantation. Pediatr Hematol Oncol 2004;21: Carcinoma midollare del rene Strouse JJ et al. Significant responses to platinum-based chemotherapy in renal medullary carcinoma. Pediatr Blood Cancer 2005;44: Bell MD. Response to paclitaxel, gemcitabine and cisplatin in renal medullary carcinoma. Pediatr Blood Cancer 2006;47:228 Leucemia acuta promielocitica refrattaria o recidivante Aplenc R et al. Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol 2008;26: Ep SSG RMS & NRSTS ICC APL 01

22 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N IDARUBICINA -Leucemia linfocitica acuta (II linea) IDROSSIUREA -Leucemia mieloide cronica -Leucemia promielocitica acuta -Leucemia mieloide acuta -Tumori del SNC -Drepanocitosi -Talassemia intermedia Aribi A et al. Combination therapy with arsenic trioxide, all-trans retinoic acid and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer 2007;109: Corey SI. New agents in the treatment of childhood leukemias and myelodysplastic syndromes. Curr Oncol Rep 2005;7: Leucemia promielocitica acuta Testi AM et al. GIMEMA-AIEOPAIDA protocol for the treatment of newly diagnosed acute promyelocitic leukaemia (APL) in children. Blood 2005;106: Leucemia mieloide acuta Liang DCI et al. Improved treatment results for childhood acute myeloid leukemia in Taiwan. Leukemia 2006;20: Lange BJ et al. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group. Blood 2008;111: Tumori SNC Dreyer ZE et al. Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG Neuro Oncol 2003;5: Drepanocitosi Zimmerman SA et al. Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anemia. Blood 2007;110: De Baun MR et al. Hydroxyurea as secondary prevention for stroke in children with sickle cell anemia. J Pediatr 2005;147: AIEOP LAM2002/ AIDA-Prot. (lap0493) GIMEMA AIEOP - ICC APL 01 - AIEOP ALCL 99 -AIEOP LLA Rec 2003

23 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 IFOSFAMIDE Nessuna -Tumore di Wilms a prognosi sfavorevole o metastatico -Epatoblastoma a prognosi sfavorevole o metastatico -Sarcoma di Ewing -Osteosarcoma -Rabdomiosarcoma -Neuroblastoma -Sarcomi dei tessuti molli -Tumori del SNC -Linfoma di Hodgkin -Linfoma non-hodgkin -Retinoblastoma -Carcinoma surrenalico Ware RE et al. Prevention of secondary stroke and resolution of transfusional iron overload in children with sickle cell anemia using hydroxyurea and phlebotomy. J Pediatr 2004;145: Talassemia intermedia Dixit A et al. Hydroxyurea in thalassemia intermedia A promising therapy. Ann Hematol 2005;84: Koren A et al. Response to hydroxyurea therapy in betathalassemia. Am J Hematol 2008;83: Sarcomi dei tessuti molli Ferrari A et al. Adult-type soft tissue sarcomas in pediatric age patients: experience at the Istituto Nazionale Tumori in Milan. J Clin Oncol 2005;23: Tumori del SNC Burzynski SR. Treatments for astrocytic tumors in children: current and emerging strategies. Paediatr Drugs 2006;8: Tekautz TM et al. Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years age and older with radiation therapy and high-dose alchilator based chemotherapy J Clin Oncol 2005;23: Linfoma di Hodgkin Schellong G et al. Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group. J Clin Oncol 2005;23: Linfoma non-hodgkin Spreafico F et al. Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in children. J Clin Oncol 2002;20: AIEOP EsPhALL - AIEOP ALCL 99 - AIEOP LNH 97 - AIEOP LH ISG/OSI - ISG/SSG III - ISG/SSG IV - AIEOP T. Wilms AIEOP RB 05 - AIEOP/ISG 02 (EW-REC) - ISG AIEOP/VHR- EW-2 - Ep SSG RMS & NRSTS 2005

24 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N Blastoma pleuropolmonare IMATINIB -Leucemia mieloide cronica Ph+ alla diagnosi o in crisi blastica -Leucemia linfoblastica acuta Ph+ -Leucemia mieloide acuta -Sindromi mielodisplastiche -Tumori stromali gastrointestinali (GIST) Voûte PA et al. Ifosfamide in the treatment of pediatric malignancies. Semin Oncol 1996;23:8-11 Seidemann K et al. Short-pulse B-non-Hodgkin lymphomatype chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin- Frankfurt-Münster Group Trial NHL-BFM 90. Blood 2001;97: Retinoblastoma De Aguirre Neto JC et al. Retinoblastoma in children older than 5 years of age. Pediatr Blood Cancer 2007;48: Carcinoma surrenalico Imataki O et al. Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases. Int J Clin Oncol 2006;11: Blastoma pleuropolmonare Büyükavci M et al. An aggressive childhood tumor mimicking pleural empyema: pleuropulmonary blastoma. J Pediatr Hematol Oncol 2006;28: Leucemia linfoblastica acuta Ph+ Stubbs MC and Armstrong SA. FLT3 as a therapeutic target in childhood acute leukaemia. Curr Drug Targets 2007;8: Fuster JL et al. Imatinib mesylate in combination with chemotherapy in four children with de novo and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica 2007;92: AIEOP TCG AIEOP EsPhALL - AIEOP LLA REC 2003

25 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 INTERFERONE ALFA- 2B Nessuna -Carcinoma del rene a cellule chiare -Anemia diseritropoietica -Leucemia mieloide cronica -Neuroblastoma -Nefroblastoma Leucemia mieloide acuta Goemans BF et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia 2005;19: Corey SI. New agents in the treatment of childhood leukemias and myelodysplastic syndromes. Curr Oncol Rep 2005;7: Skolnik JM. Tyrosine kinase inhibitors in pediatric malignancies. Cancer Invest 2007;18:1-7 Sindromi mielodisplastiche Bierings IM et al. Stem cell transplantation in pediatric leukemia and mielodisplasia: state of art and current challeges. Curr Stem Cell Res Ther 2007;2:53-63 Tumori stromali gastrointestinali (GIST) Sauseng W et al. Clinical, radiological and pathological findings in four children with gastrointestinal stromal tumors of the stomach. Pediatr Hematol Oncol 2007;24: Skolnik JM and Adamson PC. Tyrosine kinase inhibitors in pediatric malignancies. Cancer Invest 2007;18:1-7 Carcinoma del rene a cellule chiare Varan A et al. Renal cell carcinoma in children: experience of a single center. Nephron Clin Pract 2007;105:58-61 Anemia diseritropoietica Marwaha RK et al. Interferon therapy in congenital dyserythropoietic anemia type I/II. Pediatr Hematol Oncol 2005;22: Ep SSG RMS & NRSTS 2005

26 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N INTERLEUCHINA-2 Nessuna -Leucemia mieloide acuta -Neuroblastoma -Sarcomi ossei -Nefroblastoma -Carcinoma del rene a cellule chiare -Melanoma Yarali N et al. Successful management of congenital dyserythropoietic anemia type I with interferon alpha in a child. Pediatr Hematol Oncol 2005;22: Leucemia mieloide cronica Millot F et al. Results of a phase II trial testing interferonalfa 2B and cytarabine in children and adolescents with chronic myelogenous leukaemia. Pediatric Blood Cancer 2006;47: Neuroblastoma e Nefroblastoma Adamson PC et al. A phase 2 trial of all-trans-retinoic acid in combination with interferon-alpha 2a in children with recurrent neuroblastoma or Wilms tumor: a pediatric oncology branch, NCI and children's oncology group study. Pediatr Blood Cancer 2007;49: Leucemia mieloide acuta Lange BJ et al. Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group. Blood 2008;111: Neuroblastoma Osenga KL et al. A phase I clinical trial of the hu IL2 (EMD ) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: a study of the Children's Oncology Group. Clin Cancer Res 2006;12: Sarcomi ossei Luksch R et al. Immunomodulation in a treatment program including pre- and post-operative interleukin-2 and chemotherapy for childhood osteosarcoma. Tumori 2003;89: AIEOP/SICP TREP AIEOP/ISG OSTEO REC VHR

27 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 Nefroblastoma Schwinger W et al. Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients. Ann Oncol 2005;16: Carcinoma del rene a cellule chiare Selle B et al. Population-based study of renal cell carcinoma in children in Germany, : more frequently localized tumors and underlying disorders compared with adult counterparts. Cancer 2006;107: Melanoma Osenga KL et al. A phase I clinical trial of the hu IL2 (EMD ) as a treatment for children with refractory or recurrent neutroblastoma and melanoma: a study of the Children Oncology Group. Clin Cancer Res 2006;12: Schwinger W et al. Feasibility of high-dose interleukin 2 in heavily pre-treated pediatric cancer patients. Ann Oncol 2005;16:

28 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N IRINOTECANO Nessuna -Rabdomiosarcoma recidivante -Sarcomi della famiglia di Ewing recidivanti -Sarcomi dei tessuti molli -Tumori del SNC -Tumori solidi recidivanti o refrattari MELFALAN -Neuroblastoma (stadi avanzati) -Sarcomi della famiglia di Ewing a cattiva prognosi in associazione a busulfano nei regimi mieloablativi -Tumori del SNC -Sarcomi dei tessuti molli Sarcomi dei tessuti molli Bisogno G et al. Phase II study of a protracted irinotecan schedule in children with refractory or recurrent soft tissue sarcoma. Cancer 2006;106: Gupta AA and Pappo AS. New drugs for the treatment of metastatic or refractory soft tissue sarcomas in children. Future Oncol 2006;2: Tumori del SNC Mora J et al. Successful treatment of childhood intramedullary spinal cord astrocytomas with irinotecan and cisplatin. Neuro Oncol 2007;9:39-46 Tumori solidi recidivanti o refrattari Vassal G et al. Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: a joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. J Clin Oncol 2007;25: Bomgaars L et al. A phase I study of irinotecan administered on a weekly schedule in pediatric patients. Pediatr Blood Cancer 2006;46:50-55 Tumori del SNC Pérez-Martínez A et al. High-dose chemotherapy with autologous stem cell rescue as first line of treatment in young children with medulloblastoma and supratentorial primitive neuroectodermal tumors. J Neurooncol 2004;67: Sarcomi dei tessuti molli Lang P et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr 2006;218: AIEOP LAM 2002/ AIEOP LAM REC/01 - AIEOP LLA REC INTERINFAN 06 - NB-AR-01

29 BOLLETTINO UFFICIALE DELLA REGIONE TOSCANA - N. 34 -Anemia aplastica -Sindromi mielodisplastiche -Linfoistiocitosi emofagocitica -Nefroblastoma -Sindrome di Shwachman-Diamond -Retinoblastoma -Condizionamento pre-trapianto Anemia aplastica e Sindromi mielodisplastiche Stary J et al. Stem cell transplant for aplastic anemia and myelodysplastic syndrome. Bone Marrow Transplant 2005;35: Linfoistiocitosi emofagocitica Cesaro S et al. Successful engraftment and stable full donor chimerism after myeloablation with thiotepa, fludarabine and melphalan and CD34-selected peripheral allogeneic stem cell transplantation in hemophagocytic lymphohistiocytosis. Am J Hematol 2003;72: Nefroblastoma Campbell AD et al. Treatment of relapsed Wilms' tumor with high-dose therapy and autologous hematopoietic stem-cell rescue: the experience at Children's Memorial Hospital. J Clin Oncol 2004;22: Sindrome di Shwachman-Diamond Sauer M et al. Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and melphalan in a preparative regimen for children and adolescents with Shwachman-Diamond syndrome. Bone Marrow Transplant 2007;39: Retinoblastoma Matsubara H et al. A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement. Bone Marrow Transplant 2005;35: Condizionamento pre-trapianto Izaki S et al. Long-term follow-up of busulfan, etoposide and nimustine hydrochloride (ACNU) or melphalan as conditioning regimens for childhood acute leukemia and lymphoma. Int J Hematol 2007;86: SIOP- AIEOP NB Infant - AIEOP/ISG 02 (EW-REC) - ISG/SSG III ISG/SSG IV - ISG- AIEOP/VHR- EW-2 - AIEOP SNC < 3 a