1. Histiocytic and dendritic cells neoplasms: clinical behaviour and response to chemotherapy Elena Palassini Istituto Nazionale Tumori Milano Stacchiotti S, Gentile A, Grosso F, Palassini E, Collini P, Bertulli R, Dileo P, Messina A, Morosi C, Gronchi A, Dei Tos AP, Casali PG

2. Background (1) Histiocytic sarcoma (HS) Langherans cell sarcoma (LCS) Interdigitating dendritic cell sarcoma (IDCS) Follicular dendritic cell sarcoma (FDCS) Fibroblastic reticular cell tumor (FRCT) Unclassifiable dendritic cell tumor (UDCT) Group of heterogeneous neoplasms showing differentiation toward accessory cells of immune system

3. Background (2) Surgery is felt to be the mainstay of treatment in localized presentations The role of radiotherapy is undetermined Evidence of chemoresponsiveness to different regimens (including CHOP, ABVD, DHAP, IE) is based on case reports and small case series, but the role of chemotherapy remains still undefined

4. Patients and methods (1) period2002-2008 # pts24 M/F16/8 age: mean (range)yrs45 (30-79) site: nodal/extranodal12/12 stage at presentation: Iocalized/locally advanced/metastatic18/1/5

5. g UDC: 3 pts Patients and methods (2) LCS: 1HS: 5IDCS: 4FDCS: 11 UDCT: 3 Grade: low/high8/16

6. Patients and methods (3) treatment (24): surgery/radiotherapy/chemotherapy 19/10/12

7. Results (1) # pts12 adjuvant/neoadjuvant/palliative 1/3/8 HS/LCS/IDCS/FDCS/UDCT 2/1/2/6/1 Front-line doxorubicin + cisplatin

8. BIOPSYBIOPSY wks -4 036 9 121518 Pt 1, IDCS, localized disease Dox + DDP Dox + DDP Dox + DDP Dox + DDP Dox + DDP SURGERYSURGERY RTRT Treatment plan 9

9. BaselineDox + DDP x1

10. Baseline Dox + DDP x3 HE S-100

11. Results (1) evaluable for response 11 (HS/LCS/IDCS/FDCS/UDCS) (2/1/2/5/1) PR RECIST (HS/LCS/IDCS/FDCS/UDCS) 8 (2/1/1/3/1) SD RECIST (HS/LCS/IDCS/FDCS/UDCS) 2(0/0/1/1/0) PD RECIST (HS/LCS/IDCS/FDCS/UDCS) 1 (0/0/0/1/0) ■consolidation with HD chemotherapy and PBPC support 2 Front-line doxorubicin + cisplatin: activity

12. Baseline Dox + DDP x6 Pt 2, HS

13. Baseline Dox + DDP x6

14. Pt 3, FDCS BaselineDox + DDP x4 Dox + DDP x6HD IFX x1

15. Results (2) Dox + DDP: PFS in the palliative setting (8 pts) PFS median8 mos PFS <6 mos 3 pts FFP @30 mos2 pts

16. Results (3) etoposide + ifosfamide 3 PR2 PD1 gemcitabine + vinorelbine 1 PR1 gemcitabine 1 PR1 high dose ifosfamide 2 PD2 Further-line chemotherapy

17. Conclusions Small series, though among the largest in literature Doxorubicin + cisplatin is active in histiocitic and dendritic cell neoplasms (RR 73%) All subtypes seem to be sensitive Response can be short-lasting (PFS <6 mos) and tumor behaviour very aggressive Long PFS (PFS >30 mos) was observed in 3 metastatic patients out of 8 Consolidation with high-dose chemotherapy is worth testing Other drugs may be active (gemcitabine, gemcitabine and vinorelbine, ifosfamide and etoposide)

18. elena.palassini@istitutotumori.mi.it silvia.stacchiotti@istitutotumori.mi.it paolo.casali@istitutotumori.mi.it