Fludarabine, Cyclophosphamide, Doxorubicin and Rituximab for the Treatment of Post-transplant Lymphoproliferative Disease (PTLD)

Non Burkitt, Post-transplant Lymphoproliferative Disease (PTLD)

Fludarabine may be of benefit to prevent rejection of grafted solid organs in children during chemo-immunotherapy treatment for post transplant lymphoproliferative diseases (PTLDs).

Eligible to this study were patients less than 18 years old, presenting with non Burkitt, aggressive, CD20 positive PTLD, after solid organ transplants. Induction therapy consisted of two cycles of a combination of Fludarabine(30mg/sqm/day, days 1,2,3), Cyclophosphamide (750 mg/sqm/day, day 1), Doxorubicin (30 mg/sqm/day, day 1)and Rituximab (375 mg/sqm/day, day 4). Thereafter consolidation therapy was given as follows: two blocks for stage II or III with LDH less than 500 IU/L; three blocks for stage III with LDH \>500 and \< 1000 IU/L or stage IV with LDH \< 1000 IU/L; four blocks for stage III or IV with LDH \> 1000 IU/L. Blocks given were modified BFM blocks used for treatment of non Hodgkin B-lymphomas, as follows: Block 1: High Dose Methotrexate (HDMTX) 1.5 gr/sqm; Vincristine (VCR,1.5 mg/sqm); Cytarabine (from 120 to 150 mg/sqm x4); Ifosfamide (600 mg/sqm/day x5); VP-16 (80 mg/sqm/day x2); Dexamethasone (DXM,10 mg/sqm/day for 5 ays); Intrathecal Methotrexate-Cytarabine-Methylprednisolone(TIT). Block 2:HDMTX (3 gr/sqm); VCR (1.5 mg/sqm); Daunomycin (20 mg/sqm/day x2); Cyclophosphamide (160 mg/sqm/day x5); DXM (10 mg/sqm/day x5); TIT Block 3:Vindesine (3 mg/sqm); Cytarabine (3000 mg/sqm q 12 hours x4); VP-16 (100 mg/sqm q 12 hours x4); DXM (20 mg/sqm/day x5); Block 4 as Block 1. Outcome measures are: achievement of complete remission after induction therapy; incidence of infectious episodes; neurological toxicity; incidence of graft rejection; duration of complete remission.

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