Conditioning regimens Fludarabine-based conditioning for allogeneic stem cell transplantation for multiply transfused patients with Fanconi’s anemia B George, V Mathews, RV Shaji, V Srivastava, A Srivastava and M Chandy Department of Haematology, Christian Medical College, Vellore, Tamil Nadu, India Summary: A fludarabine-based protocol (fludarabine (25 mg/m 2 / day  6 days), cyclophosphamide (10 mg/kg/day  2 days) and ATG (ATGAM 10 mg/kg/day  4 days)) was used in four multiply transfused Fanconi’s anemia (FA) patients aged 5–15 years to reduce rejection during allogeneic bone marrow transplantation (BMT). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mini methotrexate. The graft source was G-CSF-stimulated bone marrow or peripheral blood stem cells (PBSC) in two patients each. All patients engrafted with median time to ANC4500/mm 3 being 14 days (range: 12–17) and unsupported platelet count 420 ,000/mm 3 being 13 days (range: 11–18). One patient had secondary graft rejection on day 56 and expired on day 69 due to fungal pneumonia. One patient who developed acute myeloid leukemia on day 56 underwent successful induction with cytosine and daunorubicin followed by peripheral blood stem cell (PBSC) rescue on day 70 and is presently in remission with complete donor chimerism and grade I GVHD. At a median follow-up of 13 months (range: 4–21), three patients (75%) are well with complete donor chimerism. Addition of fludarabine to the conditioning regimen for BMT in FA can provide additional immunosuppression for engraftment without increasing toxicity. Bone Marrow Transplantation (2005) 35, 341–343. doi:10.1038/sj.bmt.1704785 Published online 10 January 2005 Keywords: fludarabine; Fanconi’s anemia Allogeneic bone marrow transplantation (BMT) has produced excellent survival rates in patients with Fanconi’s anemia (FA) using low-dose cyclophosphamide with or without radiation therapy. 1 Graft rejection rates of 30–60% occur in multiply transfused patients with aplastic anemia requiring intensification of immunosuppression. 2 Few case reports exist on the use of fludarabine-based proto- cols as conditioning regimens for patients with FA with encouraging results 3–8 and we describe our experience in multiply transfused FA patients. Patients and methods Between 1999 and 2003, four male patients with FA underwent six antigen-matched sibling or family donor BMT at our center. The diagnosis of FA was confirmed by stress cytogenetics using mitomycin C and all had a bone marrow aspirate suggestive of aplastic anemia done 3–6 months prior to BMT. Standard karyotyping was not performed. Conditioning regimen consisted of fludarabine 25 mg/m 2 /day (day 11 to 6); cyclophosphamide 10 mg/ kg/day for 2 days (days 7 and 6), antithymocyte globulin (ATGAM, Pharmacia Upjohn, USA) 10 mg/kg/ day for 4 days (days 5 to 2). Graft source was either G-CSF-stimulated bone marrow or G-CSF-stimulated peripheral blood stem cells (PBSC) in two patients each. Supportive care Patients were nursed in HEPA-filtered rooms with ade- quate sterile precautions and barrier nursing. G-CSF (5 mg/ kg/day) was started on day þ 7 following the infusion of bone marrow or PBSC. Broad-spectrum antibiotics and antifungals were administered as per existing protocols for febrile neutropenia. Acyclovir and Septran were adminis- tered as CMV and Pneumocystis carinii prophylaxis, respectively. Ganciclovir was administered started as pre- emptive prophylaxis if the CMV polymerase chain reaction (PCR) became positive. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine (3 mg/kg/day i.v. starting day 1) and mini methotrexate (5 mg/m 2 days 1, 3 and 6). Acute GVHD was treated with either dexametha- sone or methylprednisolone. Results There were a total of four patients (all male) with a median age of 10 years (range: 5–15). The median duration from diagnosis to BMT was 34.5 months (range: 20–60) and the median number of packed red cells transfused prior to BMT was 28 (range: 22–45). Received 23 April 2004; accepted 16 September 2004 Published online 10 January 2005 Correspondence: Dr B George, Department of Haematology, Christian Medical College, Vellore 632004, Tamil Nadu, India; E-mail: biju@cmcvellore.ac.in Bone Marrow Transplantation (2005) 35, 341–343 & 2005 Nature Publishing Group All rights reserved 0268-3369/05 $30.00 www.nature.com/bmt