Can we consider fludarabine/ full dose I.V. busulfan a reduced intensity conditioning regimen?

In this study we analyzed 22 patients who received an allogeneic HSCT from matched related (n=17) or unrelated (n=5) donors, and were conditioned with FLU/BU (fludarabine 30 mg/m2/d × 4 days followed by single dose i.v. busulfan 3.2 mg/kg/d × 4 days) (n=12) or with the FLU/MEL (fludarabine 30 mg/m2/d × 5 days and melphalan 70 mg/m2/d × 2 days) (n=10) RIC regimen. Median age was 26 yrs (range: 19–51) in the FLU/BU group and 47 yrs (range: 22–57) in the FLU/MEL group (p=0.02). High risk patients were 8/12 in the FLU/BU group (7 AML in relapse, 1 CML-AP) and 3/10 in the FLU/MEL group (2 resistant NHL and 1 HD). GVHD prophylaxis was FK-506/MTX and in 9/12 FLU/BU cases (including 5 MUD) Thymoglobulin was added. All FLU/MEL and 6/12 FLU/BU patients received PBSC (median nr. CD34+ cells: 5.0 and 5.9 × 106/kg, respectively), while 6 FLU/BU received marrow cells (median nr. CD34+ cells: 1.58 × 106/kg). Median time to ANC >500 was comparable in PBSC FLU/BU (d14, range: 11–20), and PBSC FLU/MEL (d12, range: 10–15) patients, while it was longer in bone marrow FLU/BU (d 22, range: 17–37) patients (p= 0.01 and p=0.001, respectively). Time to Plt >20K was d 12 (range: 10–16) in the PBSC FLU/MEL group and d 20 (range: 17–37) in the bone marrow FLU/BUS group. Four of 6 PBSC FLU/BU patients did not have severe thrombocytopenia (<20K) after transplant. Mucositis> grade 2 was never observed. Median length of stay in the hospital after transplant was 17 days (range: 13–37) in PBSC FLU/MEL, 23 days (range: 18–42) in PBSC FLU/BU and 30d (range: 22–38) in bone marrow FLU/BU. Median chimerism levels on d30 after transplant were: 100% in FLU/MEL and 95% (1 rejection) in FLU/BU. Median follow-up for patients currently alive is 254 days (range: 145–628) in the FLU/BU group and 636 days (range: 429–715) in the FLU/MEL group. Acute GVHD grade II-IV was seen in 1 FLU/BU patient after DLI and in 1 FLU/MEL patient. Chronic GVHD is present in 2/6 FLU/BU and 4/9 FLU/MEL evaluable patients. Six of 12 patients in the FLU/BU died of relapse (n=4) and/or infection (n=2, 1 within d100) and 3 of 10 patients in the FLU/MEL died of relapse. In conclusion, since in allogeneic PBSC transplantation the FLU/BU regimen seems to have a myelotoxicity comparable to FLU/MEL, it could be used in allotransplant for elderly patients and may represent a platform for donor lymphocyte infusions in high risk patients.