Treatment of Relapsed and Refractory Acute Myeloid Leukemia with a Salvage FLAG-IDA Chemotherapy Regimen Followed by a HLA Matched Related Allogeneic PBSC Infusion without Additional Conditioning.

The clinical outcome of relapsed and refractory AML is dismal. Attempts in this setting to induce a remission, prior to an allogeneic SCT, are frequently frustrated by either failure to respond to chemotherapy or deterioration in the clinical status post chemotherapy. Since December 2005, patients with relapsed and refractory AML were offered salvage chemotherapy with a FLAG-IDA regimen (consisted of G-CSF 10mcg/kg/day starting day −1, Fludarabine 30 mg/m² x 5 days, Cytosine 2gm/m² x 5 days and Idarubicin 10mg/m² x 3 days). On day 10 of chemotherapy a G-CSF mobilized PBSC harvest from a complete HLA matched related donor was infused, targeting a cell dose of 5 x 10⁸ MNC/kg. GVHD prophylaxis consisted of low dose cyclosporine (1.5 mg/kg/day) ± short course low dose methotrexate. Eleven patients were treated with this regimen. The median age was 40 years (range: 2 – 51). There were 7 (64%) males. There were 6 relapsed cases (5 relapse-1 and one relapse-2) and 5 primary refractory cases. Of the relapsed cases, two had relapsed following a prior allogeneic SCT. Among the patients with relapsed AML, the median number of chemotherapy cycles prior to transplant was 3 (range: 2 – 5) and the median time to transplant from relapse was 5 months (range: 5 – 10). Among the 5 refractory patients, the median number of chemotherapy regimens received prior to transplant was 2 (range: 1 – 3) and the median time from diagnosis to transplant was 3 months (range: 1 – 6 months). The median number of bone marrow blasts pre-transplant was 38% (range: 5 – 70). Five cases had an ECOG performance score of 0–1 while 4 had an ECOG score of 2 and 2 had an ECOG score of 3. Salvage FLAG-IDA chemotherapy regimen was well tolerated in all cases. The median cell dose infused on day 10 was 6.59 x 10⁸ MNC/kg (range: 3.5 – 12.73). All but one patient engrafted with a median time to ANC > 500/mm³ of 13 days (range: 9 – 21) post stem cell infusion and Platelet count > 20,000/mm³ of 12 days (range: 9 – 17). One patient failed to engraft and died on day 9 secondary to a fungal pneumonia. Nine patients achieved a complete donor chimerism on day +30 post stem cell infusion. Six (55%) developed grade 2–4 acute GVHD while 2 (18%) developed grade 3–4 acute GVHD. Six of eight who could be evaluated developed chronic GVHD, all had extensive chronic GVHD. Four patients relapsed following transplant at a median of 118 days post transplant (range: 26 – 140). At the time of this analysis 5 (45%) patients are alive and in remission at a mean follow up of 278 days (range: 119 – 551). Of the remaining 6 patients, 4 relapsed and died, 1 died prior to engraftment from a fungal pneumonia and one patient died in remission from an acute cardiac event. FLAG-IDA salvage chemotherapy followed by an allogeneic PBSC graft infusion on day 10 is a reasonable option to consider for patients in this clinical situation.