Cord Blood Transplantation for Primary Refractory Acute Myeloid Leukemia

(Introduction) Patients with acute myeloid leukemia (AML) refractory to induction chemotherapy have dismal prognoses.  Although allogeneic stem cell transplant (allo-SCT) remains the only curative therapy for primary refractory AML, there have been sparse reports regarding the outcome of cord blood transplantation (CBT) for the population. (Patients and methods) We retrospectively reviewed patients diagnosed as primary refractory AML who underwent CBT at our institute from Mar. 2003 to June. 2013 consecutively.  (Results) Seventy-seven patients were included in this study.  Underlying diseases were de novo AML in 50 (65%) and AML-MRC in 27 (35%). Forty-nine (61%) were male and 30 (39%) were female.  Their median age was 59 years (range 19-72). The number of prior chemotherapy was 1 course in 28 (36%), 2 in 30 (39%), and more than 3 in 19 (25%), respectively.  Median time from diagnosis to transplantation was 162 days (range; 64-1539).  TBI+Cy/Bu+Cy was used as pretransplant conditioning regimen in 4 patients, Flu+Mel80+TBI4 in 23, Flu+Bu16+Mel80 in 26, Flu+Bu16+TBI2-4 in 12, and other RIC regimens in 12.  Nineteen patients died before engraftment.  Among the remaining 58 patients, 42 achieved neutrophil engraftment with a median of 21 days post-transplant (range; 13-45).  Nine patients received urgent 2^nd CBT for primary graft failure (n=6) or early disease relapse (n=3).  Among the 42 evaluable patients, 36 (86%) developed acute GVHD of grade II or higher, including 11 (26%) patients who developed that of grade III or IV.  Of the 36 patients who survived longer than 100 days post-transplant, 21 patients developed chronic GVHD, including 13 with limited and 8 with extensive form.  With a median observation time for survivors of 16.5 months (range; 3-94), 2 year overall survival (OS) and disease free survival (DFS) were 31.4% and 22.4%, respectively.  Cumulative incidences of relapse and non-relapse mortality (NRM) at 2 years post-transplant were 35% and 42.2%, respectively.  In univariate analysis, patients with aged 19-60 showed superior OS at 2 years compared to elderly patients (>61 years) (44.8% vs 16.4% p=0.013).  Relapse rate was significantly higher in the elderly compared to those with aged 19-60 (50.5% vs 21.7%, P<0.01), whereas NRM did not differ between the two groups (43.3% vs 40.2%, P=0.87).  Eighteen patients died of disease relapse and 36 died of NRM, including graft failure (3), infection (20), bleeding (2), organ failure (4), TMA (3) and idiopathic pneumonia syndrome (4). (Conclusion) Our results suggested that CBT is a feasible and promising treatment approach for patients with primary refractory AML.  Optimal strategies for decreasing relapse especially in the elderly should be established to improve the outcome.