Unrelated Donor Marrow Transplantation for Acute Lymphoblastic Leukemia in Japan. A Japan Marrow Donor Program Experience between 1993 and 2003.

From 1993 to 2003, 1223 patients, 0 to 61 year old, with high risk acute lymphoblastic leukemia underwent their first bone marrow transplantation through Japan Marrow Donor Program. Most transplants were performed between HLA serologically matched Japanese pairs with a few exceptions.

Of all, 520 patients underwent transplantation in the first complete remission (1CR: median follow up 488 days), and their probability of 5 year overall survival (OS) by Kaplan Meier analysis was 58.4(standard error; SE 2.8) %. The 281 patients in the 2CR (452 days) showed OS 49.4(3.7) %, 75 at the third or further CR (249 days), OS 29.5(5.9) %, and 333 at relapse or non CR(162 days), OS 16.4(2.6) %. The outcome of the younger tended to be the better except that the oldest group 51–61 year of age did fair. The GVHD prophylaxes were cyclosporine and short term methotrexate (sMTX) in 681 patients, and tacrolimus plus sMTX in 461. Among the 1CR patients, the 5 year OS of 276 patients in cyclosporine group was 52.0% (SE.3.7%) and 217 tacrolimus group showed significantly better OS, 66.5% (SE 5.7%, P=0.03). The grade II to IV, or III to IV acute GVHD developed in 47.3% or 19.1% respectively without any age difference. Acute GVHD grade I might solely favor the patients in 1CR at 5 years or earlier post-transplant, and the survival of those in 2CR was minimally affected by grade 0 to III acute GVHD. On the other hand, the presence of chronic GVHD did not improve the survival rate of the patients in 1CR, whereas the patients in 2CR achieved better survival if they had limited or extensive chronic GVHD. The importance of HLA class I DNA type matching in Japanese population has been published (N Engl J Med. 1998 Oct 22). Patients with ALL did poorly between the pairs with DNA A-locus mismatch in 1CR and 2CR, B-locus mismatch in 2CR, DRB1-locus mismatch in 2CR.

We concluded that, the unrelated donor marrow transplantation in Japan provided as good chance of survival for the patients with ALL as related donors did, despite poorer risk group they belong to. GVHD prophylaxis with tacrolimus might attain better outcome in 1CR patients, and chronic GVHD seemed to improve the OS for the patients in 2CR, but not for 1CR patients.