As we previously reported(Blood, 2005;NST-1), allogeneic stem-cell transplantation from an HLA identical sibling donor with reduced-intensity conditioning(RIST) consisting of fludarabine(FL), busulfan(BU) and antithymocyte globulin(ATG) for adult T-cell leukemia(ATL) patients(pts) appears to be a feasible treatment modality. Disease relapse, however, was the main cause of treatment failure. We conducted a second phase 1 clinical trial of RIST for ATL pts without ATG(NST-2).

Objectives: We evaluated the safety and feasibility of RIST for ATL using the same conditioning regimen except that we did not use ATG.

Patients and Methods: Between September 2003 and January 2006, 14 pts ranged from 50 and 62 years of age were enrolled. After the conditioning regimen with FL 30 mg/m2/d on days -8 to -3, BU 4 mg/kg/d on days -6 to -5, they received G-CSF-mobilized PB stem cells. The primary end points were either engraftment, as evaluated by the achievement of complete donor chimerism(CC) before d90, or the occurrence of early transplant-related mortality(TRM) before d100.

Results: All 14 pts achieved CC before d90, while two pts died of TRM before d100, thus demonstrating the successful results for the primary end points. The incidence of severe acute GVHD(grade III-IV) was 21%. A disease relapse occurred in 6 pts from d30 to d775, 5 of whom eventually died of ATL. As of July 31, 2006, 6 pts are still alive, while 8 died of either ATL(5 pts) or TRM(3 pts). The event free and overall survivals(EFS, OS) at 2 years were 40% and 43%, respectively. Among the 12 evaluable pts, the HTLV-1 proviral load decreased to an undetectable level after RIST in 9 pts. Therefore, the results of CC before d90(14/14versus[vs]14/15*), TRM before d100(2/14vs2/15*), severe acute GVHD(3/14vs5/15*), disease relapse(6/14vs9/15*), 2 year-EFS (40%vs20%*) or -OS(46%vs33%*) and the anti-HTLV-1 effects(9/12vs8/15*) were closely comparable with those of NST-1*. The incidence of early disease recurrence before d100 tended to be low(21%[3/14]vs44%*[7/16]*), thus resulting in a longer mean survival time(804 days vs 262 days*) after RIST.

Conclusion: Our two studies(NST-1, NST-2) confirmed that, whether ATG was administered or not, RIST is considered to be a feasible treatment modality. Moreover, conditioning without ATG may improve the survival by delaying a disease relapse without increasing the severity of acute GVHD. A third study (phase 2 trial of RIST without ATG) is currently underway.

Disclosures: Supported by a grant from anticancer projects of the Ministry of Health, Labour and Welfare of Japan.

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