Reduced-Intensity Cord Blood Transplantation (RICBT) Is a Feasible Approach for Advanced Adult T-Cell Leukemia (ATL).

Introduction:

ATL in advanced stage is a lymphoid malignancy with poor prognosis, its mean survival time being a few months. Allogeneic hematopoietic stem cell transplantation has been shown to be potentially curative approach, but the availability of HLA-matched donor, either of related or unrelated, limits its application to many of the patients. Cord blood has been widely used as an alternative donor cells. We report here the feasibility of RICBT for patients with advanced ATL.

Patients and Methods:

Eighteen patients with advanced ATL, including 11 acute type and 7 lymphoma type, who underwent RICBT between March 2002 and June 2005 at our institution, were retrospectively analyzed. Eighty percent of them were chemo-refractory at the time of transplant. Median age of the patients was 59 years (27–79). Pretransplant conditioning regimen consisted of fludarabine 125 mg/m², melphalan 80 mg/m² and TBI 4 Gy. GVHD prophylaxis was either cyclosporine (CSP, n=11) or tacrolimus (TAC, n=7) alone. The median number of infused nucleated cells and CD34 positive cells were 2.83 (1.95–4.83) x 10⁷ and 1.00 (0.40–2.91) x 10⁵, respectively. All the patients received CB units with HLA mismatches at 1 (n=8) or 2 (n=10) loci.

Results:

Neutrophil and platelet engraftment were observed in 15 (83.3%, median 16 days) and 14 patients (77.8 %, median 42 days). Two died before engraftment. Five of the engrafted patients (30%) developed acute GVHD (grade II–IV). Although 14 out of 15 patients who survived over 30 days achieved complete remission, 6 died of non-relapse mortality (NRM) within 100 days post-transplant (5 sepsis, 1 encephalitis), and another 6 died of relapse (median 225 days post-transplant). Five of the 7 patients who were alive beyond 100 days developed chronic GVHD (4 limited, 1 extensive). One patient experienced rapid tumor regression along with the chronic GVHD after cessation of TAC at day 146 post-transplant, indicating possible GvATL effect. Estimated 1-year overall and progression-free survival rates were 27.9 +/− 9.0 % and 17.2 +/− 12.8 %, respectively. Among 9 survivors beyond 100 days post-transplant, 5 remain alive at median follow-up of 17 months but only 2 of them remain progression free. Univariate analyses revealed high age (over 60), poor ECOG performance status (over 2) and high sIL-2R level (over 10000IU/L) as poor factors for survival. TAC dramatically decreased the day 100 mortality (14.3%) compared with CSP (45.5%).

Conclusion:

This pilot study indicates that our RICBT is feasible even for the ATL patients in advanced stage. Day 100 mortality was improved by using TAC but eventually the overall survival decreased to comparable level with CSP. To further improve the outcome, RICBT should be investigated for patients in early stage of the disease, or new approach to prevent late relapse should be explored.