Reduced-Intensity Unrelated Cord Blood Transplantation (RICBT) in Adult Patients with High-Risk Hematological Malignancies.

Abstract

Abstract <Introduction> RICBT using cyclosporine (CSP) and short-term mycophenolate mofetil (MMF) was performed on adult patients with high-risk hematological malignancies, from which data on complication measures and transplantation indications was obtained. <Subjects and Methods> From November 2003 to January 2005, RICBT was performed a total of 16 times on 14 patients. All patients were adults diagnosed with high-risk hematological malignancies, and 12 patients were not in remission. The average age of the patients was 57 years (range: 31–72 years). The average body weight of the patients was 59.1 kg (range: 48–72). The HLA match of two patients was 5/6 and 12 patients was 4/6. The average nucleated cell count was 2.55 x 107 cells/kg (range: 2.12–3.84 x 107 cells/kg). The conditioning regimen consisted of fludarabine and/or busulfan or cyclophosphamide and TBI (total body irradiation), and the intensity of therapy was adjusted based on age, disease, and systemic status. CSP and MMF were administered for GVHD (graft-versus-host disease) prophylaxis. The targeted duration of CSP and MMF administration was set at 100 and 28 days, respectively. <Results> Primary graft failure occurred in two patients. RICBT was repeated, and while the second treatment was successful in one patient, the other patient died of brain hemorrhage. Granulocyte recovery was observed in 13 patients on an average of 21 days, and platelet recovery was noted in 11 patients on an average of 43 days. Acute GVHD was assessed in 13 patients and confirmed in 12 patients, but a condition of grade II or above was seen in only three patients. Chronic GVHD was assessed in 12 patients and confirmed in six patients (limited type in five patients and extensive type in one patient). For the 16 treatments, the 100-day TRM (transplantation related mortality) was 19% (3 patients). Of the 14 patients, five remained alive and the statistically calculated one-year survival rate was 37%. Cause of death was recurrence in three patients, acute GVHD in one patient, viral infection in three patients, cerebral hemorrhage in one patient, and sudden death in one patient. Non-recurrence deaths included four patients with a past history of allogeneic transplantation, two patients with serious organ damage, and two patients with diabetic complications (two patients died of multiple causes). Of eight patients, excluding the six patients with past histories of allogeneic transplantation, serious organ damage, or diabetic complications, the 100-day TRM was 0% and the statistically calculated one-year survival rate was 54.7%. Two patients with VZV (varicella-zoster virus) infections died on days 221 and 228. <Discussion and conclusions> While the risk of graft failure is generally high for RICBT, the success rate for the present RICBT technique was extremely high. This technique also made it possible to induce proper GVHD without steroidal agents. The low recurrence rate appeared to indicate the GVL (graft versus leukemia) effects of RICBT. The high GVL effects and low 100-day TRM observed appeared to be attributable to short-term MMF administration. We believe viral infections must be prevented for a lengthy period after the cessation of immunosuppressant therapy. Our results suggest that a past history of allogeneic transplantation, severe organ damage, or diabetic complications may constitute risk factors.