Abstract
Japan Cord Blood Bank Network has established a registry for unrelated cord blood transplant (CBT) as a quality management and promotion of CBT. CBT for patients with chronic myeloid leukemia (CML) has not been established because of interferon (IFN) and molecular targeting reagents (Imatinib mesylate: STI) resulting in good cytogenetic response. We have analyzed ninety five CML patients who received an unrelated CBT between October 1998 and December 2005 via Japan Cord Blood Bank Network (JCBNW). The median age was 40 yrs (range, 16–67 yrs), and the median weight was 58 kg (range, 39–96 kg). At CBT, 41 patients were in chronic phase (CP) (12 in first; 27 in second and 2 in third CP), 13 in accelerated phase (AP) (5 in first, 5 in second and 3 in third AP), and 41 in blast crisis (BC)(27 in first, 13 in second, and 1 in third BC). Median duration between the diagnosis and CBT was 1.5 yrs (range, 0.2–14.6 yrs). Seventy four patients received a CBT as the first hematopoietic stem cell transplantation (HSCT), while the remaining 21 had previous history of HSCT. In 1st CBT patients, 10 had received chemotherapy, and 21 had IFN-based treatment, 16 had IFN and STI treatment and 25 had STI based treatment. Forty three had no cytogenetic response, 9 partial, 17 complete responses and 5 unknown. The degree of HLA disparity (rejection direction) in serological typing for class I and II antigens showed 0 mismatch(MM) in 12 patients, 1MM in 31 patients, 2 MM in 51 patients and 3MM in 1 patient, respectively. Conditioning regimen in 1st CBT consisted of myeloablative regimen in 56 patients, reduced intensity regimen in 16 and other chemotherapy combination in 2 patients, while in patients with previous history of HSCT, myeloablative regimen in 4 patients, 7 in RIST, immunosuppressant only in 3 patients, and other chemotherapy combination in 6 patients. G-CSF was administered until engraftment in 89 patients. The median number of nucleated cells (NC) /kg was 2.5 x 107 (range, 1.1–5.0) and CD34+ cells/kg was 0.8 x105 (range, 0.17–2.79). For GVHD prophylaxis, no prophylaxis were in 2 patients, CsA with or without prednisolone in 20, CsA with methotrexate (MTX) in 37, Tacrolims only in 20, Tacrolims with MTX in 11, prednisolone only in 2, and CsA with MMF in 3 patients. Neutrophil engraftment was obtained in 73 % in 1st CBT patients, while 63% in patients with previous SCT (P=NS). In 1st CBT, it was 92.3% in patients (n=13) receiving >3.0 x 107 nucleated cells (NC) /kg and 68.7% in patients (n=61) receiving less (P <0.0005). In 49 patients with neutrophil engraftment, favorable factor for platelet engraftment was NC >3.0x107/kg (P<0.0001). aGVHD was seen 63% in evaluable patients with myeloid engraftment. Two-year-OS was 49.8% in 1st CBT (67.2% in CP, 76.2% in AP, and 28.3% in BC at CBT; P<0.001), while 35.7% in patients with previous history of HSCT. Favorable factor for overall (OS), event free survival and disease free survival was CML-CP at CBT. Transplantation-related mortality (TRM) rate was 31% in 1st CBT and 33% in patients with previous history of HSCT. These results suggest that unrelated CB is considered to be an alternative source to bone marrow in patients with CML, especially in those with sufficient number of NC.
Non-Inherited Maternal Antigens Identify Acceptable HLA Mismatches: A New Policy for the Hellenic Cord Blood Bank