The inclusion of ATG resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. The survival rate was similar in the two groups, but the rate of a composite end point of chronic GVHD-free survival and relapse-free survival was higher with ATG. (Funded by the Neovii Biotech and the European Society for Blood and Marrow Transplantation; ClinicalTrials.gov number, NCT00678275.).

Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n ¼ 94) or acute lymphoblastic leukemia (n ¼ 124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n ¼ 21) or mismatched (n ¼ 197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand-and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P ¼ 0.09 and P ¼ 0.13, respectively). Sixty-nine donor-patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligandincompatible UCBT showed improved LFS (hazards ratio ¼ 2.05, P ¼ 0.0016) and overall survival (OS) (hazards ratio ¼ 2.0, P ¼ 0.004) and decreased RI (hazards ratio ¼ 0.53, P ¼ 0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P ¼ 0.012), and 5 versus 36% (P ¼ 0.005), respectively). UCBT for acute leukemia in CR from KIR-ligandincompatible donors is associated with decreased RI and improved LFS and OS.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE), usually an autosomal-recessive inherited condition, causes gastrointestinal dysmotility, ophthalmoplegia, ptosis, leukoencephalopathy and neuropathy. The chromosome 22 disorder, due to mutations in the nuclear gene TYMP encoding thymidine phosphorylase (TP), leads to the accumulation of thymidine and deoxyuridine, with mitochondrial dysfunction. This report describes a patient with an MNGIE-like syndrome with a heterozygous TYMP mutation who showed marked, but transient improvement postallogeneic haematopoietic stem cell transplantation (HSCT). The patient, showing ptosis and ophthalmoplegia, was initially managed for myasthenia gravis. She developed gastrointestinal symptoms, dysarthria, dysphagia and weakness, and MNGIE was considered due to its low TP levels and improvement after platelet transfusions. She underwent HSCT, with dramatic improvement, but regressed 18 months later despite normal TP levels, platelet counts and full chimerism. MNGIE may encompass a spectrum of disorders. TP deficiency alone is unlikely to explain all clinical signs, and other factors, including the possible development of anti-TP antibodies, which may play a role in the pathophysiology.

Our results confirm the capacity of this RIC regimen to obtain long-term remissions in patients ineligible for a conventional allo-SCT. The results suggest an important role of the development of chronic GVHD in reducing relapse and improving DFS and OS.

Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.

No abstract

This study analyzed the characteristics of 257 HLA-identical sibling transplants of granulocyte colony-stimulating factormobilized peripheral blood progenitor cells depleted of T cells by CD34 ؉ positive selection (allo-PBT/CD34 ؉ ) for their effect on the incidence of graft failure. Twenty-four patients developed graft failure (actuarial probability, 11%; 95% confidence interval, 7.1-14.9). Prognostic factors considered were sex and age of donor and recipient, donor-recipient blood group compatibility, diagnosis, disease status at transplant, conditioning regimen, cytomegalovirus serology, number of CD34 ؉ and CD3 ؉ cells infused, and cryopreservation. The major factor associated with graft failure was the number of CD3 ؉ cells in the inoculum. Twentythree of 155 patients receiving a T-cell dose in the graft less than or equal to 0.2 ؋ 10 6 /kg experienced graft failure, compared with only one of 102 patients receiving more than 0.2 ؋ 10 6 /kg (actuarial probability 18% vs 1%, respectively; P ‫؍‬ .0001). The actuarial probability of graft failure progressively increased as the number of CD3 ؉ cells in the graft decreased, which was determined by grouping the number of CD3 ؉ cells in quartiles (log-rank P ‫؍‬ .03; log-rank for trend P ‫؍‬ .003). In the multivariate analysis by the proportional hazard method, 2 covariates entered into regression at a significant level: CD3 ؉ cells less than or equal to 0.2 ؋ 10 6 /kg (risk ratio ‫؍‬ 17; P < .0001), and patients with chronic myelogenous leukemia (CML) conditioned with busulphan-based regimens (risk ratio ‫؍‬ 4.8; P ‫؍‬ .001). From these results it appears that the number of CD3 ؉ cells in the inoculumwith a threshold of 0.2 ؋ 10 6 /kg or less-is the most critical factor in maintaining a sustained engraftment in allo-PBT/CD34 ؉ from HLA-identical siblings. In addition, for patients with CML receiving 0.2 ؋ 10 6 /kg or less CD3 ؉ cells, total body irradiation might be better than busulphan-based regimens.

R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Parameters correlating with a lower response rate were advanced clinical stage, high serum beta2-microglobulin levels, and del(17p). Based on these results, R-FCM warrants further investigation in randomized clinical trials.