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.
We examined the efficacy of unrelated cord blood (CB) transplantation in children with thalassemia (n = 35) and sickle cell disease (n = 16), using data reported to 3 registries. Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allele level) in 7 or HLA mismatched at 1 (n = 18), 2 (n = 25), or 3 loci (n = 1). Transplant conditioning was myeloablative (n = 39) or reduced intensity (n = 12). Neutrophil recovery with donor chimerism was documented in 24 patients; 11 patients developed grade II-IV acute graft-versus-host disease (aGVHD) and 10 patients, chronic GVHD (cGVHD). Overall survival (OS) and disease-free survival (DFS) were 62% and 21% for thalassemia and 94% and 50% for sickle cell disease (SCD), respectively. In multivariate analysis, engraftment rate (hazard ratio [HR] 2.2, P =.05) and DFS (HR 0.4, P =.01) were higher with cell dose >5 × 107/kg. The 2-year probability of DFS was 45% in patients who received grafts with cell dose >5 × 107/kg and 13% with lower cell dose. Primary graft failure was the predominant cause of treatment failure occurring in 20 patients with thalassemia and 7 patients with SCD. Primary graft failure was fatal in 5 patients with thalassemia. These results suggest that only CB units containing an expected infused cell dose >5 × 107/kg should be considered for transplantation for hemoglobinopathy.
Among 40 allogeneic stem cell transplant recipients who developed symptomatic respiratory syncytial virus infection, including 22 patients with lower respiratory tract infection, 19 received palivizumab (9 of whom had upper respiratory tract disease). Palivizumab did not prevent progression to lower respiratory infection and had no impact on the overall survival rate.Respiratory syncytial virus (RSV) is the most common respiratory virus to cause infection after allogeneic hematopoietic stem cell transplantation (HSCT). RSV infection progresses to lower respiratory tract infection in 40%-50% of RSV-infected patients. RSV-associated pneumonia was reported to be associated with fatal outcome for more than one-half patients [1]. Although some observations indicate that early treatment of RSV infection with aerosolized ribavirin and/or hyperimmune globulin may prevent progression of disease, no definitive proof of efficacy is available for this patient population [1][2][3][4][5]. Moreover, aerosolized ribavirin cannot be used in most French hospitals because it is considered to be potentially dangerous for caretakers, and hyperimmune g-globulins are not available in France. Palivizumab, an RSV-specific monoclonal antibody, has been shown to significantly reduce the RSV load in pulmonary tissue in murine models and to lower rates of RSV infectionrelated hospitalization for high-risk infants after monthly prophylaxis [6,7]. A phase 1 study of allogeneic and autologous HSCT recipients found that stable, effective serum levels of palivizumab were maintained for 21 days, no adverse events occurred, and no anti-palivizumab antibody response occurred [8]. Since the time of that publication, palivizumab has been used in an uncontrolled manner to treat RSV infection in HSCT recipients, including those in our transplant unit, with no clear understanding of its impact on outcome. This study was conducted to estimate the impact of palivizumab treatment, if any, on prevention of progression from upper to lower respiratory tract infection and on the overall mortality rate among HSCT recipients with RSV infection.Materials and methods. We retrospectively reviewed the charts for all patients who had undergone allogeneic HSCT at our institution and who received a diagnosis of RSV infection during the period from January 1999 through March 2006. Infections were diagnosed by immunofluorescence detection of RSV antigen in nasopharyngeal aspirate and/or bronchoalveolar lavage fluid specimens. Lower respiratory tract infections were defined as radiographic pulmonary abnormalities in patients with signs and symptoms (e.g., cough, dyspnea, sputum production, and fever) [9]. The first patient received palivizumab in December 2001. Thereafter, the decision regarding whether to prescribe palivizumab was left to the discretion of the treating physician.Results of variables tested are reported as numbers of patients or median values and ranges. Groups of patients treated with palivizumab and those who were not treated with palivizumab were compa...
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