Immunological recovery following HLA-matched CD3+ TCR αß+/CD19+ depleted hematopoietic stem cell transplantation in children.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for children with both malignant and nonmalignant diseases. T-cell depletion techniques may result in reduced transplant-related mortality compared with unmanipulated grafts due to a lower incidence of GvHD. METHODS: Immune recovery and outcome were analyzed in a cohort of 23 patients with malignant and nonmalignant diseases who received CD3+TCRαß+ T- and B-cell-depleted allografts from matched donors after reduced-intensity or myeloablative conditioning. The median number of CD34+, CD3+TCRαß+, and CD19+B-cells infused was 12.7 × 106 /kg, 16.8 × 103 /kg, and 96 × 103 /kg bodyweight. RESULTS: With a median follow-up of 36 (range 1-73) months, overall survival and disease-free survival at 3 years were 65.2% and 60.8%. Eight patients died, six due to the underlying disease and two of extended visceral cGvHD. Immune reconstitution, disease-free, and overall survivals were similar compared with a historical cohort of 23 patients transplanted with matched unmanipulated bone marrow. A significant lower rate of higher grade (III-IV) aGvHD was observed in the manipulated HSCT group (8.7% vs. 26%; p = 0.001), whereas the incidence of cGvHD was equal. CONCLUSIONS: Our data suggest that this graft manipulation strategy could be a safe and effective alternative to conventional HSCT techniques in matched donors.

Infections in patients with acute myeloid leukemia treated with low-intensity therapeutic regimens: Risk factors and efficacy of antibiotic prophylaxis.

Survival of acute myeloid leukemia (AML) patients, who are unfit for high-dose chemotherapy, has significantly improved with the advent of low-intensity therapeutic regimens (LITR, comprising decitabine, azacitidine, and low-dose cytarabine). However, infectious complications are common during LITR treatment and might hamper the beneficial effect of these drugs. In this study, we aimed to evaluate the incidence of and predisposing risk factors for infections during LITR treatment of AML, as well as the value of antibiotic prophylaxis within this setting. Therefore, we retrospectively analyzed 40 AML patients, treated with 215 cycles of LITR and analyzed putative risk factors by multivariate logistic regression. Infections occurred in 53/215 (25%) of LITR cycles, resulting in death in six patients. Of the parameters assessed at the start of each LITR cycle, transfusion dependence (p=0.008) and increased LDH (p=0.027) independently predicted the occurrence of infection. Most importantly, however, antibiotic prophylaxis was independently associated with a decreased rate of infectious complications (p=0.030). It was regularly performed in neutropenic patients and even managed to eliminate low neutrophil counts as risk factor in multivariate models. These data argue for the efficacy of antibiotic prophylaxis during LITR therapy of AML and suggest its further evaluation within a prospective clinical trial.