Beatrice Saulquin

Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/105 cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/105 cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92–1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk=4.9; 95% confidence interval, 1.1–21.0; P=0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.

Impact of Cyclosporine-A Concentration on the Incidence of Severe Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

This single-center retrospective study analyzed 85 consecutive patients who underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess whether there is a correlation between exposure to cyclosporine-A (CsA; as measured by CsA concentrations during the first month after allo-SCT) and the risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD). The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo-SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and 247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in 36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI], 14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the lowest CsA concentration in the first and second weeks after allo-SCT had a significantly higher risk of grade III-IV aGVHD. In a multivariate logistic regression analysis, a higher CsA concentration measured during the first week following graft infusion was the strongest parameter significantly associated with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] = 0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration in week 1 remained significantly associated with risk of severe grade II-IV aGVHD (P = .014). We conclude that precise monitoring of CsA concentrations and adjustment of CsA dose early after allo-SCT may be effective to prevent onset of severe aGVHD.

Infectious Complications after Unrelated Umbilical Cord Blood Transplantation in Adult Patients with Hematologic Malignancies

Unrelated umbilical cord blood (UCB) is being increasingly used as an alternative stem cell source for allogeneic stem cell transplantation (allo-SCT). This retrospective study assessed infectious complications occurring in adult patients after UCB transplantation (UCBT). 31 patients received a single (n=4) or double UCBT (n=27) with a median dose of 4.7x10(7) nucleated cells/kg (range: 2.4-7.7). Patients received either a reduced-intensity conditioning (RIC; n=23) or a standard myeloablative (MA) regimen (n=8). The cumulative incidence of neutrophil recovery was 90%. Neutrophil recovery was achieved at a median time of 24 (range: 8-60) days after UCBT. The cumulative incidences of bacterial, fungal, and parasitic infections were, respectively, 16%, 10%, and 6%. Bloodstream infections were neither lethal nor required any intensive care therapy. Similarly, invasive fungal infections and parasitic infections did not cause any death in those patients with sustained engraftment. Although the cumulative incidence of cytomegalovirus (CMV) recurrence was 21%, no CMV disease was observed. With a median follow-up of 10 (range: 3-30) months, 10 patients have died (relapse, n=5; nonrelapse mortality, [NRM] n=5). Overall, the cumulative incidence of infectious-related mortality (IRM) was 8%. In conclusion, this data suggests that UCBT can be performed in adult patients with hematologic malignancies with an acceptable incidence of IRM provided a sufficient dose of nucleated cells is infused to the patient.

Prophylaxis with mycophenolate mofetil and CsA can decrease the incidence of severe acute GVHD after antithymocyte globulin-based reduced-intensity preparative regimen and allo-SCT from HLA-matched unrelated donors

Prophylaxis with mycophenolate mofetil and CsA can decrease the incidence of severe acute GVHD after antithymocyte globulin-based reduced-intensity preparative regimen and allo-SCT from HLA-matched unrelated donors

Factors predicting allogeneic PBSCs yield after G-CSF treatment in healthy donors

G-CSF mobilized PBSCs are increasingly used in allo-SCT due to their relative ease of collection and because higher CD34þ cell doses may be associated with improved transplant outcomes in some settings. However, some healthy donors may show poor mobilization response to G-CSF and poor subsequent CD34þ apheresis yields. Therefore, identifying donors at risk for poor mobilization and a reliable estimate of a healthy donor’s CD34þ cell mobilization response to G-CSF and subsequent CD34þ cells yield could be of value in optimizing transplantation approaches. The aim of this single center report was to analyze factors associated with the total CD34þ PBSC yield in an ethnically homogeneous Caucasian population of 95 healthy allogeneic adult donors. All donors received G-CSF dosed at 10mg/kg/day (Filgrastim, Amgen, France) for 5 days followed by leukapheresis. Complete blood counts (total WBC, Hb, Plts) were measured for all donors at baseline before G-CSF administration, before and after PBSC collection. Peripheral blood CD34þ cell counts were also measured before apheresis. Sixty-nine donors (73%) were healthy sibling donors, whereas 26 (27%) were healthy volunteer donors for HLA-identical unrelated transplants. All donors were undergoing their first PBSC mobilization (study period 2004–2008). Donors’ demographic characteristics are summarized in Table 1. Briefly, the median (range) age, weight and height were 47 (18–81) years, 69 (43–106) kg and 170 (150–187) cm, respectively. The median body mass index (BMI) was 23.9 (15.2–35.7) kg/m. As per the institutional policy, the targeted total number of CD34þ stem cells was between 4 and 8 10/kg recipient body weight to be collected in a maximum of three consecutive aphaeresis sessions while continuing G-CSF administration. Assessments were based on recipient body weight. Overall, the median number of the total collected CD34þ cells was 6.25 10/kg (range, 1.7–16.6), with 16 donors (17%) yielding less than 4 10/kg CD34þ stem cells. After the first apheresis, the median number of collected CD34þ cells was 4.9 10/kg (range, 1.0–16.6). Thirty-two donors (34%) underwent more than one apheresis session. No life-threatening adverse events were encountered during the mobilization and collection process. However, 11 donors (12%) experienced some adverse events during the collection process (bone pain, headache, hypotension, arrhythmia and general discomfort). Of note, no dose reduction was performed because of side effects, and none of these side effects resulted in severe morbidity or any mortality. In univariate analysis, female gender, lower weight and height, pre-G-CSF and post G-CSF Hb levels, and low CD34þ cell counts before first apheresis, were associated with significantly lower total CD34þ stem cells yields (o6.25 10/kg). In multivariate analysis, male donor gender and higher post-G-CSF CD34þ cell counts before the first apheresis were most strongly associated with a higher (46.25 10/kg) total number of collected CD34þ stem cells (OR1⁄4 6.17, 95% CI (2.39–15.93), P1⁄4 0.0001; and OR1⁄4 3.95, 95% CI (1.53–10.19), P1⁄4 0.004, respectively). A CD34þ cell yield o2 10/kg of recipient weight is usually the accepted definition of a ‘poor mobilization’. However, for the purpose of this analysis and from a practical standpoint, we chose to focus on those donors with a CD34þ stem cell yield o4 10/kg, which can be considered as a ‘non-optimal’ yield. Thus, when considering the group of 16 donors with a ‘non-optimal’ CD34þ stem cells yield (o4 10/kg), in multivariate analysis, we found that a higher post-G-CSF CD34þ cell count before the first apheresis was the strongest parameter significantly associated with a higher total number of collected CD34þ PBSCs (OR1⁄4 6.36, 95% CI (1.68–24.15), P1⁄4 0.006; Table 2). Earlier studies have yielded conflicting data regarding the effect of various donor demographic, laboratory and other factors on peak donor CD34þ mobilization responses and apheresis cell yields. Recently, Vasu et al. identified age,

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

This single centre study assessed the incidence, kinetics and predictive factors of EBV reactivation and EBV-related lymphoproliferative diseases (LPD) in 33 consecutive patients who received a reduced intensity conditioning (RIC) before umbilical cord blood transplantation (UCBT). During the first 6 months after UCBT, weekly all patients were DNA-PCR screened in the peripheral blood for EBV reactivation and were clinically monitored for clinical features attributable to EBV. The cumulative incidences of EBV reactivation (defined as an EBV load >1000 EBV copies per 105 cells measured at least once during follow-up) at 6 months and 2 years after UCBT were 9 (95% confidence interval (CI), 2–22%) and 17% (95% CI, 6–33%), respectively. In 28 patients (85%), the EBV load remained negative at all times, and none of these patients experienced any sign of LPD. Five patients (15%) experienced at least one EBV reactivation episode. EBV reactivation was observed at a median of 132 days (range, 85–438) after UCBT. Two patients developed EBV-related LPD (cumulative incidence, 6% at 3 years). With a median follow-up of 468 days (range, 92–1277) post UCBT, the OS was 62% at 3 years. Five patients died of disease progression and seven patients died of transplant-related complications, including one case of EBV-related LPD. Univariate analysis did not identify any significant risk factor associated with EBV reactivation. We conclude that patients undergoing RIC UCBT are at risk for EBV reactivation, with the need for close EBV monitoring and the use of preemptive rituximab treatment as some cases may progress to life-threatening LPD.

Reduced-intensity conditioning allogeneic stem cell transplant for relapsed or transformed aggressive B-cell non-Hodgkin lymphoma

The role of reduced-intensity conditioning allogeneic stem cell transplant (RIC allo-SCT) in aggressive B-cell non-Hodgkin lymphoma (NHL) remains a matter of debate. This single-center analysis aimed to assess the potential benefit of RIC allo-SCT in 19 consecutive patients with relapsed or transformed aggressive B-cell NHL. Aggressive transformation (primary or secondary) was documented for these patients by pathological examination. In this series, all patients but two (n = 17; 89.5%) could actually receive autologous stem cell transplant (auto-SCT) prior to RIC allo-SCT. At the time of allo-SCT, eight patients (42%) were in first complete remission (CR), six (31.5%) were beyond first CR, and five (26.5%) were in partial remission. With a median follow-up of 32 (range, 3–86) months, nine patients experienced grade 2–4 acute GVHD (47.5%) and 10 patients had extensive chronic GVHD (52.5%). Overall, the incidence of non-relapse mortality was 26% (95% CI, 8–44%). At last follow-up, 12 patients (63%) were in sustained CR. The Kaplan–Meier estimates of progression-free and overall survival rates were 68% and 68%, respectively, at 4 years. We conclude that RIC allo-SCT after auto-SCT is feasible and a potentially efficient therapy for relapsed or transformed aggressive B-cell NHL, warranting further prospective evaluation.