Xavier Cahu

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.

18F-fluorodeoxyglucose–positron emission tomography before, during and after treatment in mature T/NK lymphomas: a study from the GOELAMS group

BACKGROUND In non-cutaneous T-cell/natural killer (T/NK) lymphomas, the prognostic value of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) during or after therapy is unknown. PATIENTS AND METHODS In this retrospective study, 54 T/NK lymphoma patients were assessed using FDG-PET before (n = 40), during (n = 44) and/or after therapy (n = 31). RESULTS FDG-PET showed an abnormal FDG uptake in all cases. Interim FDG-PET was negative in 25 of 44 cases. After completion of therapy, 19 of 31 patients reached complete remission with negative FDG-PET. In ALK+ anaplastic large cell lymphomas, the 4-year progression-free survival (PFS) was 80% and the negative predictive value of post-therapy FDG-PET was 83% (n = 9). In ALK- T/NK lymphomas, the 4-year PFS was 59% for patients with a negative interim FDG-PET versus 46% for patients with a positive interim FDG-PET (P = 0.28, n = 35). Similarly, there was no statistical difference in 4-year PFS between negative and positive post-therapy FDG-PET in these lymphomas (51% and 67%, respectively, P = 0.96). The 4-year cumulative incidence of relapse from a negative post-therapy FDG-PET was 53% in ALK- T/NK lymphomas. CONCLUSIONS Although T/NK lymphomas are FDG-avid at diagnosis, a negative interim or post-therapy FDG-PET does not translate into an improved PFS in ALK- T/NK lymphomas.

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.

18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study.

This prospective pilot study aimed to evaluate the predictive value of 18F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. 18F-FDG PET/CT was systematically performed at a median of 28 (range, 24–38) days after allo-SCT. 18F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1–2 GI-GVHD and severe grade 3–4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by 18F-FDG PET/CT suggesting that noninvasive 18F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive 18F-FDG PET/CT.

Allogeneic hematopoietic stem cell transplantation following reduced-intensity conditioning regimen in children: a single-center experience.

This single‐center retrospective study reported the outcome of 19 children treated with a reduced‐intensity conditioning (RIC) regimen prior to allogeneic stem cell transplantation (allo‐SCT), for hematologic malignancies (n = 17), bone marrow failure (n = 1), and neuroblastoma (n = 1). Children were ineligible for standard myeloablative conditioning because of severe comorbidities (n = 9), a previous auto or allo‐SCT (n = 7) or a prior history of extensive chemotherapy (n = 3). All patients underwent a fludarabine‐based RIC regimen, and received grafts from matched‐related donors (n = 5), match‐unrelated donors (n = 6), or unrelated cord blood (UCB, n = 8). In this series, two patients treated with UCB failed to engraft and 63% achieved full donor chimerism at day 100 after allo‐SCT. With a median follow‐up of 537 d (range, 115–4136), treatment‐related mortality was 16% and overall survival was 47%. The principal cause of death was disease relapse (n = 7). Acute graft versus host disease (GVHD) occurred in 53% of patients, while only 10% developed extensive chronic GVHD. Overall, results from this series suggest that RIC allo‐SCT can be a valid alternative treatment option in unfit children with malignant hematological diseases. Prospective studies are needed to enlarge pediatric experience in this domain and better identify those children more suitable for a RIC allo‐SCT approach.

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.

Improvement of overall survival after allogeneic hematopoietic stem cell transplantation for children and adolescents: a three-decade experience of a single institution

Allogeneic stem cell transplantation (allo-SCT) has become an essential component of the treatment for a variety of diseases in pediatric patients. During the past decades, advances in the transplant technology, availability of hematopoietic stem cells and supportive care not only have resulted in improved outcomes, but also have expanded the transplant options. However, these features have been studied mainly in adult populations. This investigation analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allo-SCT in a single center between 1983 and 2010. In the 2000–2010, compared with the 1983–1999 period, a significantly higher 5-year overall survival (64% versus 52%, P=0.03) was observed together with a significant decrease of non-relapse mortality (27% versus 9%, P=0.0002). The progression-free survival was comparable between the two periods (49% versus 57%; P=0.17). The 5-year cumulative incidence of relapse was 24% between 1983 and 1999, and 34% between 2000 and 2010 (P=0.08). Major advances in supportive care practice have been made over the past decade, resulting in a significant survival benefit for the pediatric population undergoing allo-SCT. However, post-transplant relapse remains the leading cause of failure of this therapeutic approach, and preventing relapse represents a major challenge today.

Peripheral Blood Plasmacytoid Dendritic Cells at Day 100 Can Predict Outcome after Allogeneic Stem Cell Transplantation

The rapidly increasing use of allogeneic stem cell transplantation (allo-SCT) emphasizes the need for identifying variables predictive of its outcome. Plasmacytoid dendritic cells (pDCs) play a major role in establishing immune competence and in several autoimmune diseases. Thus, we investigated whether pDCs might influence the outcome of patients after allo-SCT in 79 consecutive patients who underwent this procedure. pDCs were identified in the blood of patients at day 100 after allo-SCT by staining peripheral blood mononuclear cells for surface markers and intracellular cytokines and analyzing them on a flow cytometer. We found the pDC level at day 100 was not influenced by patient or graft characteristics, and only the absence of previous grades II to IV acute graft-versus-host disease was significantly associated with higher levels of blood pDCs after allo-SCT (OR, .67; 95% CI, .54 to .83; P = .0004). Using the median value of pDCs at day 100 to divide the patients into 2 distinct groups, we observed that a low pDC level was correlated with a worse overall survival (55% versus 86%, P = .007). In a multivariate analysis, only low pDC level (OR, 3.41; 95% CI, 1.19 to 9.79; P = .02) and older patient age (OR, 5.16; 95% CI, 1.15 to 23.14; P = .03) were significantly predictive of increased risk of death. We conclude that monitoring of pDC may be useful for patient management and may have a significant impact on the probability of a favorable outcome of allo-SCT.

Rapid childhood T-ALL growth in xenograft models correlates with mature phenotype and NF-κB pathway activation but not with poor prognosis

Rapid childhood T-ALL growth in xenograft models correlates with mature phenotype and NF-κB pathway activation but not with poor prognosis

Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia.

Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body‐surface area (BSA) on patients’ characteristics, physicians’ strategy, dose adjustment, and clinical outcome.