Increased infection rate after preemptive rituximab treatment for Epstein-Barr virus reactivation after allogeneic hematopoietic stem-cell transplantation.

BACKGROUND: Preemptive rituximab (R) treatment decreases the incidence of Epstein-Barr virus (EBV) posttransplantation lymphoproliferative disease, but the extent of immune deficiency related to R in patients who received allogeneic hematopoietic stem-cell transplantation is unclear. The aim of our study was to evaluate the incidence of late infections and immune reconstitution after preemptive R treatment of EBV infection. METHODS: Seventy-eight patients receiving preemptive R between January 2005 and January 2010 were studied. Fifty-two of them could be matched with controls (not receiving R) according to administration of antithymoglobulin, stem-cell source and donor type, age and grade of acute graft-versus-host disease. RESULTS: Among the 78 patients with EBV reactivation treated with R, the 36-month cumulative incidence of bacterial, viral, and fungal infections was 64%, 59%, and 23%, respectively. When compared with controls, bacterial infection incidence was significantly higher in R patients (55% vs. 35%), and a slower reconstitution of B cells was observed. R patients had modest but not significantly higher nonrelapse mortality (35% vs. 15%) than controls. CONCLUSION: R has dramatically decreased risks of posttransplantation lymphoproliferative disease but is followed by a prolonged and profound B-cell deficiency associated with an excess risk of bacterial infection and higher mortality. R should be given with caution, and immunoglobulin replacement should be provided to limit these excess risks.

Female genital chronic graft-versus-host disease: importance of early diagnosis to avoid severe complications.

BACKGROUND: Genital chronic graft-versus-host disease (GVHD) is a frequent but underdiagnosed complication of allogeneic stem-cell transplantation impairing quality of life. METHODS: We identified 32 female patients with genital chronic GVHD (cGVHD) who underwent allogeneic hematopoietic stem-cell transplantation in our center between 2000 and 2010 and who were followed after transplantation in a specialized gynecological consultation. Pre- and posttransplantation clinical data and detailed acute and cGVHD data were collected. All patients received the same local treatment for genital lesions. RESULTS: At presentation, most patients complained about vaginal dryness and dyspareunia with impairment in sexual activity. Fifty percent of patients had grade I genital lesions and 50% had grade II or III lesions. Patients seen later in gynecological consultation had more severe lesions than patients seen early after transplantation. At the time of diagnosis, most patients had other cutaneous or mucous localizations of cGVHD. In most cases, lesions were stabilized or decreased with local steroids and estrogen treatment, and most patients could resume sexual activity. Treatment was more efficient in patients with mild lesions than in others. CONCLUSIONS: Genital cGVHD should be systematically searched for in women who have received allogeneic hematopoietic stem-cell transplantation in an early specialized consultation, especially in case of other cutaneous or mucous localizations of cGVHD. Local treatment associating steroids and estrogen seemed to prevent further evolution of grade I genital lesions and to avoid surgical treatment.

Risk factors and options to improve engraftment in unrelated cord blood transplantation.

Use of umbilical unrelated cord-blood (UCB) cells as an alternative source of hematopoietic cell transplantation has been widely used mainly for patients lacking an HLA-matched donor. UCB present many advantages over bone marrow or mobilized peripheral blood from volunteer donors, such as rapid availability, absence of risk for the donor, and decreased incidence of acute graft-versus-host disease. However, a significant clinical problem is delayed engraftment that is directly correlated with the number of hematopoietic stem cells in a cord-blood unit. The identification of prognostic factors associated with engraftment that can be easily modified (e.g., strategies for donor choice) and the development of new approaches including use of multiple donors, intrabone injection of UCB, ex vivo expansion, and cotransplantation with accessory cells are of crucial importance in order to circumvent the problem of delayed engraftment after UCB transplantation. Those approaches may increase the quality and availability of UCB for transplantation.

Prospective assessment of bone turnover and clinical bone diseases after allogeneic hematopoietic stem-cell transplantation.

BACKGROUND: Bone complications after hematopoietic stem-cell transplantation (HSCT) are relatively frequent. Evaluation of biomarkers of bone turnover and dual energy x-ray absorptiometry (DEXA) are not known in this context. METHODS: We prospectively evaluated bone mineral density, biomarkers of bone turnover, and the cumulative incidence of bone complications after allogeneic HSCT. One hundred forty-six patients were included. Bone mineral density was measured by DEXA 2-month and 1-year post-HSCT. The markers of bone turnover were serum C-telopeptide (C-TP), 5 tartrate-resistant acid phosphatase (bone resorption), and osteocalcin (bone formation) determined pre-HSCT and 2 months and 1 year thereafter. Potential association between osteoporosis at 2 months, osteoporotic fracture or avascular necrosis and, individual patient's characteristics and biologic markers were tested. RESULTS: C-TP was high before and 2 months after transplant. At 2 months, DEXA detected osteoporosis in more than half the patients tested. Male sex, median age less than or equal to 15 years, and abnormal C-TP before HSCT were risk factors significantly associated with osteoporosis. Three-year cumulative incidences of fractures and avascular necrosis were 8% and 11%, respectively. Children were at higher risk of fracture, whereas corticosteroid treatment duration was a significant risk factor for developing a clinical bone complication post-HSCT. Bone complications and osteoporosis are frequent after HSCT. Bone biologic markers and DEXA showed that subclinical bone abnormalities appeared early post-HSCT. CONCLUSION: The risk factors, age, gender, and C-TP easily available at the time of transplantation were identified. Biphosphonates should probably be given to patients with those risk factors.

Initial liver involvement in acute GVHD is predictive for nonrelapse mortality.

BACKGROUND: Current grading systems in acute graft-versus-host disease (GVHD) are not able to identify patients with poor prognosis at time of onset, because they take into account maximal grade. The aim of this study was to evaluate potential predictors for overall survival at disease onset. METHODS: The study sample was composed of 142 allogeneic hematopoietic stem-cell transplant recipients who developed acute GVHD after a myeloablative conditioning regimen. Factors associated with the risk of nonrelapse mortality (NRM) were analyzed with proportional hazard models. RESULTS: At time of diagnosis, GVHD involved a single organ in the majority of the patients (78%). Initial grade was I in 24%, II or III in 56% of patients. Significant risk factors for NRM were non-HLA matched sibling donor (68% vs. 55%, P=0.05), absence of methotrexate in GVHD prophylaxis (75% vs. 56%, P=0.02), initial liver involvement (80% vs. 56%, P<0.001), time to GVHD more than 24 days (76% vs. 55%, P=0.04), nonhyperacute GVHD (72% vs. 52%, P=0.016), and steroid refractory GVHD (85% vs. 44%, P<0.001). In multivariate analysis, initial liver involvement (hazard ratio 2.45; 95% confidence interval 1.46-4.12) and a non-HLA identical sibling donor (hazard ratio 1.58; 95% confidence interval 1.02-2.43) were independently associated with NRM. CONCLUSION: Initial liver involvement was an important clinical predictor and should be considered in patient management.