Fatal problems encountered in allogeneic stem cell transplantation include EBV reactivation and post transplant lymphoproliferative disorders (PTLDs) with high mortality rates. We performed a retrospective analysis in all consecutive adult and pediatric EBV reactivations and PTLD during a period of 8.5 years. There were 26 patients with EBV reactivation/PTLD out of a total of 854 transplantations giving an overall incidence of 3.0%. Specifically, the incidence of EBV-PTLD was 1.3%, whereas that of EBV reactivation was 1.8%. Median age was 46.0 and 11.0 years in the adult and pediatric patients, respectively. There were high rates (54%) of concomitant bacterial, viral, fungal and parasitic infections at the time of EBV manifestation. Variable treatment regimens were applied including in most cases an anti-CD20 regimen often in combination with virustatic compounds, polychemotherapy or donor lymphocytes. The mortality rates were 9 of 11 (82%) in patients with EBV-PTLD and 10 of 15 (67%) in patients with reactivation. Only 7 of 26 patients (27%) are alive after a median follow-up of 758 days (range 24-2751). The high mortality rates of EBV reactivation and of EBV-PTLD irrespective of multimodal treatment approaches emphasize standardization and optimization of post transplant surveillance and treatment strategies to improve control of these often fatal complications.

The ProCOUNT kit and software for semi-automated data acquisition and analysis represents a further step toward standardization of CD34 cell quantitation in peripheral blood progenitor cell apheresis products. However, the occurrence of software warnings is high, and analysis or data reevaluation by experienced staff is still mandatory. Therefore, currently there is no definite advantage of the kit and software over the existing guidelines for CD34+ analysis in peripheral blood progenitor cell grafts.

Summary Agents capable of reversing P-glycoprotein-associated multidrug resistance have usually failed to enhance chemotherapy activity in patients with solid tumours. Based on its toxicity profile and experimental potency, dexverapamil, the R-enantiomer of verapamil, is considered to be promising for clinical use as a chemosensitizer. The purpose of this early phase 11 trial was to evaluate the effects of dexverapamil on epirubicin toxicity, activity and pharmacokinetics in patients with metastatic breast cancer. A two-stage design was applied. Patients first received epirubicin alone at 120 mg m-2 i.v. over 15 min, repeated every 21 days. Patients with refractory disease continued to receive epirubicin at the same dose and schedule but supplemented with oral dexverapamil 300 mg every 6 h x 13 doses. The Gehan design was applied to the dexverapamil/epirubicin cohort of patients. Thirty-nine patients were entered on study, 25 proceeded to receive epirubicin plus dexverapamil. Dexverapamil did not increase epirubicin toxicity. The dose intensity of epirubicin was similar when used alone or with dexverapamil. In nine intrapatient comparisons, the area under the plasma concentration-time curve (AUC) of epirubicin was significantly reduced by dexverapamil (mean 2968 vs 1901 gg ml-1 h-1, P= 0.02). The mean trough plasma levels of dexverapamil and its major metabolite nor-dexverapamil were 1.2 and 1.5 gM respectively. The addition of dexverapamil to epirubicin induced partial responses in 4 of 23 patients evaluable for tumour response (17%, Cl 5-39%, s.e.,p 0.079). The remissions lasted 3, 8, 11 and 11 + months. These data suggest that the concept of enhancing chemotherapy activity by adding chemosensitizers may function not only in haematological malignancies but also in selected solid tumours. An increase in the AUC and toxicity of cytotoxic agents does not seem to be a prerequisite for chemosensitizers to enhance anti-tumour activity.

MCL is a relatively rare, but aggressive subtype of non-Hodgkin’s lymphoma. The current standard therapeutic approach for MCL combines rituximab–containing chemotherapy, followed by autologous stem cell transplantation. Using such approach, most patients will achieve complete remission (CR). However, almost all patients will experience relapse with MCL being an uncurable disease. With this background, and given its curative potential, reduced intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) may represent an attractive strategy in MCL. Here, we report a large multicenter retrospective analysis including 60 MCL patients who underwent RIC-allo-SCT. In this series, 43 patients were males. All patients but one, received at least one line of chemotherapy prior to RIC-allo-SCT including auto-SCT in 37 cases. The median number of previous therapies was 2 (range, 0–5). At time of RIC-allo-SCT, 26 patients were in CR, 20 in PR, while 14 were in stable/progressive or refractory disease. Median age at time of transplantation was 56 years (range, 33–67). Median time between diagnosis and transplantation was 3.5 years (range, 0.5–10). PBSCs were used in the majority of cases (n=56). HLA-identical sibling donors were used in 25 cases. HLA-mismatched or HLA-matched unrelated donors were used in the remaining 35 cases. Different RIC regimens were also used: fludarabine-busulfan-ATG in 17 cases, fludarabine and low-dose TBI in 10 cases, fludarabine-melphalan-ATG-rituximab in 6 cases, and other various regimens in 27 cases. In all, the RIC regimen included low-dose TBI in 14 cases, fludarabine in 56 cases and ATG in 34 cases. The median follow-up for surviving patients was 2 years (range, 0.1–8.5). Fifteen patients died of non-relapse-related causes, while 6 patients did not engraft. Disease-related deathes accounted for 6 cases. The 3-years OS estimate was 47% (95%CI, 31–60). According to disease status at transplantation, the 3-years OS estimates for patients who reached CR were 59% (95%CI, 34–77) as compared to 36%(95%CI, 8–65.5) for patients who reached PR and 17% (95%CI, 1– 49) for all others (P=0.001). According to disease status at transplantation (excluding those patients who failed to engraft), the 3-years EFS estimates for patients who reached CR were 68.5% (95%CI, 42–85) as compared to 45% (95%CI, 15–72) for patients who reached PR and 21% (95%CI, 1–57) for all others (P=0.005). Interestingly, the number of lines of chemotherapy administered prior to RIC-allo-SCT had no significant impact on OS and EFS Despite its retrospective nature, and the heterogeneity of the patients included in this analysis, these results suggest that RIC-allo-SCT may be an effective therapy in MCL, especially in those patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy.