A recent issue of Bone Marrow Transplantation included the results of a clinical trial from Minnesota of 15 pediatric patients who were transplanted with umbilical cord blood in combination with pre-expanded MSCs in an attempt to accelerate hematopoietic recovery.1 According to our present understanding, MSCs, osteoblasts and other stromal cells, including sinusoidal and endothelial, are responsible for supporting hematopoiesis and controlling HSC number. Therefore a co-transplantation of these cells, together with HSC, can be more effective in the reconstitution of hematopoiesis. This approach is especially attractive for cases with a predicted poor engraftment due to both an insufficient number of transplanted HSCs or impaired stroma.

After allogeneic hematopoietic SCT (alloHSCT), immunosuppressed patients are susceptible to opportunistic infections, and uncontrolled function of the graft can result in GVHD. Accurate immune monitoring may help early detection and treatment of these severe complications. Between October 2005 and November 2007, a total of 170 blood samples were collected from 40 patients after alloHSCT in the Hadassah Hebrew University Medical Center and from 13 healthy controls. We utilized the Cylex ImmuKnow assay for CD4 ATP levels to compare known clinically immunocompromised vs immunocompetent patients after alloHSCT. We also compared the reconstitution of WBC count to the ImmuKnow results and clinical status. The patients' clinical course correlated with the stratification of immune response established by the ImmuKnow assay for solid organ transplantation (immunocompetent vs immunocompromised), and this often differed from their WBC count. On the basis of our observations, we conclude that the ImmuKnow assay is a simple and fast immune-monitoring technique for patients undergoing alloHSCT, with potential to predict clinical course and facilitate prompt management of post-HSCT complications. The assay should be evaluated prospectively in clinical trials.

Background: Despite diagnostic and therapeutic advances, cytomegalovirus (CMV) has remained a significant complication after hematopoietic stem cell transplantation (HSCT). The widespread use of preemptive antiviral therapy has reduced the occurrence of early CMV disease and changed its epidemiology. In order to define the current trends and to establish future guidelines, we retrospectively analyzed the rate of CMV infection and disease in the following types of HSCT:

The influence of graft composition on the outcome of reduced-intensity (RIC) allogeneic PBSC transplantation (allo-PBSC) remains controversial. In this study, we analyzed the impact of CD34+ cell dose on the incidence of GVHD, and on the outcome after allo-PBSC, in 103 patients with hematological malignancies, using a uniform RIC regimen. The following variables were included in statistical analysis: (1) number of C34+ cells, (2) high-risk vs low-risk disease status, (3) matched related vs matched unrelated donor, (4) female donor to male recipient vs any other combination, (5) age of recipient (above vs below the median). Univariate and multivariate analysis did not reveal any association between CD34+ cell dose and acute grade-2 to grade-4, cGVHD, non-relapse mortality (NRM), relapse rate (RR) and OS. High-risk disease status was the only variable independently associated with increased NRM (P=0.001), increased RR (P=0.012) and decreased OS (P<0.001). The same results were obtained when analysis was restricted to a subgroup of 55 patients with myeloid neoplasms. The influence of graft composition on the outcome of RIC allo-PBSC should be further investigated via well-controlled randomized prospective studies.

21175 Background: Graft-versus-leukemia and graft-versus-tumor (GVT) effects following stem cell transplantation are well established, however, procedure related toxicity and mortality are unavoidable. In addition to limited efficacy following stem cell transplantation (SCT), graft-versus-host disease (GVHD) is unavoidable. Our protocol was designed to induce more potent anti-cancer immunotherapy by rIL-2 activated intentionally mismatched donor lymphocytes (MDL) at the stage of minimal residual disease (MRD) outpatient procedure with no SCT avoiding GVHD. Methods: Optimizing MDL was accomplished by cyclophosphamide 1,500 mg/m2 and 2 injections of alpha interferon (3x106IU) for more effective immunotherapy, aiming for depletion of regulatory T cells, followed by infusion of haploidentically mismatched lymphocytes activated with rIL-2 (6,000 IU/ml) for 4 days. On the day of cell infusion, patients received rIL-2 6x106 IU subcutaneously outpatient for 5 days. Results: A total of 41 (age 5–73, median 52) high risk patients were included: metastatic breast 13; colorectal 3; gastric 3; pancreatic 3; melanoma 3; head & neck 3; glioblastoma 2; and 6 with other solid tumors. Five patients had resistant hematological malignancies: multiple myeloma 2; non-Hodgkin's lymphoma 2 and Hodgkin's disease 1. 6 patients received lymphocytes with bispecific antibodies for targeted cell-therapy (3 with catumaxomab against CD3 & epithelial cell adhesion molecule (EpCAM); 3 with ertumaxomab directed against CD3 & Her-2/neu WHO toxicity >grade 2 was noted. 14 of evaluable patients are alive. 10/32 with solid tumors are alive, 7 with no evidence of disease > 9–91 (median 17) months (4 breast; 1 squamous cell; 1 head & neck; 1 prostate). Of 5 patients with hematological malignancies 4 are alive and disease free >18–96 (median 46) months. Conclusions: Safe induction of GVT effects may be accomplished by MDL, preferably targeted with bispecific antibodies after cyclophosphamide conditioning lymphocytes are more potent and act faster than matched lymphocytes and GVHD is avoided by rejection of donor lymphocytes. When applied at a stage of MRD, such treatment may result in operational cure. No significant financial relationships to disclose.

The only radical cure for thalassemia major patients today is the replacement of the defective hematopoietic system by allogeneic stem cell transplantation (allo-SCT). The major obstacles for the application of allo-SCT even from matched family members have been the transplant-related morbidity and mortality and graft failure that is usually associated with the recurrence of the thalassemia hematopoiesis. The outcome of allo-SCT from HLA-identical family donors is largely dependent on the age of the recipient as well as on pretransplant parameters reflecting the degree of organ damage from iron overload. In this study we report our experience of allo-SCT from matched related and unrelated donors, using a reduced toxicity conditioning consisting of fludarabine, busulfan or more recently busulfex and antithymocyte globulin, in a cohort of 20 patients with thalassemia major. The regimen-related toxicity was minimal, while the incidence of acute grade II–IV and chronic GVHD was 25 and 25%, respectively. With a median follow-up period of 39 months (range: 5–112 months) the overall survival was 100%, while thalassemia-free survival was 80%. Although the results of our study look promising, larger cohorts of patients and prospective clinical trials are required to confirm the benefits of our approach as a possible better alternative to the existing protocols.