J M Pagel

..These data suggest that anti-CD45 PRIT using an anti-CD45-SA conjugate in a syngeneic murine model of disseminated leukemia may be more effective and less toxic than directly labeled monoclonal antibodies...

..These data suggest that pretargeted methods for delivering RIT may be superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities...

..Discussion of pre-clinical studies are limited to those that offer insights into future directions for clinical RIT studies of leukemia...

..Improvements in tumor-to-normal organ ratios of radioactivity cannot be achieved using directly labeled Abs in combination but may be afforded by novel pretargeting methods...

..We hypothesize that clinical implementation of pretargeted RIT methods will provide a meaningful prolongation of survival for patients with relapsed lymphomas compared with currently available treatment strategies...

..These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of acute myeloid leukemia...

..39-1.08; P = .09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and phase 2 results are sufficiently encouraging to warrant further study...

..This study was registered at www.clinicaltrials.gov as #NCT00008177...

..Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) is a transmembrane enzyme critical for the biosynthesis of phosphoglycerides whose product, phosphatidic acid, plays a key role in raf and AKT/mTor-mediated signal transduction...

..These lymphoma xenograft data suggest that pretargeted radioimmunotherapy using either anti-CD20 or anti-CD45 conjugates is highly effective and minimally toxic...

....

..CONCLUSION: These results suggest that anti-CD20 pretargeted RIT may be superior to conventional radiolabeled antibodies in terms of radioimmunoscintigraphy, toxicity, and therapeutic efficacy for treatment of B-cell lymphomas...

..More than 90% of lymphomabearing mice could be cured with minimal toxicity using either reagent followed by 1200 muCi (44.4 MBq) 90Y-DOTA-biotin...

..05). These results establish the efficacy of 4HPR/rituximab combinations, confirm their caspase-mediated mechanism of action, and offer the potential for disease control with minimal toxicity for patients with B-cell malignancies...

..While the reasons for the higher blood and liver concentrations are unknown, the differences in the galactose structures of the clearance agents 1 and 2 may play a role...

..Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy...

..This study highlights the importance of screening the antigenic expression on lymphomas to select the optimal reagent for PRIT...

..5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma, and successfully mobilizes PBSCs...

..These promising results have prompted large-scale cGMP production of the BC8 fusion protein for clinical trials to be conducted in patients with hematologic malignancies...

..The data suggest that smaller quantities of (211)At-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less nonhematologic toxicity compared with (213)Bi-labeled antibody...

..We explored the utility of HDT and ASCT for chemoresistant HL because there are few established therapies for these patients...

..5 days, P < .001) compared with controls. These data indicate that the high CD45 expression of T-NHL allows reliable tumor targeting and disease control supporting anti-CD45 RIT for T-NHL patients...

..The rationale for incorporation of radioimmunotherapy into reduced intensity allogeneic transplantation regimens for non-Hodgkin lymphoma is discussed, as are current study designs, preliminary results, and future directions...

..To evaluate outcomes of ablative allogeneic hematopoietic cell transplantation (HCT) in older patients with hematologic malignancies...

..In this report we review clinical studies that have incorporated myeloablative doses of targeted radiation using radiolabeled antibodies in conjunction with stem cell transplant regimens...

..16 (0.52-2.61), P=0.71). These data indicate that URD HCT can provide long-term survival for CR1 AML; outcomes for 10/10 URD HCT, and possibly 9/10 URD HCT, suggest that this modality should be considered in the absence of a suitable MRD...

..52, P=0.03), chemoresistance (HR=1.82, P=0.02), > or =2 prior therapies (HR=1.8, P=0.03) and prior radiation (HR=1.99, P=0.003). These data suggest that the histologic grade of FL does not impact PFS or relapse following HDT and ASCT...

..We evaluated the organ localization of yttrium-90-labeled anti-CD45 ((90)Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD45 ((131)I-anti-CD45) antibody biodistribution in humans...

..These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at www.clinicaltrials.gov as #NCT00012207...

..With continued research, PRIT-based treatment strategies promise to become cornerstones to improved outcomes for cancer patients despite their complexities...

..Hitherto, little attention has been given to the prognostic impact of pretransplantation minimal residual disease (MRD)...

..These data suggest that further study of this antibody combination for clinical use in AML is warranted...

..These results support proceeding to anti-CD45 PRIT clinical trials for patients with both leukemia and lymphoma...

..We are optimistic that this novel approach will provide a meaningful prolongation of survival for patients with relapsed or refractory lymphomas...

....

..However, for patients with intermediate-risk disease, transplantation with peripheral blood from a 10/10 MUD is associated with lower survival than an MSD...

..D. Anderson prognostic score. The data suggest that patients with few or no comorbidities and those who undergo transplantation earlier in the disease course have the highest probability of successful outcome after allogeneic HCT...

....

..82, p = 0.03) after adjusting for FLIPI. These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT...

..We examined an "extracorporeal adsorption therapy" (ECAT) method to remove circulating unbound radioimmunoconjugate and improve the ratios of radiation delivered to B-cells in a macaque model...

..These studies add further information to the regulation of programmed cell death in leukemic cells that have to be considered when designing therapeutic strategies...

..abstract_text> ..

..We anticipate that these approaches will cure more patients and cause fewer toxicities than currently available therapies. ..