Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia

Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) in adults, data on safety and efficacy in pediatric patients are scarce. We report the use of InO in 51 children with relapsed/ refractory ALL treated in the compassionate use program. In this heavily pretreated cohort, complete remission was achieved in 67% of patients with overt marrow disease. The majority (71%) of responders were negative for minimal residual disease. Responses were observed irrespective of cytogenetic subtype or number or type of prior treatment regimens. InO was welltolerated; grade 3 hepatic transaminitis or hyperbilirubinemia were noted in 6 (12%) and grade 3/4 infections in 11 (22%) patients. No patient developed sinusoidal obstruction syndrome (SOS) during InO therapy; however, 11 of 21 (52%) patients who underwent hematopoietic stem cell transplantation (HSCT) following InO developed SOS. Downregulation of surface CD22 was detected as a possible escape mechanism in three patients who developed a subsequent relapse after InO. We conclude that InO is a well-tolerated, effective therapy for children with relapsed ALL and prospective studies are warranted. Identification of risk factors for developing post-HSCT SOS and strategies to mitigate this risk are ongoing

Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and advances in its clinical and laboratory biology have grown exponentially over the last few decades. Treatment outcome has improved steadily with over 90% of patients surviving 5 years from initial diagnosis. This success can be attributed in part to the development of a risk stratification approach to identify those subsets of patients with an outstanding outcome that might qualify for a reduction in therapy associated with fewer short and long term side effects. Likewise, recognition of patients with an inferior prognosis allows for augmentation of therapy, which has been shown to improve outcome. Among the clinical and biological variables known to impact prognosis, the kinetics of the reduction in tumor burden during initial therapy has emerged as the most important prognostic variable. Specifically, various methods have been used to detect minimal residual disease (MRD) with flow cytometric and molecular detection of antigen receptor gene rearrangements being the most common. However, many questions remain as to the optimal timing of these assays, their sensitivity, integration with other variables and role in treatment allocation of various ALL subgroups. Importantly, the emergence of next generation sequencing assays is likely to broaden the use of these assays to track disease evolution. This review will discuss the biological basis for utilizing MRD in risk assessment, the technical approaches and limitations of MRD detection and its emerging applications

Archaeological Investigations at 45CL1 Cathlapotle (1991-1996) , Ridgefield National Wildlife Refuge Clark County, Washington: a Preliminary Report

This is the preliminary report, one in a series on the archaeology of the Wapato Valley region of the Lower Columbia River. Most of the reports discuss aspects of the excavations and archaeology of two sites, the Meier site (35CO5) and Cathlapotle site (45CL1). Other related topics are also treated. Archaeological investigations at site 45CL1, Clark County, Washington, demonstrate that the locality is a very large (c 1.5ha), deeply stratified (2-4m) town site with an occupation spanning at least 1000 years (c. AD 1000 to 1840). Six large, complex depressions have been mapped. Test excavations show that these depressions represent the semisubterranean portions of residential structures, probably large plankhouses of the type common on the Lower Columbia River and the Northwest Coast in aboriginal times. The depressions may represent as many as 11 such dwellings. A seventh depression is deeply buried beneath midden deposits. The cultural deposits contain very high densities of artifacts, ecofacts (including both faunal and floral remains), debris and features. The site is near the Columbia River on a very active flood plain, resulting in site stratigraphy produced by a combination of active cultural and alluvial depositional processes. Site 45CL1, given its location and size, is the best candidate to be the site of Cathlapotle, a Middle Chinookan town visited by Lewis and Clark in 1806, as well as by other early Europeans in the area. The site is extraordinarily well preserved, having undergone only minor alterations since its abandonment, probably in the third or fourth decade of the 19th century AD