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To determine whether in vivo T-cell depletion, which lowers GVHD, abrogates the antileukemic benefits of myeloablative total body irradiation–based conditioning and unrelated donor transplantation, in the present study, we analyzed 715 children with acute lymphoblastic leukemia. Patients were grouped for analysis according to whether conditioning included antithymocyte globulin (ATG; n = 191) or alemtuzumab (n = 132) and no in vivo T-cell depletion (n = 392). The median follow-up time was 3.5 years for the ATG group and 5 years for the alemtuzumab and T cell–replete groups. Using Cox regression analysis, we compared transplantation outcomes between groups. Compared with no T-cell depletion, grade 2-4 acute and chronic GVHD rates were significantly lower after in vivo T-cell depletion with ATG (relative risk [RR] = 0.66; P= .005 and RR = 0.55; P< .0001, respectively) or alemtuzumab (RR = 0.09; P< .003 and RR = 0.21; P< .0001, respectively). Despite lower GVHD rates after in vivo T-cell depletion, nonrelapse mortality, relapse, overall survival, and leukemia-free survival (LFS) did not differ significantly among the treatment groups. The 3-year probabilities of LFS after ATG-containing, alemtuzumab-containing, and T cell–replete transplantations were 43%, 49%, and 46%, respectively. These data suggest that in vivo T-cell depletion lowers GVHD without compromising LFS among children with acute lymphoblastic leukemia who are undergoing unrelated donor transplantation with myeloablative total body irradiation–based regimens.

There is no consensus about the best donor for children with non-malignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We now evaluate the 2-year Overall Survival after Umbilical Cord Blood Transplantation (UCBT) in patients with non-malignant disorders from 2009-2020 enrolled on a prospective clinical trial using either 5/6 or 6/6 umbilical cord blood as cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. 55 children were enrolled, median age 5 mo. (range, 1–111 mo.); PID (45), metabolic (5), HLH (1), and hematologic disorders (4). Twenty-six patients had persistent infections prior to transplant. 19 (34%) were 6/6 matched, 36 (66%) were 5/6 HLA matched. The overall survival (OS) at 2 years was 91% (95% CI:79-96%) with a median follow up of 4.3 years. The median time to neutrophil and platelet recovery were 17 days (range,5-39 days) and 37 days (range,20-92 days), respectively. All but one evaluable patient achieved full donor chimerism. The cumulative incidence of aGvHD grade II-IV by day 100 was 16% (n=9). All patients with viral infections at the time of transplant cleared the infection at a median time of 54 days (range, 44-91 days). All evaluable patients have had correction of their immune or metabolic defect. We conclude that in the absence of a MRD, UCBT following myeloablative conditioning without serotherapy is an excellent curative option in young children with non-malignant disorders. This trial is registered at www.clinicaltrials.govas NCT00950846.

Pleasures and Sufferings of Different World: The Novels of Adam ZameenzadPaul Scott: Conflicts and ObsessionsHaroun and the Sea of Stories Salman Rushdie (Granta, 1990), hb. £12.99How Many Miles to Babylon?, Adewale Maja-Pearce (Heinemann, 1990) hb. £13.95Isara: A Voyage Around 'Essay', Wole Soyinka (Methuen, 1990), hb. £12.99Chinua Achebe. Cambridge Studies in African and Caribbean Literature, 1, C.L. Innes (Cambridge University Press, 1990), hb. £25Sunshine and Shadow: A Caribbean Anthology, eds. Roy and Clifford Narinesingh (Cassell, 1980, reprinted 1981, 1986)Squeeze Words Hard: Poetry for Gcse, eds. Maureen Alcorn and Amanda Ebborn (Longman 1990)De Home Place: Poems for Renewal by Young People of Caribbean Origin, ed. Abdul Malik (Panrun Collective, 1990) pb. £3.95Stories From South Asia, ed. John Welch (Oxford University Press, 1989), pb. £3.95Crisis and Creativity in New Literatures in English, (Editions Rodopi B.V.)Cross/Cultures 1: Readings in Post/Colonial Literature, ed. Geoffrey Davis and Hena Maes-Jelinek (hb., Dutch fl. 150)Cross/Cultures 2: Canada, ed. Geoffrey Davis (pb., Dutch fl. 35)Cross/Cultures 3: Contents of African Literature, ed. Albert Gerard (pb., Dutch fl. 70)

Anisotropy of anhysteretic susceptibility (AAS) is a recently developed high-resolution method of measuring the magnetic fabric of rocks. In order to test the applicability and limitations of AAS for estimation of strain orientations in weakly-deformed and weakly magnetic rocks, we have used the method to examine the magnetic fabric of samples from a series of sites in limestones of the Helderberg and Onondaga formations along a 500-km E-W transect across New York State. Two distinct shortening directions have been previously identified and interpreted in terms of two separate phases of Alleghenian deformation. Over most of the transect, minimum anhysteretic susceptibility axes within the plane of bedding closely parallel the compression direction of the earlier (“Lackawanna”) phase. A few sites show minimum anhysteretic susceptibility parallel to the later (“Main”) phase. The threshold for resolution of the tectonic signal by AAS is at anhysteretic susceptibilities of about 2 × 10 −5(SI) and strain magnitudes of 0.5 to 1% as recorded by twinning in calcite. The central part of the transect exhibits minimum horizontal anhysteretic susceptibility perpendicular to the inferred tectonic compression, rather than parallel to it. We attribute this to either: (a) anisotropic transmission of stresses from the larger calcite matrix grains to the smaller magnetite grains during twinning; or (b) preferential recording of a late-stage non-coaxial stress direction in this area by late diagenetic magnetite.

A single injection of isolated fragments of group A streptococcal cell walls into the joints of rabbits stimulated an initial acute reaction which was followed by a prolonged inflammatory process. The chronic process was characterized by hyperplasia of the synovial cells, diffuse infiltration of the villi by macrophages, and focal collections of lymphocytes in the stroma of the villi. These histological changes were similar to those seen in the early stages of rheumatoid arthritis. Antibodies specific for the mucopeptide and group-specific C polysaccharide antigens of group A streptococcal cell walls were labeled with either fluorescein or 125I, and were used to demonstrate antigen in the synovial tissues. The antigens persisted within macro-phages for at least 5 weeks. Their presence correlated with the evolution of the chronic inflammatory process.

A single intraperitoneal injection of a sterile extract of sonically disrupted group A streptococcal cells induced an inflammatory process in the hearts of mice. The cardiac lesions, in terms of their distribution and histological features, are similar to the cardiac lesions of rheumatic fever.

High risk or relapsed pediatric acute myeloid leukemia (AML) is potentially curable with allogeneic hematopoietic stem cell transplantation (HSCT). The use of a matched related donor (MRD) is the standard of care for these patients, but in the majority of patients a MRD is not available. Significant improvements have been made with supportive care practices, but there are limited outcome data for AML in pediatric patients transplanted in the contemporary era. We report retrospective results of HSCT in eighty-seven pediatric patients with high risk or relapsed AML performed at a single institution between 2008 and 2018.

Mechanical and thermal property values of carbon fiber-reinforced polymer (CFRP) composites are readily available. However, the small diameter and thermal anisotropy of the carbon filaments pose significant challenges for measuring thermal diffusivity of the constituent fibers. As a result, the literature describes many techniques to address this issue. Here, a new method for the direct, bulk measurement of on-axis thermal diffusivity of a matrix-free carbon fiber bundle is reported. Aligned carbon fiber tows were uniformly compacted into a collimated, cylindrical bundles using heat-shrink tubing, and fixed such that the fibers remained unwetted, in the center of an epoxy disk, which was subsequently analyzed for thermal diffusivity using laser flash analysis.

Off Label Use: IND cell therapy product.

We have previously demonstrated that hematological malignancies contain a distinct “side-population” (SP), which is characterized by the active transport of Hoechst fluorescent dye. The mechanisms responsible for Hoechst efflux also contribute to resistance of the SP to chemotherapy. This population has also been shown to be enriched for tumor initiating cells in several human cancer models. We hypothesize that targeting the cancer “SP” cells using immunotherapy may prevent relapse by eliminating the cell population that: is least sensitive to chemotherapy and has tumor repopulating potential. In this study we characterized SP cells in ten human lymphoma cell lines. Five of the 11 lymphoma cell lines tested (HDLM2, L428, Ramos, Toledo, Karpas) had a distinct SP ranging from 0.8–2% of total cells. We subsequently found SP cells with tumor associated markers in biopsy samples from patients with Hodgkin’s Lymphoma, T-cell Lymphoma, and Follicular lymphoma. Culture of the sorted cell lines show that SP but not the non-SP cells produced progeny that were both SP and non-SP cells. Gene expression analysis of the SP showed increased expression of ABCG2 and other ABC transporters that mediate both the transport of Hoechst dye and selected chemotherapeutic agents out of the cell. We evaluated whether lymphoma cell lines with an SP are resistant to the chemotherapeutic drug gemcitabine. The viability of lymphoma lines containing SP cells was significantly higher (mean 59.8%; range 37.4–87.8%%) than the viability of lines without an SP (mean 9.3% range 3.0%–12.2%) when cultured with 10nM gemcitabine for 3 days. The SP component of the lymphoma cells became enriched 10 fold when cultured with gemcitabine. Furthermore, when equal numbers of SP and non-SP cells were grown in separate fractions with gemcitabine, there was reduced viability of the non-SP (2,247 +/−294 mean counts per minute (cpm)) by thymidine assay. In contrast, the viability of the SP was preserved (13,200 +/− 7500 mean cpm). There was no difference in the viability between the untreated SP and Non SP, so that the gemcitabine rather than the Hoechst dye accounts for the differences in viability. Although lymphoma SP cells are resistant to chemotherapeutic agents, they also express higher levels of tumor associated antigens that are known targets for cytotoxic T cells. Hence RT-PCR and immunohistochemistry both show that SP cells are HLA positive and have increased expression of MAGE-4, SSX2, Survivin and NY-ESO transcripts and protein compared to non-SP cells from the same tumor. In IFNγ ELISPOT assays, we have shown that T cells secrete IFNγ in response to SP targets. Hence, lymphoma cell lines and primary lymphoma tissue contain chemotherapy-resistant SP cells which express tumor associated antigens and may be targeted by specific T cells.