Unrelated Cord Blood Transplantation for Acute Leukemia Diagnosed in the First Year of Life: Outcomes and Risk Factor Analysis

Infant acute leukemia still has a poor prognosis, and allogeneic hematopoietic stem cell transplantation is indicated in selected patients. Umbilical cord blood (UCB) is an attractive cell source for this population because of the low risk of chronic graft-versus-host disease (GVHD), the strong graft-versus-leukemia effect, and prompt donor availability. This retrospective, registry-based study reported UCB transplantation (UCBT) outcomes in 252 children with acute lymphoblastic leukemia (ALL; n = 157) or acute myelogenous leukemia (AML; n = 95) diagnosed before 1 year of age who received a single-unit UCBT after myeloablative conditioning between 1996 and 2012 in European Society for Blood and Marrow Transplantation centers. Median age at UCBT was 1.1 years, and median follow-up was 42 months. Most patients (57%) received a graft with 1 HLA disparity and were transplanted in first complete remission (CR; 55%). Cumulative incidence function (CIF) of day 100 acute GVHD (grades II to IV) was 40% ± 3% and of 4-year chronic GVHD was 13% ± 2%. CIF of 1-year transplant-related mortality was 23% ± 3% and of 4-year relapse was 27% ± 3%. Leukemia-free-survival (LFS) at 4 years was 50% ± 3%; it was 40% and 66% for those transplanted for ALL and AML, respectively (P = .001). LFS was better for patients transplanted in first CR, regardless of diagnosis. In multivariate model, diagnosis of ALL (P = .001), advanced disease status at UCBT (<.001), age at diagnosis younger than 3 months (P = .012), and date of transplant before 2004 were independently associated with worse LFS. UCBT is a suitable option for patients diagnosed with infant acute leukemia who achieve CR. In this cohort, patients with AML had better survival than those with ALL

Efficient solution of nonlinear models expressed in S-system canonical form

The S-system is emerging as a general canonical form for analysis of nonlinear models. Models expressed within this regularly structured system of nonlinear ordinary differential equations are obtained by applying either of two different strategies: (A) Direct derivation of an S-system utilizing the Power Law Formalism; or (B) exact recasting of an existing, well established model into S-system form. By capitalizing on the regular structure of S-systems, efficient formulas for numerical solution of this general class have been developed. For any S-system it can be shown that these formulas are more efficient than conventional multistep formulas of the same order. For implemented methods, the actual improvements in efficiency are considerably more than the minimum estimates. Preliminary tests show that time required for solution of S-systems is reduced by one or two orders of magnitude -- the relative improvement in efficiency increases with size and complexity of the problem, and with degree of accuracy required.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27485/1/0000528.pd

Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.This study was partially supported by grant no. SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain

HLA identical related cord blood transplantation for patients with transfusion-dependent thalassemia and sickle cell disease

48th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT) -- MAR 19-23, 2022 -- CZECH REPUBLIC[No Abstract Available]European Soc Blood ; Marrow Transplanta

The melatonin analog IQM316 may induce adult hippocampal neurogenesis and preserve recognition memories in mice

Neurogenesis in the adult hippocampus is a unique process in neurobiology that requires functional integration of newly generated neurons, which may disrupt existing hippocampal network connections and consequently loss of established memories. As neurodegenerative diseases characterized by abnormal neurogenesis and memory dysfunctions are increasing, the identification of new anti-aging drugs is required. In adult mice, we found that melatonin, a well-established neurogenic hormone, and the melatonin analog 2-(2-(5-methoxy-1H-indol-3-yl)ethyl)-5-methyl-1,3,4-oxadiazole (IQM316) were able to induce hippocampal neurogenesis, measured by neuronal nuclei (NeuN) and 5-bromo-2¿-deoxyuridine (BrdU) labeling. More importantly, only IQM316 administration was able to induce hippocampal neurogenesis while preserving previously acquired memories, assessed with object recognition tests. In vitro studies with embryonic neural stem cells replicated the finding that both melatonin and IQM316 induce direct differentiation of neural precursors without altering their proliferative activity. Furthermore, IQM316 induces differentiation through a mechanism that is not dependent of melatonergic receptors (MTRs), since the MTR antagonist luzindole could not block the IQM316-induced effects. We also found that IQM316 and melatonin modulate mitochondrial DNA copy number and oxidative phosphorylation proteins, while maintaining mitochondrial function as measured by respiratory assays and enzymatic activity. These results uncover a novel pharmacological agent that may be capable of inducing adult hippocampal neurogenesis at a healthy and sustainable rate that preserves recognition memories.The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: This study was supported by grants from the Instituto de Salud Carlos III (FIS2015/ 00780), FEDER, and CIBERNED and awarded to E. Carro. M. I. Rodríguez-Franco gratefully acknowledges the financial support of the Spanish Ministry of Economy and Competitiveness (MINECO, Grants SAF2015-64948-R and SAF2012-31035, partially financed by FEDER funds) and CSIC (Grant PIE-201580E109). M.F.R. thanks the JAE-Predoctoral Contract (Grant JAE-Pre-2009-106) cofinanced by the CSIC and the European Social Fund. D. Acuña-Castroviejo also acknowledges grants from the Instituto de Salud Carlos III, Spain (RD12/0043/0005, PI13-981) and from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain (P07-CTS-03135).Peer Reviewe

Chronic graft-versus-host disease features in double unit cord blood transplantation according to National Institutes of Health 2005 cGVHD Consensus criteria

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease