A complete list of definite, as well as possible, indications for hemopoietic stem cell transplantation in primary immunodeficiency is provided. Included are: severe combined immunodeficiency, ...profound T cell defects, autoimmune and autoinflammatory syndromes, innate immune defects, hemophagocytic disorders, and other conditions. Some causes and limitations are included.
Summary Background In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by ...graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. Methods This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0–40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m2 infants <9 kg 1·2 mg/kg; one dose per day on days −8 to −3), serotherapy (anti-thymocyte globulin 10 mg/kg, one dose per day on days −4 to −1; or thymoglobuline 2·5 mg/kg, one dose per day on days −5 to −3; or low-dose alemtuzumab <1 mg/kg on days −8 to −6), and low-dose (50–72% of myeloablative dose) or targeted busulfan administration (recommended cumulative area under the curve: 45–65 mg/L × h). Busulfan was administered mainly intravenously and exceptionally orally from days −5 to −3. Intravenous busulfan was dosed according to weight-based recommendations and was administered in most centres (ten) twice daily over 4 h. Unmanipulated bone marrow or peripheral blood stem cells from HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. Results 56 patients (median age 12·7 years; IQR 6·8–17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14–39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16–22) for neutrophils and 21 days (IQR 16–25) for platelets. At median follow-up of 21 months (IQR 13–35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86·46–99·09) and of EFS was 91% (79·78–96·17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III–IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (≥90%) myeloid donor chimerism was documented in 52 (93%) surviving patients. Interpretation This reduced-intensity conditioning regimen is safe and efficacious in high-risk patients with chronic granulomatous disease. Funding None.
The aim of this study was to evaluate the accuracy of dual-echo (DE) magnetic resonance imaging (MRI) with and without fat and water separation for the quantification of liver fat content (LFC) in ...vitro and in patients undergoing liver surgery, with comparison to histopathologic analysis.
MRI was performed on a 1.5-T scanner using a three-dimensional DE MRI sequence with automated reconstruction of in-phase (IP) and out-of-phase (OP) and fat-signal-only and water-signal-only images. LFC was estimated by fat fractions from IP and OP images (MRI(IP/OP)) and from Dixon-based fat-only and water-only images (MRI(DIxON)). Seven phantoms containing a titrated mixture of liver and fat from 0% to 50% were examined. Forty-three biopsies in 22 patients undergoing liver surgery were prospectively evaluated by a pathologist by traditional determination of the cell-count fraction and by a computer-based algorithm, the latter serving as the reference standard.
In vitro, both MRI(IP/OP) and MRI(DIxON) were significantly correlated with titrated LFC (r = 0.993, P < .001), with a smaller measurement bias for MRI(IP/OP) (+2.6%) than for MRI(DIxON) (+4.5%). In vivo, both MRI(IP/OP) and MRI(DIxON) from DE MRI were correlated significantly better with computer-based histologic results (P < .001) and showed significantly smaller measurement bias (4.8% vs 21.1%) compared to histologic cell-count fraction (P < .001). Measurement bias was significantly smaller for MRI(IP/OP) than for MRI(DIxON) (P < .001).
DE MRI allows the accurate quantification of LFC in a surgical population, outperforming traditional histopathologic analysis. DE MRI without fat and water separation shows the highest accuracy and smallest measurement bias for the quantification of LFC.
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