Graft-versus-Host disease Prophylaxis with Everolimus and Tacrolimus Is Associated with a High Incidence of Sinusoidal Obstruction Syndrome and Microangiopathy: Results of the EVTAC Trial

AbstractA calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

18F-FDG-PET/CT for detection of extramedullary acute myeloid leukemia

Myeloid sarcoma in acute myeloid leukemia has been clearly defined by the World Health Organization but studies regarding the prevalence and the prognostic impact of extramedullary acute myeloid leukemia have not been conducted. We performed 18Fluoro-deoxy-Glucose Positron Emission Tomography/Computed Tomography scans in 10 patients with de novo and relapsed acute myeloid leukemia and histologically proven extramedullary disease. The scans were able to detect the known extramedullary lesions in 9 out of 10 patients (90%). Furthermore, additional extramedullary sites were detected in 6 patients (60%). Thus, it is possible to identify known and clinically undetectable extramedullary manifestations of acute myeloid leukemia. Since most of these patients relapsed within a short period of time after initiation of therapy or had refractory disease, the detection of extramedullary disease with 18Fluoro-deoxy-Glucose Positron Emission Tomography/Computed Tomography might be helpful in the development of individual treatment algorithms for these high-risk patients. (ClinicalTrials.gov Identifier: NCT01278069)

Genetic risk score and the risk of TPOAb-positivity.

<p>GRS, genetic risk score (based on rs11675434, rs653178, rs10944479, rs1230666, rs2010099).</p>a<p>Adjusted for age and gender</p

Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.

<p>Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.</p

Newly identified loci associated with TPOAb-positivity and/or serum TPOAb levels reaching genome wide significance.

<p>Chr., chromosome</p>a<p>Risk allele frequency: Weighted mean frequency of the risk allele across all included cohorts.</p>b<p>Adjusted for age and gender</p>c<p>Expressed in sd of natural logarithm transformed serum TPOAb level, adjusted for age and gender</p

Newly identified TPOAb associated loci and the risk of thyroid disease in stage 1 and 2 populations.

<p>All analyses adjusted for age and gender.</p><p><i>ATXN2</i>-rs653178 is in high LD with <i>SH2B3-</i> rs3184504</p><p><i>MAGI3-</i>rs1230666 is in high LD with <i>PTPN22-</i>rs2476601</p

Newly identified TPOAb associated loci, genetic risk scores and the risk of goiter.

<p>GRS, genetic risk score (based on rs11675434, rs653178, rs10944479, rs1230666, rs2010099).</p>a<p>Adjusted for age, gender, and body surface area.</p><p><i>ATXN2</i>-rs653178 is in high LD with <i>SH2B3</i>-rs3184504.</p><p><i>MAGI3</i>-rs1230666 is in high LD with <i>PTPN22</i>-rs24756601.</p