Diagnosis and classification of acute myeloid leukemia (AML) are based on morphology and genetics. An increasing number of gene mutations have been found, and some are used for risk classification in ...AML patients with normal karyotype (cytogenetically normal (CN)-AML). In this systematic review and meta-analysis, we examined three frequent mutations in CN-AML: mutations of
fms
-related tyrosine kinase 3 (
FLT3-ITD
), mutated nucleophosmin (
NPM1
), and mutations of the CCAAT enhancer-binding protein alpha (
CEBPA
) gene. A systematic literature search of publications listed in the electronic databases (Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge and Cochrane) from 2000 up to March 2012 was performed (Fig.
1
). Nineteen studies were included and qualitatively analyzed. Two to four studies entered the quantitative meta-analysis incorporating 1,378 to 1,942 patients with CN-AML. Meta-analysis for overall survival (OS) and relapse-free survival (RFS) showed
FLT3
-ITD to predict an unfavorable prognosis, with hazard ratios (HR) of 1.86 and 1.75, respectively. In contrast, meta-analysis of the impact of
NPM1
and
CEBPA
mutations on OS yielded an HR of 0.56 for each mutation, while analysis of impact on RFS produced HRs of 0.37 and 0.42, respectively. This systematic review and meta-analysis aimed to evaluate the prognostic value of mutations in the
NPM1
,
CEBPA
, and
FLT3
genes.
FLT3
-ITD was associated with worse prognosis, whereas mutations in
NPM1
and
CEBPA
genes were associated with a favorable prognosis.
This review summarises the present state of research on health inequalities using a social network perspective, and it explores the available studies examining the interrelations of social ...inequality, social networks, and health.
Using the strategy of a scoping review, as outlined by Arksey and O'Malley (Int J Sci Res Methodol 8:19-32, 2005), our team performed two searches across eight scientific, bibliographic databases including papers published until October 2021. Studies meeting pre-defined eligibility criteria were selected. The data were charted in a table, and then collated, summarised, and reported in this paper.
Our search provided a total of 15,237 initial hits. After deduplication (n = 6,168 studies) and the removal of hits that did not meet our baseline criteria (n = 8,767 studies), the remaining 302 full text articles were examined. This resulted in 25 articles being included in the present review, many of which focused on moderating or mediating network effects. Such effects were found in the majority of these studies, but not in all. Social networks were found to buffer the harsher effects of poverty on health, while specific network characteristics were shown to intensify or attenuate the health effects of social inequalities.
Our review showed that the variables used for measuring health and social networks differed considerably across the selected studies. Thus, our attempt to establish a consensus of opinion across the included studies was not successful. Nevertheless, the usefulness of social network analysis in researching health inequalities and the employment of health-promoting interventions focusing on social relations was generally acknowledged in the studies. We close by suggesting ways to advance the research methodology, and argue for a greater orientation on theoretical models. We also call for the increased use of structural measures; the inclusion of measures on negative ties and interactions; and the use of more complex study designs, such as mixed-methods and longitudinal studies.
Increasing numbers of patients are receiving reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation. We hypothesized that the use of bone marrow graft might ...decrease the risk of graft-versus-host disease compared to peripheral blood after reduced intensity conditioning regimens without compromising graft-versus-leukemia effects. Patients who underwent reduced intensity conditioning regimen allogeneic hematopoietic stem cell transplantation from 2000 to 2012 for acute leukemia, and who were reported to the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation were included in the study. Eight hundred and thirty-seven patients receiving bone marrow grafts were compared with 9011 peripheral blood transplant recipients after reduced intensity conditioning regimen. Median follow up of surviving patients was 27 months. Cumulative incidence of engraftment (neutrophil ≥0.5×10(9)/L at day 60) was lower in bone marrow recipients: 88% versus 95% (P<0.0001). Grade II to IV acute graft-versus-host disease was lower in bone marrow recipients: 19% versus 24% for peripheral blood (P=0.005). In multivariate analysis, after adjusting for differences between both groups, overall survival Hazard Ratio (HR) 0.90; P=0.05 and leukemia-free survival (HR 0.88; P=0.01) were higher in patients transplanted with peripheral blood compared to bone marrow grafts. Furthermore, peripheral blood graft was also associated with decreased risk of relapse (HR 0.78; P=0.0001). There was no significant difference in non-relapse mortality between recipients of bone marrow and peripheral blood grafts, and chronic graft-versus-host disease was significantly higher after peripheral blood grafts (HR 1.38; P<0.0001). Despite the limitation of a retrospective registry-based study, we found that peripheral blood grafts after reduced intensity conditioning regimens had better overall and leukemia-free survival than bone marrow grafts. However, there is an increase in chronic graft-versus-host disease after peripheral blood grafts. Long-term follow up is needed to clarify whether chronic graft-versus-host disease might increase the risk of late morbidity and mortality.
To evaluate prognostic factors for relapse-free survival (RFS) and overall survival (OS) and to assess the impact of different postremission therapies in adult patients with core binding factor (CBF) ...acute myeloid leukemias (AML).
Individual patient data-based meta-analysis was performed on 392 adults (median age, 42 years; range, 16 to 60 years) with CBF AML (t(8;21), n = 191; inv(16), n = 201) treated between 1993 and 2002 in prospective German AML treatment trials.
RFS was 60% and 58% and OS was 65% and 74% in the t(8;21) and inv(16) groups after 3 years, respectively. For postremission therapy, intention-to-treat analysis revealed no difference between intensive chemotherapy and autologous transplantation in the t(8;21) group and between chemotherapy, autologous, and allogeneic transplantation in the inv(16) group. In the t(8;21) group, significant prognostic variables for longer RFS and OS were lower WBC and higher platelet counts; loss of the Y chromosome in male patients was prognostic for shorter OS. In the inv(16) group, trisomy 22 was a significant prognostic variable for longer RFS. For patients who experienced relapse, second complete remission rate was significantly lower in patients with t(8;21), resulting in a significantly inferior survival duration after relapse compared with patients with inv(16).
We provide novel prognostic factors for CBF AML and show that patients with t(8;21) who experience relapse have an inferior survival duration.
We investigated the prognostic impact of minimal residual disease (MRD) monitoring in acute myeloid leukemia patients harboring DNA methyltransferase 3A-R882H/-R882C mutations (DNMT3A
). MRD was ...determined by real-time quantitative PCR (RQ-PCR) in 1494 samples of 181 DNMT3A
patients. At the time of diagnosis, DNMT3A
transcript levels did not correlate with presenting clinical characteristics and concurrent gene mutations as well as the survival end points. In Cox regression analyses, bone marrow (BM) DNMT3A
transcript levels (log10-transformed continuous variable) were not associated with the rate of relapse or death. DNMT3A
transcript levels were significantly higher in BM than in blood after induction I (P=0.01), induction II (P=0.05), consolidation I (P=0.004) and consolidation II (P=0.008). With regard to the clinically relevant MRD time points, after two cycles of induction and at the end of therapy, DNMT3A
transcript levels had no impact on the end point remission duration and overall survival. Of note, only a minority of the patients achieved RQ-PCR negativity, whereas most had constantly high DNMT3A
transcript levels, a finding which is consistent with the persistence of clonal hematopoiesis in hematological remission.
Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies, including a reduced intensity allogeneic transplant (RICalloSCT). ...We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting.
A total of 183 patients, median age 45 years (range 21–69), had undergone an autoSCT at a median of 30 months before the RICalloSCT. Before the RICalloSCT, they had received a median of four lines (range 3–10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%).
With a median follow-up of 59 months, the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post-autoSCT and RICalloSCT was 14 and 43 months, respectively. The 5-year relapse/progression rate, progression-free survival and overall survival were 16%, 48% and 51%, respectively, and were associated with age and disease status at RICalloSCT.
These data suggest that an RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT.
Diagnosis of acquired von Willebrand syndrome (AVWS) remains challenging. Diagnostic algorithms suggest the use of factor VIII (FVIII:C), von Willebrand factor antigen (VWF:Ag), ristocetin cofactor ...(VWF:RCo), and collagen-binding capacity (VWF:CB), but the sensitivity of these and other laboratory tests for the diagnosis of AVWS is unknown.
To analyze the capacity of laboratory tests, including point-of-care testing (POCT), for the identification of patients with AVWS.
Thirty-five consecutive patients were enrolled with AVWS diagnosed because of a history of recent onset of bleeding, a negative family history of von Willebrand disease, and abnormal plasma VWF multimers.
According to our inclusion criteria, all patients had bleeding symptoms, and the VWF high molecular weight multimers were either decreased or absent. Regarding POCT, PFA-100 was inconclusive, due to anemia or thrombocytopenia, in 29%; the sensitivity was 80% in the remaining patients. The sensitivity of VWF:Ag (23%), VWF:RCo/Ag ratio < 0.7 (26%), VWF:CB/Ag ratio < 0.7 (46%), anti-VWF antibodies (15%) and VWF propeptide/Ag ratio (22%) was too low to rule out the disease. A combination of VWF:Ag < 50 IU dL(-1), VWF:RCo/Ag ratio < 0.7 and VWF:CB/Ag ratio < 0.8 yielded a sensitivity of 86%. Patients diagnosed only because of abnormal VWF multimers showed similar clinical characteristics as other patients.
Early diagnosis of AVWS is difficult, due to lack of sensitivity of the tests used. A substantial number of patients present with normal or increased test results, emphasizing the importance of multimer analysis in all patients with suspected AVWS.
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