1,722,211 research outputs found
GEMTUZUMAB OZOGAMICIN COMBINED WITH INDUCTION CHEMOTHERAPY IN YOUNG ADULTS WITH ACUTE MYELOID LEUKEMIA: REVIEW AND PERSPECTIVES.
Full text linkProgress in treatment of acute myeloid leukemia (AML) is slow. Many new
agents have been tested, but few were approved. Gemtuzumab Ozogamicin (GO) is a new AML-targeted drug that is composed by a monoclonal antibody targeting a surface antigen of myeloid leukemic cells (CD33) combined with a potent cytotoxic (calicheamicin). We review here the studies of GO in AML,
including an update of the Italian studies, and we trace back the story of a drug that was developed 15 years ago and, regrettably, is no longer available for
the treatment of AML, with the exception of Japan. GO was approved by the US FDA for the second-line treatment of AML in the elderly, and was shown by
several European large prospective and randomized studies to be active also in first line, both alone, but particularly in combination with standard chemotherapy.
Regrettably, a registration study that was performed in US could not confirm the superiority of GO and chemotherapy on chemotherapy alone, and the drug
was withdrawn. The differences among the US and the European studies are discussed. The profile of the AML patients who are expected to benefit more by the reintroduction of GO is proposed: first-line, less than 60 years old, CD33 expressed in more than 20% leukemic cells, low/intermediate cytogenetic risk, and low expression of the PGP multidrug resistance protein
Chronic myeloid leukemia: the concepts of resistance and persistence and the relationship with the BCR-ABL1 transcript type
No full textChronic myeloid leukemia is driven by a hybrid gene, BCR-ABL1, that codes for a leukemogenic tyrosine kinase (TK) protein of 210 KDa (p210BCR-ABL1). Resistance to TK inhibitor (TKI) therapy occurs in relatively few patients, no more than 10%, while persistence of minimal residual disease during TKI therapy occurs in the great majority of patients. Resistance is a cause of death, persistence is compatible with a fairly normal length and quality of life, but may require lifelong treatment. The causes of resistance are heterogeneous, including the development of other genomic abnormalities or the altered expression of other genes, requiring different treatments. The causes of persistence may not be the same as those of resistance. We hypothesize that the variability in breakpoint position within the Major-breakpoint cluster region (M-bcr), resulting in two different messenger RNAs that may or may not include exon 14 of BCR (e13a2 and e14a2, respectively), and, as a consequence, in two p210BCR-ABL1 proteins that differ by 25 amino acids, may be a cause of persistence. The hypothesis is based on a critical review of the relationships between the BCR-ABL1 transcript types, the response to TKIs, the outcome of treatment, and the immune response, suggesting that the e14a2 transcript is associated with more and deeper molecular responses, hence with a higher probability of achieving treatment-free remission (TFR). Investigating this putative cause of persistence may help bringing more patients into stable TFR
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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