Subject(s)
DNA-Binding Proteins/genetics , Erythroid Precursor Cells/enzymology , Interferon-alpha/therapeutic use , Janus Kinase 2/genetics , Mutation , Polyethylene Glycols/therapeutic use , Proto-Oncogene Proteins/genetics , Dioxygenases , Erythroid Precursor Cells/cytology , Humans , Interferon alpha-2 , Recombinant ProteinsABSTRACT
PURPOSE: Patients with adult acute myeloid leukemia (AML) with intermediate cytogenetics remain a heterogeneous group with highly variable individual prognoses. New molecular markers could help to refine cytogenetic stratification. EXPERIMENTAL DESIGN: We assessed P-glycoprotein (Pgp) activity and Flt3 internal tandem duplication (ITD+) because of their known prognostic value and because they might lead to targeted therapy. We did a multivariate analysis on 171 patients with adult AML treated in the European Organization for Research and Treatment of Cancer protocols. RESULTS: ITD+ and high Pgp activity (Pgp+) were found in 26 of 171 (15%) and 55 of 171 (32%) of all patients, respectively. ITD and Pgp activities were negative in 94 of 171 (55%, Pgp-ITD- group), mutually exclusive in 73 of 171 (43%, Pgp-ITD+ and Pgp+ITD- groups), and only 4 of 171 (2%, Pgp+ITD+ group) patients were positive for both. In multivariate analyses, Pgp+ITD+ (P < 0.0001) and age (P = 0.0022) were independent prognostic factors for the achievement of complete remission (CR). Overall survival (OS), CR achievement (P < 0.0001), WHO performance status (P = 0.0007), and Pgp+ITD+ status (P = 0.0014) were also independent prognostic factors. In 95 patients with intermediate cytogenetics, the CR rates of ITD+ patients were 40% versus 62% for ITD- (P = 0.099) and 41% versus 67% (P = 0.014) for Pgp+ versus Pgp- patients. In the Pgp-ITD- group (41 of 95), CR rates were 70% versus 44% for others (P = 0.012), OS achieved 48% versus 16% (P < 0.0001) and disease-free survival was 56% versus 27% (P = 0.024), respectively. Furthermore, the OS curves of the intermediate cytogenetics-Pgp-ITD- group were not significantly different from the favorable cytogenetic group. CONCLUSION: Flt3/ITD and Pgp activity are independent and additive prognostic factors which provide a powerful risk classification that can be routinely used to stratify the treatment of patients with intermediate cytogenetic AML. ITD+ and Pgp+ patients should be considered for targeted therapy.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B/metabolism , Gene Duplication , Leukemia, Myeloid/genetics , Leukemia, Myeloid/metabolism , fms-Like Tyrosine Kinase 3/genetics , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Cytogenetic Analysis , Follow-Up Studies , Humans , Leukemia, Myeloid/diagnosis , Middle Aged , Multivariate Analysis , Prognosis , Remission Induction , Risk Factors , Survival Rate , Tandem Repeat Sequences , Treatment OutcomeSubject(s)
Polycythemia Vera/diagnosis , Polycythemia Vera/genetics , Polycythemia/diagnosis , Polycythemia/genetics , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Adult , Aged , Aged, 80 and over , Autoanalysis , Cell Line, Tumor , Female , Humans , Janus Kinase 2 , Male , Middle Aged , Mutation , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Polycythemia Vera/classification , Polymorphism, Single Nucleotide , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction/methods , Sensitivity and Specificity , TemperatureABSTRACT
Endogenous erythroid colonies (EECs), a typical characteristic of polycythemia vera (PV), could be observed in essential thrombocythemia (ET). Erythroid progenitors culture carried out in 34 previously untreated patients with unequivocal ET showed EECs in 35% of the cases. During a mean follow up of 4 years after the culture, the 12 EECs(+) and the 22 EECs(-) patients did not show any difference for a thrombotic or haemorrhagic complication, and the only one patient who showed an involvement of erythropoiesis was in the EECs(-) group.
Subject(s)
Erythroid Precursor Cells/pathology , Thrombocythemia, Essential/pathology , Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Colony-Forming Units Assay , Erythropoiesis , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Humans , Incidence , Male , Middle Aged , Prognosis , Prospective Studies , Risk , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/diagnosis , Thromboembolism/epidemiology , Thromboembolism/etiologyABSTRACT
Erythropoietic and granulopoietic expansion after bone marrow transplantation (BMT) are reviewed in 60 allogeneic and autologous BMT. Morphological dyserythropoiesis was more prominent than dysgranulopoiesis. Dyserythropoiesis was present with increased HbF synthesis and i antigen expression. We did not find nocturnal paroxysmal hemoglobinuria and leukocytic alkaline phosphatase level was high. CFU-GM progenitors were still reduced in number 1 year after BMT. The clusters/colonies ratio, increased at day 12 after BMT was normal by day 100. No difference between autologous and allogeneic BMT was observed.
