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Biomedical subjects

P Valent

Publications and source records attributed to P Valent.

At least 19 recordsLinked to original sources
PubMed2007

Expression of the target receptor CD33 in CD34+/CD38-/CD123+ AML stem cells.

BACKGROUND: CD33 (Siglec-3) is becoming increasingly important as a target of antibody-mediated therapy in acute myeloid leukaemia (AML). In normal myelopoiesis, expression of CD33 is restricted to advanced stages of differentiation, whereas primitive stem cells do not express CD33. In the present study, we asked whether leukaemic stem cells in patients with AML express CD33. MATERIALS AND METHODS: A multicolour-staining technique was applied in 11 patients with AML, and leukaemic progenitors defined as CD34(+)/CD38(-)/CD123(+) cells. AML stem cells were purified by cell sorting and were examined for expression of CD33 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In all patients in whom the majority of myeloblasts expressed CD33 (n = 8), AML progenitors reacted with the CD33 antibody P67.6. Repopulation experiments utilizing irradiated NOD/SCID mice confirmed that AML stem cells in these patients reside within the CD33(+) subpopulation of the leukaemic clone. Moreover, highly purified AML stem cells (> 98% purity) from patients with CD33(+) AML were found to express CD33 mRNA in RT-PCR analyses. CD33 was neither detectable on CD34(+)/CD38(-) cells in normal bone marrow nor on leukaemic stem cells in patients with CD33-negative AML. CONCLUSIONS: Leukaemic stem cells in patients with CD33(+) AML express CD33. This observation is in favour of novel treatment concepts employing CD33-targeting antibodies in AML.

Acute Disease↗
PubMed2006

Enumeration and immunohistochemical characterisation of bone marrow basophils in myeloproliferative disorders using the basophil specific monoclonal antibody 2D7.

BACKGROUND: Basophils are highly specialised granulocytes that express a unique profile of antigens and increase in myeloproliferative disorders (MPD). In chronic myeloid leukaemia (CML), basophilia is a diagnostic and prognostic determinant. So far, however, no reliable approach for routine detection and enumeration of bone marrow basophils has become available. OBJECTIVE: To detect and enumerate basophils in bone marrow sections in patients with CML and other MPD. METHODS: The anti-basophil antibody 2D7 was applied to paraffin embedded bone marrow sections from normal/reactive subjects (n = 31), patients with CML (chronic phase, n = 37; accelerated phase, n = 9), and other MPD (chronic idiopathic myelofibrosis (CIMF), n = 20; polycythaemia vera (PV), n = 20; essential thrombocythaemia (ET), n = 20; indolent systemic mastocytosis (ISM), n = 7). RESULTS: As assessed by serial section staining, 2D7(+) cells were found to co-express myeloperoxidase, histidine decarboxylase, CD9, and CD43, but did not express B cell or T cell restricted antigens. 2D7(+) bone marrow cells were found to increase in CML compared with normal/reactive bone marrow and other MPD (median numbers of 2D7(+) cells/mm(2): CML, 33; normal/reactive bone marrow, 6; CIMF, 10; PV, 6; ET, 5; ISM, 3; p<0.05). The highest basophil counts were recorded in accelerated phase CML (115/mm(2)). CONCLUSIONS: A novel immunohistochemical procedure has been established for basophil detection in normal bone marrow and MPD. This approach should help in the quantification of bone marrow basophils at diagnosis and during anti-leukaemic treatment.

Adult↗
PubMed2006

Pathogenesis, clinical features, and treatment advances in mastocytosis.

Systemic mastocytosis (SM) is characterized by the abnormal growth and accumulation of mast cells (MC) in one or more organs. The interaction between the cytokine stem cell factor (SCF) and its cognate receptor, the c-kit receptor tyrosine kinase (KIT), plays a central role in regulating MC growth and differentiation. Whereas germline and somatically acquired activating mutations of KIT have been identified in SM, the issue as to whether individual KIT mutation(s) are necessary and sufficient to cause MC transformation remains unclear based on currently available data. Activating mutations of platelet-derived growth factor receptor-alpha (FIP1 L1-PDGFRA) are identified in a significant number of SM cases that have associated eosinophilia. To date, as with gastrointestinal stromal tumors, activating mutations of KIT and PDGFRA appear to be alternative and mutually exclusive genetic events in SM. The World Health Organization has specified criteria for classification of SM into six major subtypes: cutaneous mastocytosis, indolent systemic mastocytosis (ISM), systemic mastocytosis with an associated clonal hematological non-mast-cell disorder (SM-AHNMD), aggressive systemic mastocytosis (ASM), mast cell leukemia, and mast cell sarcoma. The ability to molecularly classify individual SM cases based on the presence or absence of specific mutations allows for molecularly targeted therapy in a growing number of cases. Imatinib mesylate therapy might result in complete remission of SM cases with wild-type KIT, certain KIT mutations, such as F522C, or the FIP1L1-PDGFRA fusion gene, but not of D816V-KIT-bearing SM. For the latter, interferon-alpha and 2-CdA are potential first- and second-line therapeutic options. Other drugs under investigation include novel tyrosine kinase inhibitors, as well as NF-kappaB inhibitors, which might display greater selectivity towards D816V-KIT as compared to wild type KIT. The pathogenesis of mastocytosis, its major clinical subtypes, and recent treatment advances are discussed in this chapter.

Animals↗
PubMed2006

Gastro-duodenal digestion products of the major peanut allergen Ara h 1 retain an allergenic potential.

BACKGROUND: The process of gastro-duodenal digestion may play a role in determining the allergenic properties of food proteins. The sensitizing and allergenic potential of digestion products of highly degraded allergens, such as the major peanut allergen Ara h 1, is currently under debate. We evaluated the effect of in vitro gastro-duodenal digestion of Ara h 1 on T cell reactivity and basophil histamine release. METHODS: An in vitro model of gastro-duodenal digestion was used to investigate changes in the allergenic properties of Ara h 1 using in vitro assays monitoring T cell reactivity (proliferation, cytokine production) and histamine release of basophils from peanut allergic individuals. The digestion process was monitored using an SDS-PAGE gel. RESULTS: In vitro gastric digestion led to rapid degradation of Ara h 1 into small fragments M(r) L5600. Gastric digestion did not affect the ability of Ara h 1 to stimulate cellular proliferation. Gastro-duodenal digestion significantly reduced its ability to stimulate clonal expansion (P<0,05; Wilxocon's signed rank test). The Th-2 type cytokine polarization of T cells from peanut allergic donors (IFN-gamma/IL-13 ratio and IFN-gamma/IL-4 ratio of CFSE(low) CD4(+) T cells) remained unchanged regardless of the level of digestion. Histamine release of basophils from peanut allergic individuals was induced to the same extent by native Ara h 1 and its digestion products. CONCLUSION: Gastro-duodenal digestion fragments of Ara h 1 retain T cell stimulatory and IgE-binding and cross-linking properties of the intact protein.

Allergens↗
PubMed2006

In vivo effects of imatinib mesylate on human haematopoietic progenitor cells.

BACKGROUND: Imatinib mesylate has considerable antineoplastic activity in patients with chronic myeloid leukaemia (CML) and some solid tumours. Although originally regarded as nontoxic for normal haematopoiesis, mild to moderate myelosuppression is a commonly observed side-effect of this treatment. Recently, this molecule has been shown to suppress normal haematopoietic progenitor cells in vitro. This is the first study that has investigated the effect of imatinib on haematopoietic progenitor cells in vivo. MATERIALS AND METHODS: We investigated the number of circulating haematopoietic progenitor cells in 79 patients with CML and five patients with solid tumours who were treated with imatinib for at least 3 months. Bone marrow progenitor cells were assessed in a subgroup of 18 patients with CML after 12 months of imatinib treatment. Results were compared with haematopoietic progenitor cell numbers of normal controls. RESULTS: Circulating progenitors of all classes were significantly decreased in CML up to 24 months of imatinib therapy compared with healthy controls (median progenitor cells in CML after 12 months: CFU-GM 62, range 0-2543; BFU-E 216, range 0-3259; CFU-GEMM 0, range 0-139; versus controls: CFU-GM 208, range 50-936; BFU-E 690, range 120-1862; CFU-GEMM 20, range 4-77; P < 0.001). Similar reductions in the number of progenitor cells derived from bone marrow were found in a subgroup of 18 patients with CML. In patients with solid tumours the number of circulating progenitor cells was significantly lower under treatment with imatinib when compared with the controls. Withdrawal of imatinib in a patient with a malignant brain tumour resulted in a prompt normalization of circulating progenitors. CONCLUSIONS: This study suggests that imatinib exerts myelosuppressive effects through inhibition of haematopoietic progenitor cells.

Adolescent↗
PubMed2006

Evaluation of neoplastic human mast cells by tryptase-immunoelectron microscopy.

AIMS: To analyse and characterize the ultrastructural morphology of normal tissue mast cells (MC) and neoplastic bone marrow MC. METHODS: We have examined the ultrastructure and cytomorphological features of MC derived from cord blood cells, neoplastic bone marrow MC in patients with systemic mastocytosis (SM, n = 4), myelomastocytic leukaemia (MML, n = 2), mast cell leukaemia (MCL, n = 2) and tryptase-positive acute myeloid leukaemia (AML, n = 4). RESULTS: Based on their ultrastructure and morphology, four distinct cell types could be delineated: (i) mature well-granulated tissue MC exhibiting a round central nucleus; (ii) atypical MC type I with oval nuclei, hypogranulated cytoplasm, and prominent surface projections; (iii) immature atypical MC with bi- or polylobed nuclei (atypical MC type II = promastocytes); and (iv) metachromatic blasts. Type I atypical MC were detected in a patient with indolent SM, whereas type II MC and metachromatic blasts were primarily found in MML, MCL and tryptase-positive AML. In all samples examined, the identity of MC could be reconfirmed by immunoelectron microscopy, irrespective of the stage of cell maturation or the disease variant, all types of MC contained tryptase in their cytoplasmic granules. CONCLUSION: Immunoelectron microscopy may be a helpful approach in confirming the identity of neoplastic MC in myeloid neoplasms.

Adult↗
PubMed2006

Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells.

BACKGROUND: Statins are inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, a key enzyme in mevalonic acid (MVA)-dependent signaling. Recent data suggest that statins exhibit profound inhibitory effects on growth and function of various immune cells. In the present study, we examined the in vitro effects of five different statins on primary human mast cells (MCs), MC progenitors, and the human MC line HMC-1. METHODS: Histamine release experiments were conducted on isolated MCs using statins and an anti-immunoglobulin E (IgE) antibody. Culture experiments were performed with stem cell factor (SCF) and interleukin (IL)-6, and cord blood-derived progenitors. RESULTS: Preincubation of primary lung MCs with cerivastatin or atorvastatin (1-50 microM) for 24 h resulted in inhibition of anti-IgE-induced release of histamine. The effects of both statins were dose-dependent. Moreover, both statins, and to a lesser degree lovastatin, were found to inhibit the SCF-induced differentiation of MCs from their progenitors. The other statins tested (simvastatin, pravastatin) did not affect mediator release or growth of MCs. CONCLUSIONS: Cerivastatin and atorvastatin act as inhibitors of growth and function of human MCs.

Apoptosis↗
PubMed2006

Detection of novel leukocyte differentiation antigens on basophils and mast cells by HLDA8 antibodies.

BACKGROUND: Basophils (BA) and mast cells (MC) are important effector cells in allergic reactions. Development, growth and effector cell functions are regulated by a network of cytokines, other ligands, and respective cell surface antigens. METHODS: We examined the expression of novel CD antigens on human BA, lung MC, the BA cell line KU-812, and the MC line HMC-1. Expression of surface antigens was analyzed by monoclonal antibodies (mAb) of the HLDA8 workshop and flow cytometry. RESULTS: Basophils were found to stain positive for CXCR1 (CD181), CCR1 (CD191), CCR2 (CD192), CCR7 (CD197), IL-18Ralpha (CDw218a), IL-18Rbeta (CDw218b), TRAIL-R1 (CD261), TRAIL-R2 (CD262), TACI (CD267), TLR-4 (CD284), LAIR1 (CD305), EMR-2 (CD312), JAM1 (CD321), and JAM2 (CD322). Lung MC were found to react with mAb against EMR-2 (CD312) and JAM1 (CD321). KU-812 cells were found to stain positive for CXCR1 (CD181), TRAIL-R2 (CD262), B7H2 (CD275), TLR-4 (CD284), JAM1 (CD321), and E-Cadherin (CD324). HMC-1 cells were recognized by mAb against TRAIL-R2 (CD262), B7H2 (CD275), LAIR1 (CD305), EMR-2 (CD312), JAM1 (CD321), and Siglec-6 (CDw327). CONCLUSIONS: Extensive phenotyping with antibodies against novel CD antigens provides further evidence that BA and MC represent two separate hematopoietic cell lineages with unique phenotypic properties observed in mature cells as well as malignant immature cells. Further studies are required to define the functional role of these CD antigens expressed in BA and MC.

Antibodies, Monoclonal↗
PubMed2006

The complement component C5a induces the expression of plasminogen activator inhibitor-1 in human macrophages via NF-kappaB activation.

BACKGROUND: Atherosclerosis is considered to be a chronic inflammatory disorder. Activation of the complement cascade is a major aspect of chronic inflammatory diseases. Complement components were identified in atherosclerotic plaques, and a correlation between adverse events and C5a plasma levels was found. These findings support the notion that complement activation contributes to development and progression of atherosclerotic lesions. OBJECTIVES: We investigated whether complement components C3a and C5a regulate plasminogen activator inhibitor (PAI-1) in human macrophages. METHODS: Human monocyte-derived macrophages (MDM) and human plaque macrophages were cultured and incubated with the complement component C5a. RESULTS: C5a increased PAI-1 up to 11-fold in human MDM and up to 2.7-fold in human plaque macrophages. These results were confirmed at the mRNA level using real time-polymerase chain reaction. Pertussis toxin or anti-C5aR/CD88 antibody completely abolished the effect of recombinant human C5a on PAI-1 production, suggesting a role of the C5a receptor. Experiments with antitumor necrosis factor (TNF)-alpha antibodies and tiron showed that the effect of C5a was not mediated by TNF-alpha or oxidative burst. Furthermore C5a induced NF-kappaB binding to the cis element in human macrophages and the C5a-induced increase in PAI-1 was completely abolished by an NF-kappaB inhibitor. CONCLUSIONS: We conclude that C5a upregulates PAI-1 in macrophages via NF-kappaB activation. We hypothesize that - if operative in vivo- this effect could favor thrombus development and thrombus stabilization in the lesion area. On the other hand one could speculate that C5a-induced upregulation of PAI-1 in plaque macrophages could act as a defense mechanism against plaque destabilization and rupture.

Cells, Cultured↗
PubMed2006

An unusual case of systemic mastocytosis associated with chronic lymphocytic leukaemia (SM-CLL).

AIMS: Whereas focal accumulations of reactive lymphocytes around mast cell (MC) infiltrates are often seen in indolent systemic mastocytosis (ISM) involving the bone marrow, an association of systemic mastocytosis (SM) with malignant lymphoma/lymphatic leukaemia is very rare. This report contributes to the differential diagnosis of ISM by demonstrating that such lymphocytic aggregates may be neoplastic. METHODS: Biopsy specimens (bone marrow and gastrointestinal mucosa) of a 69 year old woman with mild blood lymphocytosis and a history of urticaria pigmentosa-like skin lesions that had disappeared a few years earlier, were investigated immunohistochemically using antibodies against CD3, CD5, CD20, CD23, CD25, CD34, CD117, chymase, and tryptase. Rearrangements of the IgH and TCRy genes were studied by seminested PCR. Mutation analysis of c-kit was performed by melting point analysis of nested PCR using amplified DNA from pooled microdissected single cells (MC and B cells) of both sites. RESULTS: The histomorphological features of the bone marrow corresponded to that of ISM with multifocal accumulations of MC surrounded by clusters of lymphocytes of mature appearance. However, these lymphocytes revealed an aberrant immunophenotype with coexpression of CD5, CD20, and CD23, thus enabling the final diagnosis of SM with an associated clonal haematological non-MC lineage disease, in particular SM with associated B cell chronic lymphocytic leukaemia (SM-CLL). Monoclonality for both ISM and B-CLL could be confirmed by demonstrating the typical activating c-kit point mutation D816V in bone marrow MC, and a monoclonal IgH rearrangement in bone marrow B cells. CONCLUSIONS: Usually, focal accumulations of lymphocytes around MC infiltrates in the bone marrow of patients with SM are reactive in nature (lymphocytosis). However, a low grade malignant lymphoma should also be included in the differential diagnosis. We describe here the first case, to our knowledge, with synchronous diagnosis of SM and associated B-CLL. This diagnosis could only be established by application of appropriate immunohistochemical and molecular techniques, as the bone marrow histology on first investigation resembled that of typical ISM.

Aged↗
PubMed2006

The tryptase positive compact round cell infiltrate of the bone marrow (TROCI-BM): a novel histopathological finding requiring the application of lineage specific markers.

AIMS: Compact tryptase-positive round cell infiltrates of the bone marrow (TROCI-BM) are very rare histopathological findings and may pose challenging problems with regard to the cell type involved (either mast cells or basophilic granulocytes) and the exact diagnosis. METHODS: A selected panel of immunohistochemical markers against mast cell and basophil related antigens, including CD25, CD34, CD117/Kit, and the 2D7 antigen (which is found only in basophilic granulocytes) on a total of 410 routinely processed bone marrow biopsy specimens (including 88 cases of systemic mastocytosis (SM), 20 cases of chronic myeloid leukaemia (CML), 92 cases of myeloid neoplasms other than CML, and 210 controls with normal/reactive bone marrows). RESULTS: In total, 17 cases with TROCI-BM could be identified: 11 SM (including two cases of well-differentiated SM and two mast cell leukaemias; MCL), 2 myelomastocytic leukaemia (MML), 2 CML with excess of basophils (secondary basophilic leukaemia (CMLba)), and 2 tryptase positive acute myeloid leukaemia (AML). Regarding the cell types involved, TROCI-BM cells were found to express CD117/Kit in all cases of SM and MCL. In MML and tryptase postitive AML, TROCI-BM cells were found to coexpress CD34 and Kit. The basophil specific antigen 2D7 was only detected in CD34/Kit negative TROCI-BM cells in two patients with CMLba. The activating point mutation D816V was detected in 8/11 patients with SM but not in any of the other haematological malignancies. CONCLUSIONS: In summary, a total of six rare myeloid neoplasms may present with a novel immunohistochemical phenomenon tentatively termed TROCI-BM.

Adult↗
PubMed2006

"Occult" mastocytosis with activating c-kit point mutation evolving into systemic mastocytosis associated with plasma cell myeloma and secondary amyloidosis.

A case of a 70-year-old man presenting with exsudative enteropathy due to light-chain-associated amyloidosis is reported. The diagnosis of systemic mastocytosis associated with IgG/lambda plasma cell myeloma and secondary generalised amyloidosis was carried out by morphological evaluation of bone marrow biopsy. The c-kit point mutation D816Y was detected by molecular analysis. Two years before, a cystadenolymphoma of the left parotid gland had been removed. A moderate increase of loosely scattered spindle-shaped mast cells, a subpopulation of them expressing CD25, an antigen that is not expressed by normal or reactive mast cells, was shown by retrospective analysis carried out on an intraparotideal lymph node. The c-kit mutation D816Y was shown by the molecular analysis of the lymph node. In summary, the notion that systemic mastocytosis may very rarely be associated with B cell neoplasms and that neoplastic mast cell infiltrates may be obscured because of only a minimal increase of atypical mast cells, which are outnumbered by other non-neoplastic cells in the same tissue, is supported by this case. This finding was preliminarily termed "occult" mastocytosis.

Aged↗
PubMed2005

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Adolescent↗
PubMed2005

Detection of differentiation- and activation-linked cell surface antigens on cultured mast cell progenitors.

BACKGROUND: Mast cells (MC) are multifunctional effector cells of the immune system. They derive from uncommitted CD34(+) hemopoietic progenitor cells (HPC). Depending on the stage of maturation and the environment, MC variably express differentiation- and activation-linked antigens. Little is known, however, about the regulation of expression of such antigens in immature human MC. METHODS: We analyzed expression of CD antigens on human MC grown from cord blood-derived CD34(+) HPC. The HPC were isolated by magnetic cell sorting (MACS) and FACS to >97% purity, and were cultured in stem cell factor (SCF) and interleukin (IL)-6 with or without additional cytokines (IL-4 or IL-10) in serum-free medium. The cell surface phenotype of MC was determined by monoclonal antibodies and flow cytometry. RESULTS: Cultured MC progenitors were found to react with antibodies against various CD antigens including CD58, CD63, CD117, CD147, CD151, CD203c, and CD172a, independent of the growth factors used and time-point investigated (days 14-42). CD116 [granulocyte-macrophage colony-stimulating factor receptor alpha (GM-CSFRalpha)] and CD123 (IL-3Ralpha) were expressed on MC precursors on day 14, but disappeared thereafter. Cultured MC did not express CD2, CD3, CD5, CD10, CD19, or CD25. Addition of IL-10 to MC cultures showed no effect on expression of CD antigens. However, IL-4 was found to promote expression of CD35 and CD88 on cultured MC without changing expression of other CD antigens. CONCLUSIONS: Most MC antigens may already be expressed at an early stage of mastopoiesis. Whereas IL-3R and GM-CSFRs are lost during differentiation of MC, these cells may acquire complement receptors (CD35, CD88) under the influence of distinct cytokines.

Animals↗
PubMed2004

Vaccination with genetically engineered allergens prevents progression of allergic disease.

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.

Allergens↗
PubMed2004

Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse.

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.

Acute Disease↗