We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points ...

Conventional cytogenetics (CC) at clinical diagnosis shows a normal karyotype in 40-60% of de novo myelodysplastic syndromes (MDSs). Fluorescence in situ hybridization (FISH) might detect occult aberrations in these patients. Therefore, we have used FISH to check 57 MDS patients who were karyo-typically normal on CC. At clinical diagnosis, FISH ...

BACKGROUND: Levels of the soluble form of CD86 (sCD86) are elevated in a proportion of patients with leukemia. Although it is a potential modulator of antitumor responses, the significance of sCD86 in patients with hematologic malignancies is unknown. METHODS: The authors evaluated sCD86 levels by enzyme-linked immunosorbent assay in patients ...

We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes. FISH analysis for trisomy 12, 13q14 deletion, and monosomy of TP53 (also known as ...

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH ...

BACKGROUND AND OBJECTIVES: Flow cytometry enumeration of peripheral blood CD34-positive cells provides reliable measurements of circulating hematopoietic progenitors in humans. Since the absolute number of circulating CD34-positive cells has been previously found to be elevated in myelofibrosis with myeloid metaplasia (MMM), we prospectively studied the clinical utility of this parameter ...

We have developed a sensitive, competitive, nested reverse transcription polymerase chain reaction (RT-PCR) titration assay that quantifies the number of Wilm's tumour (WT1) gene transcripts in bone marrow (BM) and peripheral blood (PB), coupled with a competitive RT-PCR protocol for the ABL gene as control. We studied BM/PB samples from ...

We analyzed in vitro growth characteristics of bone marrow mononuclear cells (BMMCs) from 322 patients with acute myeloid leukemia (AML) in relation to cytogenetic abnormalities. Median colony growth was low in each of the cytogenetic changes associated with a favorable outcome. Most karyotypic abnormalities in the intermediate prognosis group were ...

During a 10-year period (1992-2001) in the region of Southern Denmark, 337 patients aged 15 years or older (range 16-93 years, median 67 years) were diagnosed with acute myeloid leukaemia (AML). Cytogenetic analysis was carried out in 90%, of whom 53% had clonal chromosome aberrations. Some 24% and 31% had ...

In order to investigate the safety and efficacy of stem cell mobilization in chronic myeloid leukemia patients under imatinib therapy we treated 10 such patients with granulocyte colony-stimulating factor. We observed that none of the patients developed progressive disease under this treatment. Instead, sufficient CD34+ apheresis could be performed in ...

BACKGROUND: Older age is a consistent poor prognostic factor in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). Whether this is related to an intrinsic worse disease biology or to inadequate drug delivery or excessive treatment-associated toxicity is unknown. The availability of imatinib mesylate, a selective, Bcr-Abl-targeted therapy that ...

Eighty-three patients with various chronic myeloproliferative disorders [polycythemia vera (PV), essential thrombocytosis (ET), idiopathic myelofibrosis (IMF)] were analyzed for the occurrence of acute myeloid leukemia (AML) and myelodysplasia (MDS) during treatment with hydroxyurea (HU) alone or HU following treatment with busulphan (BU). A total of 58 patients (29 PV, 14 ...

We prospectively evaluated mixed chimerism (MC) in the T cell and myeloid lineages and its correlation to busulphan, single-dose total body irradiation (TBI) and fractionated TBI (fTBI) conditioning in 180 patients with haematological malignancies after allogeneic stem cell transplantation (SCT). In all patients receiving busulphan, the area under curve (AUC) ...

Monitoring of minimal residual disease (MRD) becomes increasingly important in the risk-adapted management of patients with acute myeloid leukemia (AML). In selected patients with AML, multiparameter flow cytometry has shown accuracy and sensitivity in the quantification of MRD levels with independent prognostic impact. The applicability of this approach is superior ...

Approximately 11,000 Americans will be diagnosed with acute myeloid leukemia (AML) in 2003, and about 75% ultimately will die from the disease. Despite significant advances in understanding biologic, molecular, and cytogenetic aspects of this malignancy, several other areas remain poorly understood. During the 1990s, significant advances in the characterization of ...

OBJECTIVE: To describe clinical and laboratory features of a cohort of patients with chronic myelogenous leukemia (CML) who developed Ph(-), trisomy 8(+) metaphases while on treatment with imatinib mesylate. PATIENTS AND METHODS: Conventional cytogenetics and triple-color interphase fluorescence in situ hybridization were used to identify 5 of 310 studied patients ...

We have previously reported that children with B-precursor acute lymphoblastic leukemia (ALL) who remained in remission after successfully completing therapy had leukemia cells detectable by polymerase chain reaction (PCR) (N Engl J Med 1997;336(5):317-23). These patients were treated by an institutional protocol (P89-04) that lacked the post-remission intensification features of ...

Minimal residual disease (MRD) can be detected in the marrows of children undergoing chemotherapy either by flow cytometry or polymerase chain reaction. In this study, we used four-color flow cytometry to detect MRD in 1016 children undergoing therapy on Children's Oncology Group therapeutic protocols for precursor-B-cell ALL. Compliance was excellent, ...

Hematological malignancies in Jehovah's Witnesses are often difficult to cure since these patients deny transfusions. By a retrospective analysis, we report the possibility of treating some tumors, mostly hematological, with either autologous or allogeneic bone marrow transplantation (BMT) without blood support. Eight patients were evaluated, including lymphoma (two patients), acute ...

Neoangiogenesis has been shown to play an important role in the pathogenesis of acute myeloid leukemia (AML). Autocrine and paracrine secretion of angiogenic and hematopoietic growth factors such as vascular endothelial growth factor (VEGF) and stem cell factor (SCF) in the bone marrow microenvironment may promote proliferation and survival of ...

Fourteen adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. ...

BACKGROUND: In vitro and clinical data suggest a therapeutic role for alpha2 interferon (IFN) in the treatment of the chronic myeloproliferative disorders. Accordingly, a multiinstitutional, Phase II trial of IFN in patients with agnogenic myeloid metaplasia (AMM), essential thrombocythemia (ET), and polycythemia rubra vera (PRV) in the spent phase was ...

Vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML) and high vascular endothelial growth factor (VEGF) levels correlate with worse survival. We analyzed the significance of VEGF-receptor 1 (VEGF-R1) and VEGF-R2 levels in bone marrow samples from 170 CML patients (137 chronic, 24 accelerated, and ...

The authors present a series of three paediatric patients with trisomy 21 who developed significant bradycardia during inhalation induction with sevoflurane. All three were undergoing adenotonsillectomy. The possible association of such problems with trisomy 21 and treatment options are reviewed. Although the occurrence of bradycardia in these three patients may ...

BACKGROUND: An increase in colony-forming progenitor cells (CFU) is typically seen in myeloproliferative disorders (MPD). Systemic mastocytosis (SM) is a haemopoietic neoplasm involving myeloid progenitors similar to MPD. In the present study, we measured the levels of peripheral blood (pb) and bone marrow (bm) CFU in patients with different categories ...

Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our ...

Fluorescence in situ hybridization for the BCR/ABL rearrangement in 138 bone marrow specimens from 59 Philadelphia(+) (Ph(+)) chronic myelogenous leukemia (CML) patients, 35 Ph(+) acute lymphoblastic leukemia (ALL) patients, and 57 Ph(-) ALL patients was used. Sixteen (27.1%) of the 59 CML patients had deletions of the residual ABL gene ...

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute ...

Acute myeloid leukemia (AML) cases with 11q23 abnormalities involving the MLL gene comprise one category of recurring genetic abnormalities in the WHO classification. In an unselected series of 1897 AML cases, 54 patients with an 11q23/MLL rearrangement were identified, resulting in an incidence of 2.8%. The incidence of AML with ...

To elucidate the biologic and clinical heterogeneity of adult pro-B acute lymphoblastic leukemia (ALL) (ie, terminal deoxynucletidyl-transferase-positive[TdT+], CD19+, CD10-, surface immunoglobulin-negative [SIg-]), we evaluated 66 patients enrolled in the Italian multicentric Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 study between October 1996 and December 1999. The ALL1/AF4 fusion transcript, originating ...

BACKGROUND: Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD). METHODS: The authors investigated the ...

BACKGROUND AND OBJECTIVES: Detection of minimal residual disease (MRD) by multiparameter flow cytometry is an emerging prognostic factor in patients with acute myeloid leukemia (AML). The present analysis aimed at improving the applicability of this approach to more patients with AML. DESIGN AND METHODS: Bone marrow samples from unselected patients ...

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source ...

We evaluated bone marrow pathologic features and cytogenetic and molecular genetic status of 13 patients with interferon-resistant, chronic-phase chronic myeloid leukemia (CML), treated with imatinib mesylate (Gleevec). All had morphologic evidence of CML in the blood and bone marrow and were positive for bcr-abl by reverse transcriptase-polymerase chain reaction, fluorescence ...

BACKGROUND: It has recently been shown that t (12;21) (p13;q 22) is the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL). We have analyzed this translocation in an attempt to evaluate its incidence and to monitor minimal residual disease (MRD) with t (12; 21) rearrangement by detection ...

Two cases of acute myeloblastic leukemia (AML) evolving from aplastic anemia are presented. The first case was diagnosed 18 years ago, and treatment with bolus methylprednisolone, prednisolone, and androgens resulted in partial hematological response. Severe pancytopenia recurred, and AML M0 by French-American-British classification developed. The second case was diagnosed 7 ...

PURPOSE: The tyrosine kinase inhibitor imatinib mesylate inhibits the function of the Bcr-Abl oncoprotein associated with Philadelphia-positive chronic myelogenous leukemia (CML). Anagrelide suppresses megakaryocyte proliferation and differentiation. The objectives of this study were to investigate the feasibility and safety of imatinib mesylate and anagrelide combination therapy in patients with Ph-positive ...

Primary myelodysplasia (MDS) without an increased number of blasts is a rare finding in childhood. We performed a retrospective analysis of 67 children with a diagnosis of primary MDS to determine the clinical and hematologic course of the disease. The median age at diagnosis was 8.3 years (range, 0.3-18.1 years). ...

PURPOSE: To determine whether pattern of WT1 gene expression is a useful marker for establishing prognosis and tracking disease progression in patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: We performed a quantitative assessment of the WT1 transcript amount by real-time quantitative polymerase chain reaction (RQ-PCR) in 173 samples (131 ...

Prospective analysis of the importance of the plasma levels of beta-2 microglobulin (B2M) in 553 patients with myelodysplastic syndrome (MDS) found that B2M is an independent prognostic variable for survival with weighted significance second only to the karyotype. The incorporation of the B2M covariate into risk assessment of MDS patients ...

The category of "refractory anemia with excess blasts in transformation" (RAEB-T) has been abandoned in the new WHO-classification of myelodysplastic syndromes (MDS). The majority of patients previously belonging to this category are now classified as acute myeloid leukaemia (AML). In the FAB-classification, patients had been assigned to the RAEB-T category ...

A 69-year-old man with relapsed acute lymphoid leukemia was treated with adriamycin, vincristine, and prednisolone. During this chemotherapy, the patient developed sepsis and meningitis. Although many kinds of antimicrobial drugs, including imipenem, meropenem, amphotericin-B, and gamma-globulin were administered, the patient died of respiratory failure. A positive result for Enterococcus faecalis ...

BACKGROUND: The goal of this study concerned the pretherapeutic identification of high-risk acute myeloid leukemia (AML) patients by data pattern analysis from flow cytometric immunophenotype, cytogenetic, and clinical data. METHODS: Sixty-seven parameters of AML patients at diagnosis were classified for predictive information by algorithmic data sieving using iteratively self optimizing ...

Imatinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML). With imatinib, complete cytogenetic response (CCR) can be achieved in over 70% of newly diagnosed patients with CML. However, the optimal long-term management of ...

AIMS, BACKGROUND AND STUDY DESIGN: Few studies have investigated the karyotypes of colorectal carcinomas with emphasis on the correlation between cytogenetic findings and clinicopathologic features. The aim of our study involving 20 colorectal adenocarcinomas was to determine their genomic alterations at the chromosomal level by correlating the cytogenetic findings with ...

We evaluated the methylation status of p15 gene in a series of 65 patients with newly diagnosed acute promyelocytic leukemia (APL) receiving homogeneous treatment. Moreover, in 32 of them, the methylation status of p15 gene was correlated to the p15 m-RNA expression. In total, 31 patients had no p15 methylation ...

BACKGROUND: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with myeloproliferative disorders (MPD), including agnogenic myeloid metaplasia (AMM), chronic myeloid leukemia in blastic phase (CML-BP), and chronic myelomonocytic leukemia (CMML). VEGF is a soluble, circulating, angiogenic molecule that acts through ...

In the management of chronic myeloid leukemia (CML), cytogenetic response (CgR) has been recognized as an important prognostic factor and is used in predicting patient outcome. Imatinib (Gleevec) (formerly STI571), a potent inhibitor of BCR-ABL, is very effective in inducing CgRs in chronic-phase CML patients, even in late chronic-phase patients ...

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoietic stem cell disorders, while, immunological abnormalities are frequently observed in patients with MDS. Several reports revealed that about 10% of MDS patients have clinical autoimmune disorders like skin vasculitis, rheumatic disease, or autoimmune hemolytic anemia. Furthermore, serological immunological abnormalities ...

With the introduction of imatinib (Gleevec) (formerly STI571) for the treatment of chronic myeloid leukemia (CML), the various diagnostic methods used to monitor patients must be re-evaluated. Conventional cytogenetics has been the established method for follow-up of patients treated with interferon-alpha (IFN-alpha), and the prognostic value of major and complete ...