267 research outputs found
Translational Studies in Elderly Patients with Acute Myeloid Leukemia
The production of blood cells (hematopoiesis) takes place in the bone marrow. Acute myeloid
leukemia (AML) is a clonal disease, which is characterized by an increase in the number of
myeloid cells in the bone marrow and an arrest in their maturation. This frequently results in a
severe suppression of normal hematopoiesis (granulocytopenia, anemia and/or
thrombocytopenia).1,2
AML is a heterogeneous disease, characterized by a diversity of morphologic, cytogenetic and
immunophenotypic features. Until recently, the morphologic classification was according to
the French-American-British group,3-5 which distinguishes AML into nine distinct subtypes
(FAB M0-M7, M4eo) that differ with respect to the particular myeloid lineage involved and
the degree of leukemic-cell differentiation. This distinction is based on the morphologic
appearance of the blasts and their reactivity with histochemical stains. In addition,
immunologic methods have been incorporated into the diagnostic criteria for some FABgroups,
e.g. M0 and M7.6,7 Cytogenetic abnormalities of the chromosomes in the leukemic
blasts have also been shown to be associated with specific FAB subtypes, e.g. t(15;17) with
acute promyelocytic leukemia (APL; AML M3).8 Recently, the World Health Organization
(WHO) has proposed a new classification for myeloid neoplasms.9 In this classification,
genetic features (cytogenetic and molecular genetic) and clinical features have been integrated
with morphology and immunophenotype to define distinct disease entities. Within the
category of AML, four main groups have been recognized: 1. AML with recurrent
cytogenetic translocations; 2. AML with myelodysplasia-related features; 3. therapy-related
AML and MDS; and 4. AML not otherwise specified
The pedicled omentoplasty and split skin graft (POSSG) for reconstruction of large chest wall defects. A validity study of 34 patients
The aim of this study was to evaluate retrospectively the results of pedicled omentoplasty and split skin graft (POSSG) in reconstructing (full thickness) chest wall defects, and to define its role as a palliative procedure for local symptom control. Thirty-four patients with recurrent breast cancer (n = 25), radiation-induced necrosis (n = 5) or sarcoma (n = 4) of the chest wall were selected for the study. All patients underwent curative or palliative chest wall resection with reconstruction by pedicled omentoplasty and split skin graft (POSSG), between 1986 and 1994. Reconstructive outcome, complications, local tumour and symptom control following surgery was measured. The most common complication was shown to be partial necrosis of the omental flap (35%), followed by respiratory problems (26%), facial hernia (26%) and thoracic wound problems (15%), which were mostly treated in a conservative way (68%). The 3-year local tumour-free interval after POSSG in patients curatively treated for breast cancer is 16%. Seventy per cent of the patients who underwent palliative resection had longstanding relief of local pain, bleeding or foetor due to local tumour growth. It can be concluded that large (full thickness) chest wall defects after resection of local recurrence, primary malignancy or osteoradionecrosis of the chest wall can successfully be reconstructed by POSSG. Chest wall resection in patients treated with palliative intention is effective in local symptom control
Influence of genetic polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 genes on survival and therapy-related toxicity in multiple myeloma
We investigated the role of single nucleotide polymorphisms in genes encoding for drug-metabolizing enzymes in 209 newly diagnosed multiple myeloma patients included in a clinical trial comparing single with double intensive therapy. We observed no significant association between polymorphisms in CYP3A4, CYP3A5, MDR1, GSTM1 and GSTT1 and outcome either after treatment with induction chemotherapy or after high-dose therapy
Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients
Paraneoplastic cerebellar degeneration (PCD) is a heterogeneous group of
disorders characterized by subacute cerebellar ataxia, specific tumour
types and (often) associated antineuronal antibodies. Nine specific
antineuronal antibodies are associated with PCD. We examined the relative
frequency of the antineuronal antibodies associated with PCD and compared
the neurological symptoms and signs, associated tumours, disability and
survival between groups of PCD with different antibodies. Also, we
attempted to identify patient-, tumour- and treatment-related
characteristics associated with functional outcome and survival. In a
12-year period, we examined >5000 samples for the presence of antineuronal
antibodies. A total of 137 patients were identified with a paraneoplastic
neurological syndrome and high titre (> or =400) antineuronal antibodies.
Fifty (36%) of these patients had antibody-associated PCD, including 19
anti-Yo, 16 anti-Hu, seven anti-Tr, six anti-Ri and two anti-mGluR1.
Because of the low number, the anti-mGluR1 patients were excluded from the
statistical analysis. While 100% of patients with anti-Yo, anti-Tr and
anti-mGluR1 antibodies suffered PCD, 86% of anti-Ri and only 18% of
anti-Hu patients had PCD. All patients presented with subacute cerebellar
ataxia progressive over weeks to months and stabilized within 6 months.
The majority of patients in all antibody groups had both truncal and
appendicular ataxia. The frequency of nystagmus and dysarthria was lower
in anti-Ri patients (33 and 0%). Later in the course of the disease,
involvement of non-cerebellar structures occurred most frequently in
anti-Hu patients (94%). In 42 patients (84%), a tumour was detected. The
most commonly associated tumours were gynaecological and breast cancer
(anti-Yo and anti-Ri), lung cancer (anti-Hu) and Hodgkin's lymphoma
(anti-Tr and anti-mGluR1). In one anti-Hu patient, a suspect lung lesion
on CT scan disappeared while the PCD evolved. Seven patients improved by
at least 1 point on the Rankin scale, while 16 remained stable and 27
deteriorated. All seven patients that improved received antitumour
treatment for their underlying cancer, resulting in complete remission.
The functional outcome was best in the anti-Ri patients, with three out of
six improving neurologically and five were able to walk at the time of
last follow-up or death. Only four out of 19 anti-Yo and four out of 16
anti-Hu patients remained ambulatory. Also, survival from time of
diagnosis was significantly worse in the anti-Yo (median 13 months) and
anti-Hu (median 7 months) patients compared with anti-Tr (median >113
months) and anti-Ri (median >69 months). Patients receiving antitumour
treatment (with or without immunosuppressive therapy) lived significantly
longer [hazard ratio (HR) 0.3; 95% confidence interval (CI) 0.1-0.6; P =
0.004]. Patients > or =60 years old lived somewhat shorter from time of
diagnosis, although statistically not significant (HR 2.9; CI 1.0-8.5; P =
0.06)
MDR1 gene-related clonal selection and P-glycoprotein function and expression in relapsed or refractory acute myeloid leukemia
The expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, is an
independent adverse prognostic factor for response and survival in de novo
acute myeloid leukemia (AML). Little is known about MDR1 expression during
the development of disease. The present study investigated whether MDR1
gene- related clonal selection occurs in the development from diagnosis to
relapsed AML, using a genetic polymorphism of the MDR1 gene at position
2677. Expression and function of P-gp were studied using monoclonal
antibodies MRK16 and UIC2 and the Rhodamine 123 retention assay with or
without PSC 833. No difference was found in the levels of P-gp function
and expression between diagnosis and relapse in purified paired blast
samples from 30 patients with AML. Thirteen patients were homozygous for
the genetic polymorphism of MDR1 (n = 7 for guanine, n = 6 for thymidine),
whereas 17 patients were heterozygous (GT). In the heterozygous patients,
no selective loss of one allele was observed at relapse. Homozygosity for
the MDR1 gene (GG or TT) was associated with shorter relapse-free
intervals (P =.002) and poor survival rates (P =.02), compared with
heterozygous patients. No difference was found in P-gp expression or
function in patients with AML with either of the allelic variants of the
MDR1 gene. It was concluded that P-gp function or expression is not
upregulated at relapse/refractory disease and expression of one of the
allelic variants is not associated with altered P-gp expression or
function in AML, consistent with the fact that MDR1 gene-related clonal
selection does not occur when AML evolves to recurrent disease. (Blood.
2001;97:3605-3611
Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation
Recipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease (EBV-LPD). We studied whether preemptive therapy with rituximab prevents EBV-LPD, LPD-mo
Tumor Volume as an Alternative Response Measurement for Imatinib Treated GIST Patients
Background: Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS). Methods: LM from 84 GIST p
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