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X Yataganas

Publications and source records attributed to X Yataganas.

At least 37 records · Page 2Linked to original sources

Evidence for sinoatrial blockade associated with high dose cytarabine therapy.

Cytarabine therapy is rarely complicated by cardiotoxicity. The present report describes the clinical course of a 35-year-old female patient with acute myelogenous leukemia in complete remission, who developed sinus bradycardia while on high dose cytarabine as a consolidation therapy. The electrocardiographic findings suggested that bradycardia was most probably the result of sinoatrial blockade. The available information regarding a possible association of cytarabine with disturbances of cardiac rhythm is reviewed.

Adult↗

Somatic hypermutation of immunoglobulin variable region genes: focus on follicular lymphoma and multiple myeloma.

Analysis of the rearranged immunoglobulin variable region gene hypermutation has provided important information concerning the clonal history and ontogenetic origin of various B-cell lymphoproliferative disorders. Under the selective pressure of antigen, mutational events in immunoglobulin genes will fine tune survival of B-cell clones bearing immunoglobulin with high affinity for antigen. Our studies aimed at analyzing neoplastic disorders originating from germinal and post-germinal center B-cells: follicular lymphoma and multiple myeloma, respectively. Despite the already acknowledged evidence for a selectable distribution of mutations within the clonal immunoglobulin variable heavy chain genes, very little is known about the contribution of light chains in the process of antigen selection. In follicular lymphoma, a more limited pattern of somatic mutation with less evidence of antigen selection was observed in variable kappa light chain genes (40%) than in their partner heavy chain genes (80%). In myeloma, hypermutation of variable light chain genes, with a distribution suggestive of antigen selection, was frequently observed. Based on these data and recent reports it appears that the light chain expressed by the clonogenic myeloma B-cells plays a pivotal role in the antigen selection process. Additionally, abortive kappa light chain variable region genes in lambda-expressing myelomas carried a significant number of somatic mutations indicating that the cell of origin is open to the hypermutation machinery at that particular developmental stage irrespective of antigen selection.

Amino Acid Sequence↗

A novel chromosomal abnormality involving chromosomes 2 and 18 in a patient with myelodysplastic syndrome.

Cytogenetic analysis of bone marrow cells from a patient with myelodysplastic syndrome associated with eosinophilia showed a complex translocation with a 46,XY,t(2;18;2)(p23;q11;q32) karyotype. The patient has refractory anemia (RA) according to the French-American-British Cooperative Group (FAB) classification, and after 90 months of follow-up he shows no evidence of leukemic transformation. This chromosomal abnormality has not been previously described in myelodysplastic syndromes and may be associated with good prognosis as the patient has been stable for a long time.

Adult↗

Trisomy 8 in a patient who responded to therapy with all-trans-retinoic acid and developed paroxysmal nocturnal haemoglobinuria.

Trisomy 8 is the most common numerical chromosomal abnormality in myelodysplastic syndromes (MDS). Paroxysmal nocturnal haemoglobinuria (PNH) is an aquired haemolytic anaemia, clonal in nature, due to somatic mutation. PNH may evolve to aplastic anaemia, to MDS or to acute myeloid leukaemia. We present a patient who had trisomy 8 mosaicism at disease presentation who received therapy with all-trans-retinoic acid, responded to therapy, and developed PNH in the course of the disease. Cytogenetics at the time of PNH diagnosis showed a normal karyotype.

Adolescent↗

Detection of "PNH red cell" populations in hematological disorders using the Sephacryl Gel Test micro typing system.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterised by an unusual sensitivity of abnormal red cell population(s) to complement lysis, due to a complete or incomplete defect of various surface molecules, including CD55 and CD59. PNH has been associated with various hematological disorders. Using a newly introduced method, the Sephacryl gel test microtyping system, we investigated the presence of CD55 or CD59 defective red cell populations in several hematological disorders. It was also found that a large proportion of such patients possess CD55 deficient populations, while a smaller but still significant proportion possess CD59 deficient populations. Defective red cell populations were detected in normal subjects as well. These findings need further investigation. Nevertheless the Sephacryl Gel Test microtyping system although non specific, seems to be useful in screening for the PNH and/or "PNH-like" red cell defect in several hematological disorders.

CD55 Antigens↗

Leukaemia cutis preceding acute myelomonocytic leukaemia.

We report a case of acute myelomonocytic leukaemia (AMML) who presented with a striking leukaemic infiltration in the frontal area of the scalp that was also rapidly followed by infiltrates in other sites of the skin, mainly in the upper thoracic wall. Leukaemic skin infiltration developed independently of his haematological status; nevertheless, he rapidly progressed to acute leukaemia. We emphasise the importance of early recognition and identification of such lesions with a subsequent early application of systematic antileukaemic therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Development of plasma cell tumors during treatment of multiple myeloma.

Plasma cell tumors (plasmacytomas-PCT) of the bone, or extramedullary PCT, may be diagnosed in patients with or without the diagnostic criteria for systemic multiple myeloma (MM). The reason for the local development of these tumors is not clear. Recent reports emphasize the contribution of CT and MRI in the detection of bone lesions and their expansion into the soft tissues. We report the development of PCT in nine patients with MM under maintenance treatment with alpha-IFN, of whom six had no evidence of systemic relapse and three had indications of early relapse. The PCT were located in the pelvis (4), thoracic (3), cervical (1), and lumbar (2) spine and in 8/9 cases were not demonstrable on plain X-rays. These observations suggest that frequent screening with advanced imaging techniques may detect local disease expansion in asymptomatic patients. Early application of radiochemotherapy may improve prognosis.

Adult↗

Analysis of the kappa light chain variable region in multiple myeloma.

The study of immunoglobulin heavy chain gene rearrangements in multiple myeloma has revealed extensive divergence from the germline sequences, but no intraclonal diversity with disease evolution. Our study investigated the state of the rearranged kappa light chain variable region (V kappa) gene segments as well as abortive V kappa family gene usage in cases of multiple myeloma expressing lambda light chain. We studied 11 cases of kappa and five cases of lambda light chain-expressing multiple myeloma. Total cellular RNA was extracted from the bone marrow of patients with overt disease and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to amplify clonally rearranged variable region sequences. Direct nucleotide sequencing by the dideoxy-chain termination method was performed on the RT-PCR products. We did not observe preferential usage of certain V kappa gene families. Mutation frequencies of the V kappa segments varied in number. In the majority of cases, extensive somatic mutations occurred within the complementarity determining regions (CDRs) of V kappa, whereas only a limited degree of divergence from the germline was observed in others. In all cases studied. replacement mutations tended to cluster in the CDRs, a finding compatible with an antigen-driven somatic hypermutation process. In 3/5 cases of lambda light-chain expressing multiple myeloma, abortively rearranged V kappa gene segments were amplified from genomic DNA; in two cases a non-templated nucleotide insertion rendering the V kappa sequences out-of-frame was observed, and in the third a stop codon was identified in the open reading frame of the V kappa sequence. Somatic mutations were observed in all cases of abortive V kappa genes studied; however, their distribution does not suggest selection by antigen. We conclude that somatic mutations observed in the V kappa regions of myeloma cells are of variable extent and suggest operation of the antigen selection process. Lack of or minimal somatic hypermutation in a few cases may be in some way implicated in the biological heterogeneity of the disease.

Amino Acid Sequence↗

Reverse transcription polymerase chain reaction for the diagnosis and molecular monitoring of the PML/RAR alpha fusion gene in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by a specific t(15;17) translocation and a high rate of response to all-trans retinoic acid. The translocation generates a PML/RAR alpha chimeric gene which is transcribed in a fusion PML/RAR alpha mRNA. In this study, by using RT-PCR, we examined 14 APL patients for PML/RAR alpha fusion gene transcripts. Eight patients were studied at diagnosis, 2 at relapse, 1 both at relapse and after reinduction, 1 both at diagnosis and after three cycles of consolidation chemotherapy, and 2 patients were examined for minimal residual disease (MRD) 4 months after completing treatment. A positive result was observed in all 14 cases. Two patients who were in complete hematologic remission had evidence of hematologic relapse soon after the positive test. We conclude that RT-PCR for APL yields important diagnostic and prognostic information for the APL patients.

Adolescent↗

Hypereosinophilia associated with monosomy 7.

Cytogenetic analysis of bone marrow cells from a patient with anemia, marked leukocytosis with eosinophilia, and thrombocytopenia showed monosomy 7 in all metaphases examined. The patient has refractory anemia (RA) according to FAB classification. Because of the hypereosinophilia of the patient, PCR technique was performed and no bcr-abl mRNA, specific for chronic myelogenous leukemia, was detected. Monosomy 7 has not been previously described in cases with hypereosinophilia. We assume, according to previous reports, that multiple genetic lesions can be involved in the pathogenesis of hypereosinophilia in this patient.

Aged↗

Correction of anaemia and thrombocytopenia in a case of adult type I osteopetrosis with recombinant human erythropoietin (rHuEPO).

A case of adult osteopetrosis Type I was diagnosed in a 22-year-old female. She presented for investigation of anaemia with 'myelophthisic' characteristics and extramedullary haemopoiesis which was resistant to haematinics, nandrolone and low-dose corticosteroids. She became progressively transfusion-dependent with gradually worsening thrombocytopenia. She was successfully treated with recombinant erythropoietin. Anaemia as well as thrombocytopenia were corrected. There appeared to be a synergistic action of erythropoietin with steroids.

Adult↗

Correlation of the site of M-bcr breakpoint with chronic phase duration, blastic crisis lineage and thrombocytosis in Ph1-positive chronic myelogenous leukemia.

The breakpoints on chromosome 22 in CML occur within a 5.8 kb region called the Major breakpoint cluster region (M-bcr). DNA mapping within the M-bcr region was performed in 41 long term followed Ph1-positive CML patients using the Southern blot technique. The purpose of this study was to determine whether localization of M-bcr breakpoint correlates with the length of chronic phase of the disease, blastic crisis lineage and thrombocytosis at the time of initial diagnosis. Our results fail to indicate any correlation between breakpoint localization and duration of chronic phase, blastic crisis lineage and platelet count at diagnosis.

Blast Crisis↗

'Fetal' erythropoiesis following bone marrow transplantation as estimated by the number of F cells in the peripheral blood.

The aim of this study was to define factor(s) influencing fetal erythropoiesis following bone marrow transplantation. Thirty-one transplanted patients (14 males, 17 females) were studied. The underlying diseases were chronic myelogenous leukaemia (CML, 18 patients), acute myeloblastic leukaemia (AML, 7 patients) and acute lymphoblastic leukaemia (ALL, 6 patients). Reticulocyte and peripheral F cell estimation was carried out in donors and patients before transplantation and repeatedly during recovery. For F cell estimation, an indirect immunofluorescence assay was utilized. A significant increase above pre-BMT values in the percentage of F cells was observed in all patients from days 11 to 40 after transplantation. The increase of F cells on days 15, 18, 25, 32, 40 and 50 after transplantation was statistically significant in 14 patients who had shown an increase of F cells following chemotherapy (high responders) compared with the remaining 17 patients who did not respond so significantly. This finding supports the influence of the host bone marrow micro environment. The nature of the mechanisms operating remains to determined.

Adolescent↗

The effect of recombinant alpha-interferon on natural killer cell activity and clinical course in patients with myelodysplastic syndrome.

Thirteen patients with myelodysplastic syndrome (MDS) were included in this study and consented to treatment with recombinant alpha-interferon (a-IFN). These patients were subclassified: six as RAEB, one as RAEB-T and six as CMML. T-cell subsets and natural killer cells were identified in the peripheral blood with the use of monoclonal antibodies and natural killer cell activity (NKa) was assayed before, during and after a-INF treatment. The treatment schedule consisted of 2.0 MU/m2 sc t.i.w. continuously for the three months. Prior to treatment, NKa was found decreased in 11 of 13 patients as compared to that of normal individuals. Following a-IFN administration, a rise of NKa was observed in eight of the eleven patients. In those who responded, a-IFN was continued for 1 to 21 months. Alpha-IFN treatment was myelosuppressive for most of the patients, but transient increase of the number of neutrophils and platelets was observed in 3 and of the reticulocytes in one patient. Disease progression was recorded in 9/13 patients (69%) at a median time of 17.3 months. The median overall survival was 30.5 months (range 7.5 to 65+ months). No evidence of a relationship was found between the rise in Nka and the limited clinical improvement observed. Two NKa responders under continuous a-IFN treatment are in stable clinical condition for 36+ and 65+ months. The study provides only limited evidence that a-IFN may improve the clinical course of patients with MDS.

Aged↗

alpha Interferon treatment of essential thrombocythaemia and other myeloproliferative disorders with excessive thrombocytosis.

The effect of recombinant interferon alfa-2b on platelet count, thrombocytosis-associated symptoms and marrow fibrosis was studied in 18 patients with myeloproliferative diseases and associated thrombocytosis (nine with essential thrombocythaemia, three with polycythaemia vera, three with myelofibrosis and three with chronic myelogenous leukaemia). A reduction of the platelet count below 600 x 10(9)/L was achieved in 94%, and below 400 x 10(9)/L in 77% of the patients within 8 to 330 days of treatment. The selective thrombocytosis-reducing effect of alpha interferon was maintained for long periods of time in most patients without serious side effects. Thrombocytosis-associated symptoms were relieved once the number of platelets was reduced to near normal levels. Marrow reticulin content was found to be reduced after treatment in two of the seven patients studied. Side effects of alpha interferon were flu-like symptoms, which usually subsided within 7 days of treatment.

Adult↗

Randomized clinical trial comparing ceftriaxone/amikacin versus ceftazidime/amikacin as initial therapy of febrile episodes in neutropenic patients.

Neutropenic patients with underlying hematologic (usually malignant) diseases were randomized to receive either 2 g ceftriaxone once daily +0.5 g amikacin or 2 g ceftazidime twice daily +0.5 g amikacin b.i.d. when fever was higher than 38 degrees C and granulocyte counts less than 0.5 x 10(9)/l. 25 patients were included in each treatment group. Successful outcome of treatment was observed in 28 (13/15) and in an additional 5 (2/3) patients after modification of the therapy. Tolerability was excellent in both groups.

Adolescent↗

Effect of recombinant alpha-interferon administration on peripheral blood lymphocyte subpopulations and natural killer cell activity in patients with refractory anemia with excess of blasts.

Peripheral blood lymphocyte subpopulations and natural killer cell activity (NKa) were determined in 7 patients with refractory anemia with excess of blasts (RAEB) subjected to alpha-interferon (alpha-IFN) administration. Patients received subcutaneously 3 MU alpha-IFN three times a week for 3 consecutive months, and studies were done just before and one month after the cessation of alpha-IFN administration. Before starting alpha-IFN, the patients NKa was severely reduced in relation to control (p less than 0.001), natural killer (NK) cells (CD16+ cells) and suppressor/cytolytic T-lymphocytes (CD8+ cells) were within normal range, while helper/inducer T-lymphocytes (CD4+ cells), as well CD4+/CD8+ cell ratio, were significantly reduced (p less than 0.001 and p less than 0.001, respectively). Significant diminution was also noted in B-lymphocyte numbers (CD19+ cells) (p less than 0.05). Following alpha-IFN administration, NKa values increased significantly in comparison to pre-IFN values (p less than 0.05), but failed to reach normal range. CD3+ cells and CD8+ cells decreased (p less than 0.05 and p less than 0.02), while CD4+ cells and CD4+/CD8+ cell ratio did not change significantly. A statistically significant rise was observed in CD16+ cells (p less than 0.05). The sensitivity of NK-cells against alpha-IFN and interleukin-2 (IL-2) added in vitro, was also significantly increased (p less than 0.05). The findings indicate that alpha-IFN administration may affect some disturbed immunologic functions in patients with RAEB, but further studies are needed to elucidate the mechanism and the extent of this action.

Aged↗