Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55-year-old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50--95% myeloblast cells and 95--100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,-6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated 90% of metaphases by autoradiography. The second patient, a 49-year-old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,-13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.
 ...
PMID:Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera. 60 27

Therapy with alpha-interferon (IFN alpha) can suppress the Ph1-positive hemopoiesis in a percentage of patients with chronic myelogenous leukemia (CML). We used IFN alpha to treat a 30-year-old CML patient, characterized by favourable prognostic signs (such as low leukocytosis, absence of splenomegaly and no increase in bone marrow blasts) at diagnosis, and obtained a complete remission, as evaluated by Southern blot and cytogenetic analysis, after one year of treatment. However, the polymerase chain reaction (PCR) revealed the persistence of a minimal residual disease. The IFN alpha therapy was stopped and the hematological status remained stable until eighteen months later, when a cytogenetic analysis revealed the appearance of a clone characterized by t(9;22) and trisomy 8, accounting for 30% of bone marrow metaphases. This cell population spontaneously regressed in the following months, before any cytotoxic treatment. However, as leukemic cells, detected by PCR, were still present, the patient received a high dose chemotherapy, which induced the complete eradication of the Ph1-positive clone, as demonstrated by the absence of bcr-abl transcript at the PCR reaction. Molecular and cytogenetic remission persist one year later, without any further therapy.
 ...
PMID:Transient cytogenetic relapse in a Ph1-positive chronic myelogenous leukemia patient previously treated with alpha-interferon. 162 97

We describe the clinical and laboratory findings of 78 adult patients with T-prolymphocytic leukemia (T-PLL) studied over the last 12 years. The main disease features were splenomegaly (73%), lymphadenopathy (53%), hepatomegaly (40%), skin lesions (27%), and a high leukocyte count (greater than 100 x 10(9)/L in 75%) with nucleolated prolymphocytes. A variant form with small, less typical cells was recognized in 19%. Membrane markers defined a postthymic phenotype TdT-, CD2+, CD3+, CD5+, CD7+; in 65%, the cells were CD4+ CD8-, in 21%, they coexpressed CD4 and CD8, and, in 13%, they were CD4- CD8+. Serology for human T-cell leukemia/lymphoma virus Type-I (HTLV-I) was negative in the 27 cases investigated. Cytogenetic analysis in 30 cases showed a consistent abnormality of chromosome 14, usually inv (14), with breakpoints at q11 and q32 in 76% of cases. Trisomy 8, including iso8q, was shown in 53%; t (11;14)(q13;q32) was documented in one case; and one had a normal karyotype. The clinical course was progressive with a median survival of 7.5 months. Thirty-one patients were treated with 2' deoxycoformycin and 15 responded (3 complete remissions and 12 partial remissions); the response rate (48%) increased to 58% in patients with a CD4+ CD8- phenotype. The median survival of responders was 16 months and of nonresponders 10 months; other treatments were less effective. T-PLL is a distinct clinico-pathologic entity with aggressive course and characteristic chromosome abnormalities. A subgroup of patients may benefit from deoxycoformycin.
 ...
PMID:Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. 174 86

A retrospective clinical review of 41 patients with chronic myelomonocytic leukemia revealed a median age of 66 years and a male:female ratio of 2.4:1. The disease was preceded by a myelodysplastic syndrome of a different subtype in 24% of the patients and transformed into acute leukemia in 24%. Splenomegaly was present in 54% of the patients and reached massive proportions in 24%. Chromosomal abnormalities occurred in 34% of those studied, most commonly in the younger age group; the most frequent were trisomy 8, monosomy 7, and deletions involving the long arms of chromosomes 20 and X. Polyclonal hypergammaglobulinemia was detected in 47% of the patients in whom serum protein electrophoresis was done. The median survival was 3 years. With use of univariate analysis, the statistically significant prognostic determinants were hemoglobin level, the "modified Bournemouth score," and bone marrow blast cell percentage. When these factors were subjected to a multivariate analysis, only bone marrow blast cell percentage was an independent prognostic determinant. Orally administered hydroxyurea controlled leukocytosis and splenomegaly in some patients without affecting the overall prognosis.
 ...
PMID:Chronic myelomonocytic leukemia: natural history and prognostic determinants. 259 15

Thirteen patients with simple monosomy 7 presented with pallor in 11, easy bruisability in five, splenomegaly in four, no infections, refractory anaemia in all, granulocytopenia in seven, monocytosis in three, leucocytosis in four and thrombocytopenia in eight. Peripheral blood and bone marrow findings were consistent with myelodysplastic syndrome (MDS) type I in three, type II in two, type III in two, type IV in three and acute myelofibrosis in three patients. Transformations to acute leukaemia in seven patients were M2 in one, M4 in four, megakaryoblastic in one and undifferentiated in one. Lack of chromosome 7 in 12-85% of analysed cells at initial presentation of MDS progressed to nearly 100% during blastic transformation. At that time an additional change in the long arm of chromosome 3 was seen in two patients and trisomy 8 in 6% of analysed cells in a third case. The median survival time was 12 months for MDS and 3 months for acute leukaemia. Simple monosomy 7 appears to be largely confined to young children and elderly people.
 ...
PMID:Simple monosomy 7 and myelodysplastic syndrome in thirteen patients without previous cytostatic treatment. 346 39

Clinical and laboratory features of seven patients with acute leukemia associated with the (4;11) chromosome translocation are presented. Leukemic blasts of these patients showed lymphoid morphology in 6 (although 1 was treated for monoblastic leukemia 3 years earlier) and monocytoid morphology in 1, were positive for TdT and HD 37 (CD 19) in 6 patients, whereas weak expression of CALLA was seen in only 1 patient and T-lineage-associated antigens in none. Leukemic blasts from four patients showed the simultaneous expression of B-lymphoid and myeloid antigens, suggesting leukemogenesis in a very early multipotent progenitor cell. In 2 patients an isochromosome of the long arm of No. 7 chromosome was found in the leukemic karyotypes in addition to t (4; 11) (q 21; q 23); in one instance present at diagnosis, in the other one occurring at relapse. In one other patient leukemia karyotype also demonstrated trisomy 8. Leukemic cells of three patients were investigated by molecular genetics and demonstrated immunoglobulin gene rearrangements for the Ig heavy chain sequences but not for the light chain constant regions and T cell receptor sequences. All patients were treated by intensive chemotherapy. Four of the 7 patients are in continuous complete remission. The longest event-free survival time (over 2 1/2 years) was seen in one patient who had also DOWN-syndrome. Including these 7 patients a clinical analysis of 71 patients with t (4; 11) acute leukemia was made, emphasizing the following characteristics at diagnosis: female sex (62%), age under 2 years (49%), leukocyte count over 100 X 10(9)/1 (61%), splenomegaly (80%), CNS-disease (11%). Survival of over 2 years was reported in less than 15% of the patients. It remains to be seen if risk-adapted treatment can alter the course of this early B-precursor acute leukemia with hitherto very bad prognosis.
 ...
PMID:Acute leukemia with chromosome translocation (4;11): 7 new patients and analysis of 71 cases. 349 35

Three patients had leukocytosis of large granular lymphocytes and chronic neutropenia. Clonal chromosomal abnormalities (trisomy 8 and trisomy 14) and lymphocytic infiltration of splenic red pulp, hepatic sinusoids, and bone marrow indicated the neoplastic nature of the large granular lymphocytes. Demonstration of a T3+, T8+, HNK-1 + phenotype and low natural killer cell activity that was augmented by interferon treatment showed the leukemic cells to be immature natural killer cells. Multiple autoantibodies were present and included rheumatoid factor and antinuclear, antineutrophil, antiplatelet, and antierythrocyte antibodies, suggesting a defect of B-cell immunoregulation. In addition, in-vitro studies showed impaired suppression of immunoglobulin biosynthesis by abnormal cells from one patient. Antineutrophil antibodies and absence of direct cell-mediated inhibition of granulocyte-macrophage colony formation supported a humoral immune mechanism for the neutropenia. In these patients the syndrome of splenomegaly, multiple autoantibodies with neutropenia, and lymphocytosis of large granular lymphocytes is due to a neoplastic proliferation of immature natural killer cells.
 ...
PMID:Leukemia of large granular lymphocytes: association with clonal chromosomal abnormalities and autoimmune neutropenia, thrombocytopenia, and hemolytic anemia. 396 54

A 59-year-old man presented with a granulocytic sarcoma arising in the manubrium, and splenomegaly. The blood count showed 1.2 x 10(9)/l eosinophils and a marrow aspirate was hypercellular with eosinophilia. Cytogenetic analysis of the marrow revealed a novel t(3;4) (p13;q12) and analysis of cells aspirated from the granulocytic sarcoma showed the same abnormality and an additional trisomy 8. Intensive chemotherapy and local radiotherapy led to resolution of the chest mass but persistence of the chromosome translocation in the marrow.
 ...
PMID:Karyotypic evolution in a granulocytic sarcoma developing in a myeloproliferative disorder with a novel (3;4) translocation. 779 73

To date, neither the clinical significance of isolated trisomy 8, the most frequent trisomy in acute myeloid leukemia (AML), nor the effect of age within a single cytogenetic group has been examined. We report a large cohort of adult trisomy 8 patients and examine whether increasing age within a homogeneous cytogenetic group alters clinical outcome. Characteristics and outcome of patients with isolated trisomy 8 enrolled in the prospective Cancer and Leukemia Group B (CALGB) cytogenetic study CALGB 8461 are described. Isolated trisomy 8 was identified in 42 (3.03%) of 1387 patients enrolled in five CALGB treatment protocols. These patients had a median age of 64 (range, 16-79) years, 50% female proportion, and a low frequency of hepatomegaly (10%) or splenomegaly (10%). Laboratory features included a median white blood count of 7.3 x 10(9)/L, nonspecific French-American-British distribution, with 36% of patients having Auer rods. Treatment outcome was unsatisfactory with a complete remission (CR) rate of 59%, median CR duration of 13.6 months, and median survival of 13.1 months. Older age adversely affected outcome; trisomy 8 patients > or =60 years had both an inferior CR rate (40% versus 88%; P = 0.004) and overall survival (median, 4.8 versus 17.5 months; P = 0.01), as compared with those <60 years of age. Of the patients <60 years of age, only four remain alive, and all received noncytarabine-based intensive chemotherapy, followed in three cases by autologous (n = 2) or allogeneic (n = 1) stem cell transplant in CR1. Adults with AML and isolated trisomy 8 have a poor outcome that is accentuated by increasing age and is rarely cured with cytarabine-based therapy. Alternative investigational treatments should be considered for individuals with this AML subset.
 ...
PMID:Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: results from Cancer and Leukemia Group B 8461. 960 82

There has not been a reported series of children with therapy-induced myelodysplastic syndrome/acute myeloid leukemia (tMDS/tAML) who were treated systematically. This paper describes 24 children with tMDS/tAML who were assigned randomly to standard- or intensive-timing induction on protocol CCG 2891. Presenting features and outcomes of those children were compared with those of 960 patients with de novo MDS (62 patients) or AML (898 patients). Children with tMDS/tAML were older at presentation (P =.015), had lower white blood cell counts (P =.01), and were more likely to have MDS (21% vs 7%) (P =.02) and trisomy 8 (P =.06). Fewer had hepatomegaly (P =.02), splenomegaly (P =.03), hepatosplenomegaly (P =.02), or classic AML translocations [t(8;21), t(15;17), 16q22; P =.02]. They had a poorer induction rate (50% vs 72%, P =.016), overall survival (26% vs 47% at 3 years, P =.007), and event-free survival (21% vs 39% at 3 years, P =.023). Disease-free survival after achieving remission was similar (45% vs 53%, P =.868). Children with tMDS/tAML who received intensive-timing induction had better outcomes than those who received standard-timing induction (overall survival 32% vs 0%, P =.54). In this study, the latency period to development of tMDS/tAML was the same for presumed alkylator-induced as for topoisomerase-induced myeloid leukemia. The findings of this study confirm that most children with tMDS/tAML have disease resistant to current therapies. Standard-timing induction appears less effective for this population.
 ...
PMID:Acute myeloid leukemia and myelodysplastic syndrome in children treated for cancer: comparison with primary presentation. 1209 32


1 2 Next >>