11/71. leukemia and myelodysplasia effect of multiple cytotoxic therapy in essential thrombocythemia.Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by increased risk of thrombosis and/or hemorrhages. Cytotoxic drugs are mostly used in patients at high risk for thrombotic complications, while their use is still debated in low risk patients because of the risk of leukemia or secondary neoplasm. We discuss the leukemic risk of available treatment strategies in a large cohort of patients. Over a 12 years period we treated 23 patients with busulfan (BU), 1 with pipobroman (Pi), 6 with 32P, 48 with hydroxyurea (HU) in 62 cases associated with acetyl salicylic acid (ASA) while 77 patients received ASA alone and 33 did not receive any therapy. We observed 2 cases of acute leukemia (AL) and 1 of myelodysplastic syndrome (MDS). One of these patients had been treated with 32P and Pi these after with and the other two with BU and HU. They represented 23% of all patients treated with more than 1 cytotoxic agent, 16.6% of 32P treated subjects, 4% of those with HU and 6.4% of those with BU. The case of MDS occurred in a 81 years old female and represents 4% of cases of ET over the 70 years of age. No cases of AL or MDS were observed in patients not receiving cytotoxic therapy (with or without ASA). According to our experience the use of more than one cytotoxic agent in ET confirms the increase in the risk of leukemia in these cases. However, none of the patients treated with HU alone, even for more than 10 years (12 cases) developed AL. No treatment or therapy with ASA alone may be the best choice in young patients with ET with a low risk of thrombotic complications.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
12/71. Detailed genome-wide screening for inter- and intrachromosomal abnormalities by sequential G-banding and RxFISH color banding of the same metaphase cells.While the now-classic chromosome banding methods, such as G-banding, remain the techniques of choice for the initial screening for karyotypic abnormalities, sometimes chromosomal rearrangements involve segments too small or too similarly banded to be detected or described adequately by these techniques. The necessity to use a genome-wide, fluorescence in situ hybridization (FISH)-based screening technique as a complement to G-banding is especially obvious in cases where the information obtained by the latter analysis does not provide an adequate guide to the choice of probes for chromosome-specific FISH. Furthermore, the same metaphase cells should ideally be used for both G-banding and FISH analysis to overcome the scarcity of metaphases observed in many cases and to ensure the correct interpretation of chromosomal aberrations in cytogenetically unstable neoplasms with massive cell-to-cell karyotypic variability. We describe a protocol which enables cross-species color banding (RxFISH), a new FISH-based screening technique that simultaneously imparts specific color banding patterns on all chromosomes, of preparations that have been G-banded and mounted for up to several years, as well as a procedure allowing chromosome-specific painting of the same metaphase cells to resolve whatever doubts persist after the preceding G-banding and RxFISH analyses. This approach makes possible a detailed, genome-wide screening for inter- and intrachromosomal abnormalities including archival cases whose karyotypic rearrangements had been incompletely identified by G-banding.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
13/71. Prolonged complete remission of myelodysplastic syndrome treated with danazol, retinoic acid and low-dose prednisone.Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic neoplasms. Different medications have been tried in MDS; however, no effective treatment has been yet established. We report a patient with MDS who achieved a complete remission in response to combination therapy of danazol, retinoic acid, and prednisone. A 53-year-old female presented with pancytopenia, macrocytosis, and hypercellular bone marrow with erythroid hyperplasia and dysplasia and 10% ringed sideroblasts. Cytogenetic studies revealed the presence of two abnormal clones. She was diagnosed as having MDS-refractory anemia and was given blood transfusions to maintain blood cell counts at acceptable levels. At the same time, she was started on a combination of danazol (600 mg/day), retinoic acid (100 mg/day), and prednisone (10 mg every other day). Fourteen months later, the patient was in complete hematologic remission; she had normal peripheral blood count, and the blood smear showed normal morphology. Bone marrow studies revealed normal trilineage hematopoiesis. She was continued on the same combination treatment for 86 months, and she remained in complete clinical remission. Eighty-eight months from diagnosis, she relapsed with acute myeloid leukemia. This is the first reported case of MDS-RA that sustained a complete hematologic remission for a prolonged period in response to this combination treatment. This report indicates that restoration of normal hematopoiesis, prolongation of disease-free survival, and delay in the transformation to acute leukemia may be achieved by this combination of treatment in a subset of patients with MDS, especially refractory anemia with severe thrombocytopenia.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
14/71. A heterozygous frameshift mutation in the fanconi anemia C gene in familial T-ALL and secondary malignancy.BACKGROUND: patients with fanconi anemia (FANC) have a well documented increased risk to develop malignancies, especially Acute Myeloid leukemia (AML) and Myelodysplastic Syndrome (MDS). The risk for heterozygous individuals is not clear, epidemiological data are inconsistent. If the risk for heterozygous individuals to develop malignancies was increased, they should be found in groups of patients with AML or MDS at higher proportion than in the normal population. We are currently screening a pediatric population with hematologic malignancies for mutations in the FANCA, FANCC and FANCG gene, and report here on siblings carrying a heterozygous frameshift mutation in the FANCC Gene. patients AND methods: Using PCR based single strand conformational analysis we screened the dna from pediatric patients suffering from 1 degree or 2 degrees MDS, CMML/JMML or AML for mutations in the FANCA (43 exons), FANCC (14 exons) and FANCG (14 exons) gene, and included one patient with refractory T-ALL, being the brother of a patient with T-ALL and MDS transforming into AML. Aberrant PCR products were directly sequenced. Flowcytometric measurement of mitogen-sensitivity and G2-phase arrest is used to evaluate cultured stimulated lymphocytes from individuals carrying FANC-mutations. RESULTS: A novel heterozygous frame-shift mutation, 377-378delGA in the FANCC gene was found in 2 siblings, both suffering from T-ALL with subsequent MDS transforming to AML in one of them. No other mutation was found by direct sequencing of the complete FANCC gene. Both patients died under therapy. The parents (first degree cousins) and one healthy brother are also carriers. Their lymphocytes show a higher mutagen sensitivity than normal, but do not get blocked in g2 phase as being typical for fanconi anemia. CONCLUSION: As the mutation causes a premature Stopcodon within exon 4 of the FANCC gene it has to be regarded as a causal FANCC gene defect. The findings within this family support the hypothesis of an increased risk to develop malignancies in heterozygous carriers of FANC-mutations. A systematic screening of further patients is needed, and we are currently examining a larger cohort to get a better estimate of the true risk of heterozygosity.- - - - - - - - - - ranking = 17.782636749908keywords = malignancy (Clic here for more details about this article) |
15/71. Concurrent Langerhans cell histiocytosis and myelodysplasia in children.BACKGROUND: Langerhans cell histiocytosis (LCH) is characterized by the proliferation of abnormal histiocytes (langerhans cells), whose origin as a reactive process or a neoplastic disorder is still poorly understood. Although LCH has been recorded as being associated with malignant neoplasms, concurrence of LCH and myelodysplastic syndrome has not been reported so far. PROCEDURE: We report on four children aged 23, 25, 26, and 53 months with multisystem LCH with organ dysfunction (bone marrow and liver) whose bone marrow pictures, taken at diagnosis, revealed the presence of myelodysplastic abnormalities (RA, RAEB, RAEB-t). RESULTS: We suggest that the commonly used expression of "organ dysfunction," which refers to clinical and functional alterations, could be explained by a myelodysplastic-like disorder. CONCLUSIONS: The contemporary presence of both events may provide a better understanding of the pathogenesis of LCH, especially in young children with multisystem disease and organ dysfunction, who are known to have a very poor outcome.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
16/71. Therapy-related myelodysplastic syndrome of recipient origin after allogeneic bone marrow transplantation for acute lymphoblastic leukaemia.Therapy-related myelodysplastic syndrome (t-MDS) is a very rare complication of allogeneic bone marrow transplantation (BMT). A woman with T acute lymphoblastic leukaemia (T-ALL) received an allogeneic BMT from a donor with the beta-thalassaemic trait. Five years after BMT, the red cell indices returned to normal after an initial conversion to microcytosis, implying autologous haematopoietic regeneration. Seven years after BMT, thrombocytopenia developed and marrow examination confirmed t-MDS, with a characteristic karyotype 46,XX,inv(3)(q21;q26), del(5)(q13),add(17)(p11). Retrospective molecular analysis of donor/recipient chimaerism showed gradual regeneration of recipient cells after BMT, culminating at the time of t-MDS. Our findings illustrate the unusual occurrence of t-MDS after allogeneic BMT. Re-emergence of recipient haematopoesis may herald the development of a haematological malignancy different from the original neoplastic clone for which the BMT was performed.- - - - - - - - - - ranking = 512.0412102863keywords = haematological malignancy, malignancy (Clic here for more details about this article) |
17/71. Chromosomal aberrations in bloom syndrome patients with myeloid malignancies.bloom syndrome (BS) predisposes affected individuals to a wide variety of neoplasms including hematological malignancies. Thus far, cytogenetic findings in hematological neoplasms have been reported in only a few BS patients. We present the karyotypic findings in a BS patient diagnosed with acute myeloid leukemia (AML), FAB subtype M1, and a review of the literature, showing the preferential occurrence of total or partial loss of chromosome 7 in BS patients with AML or myelodysplastic syndromes (MDS).- - - - - - - - - - ranking = 2keywords = neoplasm (Clic here for more details about this article) |
18/71. FISH characterization of t(8;12)(q12;p13) observed as the sole karyotypic anomaly in a myelodysplastic syndrome patient.We report a t(8;12)(q12; p13) as the sole cytogenetic anomaly in a patient with a myelodysplastic syndrome (MDS). By means of FISH, we mapped the genomic region involved in the breakpoint (bkp) on both chromosomes. The 12p13 bkp mapped between markers WI-664 and WI-9218, immediately distal to the breakpoint cluster region frequently involved in hematological neoplasms targeted by y964C10. The 8q12 bkp (not yet investigated by FISH) was characterized and found to occur between markers WI-3263 and D8S524 within the region recognized by y874E10.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
19/71. Unrelated clonal chromosome abnormalities in myelodysplastic syndromes and acute myeloid leukemias.Most neoplasms are monoclonal and the tumor cells are believed to be the progeny of a single transformed cell. Clonality has been demonstrated by X-chromosomal enzymes, immunoglobulin and T-cell receptor gene rearrangements, or clonal cytogenetic abnormalities. Nevertheless, cytogenetically unrelated clones with disparate chromosome abnormalities are found infrequently in hematologic malignancies. We report four kinds of coexisting independent clones, 8/ 21, der(1;7)/ 8, del(9)/-X/i(Xq), and i(7p)/ 11, respectively, which to our knowledge mostly have not been reported in same individuals, in two myelodysplastic syndrome and two acute myeloid leukemia cases.- - - - - - - - - - ranking = 1keywords = neoplasm (Clic here for more details about this article) |
20/71. pulmonary alveolar proteinosis as a terminal complication in myelodysplastic syndromes: a report of four cases detected on autopsy.Secondary pulmonary alveolar proteinosis (PAP) is one of the complications of hematologic malignancy and immunosuppressive diseases. We encountered four cases of myelodysplastic syndrome (MDS) associated with PAP detected on autopsy. They consisted of two refractory anemia (RA) and two patients with refractory anemia with excess blasts in transformation (RAEBt) at the time of MDS diagnosis, but all of them developed leukemic phase and were resistant to chemotherapy at the time of pulmonary episodes. Of the four MDS patients, two also had pulmonary aspergillosis. Previously, 69 patients with PAP associated with hematologic disorders have been reported, but there have been only seven cases with MDS, including our four patients. Of the 69 reported cases of PAP in hematologic malignancies, 24/63 (38%) informative patients with infection had fungal infections of the lung; 2/7 (29%) MDS cases had fungal infection. We should, therefore, pay careful attention to this possibility in cases of MDS with lung complications, including PAP, especially in patients in the leukemic phase of MDS.- - - - - - - - - - ranking = 4.4456591874769keywords = malignancy (Clic here for more details about this article) |
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