1/8. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. genes chromosomes Cancer 27:229-238, 2000.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
2/8. Interstitial deletion of the short arm of chromosome 12 during clonal evolution in myelodysplastic syndrome with t(5;12)(q13;p13) involving the ETV6 gene.We report here a 65-year-old man with a myelodysplastic syndrome (MDS), refractory anemia with excess of blasts. He had received chemotherapy with tegafur for renal carcinoma. Chromosome analysis of bone marrow cells revealed complex karyotypes; del(5)(q13) was observed in all 20 metaphase spreads, and two related aberrations, add(12)(p11) and add(12)(p13), were detected in 13 and 7 cells, respectively. fluorescence in situ hybridization (FISH) analysis with chromosome-specific DNAs revealed that these alterations originated from a reciprocal translocation (5;12)(q13;p13). Therefore, del(5)(q13), add(12)(p11), and add(12)(p13) were revised as der(5)t(5;12)(q13;p13), der(12)del(12)(p11p13)t(5;12)(q13;p13), and der(12)t(5;12)(q13;p13), respectively. fluorescence in situ hybridization with a series of cosmid probes spanning the ETV6 gene showed that the 12p13 breakpoint on the der(12)t(5;12)(q13;p13) was located in intron 1, but the exon 1 signal was deleted. Our results suggest that a fusion gene was generated between the 5'-end of an unidentified partner at 5q13 and the 3'-end of ETV6 by t(5;12)(q13;p13), and that the interstitial deletion (12)(p11p13) occurred following t(5;12) during clonal evolution. del(12)(p11p13), including the rearranged ETV6 gene, may be implicated in the progression of MDS.- - - - - - - - - - ranking = 5keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
3/8. hematopoietic stem cell transplantation in children with hematological malignancies across HLA barriers--reasonable alternative?The aim of this study was to evaluate the efficiency and risks of T-cell depletion in prevention of graft versus host disease (GVHD) using HLA haploidentical family donors as an alternative source of hematopoietic stem cells (HSC) in children with hematological malignancies without suitable matched donor. Ten children, median age 12 years (range, 3-17), were transplanted from haploidentical family donors for acute lymphoblastic leukemia (n = 4), acute myelogenous leukemia (n=2), chronic myelogenous leukemia (n = 2), non-Hodgkin lymphoma (n = 1) and myelodysplastic syndrome (n = 1). parents were donors for nine, sibling for one patient. T-cell depletion of HSC was performed using CellPro followed by antiCD2/CD3 depletion in 7, and CliniMacs magnetic sorting in 3 grafts. Primary engraftment was achieved in nine patients. Patient with graft failure was successfully re-grafted. Primary acute GVHD was diagnosed in one patient who got higher amount of T-cells in the graft. Secondary GVHD was induced by add-backs of lymphocytes in four patients. Three patients developed chronic GVHD. Four patients died due to transplant related mortality (40%), one from veno-occlusive disease, two due to CMV pneumonia and one of aspergillosis with extensive chronic GVHD. Four patients relapsed with leukemia within 35-98 days post transplant, three without previous signs of GVHD, and all died. Two patients are alive and well 26 and 42 months after transplant. Haploidentical family donors appear to be a reasonable alternative option for patients with urgent indications for allogeneic transplant and/or without a matched donor.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
4/8. Bone marrow aspirates as part of routine donor assessment for allogeneic blood and marrow transplantation can reveal presence of occult hematological malignancies in otherwise asymptomatic individuals.Pre transplant screening work-up of donors for allogeneic blood and marrow transplantation is essential in an effort to minimize risks to the recipient and protect the donor. At Princess Margaret Hospital, every potential donor is screened with a bone marrow aspirate. The case histories of three asymptomatic potential donors who presented within 1 year with normal complete blood counts, history and physical examination are presented. A 65-year-old male patient was diagnosed with smouldering multiple myeloma, a 72-year-old male patient with chronic lymphocytic leukemia and a 42-year-old male patient with myelodysplastic syndrome. bone marrow examination led to the diagnosis in each one of these cases. Of note is that each of the potential donors was discovered to have the same disease as the transplant recipient. in vitro clonogenic hemopoietic progenitor assays were compared to those of 20 normal volunteers. Inferior growth of hemopoietic progenitor colonies in all three was noted. In conclusion, particularly in older donors and donors with potential for familial malignancies, more screening investigations including bone marrow aspiration may be reasonable to investigate for occult hematological malignancies prior to stem cell donation. Clonogenic assays can contribute to detect hemopoietic abnormalities pre transplant.- - - - - - - - - - ranking = 0.2952519855282keywords = myelodysplastic (Clic here for more details about this article) |
5/8. Secondary hematological malignancies after breast cancer chemotherapy.According to several reports, the 10 year incidence of secondary acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) after systemic chemotherapy is approximately 1.5%. The cumulative risk increases by 0.25--1% for the first 8 years after treatment. We have reported only 6 cases of hematological malignancies (0.3%) after breast cancer chemotherapy in our institute. We detected 2 cases of secondary AML and 1 case of MDS, 19, 52 and 12 months, respectively, after systemic chemotherapy for breast cancer. Published data on the occurrence of secondary hematological malignancies other than AML or MDS in this setting are scarce. We encountered diffuse large B-cell lymphoma, angioimmunoblastic lymphoma and mantle cell lymphoma as secondary hematological malignancies after systemic chemotherapy for breast cancer.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
6/8. Breakthrough trichosporonosis in patients with hematologic malignancies receiving micafungin.BACKGROUND: Micafungin is a newly approved antifungal agent in the echinocandin class that is active against candida species and aspergillus species. However, this agent has limited activity against a number of fungi, including Trichosporon species. We describe 4 patients who developed disseminated trichosporonosis during the use of micafungin. No cases of trichosporonosis had been seen in the 2 years prior to January 2003, when micafungin became available in our hospital. methods: We reviewed microbiological records of patients at Kameda General Hospital (Kamogawa City, Chiba, japan) from 1 January 2002 to 31 July 2005, and identified 4 patients whose blood culture results were positive for Trichosporon species. RESULTS: Since January 2003, four patients--3 with acute myelocytic leukemia and 1 with myelodysplastic syndrome--developed disseminated trichosporonosis while receiving treatment with micafungin with or without amphotericin b. The initial 2 isolates were identified as Trichosporon beigelii, and the later 2 isolates were identified as Trichosporon asahii. All 4 patients received micafungin, and 2 also received amphotericin b concomitantly. Minimal inhibitory concentrations of micafungin were >16 microg/mL for the 2 isolates available for susceptibility testing. One patient with hematologic recovery (neutrophils >500 cells/mm3) showed elimination of the fungus after receiving treatment with voriconazole. However, the 3 other patients without hematologic or immunological recovery died of disseminated infection. CONCLUSIONS: The rarity of trichosporonosis in our hospital and its emergence after the introduction of micafungin therapy support the idea that micafungin may exert a significant, selective pressure toward resistant fungi, such as Trichosporon species. Therefore, care should be taken regarding the possibility of trichosporonosis in patients receiving micafungin with or without amphotericin b.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
7/8. XYY male and hematologic malignancy.Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
8/8. abscess-forming neutrophilic dermatosis: report of three cases associated with hemopathies.BACKGROUND: The development of different types of neutrophilic dermatosis is reported to occur in the course of malignant hemopathies. These concern mainly Sweet's syndrome, pyoderma gangrenosum, erythema elevatum et diutinum and neutrophilic eccrine hidradenitis. OBSERVATIONS: We have recently encountered the cases of 3 patients who presented all with multiple acneiform papules and dome-shaped aseptic abscesses leaving scars. Pus was sterile in all except case 3 in which slight staphylococcus aureus growth was shown. However, in this patient, only steroids were effective demonstrating that this bacterium was not responsible for the disease. Histopathology disclosed a dense dermal polymorphonuclear neutrophil infiltrate and some mononuclear cells. Two of these patients had myelodysplastic syndromes while one had IgA myeloma. CONCLUSION: abscess-forming neutrophilic dermatosis seems to be another type of neutrophilic dermatosis associated with hematological malignancies.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |