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Thromb Res. 2000 Oct 1;100(1):27-34.
Platelet glycoprotein expression in patients with myelodysplastic syndrome.

Seidl C, Siehl J, Ganser A, Hofmann WK, Fischer M, Kirchmaier CM, Hoelzer D, Seifried E.

Department of Haematology and Oncology, J-W Goethe University, Frankfurt/Main, Germany.

Myelodysplastic syndromes (MDS) are characterized by a haematopoetic insufficiency that can lead to acute leukemia. A multistep pathogenesis caused by a clonal stem cell defect affecting several differentiation pathways has been proposed for MDS. Contrary to the better characterized alteration of lymphoid and myeloid differentiation, defects in thrombocytopoesis in MDS remain less clear. In the present study, we analyzed the expression of platelet glycoprotein (GP) Ia/IIa, IIb/IIIa, Ib/IX, and IV in 21 MDS patients (12 RA, 2 RARS, 4 RAEB, 1 RAEB-T, 2 CMML) and healthy controls by flowcytometric analysis and quantitation of platelet GP RNA using fluorescence-based PCR. We observed a reduced cell surface expression of GPIb (p<0.01) and GPIIb/IIIa (p<0.01), while GPIa/IIa and GPIV expression was only marginally different between patients and controls. In contrast, there was a two-fold increase of platelet GPIb and GPIIb RNA and a three-fold increase of GPIV RNA among MDS patients. Increased levels of platelet GPIb and GPIIb RNA were significantly more prominent among patients with RAEB(-T)/CMML (p<0. 05) in comparison to patients with RA/RARS. In conclusion, we demonstrate alterations in the cell surface expression and RNA content of platelet GPs in MDS patients. These data are consistent with dysmegakaryocytopoiesis and a defect in thrombocytopoiesis among MDS patients resulting from the clonal stem cell defect in MDS.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11053613&dopt=Abstract

Vox Sang. 2000;79(2):94-9.
Automated collection of peripheral blood stem cells with the COBE spectra for autotransplantation.

Heuft HG, Dubiel M, Kingreen D, Oertel J, De Reys S, Rick O, Serke S, Schwella N.

Blood Bank and Division of Hematology/Oncology, Department of Internal Medicine, Charite University Hospital/Virchow Clinic, Humboldt University, Berlin, Germany.

BACKGROUND: A convenient, effective and safe peripheral blood stem cell (PBSC) apheresis procedure is desirable to cope with the increasing requirements for PBSC collections. We performed PBSC harvesting with the novel COBE Spectra AutoPBSC(TM) system using the default software configuration recommended by the manufacturer. We analyzed collection parameters and clinical efficiency of harvested autografts following high-dose chemotherapy (HDCT). PATIENTS AND METHODS: Eighty-one patients underwent 102 harvests after standard chemotherapy plus filgrastim (5-10 microg/kg/day) to obtain a target of >/=2.5 x 10(6) CD34+ cells/kg for autologous blood stem cell transplantation. Conventional-volume leukaphereses (median: 11 liters) were performed using the manufacturer's standard software default regarding inlet flow, harvest/chase volume (3/7 ml) and number of collection cycles. The ratio of ACD-A to whole blood was initially set at 1:12 (56 collections), later at 1:10 (46 aphereses). RESULTS: With respect to preapheresis counts of 93 (9-876) CD34+ cells/microl, 69 patients (85.2%) achieved >/=2.5 x 10(6) CD34+ cells/kg by the first apheresis. PBSC products contained medians of 5.0 x 10(6) (0.7-77.3) CD34+ cells/kg and 13.8 x 10(4) (2.3-105.0) CFU-GM/kg. A preapheresis count of >/=40 CD34+ cells/microl predicted a single-apheresis yield of >/=2.5 x 10(6) CD34+ cells/kg. Apheresis products showed a high mononuclear cell (MNC) purity of >/=89%. The median overall collection efficiency of CD34+ cells (CD34-CE) was 42.6% (12.2-87.4). The CD34-CE decreased significantly with increasing numbers of circulating CD34+ cells: 52.5% at CD34+ cells <40/microl versus 41.0% at CD34+ cells >/=40/microl (p </= 0. 002). Coagulation problems occurred in 3 of 56 procedures at an ACD-A to whole blood ratio of 1:12, but in no case at 1:10. Patients who underwent HDCT and autologous blood stem cell transplantation (n = 40) engrafted in a median time of 9 (8-13) days for absolute neutrophil counts >0.5 x 10(3)/microl, 10 (8-13) days for WBC >1.0 x 10(3)/microl and 11 (8-17) days for platelets >20 x 10(3)/microl. CONCLUSIONS: As a result of efficient PBSC mobilization, a single conventional-volume leukapheresis with the COBE Spectra AutoPBSC system resulted in hematopoietic autografts with >/=2.5 x 10(6) CD34+ cells/kg in 85% of patients. Following the standard PBSC apheresis recommendations of the manufacturer, the AutoPBSC system assures PBSC products with a high MNC purity and a moderate CD34-CE that declines significantly at increasing levels of circulating CD34+ cells. Leukaphereses performed at an ACD-A to whole blood ratio of 1:10 should run without coagulation problems. 2000 S. Karger AG, Basel

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054047&dopt=Abstract

Br J Haematol. 2000 Sep;110(4):876-9.
Involvement of natural killer cells in patients with myelodysplastic syndrome carrying monosomy 7 revealed by the application of fluorescence in situ hybridization to cells collected by means of fluorescence-activated cell sorting.

Miura I, Kobayashi Y, Takahashi N, Saitoh K, Miura AB.

Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan. ikued.akita-u.ac.jp

Monosomy 7 is the most frequent chromosome abnormality among patients with secondary myelodysplastic syndrome (MDS). We used fluorescence in situ hybridization (FISH) and fluorescence-activated cell sorting (FACS) in order to clarify the lineage involvement. Four patients, three with de novo MDS and one with secondary MDS, were enrolled in this study. Monosomy 7 was observed in pluripotent stem cells (CD34(+)Thy-1(+)), and in B (CD34(+)CD19(+)) and T/natural killer (NK) progenitors (CD34(+)CD7(+)). The number of abnormal cells of B (CD19(+)) and T (CD3(+)) cells was below the cut-off value, but approximately 60% of the NK cells (CD3-CD56(+)) contained monosomy 7 in three of the patients.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054073&dopt=Abstract

Br J Haematol. 2000 Sep;110(4):887-93.
Feasibility and recent improvement of autologous stem cell transplantation for acute myelocytic leukaemia in patients over 60 years of age: importance of the source of stem cells.

Gorin NC, Labopin M, Pichard P, Sierra J, Fiere D, Rio B, Meloni G, Sanz MA, Iriondo A, Fouillard L, Frassoni F.

European Data Management Office (Centre International Greffes AP-HP) Paris, France. The Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. gorixt.jussieu.fr

A total of 193 patients with acute myelocytic leukaemia (AML) [147 in first complete remission (CR1)], ranging from 60 years to 75 years of age (median 63 years), were autografted between January 1984 and December 1998. The source of stem cells was peripheral blood (PB) in 128 patients, bone marrow in 51 patients and a combination of both in 14 patients. Total body irradiation (TBI) was used in 34 cases. Ninety-seven per cent of patients had successful engraftment of neutrophils on day 15 (range days 7-71) and of platelets on day 30 (range days 9-894). In patients autografted in CR1, the transplant-related mortality (TRM) was 15 +/- 4%, the relapse incidence (RI) was 58 +/- 5%, the leukaemia-free survival (LFS) was 36 +/- 5% and the overall survival was 47 +/- 5% at 3 years. The source and dose of stem cells were studied in particular; in patients transplanted in CR1, the RI was 44 +/- 11% in those receiving marrow compared with 63 +/- 6% in those receiving PB (P = 0.04). Patients autografted in CR1 who received higher granulocyte-macrophage colony-forming units (CFU-GM) doses (above the median) had a lower RI (47 +/- 11% vs. 79 +/- 9%, P = 0.009). There was a significant improvement in patients transplanted after March 1996; for those in CR1, the RI was 41 +/- 8% vs. 65 +/- 6% (P = 0.01), the LFS was 53 +/- 8% vs. 28 +/- 5% (P = 0.01) and the overall survival was 72 +/- 7% vs. 36 +/- 6% (P = 0.02). By multivariate analyses, significant factors for the outcome were the date of transplant with recent improvement and the source of stem cells, with a lower RI for marrow. Autologous stem cell transplantation (ASCT) is a potential therapeutic approach in patients with AML over 60 years of age; results have improved recently.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054076&dopt=Abstract

Br J Haematol. 2000 Sep;110(4):894-6.
Cytomegalovirus colitis after autologous transplantation for multiple myeloma.

Ramsey DJ, Schey SA.

Department of Haematology, Guy's Hospital, London, UK. pip.farnswortstt.sthames.nhs.uk

Bone marrow or stem cell transplantation is an established therapy for haematological malignancies. We report a cytomegalovirus (CMV) IgG +ve 56-year-old patient who underwent autologous rescue with CD34(+) selected peripheral blood stem cells as part of consolidation therapy for multiple myeloma and subsequently developed CMV colitis. In contrast to infection secondary to human immunodeficiency virus (HIV), CMV colitis has not previously been described in this context. We discuss this case and issues arising from it related to the use of CD34+ selected stem cells for transplantation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11054077&dopt=Abstract

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