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Cytogenetic observations in myelodysplastic syndromes (MDS) before and after GM-CSF
SecondInternational Conference on Myelodysplastic Syndromes CLONAL CHROMOSOME ABNORMALITIES IDENTIFY MYELODYSPLASTIC SYNDROME (MDS) COMPLICATING HAIRY CELL LEUKEMIA (HCL). Campagnoli C., Bernasconi P., Pagnucco G., Alessandrino E.P., Uccelli E., Boni M. Chair of Hematology University of Pavia. From 1974 to 1990 we consecutively studied 105 HCLs and found an association between this disorder and MDS in only three pts (one RA, one RAEB and one CMML). In two MDS preceeded HCL with a median interval of nine months, while in the remaining CMML occurred 32 months after HCL. All three pts obtained CR from HCL after interferon. At that time cytogenetic analysis detected clonal chromosome rearrangements in all pts. A de1 (5)(q) was present in the RA pt, while a t(9;ll) in the RAEB one rapidly evolving in ANLL-M5. A t(6;9) was observed in CMML and with was associated other rearrangements. All reported the abnormalities have never been described in HCL and are specifically found in MDS, therefore this last disorder in our pts is not HCL associated but represents a distinct clinico-hematological entity.
A CASE OF PPE-MYELODYSPLASIA.
G.S.Masters, G.B.Tennant, P.G.Cachia, R.A.Padua & J.A.Whittaker, P.W.Thompson, Department of Haematology, UWCM, A.Jacobs. Cardiff. We report a case in which evidence of secondary myelodysplasia has preceded abnorand function marrow bone malities of The patient is a 31 year old morphology. female with stage IVA nodular sclerosinq Hodgkin's Disease who achieved complete remission with standard MOPP chemotherapy in 1987. In 1990 she had a left cervical lymph node relapse treated with radiotherapy. Bonemarrow normal but 7/20 metaphases morphology was Peripheral blood contained a lg- deletion. counts and morphology were normal but peripheral blood BFU-E formation was reduced and CFIJ-GM formation was absent - abnormalities commonly associated with MDS and rarely found in patients in remission from lymphoma. This patient has apparently normal bone marrow function and morphology but the'investigations is demonstrate an abnormal clone which affecting progenitor growth in vitro and may be evolving into secondary MIX.
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R.J. Jacobson, J. Evers, E. Himoe, D. St. Germain. Georgetown University Medical Center, Washington D.C. 20007. Five patients with MDS (ANC< 1500/dl) were treated with GM-CSF in Bone doses of up to 5 mcg/kg/day. marrow morphology and karyotypes were evaluated prior to GM-CSF administration. Initially no patient had marrow blast cells >20% and 4 patients had marrow chromosomal abnormalities. Following GM-CSF treatment, all patients had increases in their ANC and in 3 patients the abnormal karyotypes persisted in 100% of metaphases. One patient with RAEB (17% blasts) and trisomy 8 in 20% of marrow metaphases prior to GM-CSF, responded to the growth factor with an increase in neutrophils, a decrease in marrow blasts to 5% and a return of a normal karyotype. These observations indicate that following GM-CSF therapy in some MDS patients the mature circulating w.b.c. are derived from neoplastic abnormal progenitor cells while in other cases the GM-CSF may favor the recovery and differentiation of normal myeloid precursors.
CHROMOSOME ANALYSES OF COLONIES IN MYELODYSPLASTIC SYNDROME Inge H8ghXristiansen, Birgitta Swolin, StigR6djer. Eva
Hellsttim. Hospital, Departme@of Clinical Chemistry, Sahlgren's Medicine, Ostra Hospital, University of G6teborg and Department of Medicine, Huddinge Hospital, University of Stockholm, Sweden. The myelodysplastic syndromes (MDS)areconsidered clonal diseases and 30-7046 of the patients have chromosome aberrations in bone marrow cells. Bone marrow stem cells from patients with MDS showa reduced capacity of forming colonies invitro and the growth pattern has prognostic value. It is not fully investigated whether the growth of colonies in vitro originates from stem cells with a normal karyotype or from chromosomally abnormal cells. The aim of our study was to investigate the growth in vitro of stem cells from patients with MDS and a known chromosome abenation and to analyse the single colonies cytogenetically. Materials and methods; 8 patients with MDS according to FAB-criteria and with a known chromosome abenation were included. Stem cells from bone marrow and peripheral blood were cultured in a semisolid medium and the number of colonies were scored. Cbromoaome preparation was performd on single colonies plucked with a microtechnique after synchronisation of the colonies. Metaphases were analysed after Gbanding. Results: CFU-GM were found in all patients while no BFU-E
werexeeninhvopatients. Cytogenetic examination of the colonies showedxrowth frombothnormal andnatholonical stem cells. The proportion of pathological co&ties v&i2 from 25% to 100%. The relation between chromosome aberration, growth pattern and type of colonies analysed will be presented.
A CASE OF PPE-MYELODYSPLASIA.
G.S.Masters, G.B.Tennant, P.G.Cachia, R.A.Padua & J.A.Whittaker, P.W.Thompson, Department of Haematology, UWCM, A.Jacobs. Cardiff. We report a case in which evidence of secondary myelodysplasia has preceded abnorand function marrow bone malities of The patient is a 31 year old morphology. female with stage IVA nodular sclerosinq Hodgkin's Disease who achieved complete remission with standard MOPP chemotherapy in 1987. In 1990 she had a left cervical lymph node relapse treated with radiotherapy. Bonemarrow normal but 7/20 metaphases morphology was Peripheral blood contained a lg- deletion. counts and morphology were normal but peripheral blood BFU-E formation was reduced and CFIJ-GM formation was absent - abnormalities commonly associated with MDS and rarely found in patients in remission from lymphoma. This patient has apparently normal bone marrow function and morphology but the'investigations is demonstrate an abnormal clone which affecting progenitor growth in vitro and may be evolving into secondary MIX.
23
R.J. Jacobson, J. Evers, E. Himoe, D. St. Germain. Georgetown University Medical Center, Washington D.C. 20007. Five patients with MDS (ANC< 1500/dl) were treated with GM-CSF in Bone doses of up to 5 mcg/kg/day. marrow morphology and karyotypes were evaluated prior to GM-CSF administration. Initially no patient had marrow blast cells >20% and 4 patients had marrow chromosomal abnormalities. Following GM-CSF treatment, all patients had increases in their ANC and in 3 patients the abnormal karyotypes persisted in 100% of metaphases. One patient with RAEB (17% blasts) and trisomy 8 in 20% of marrow metaphases prior to GM-CSF, responded to the growth factor with an increase in neutrophils, a decrease in marrow blasts to 5% and a return of a normal karyotype. These observations indicate that following GM-CSF therapy in some MDS patients the mature circulating w.b.c. are derived from neoplastic abnormal progenitor cells while in other cases the GM-CSF may favor the recovery and differentiation of normal myeloid precursors.
CHROMOSOME ANALYSES OF COLONIES IN MYELODYSPLASTIC SYNDROME Inge H8ghXristiansen, Birgitta Swolin, StigR6djer. Eva
Hellsttim. Hospital, Departme@of Clinical Chemistry, Sahlgren's Medicine, Ostra Hospital, University of G6teborg and Department of Medicine, Huddinge Hospital, University of Stockholm, Sweden. The myelodysplastic syndromes (MDS)areconsidered clonal diseases and 30-7046 of the patients have chromosome aberrations in bone marrow cells. Bone marrow stem cells from patients with MDS showa reduced capacity of forming colonies invitro and the growth pattern has prognostic value. It is not fully investigated whether the growth of colonies in vitro originates from stem cells with a normal karyotype or from chromosomally abnormal cells. The aim of our study was to investigate the growth in vitro of stem cells from patients with MDS and a known chromosome abenation and to analyse the single colonies cytogenetically. Materials and methods; 8 patients with MDS according to FAB-criteria and with a known chromosome abenation were included. Stem cells from bone marrow and peripheral blood were cultured in a semisolid medium and the number of colonies were scored. Cbromoaome preparation was performd on single colonies plucked with a microtechnique after synchronisation of the colonies. Metaphases were analysed after Gbanding. Results: CFU-GM were found in all patients while no BFU-E
werexeeninhvopatients. Cytogenetic examination of the colonies showedxrowth frombothnormal andnatholonical stem cells. The proportion of pathological co&ties v&i2 from 25% to 100%. The relation between chromosome aberration, growth pattern and type of colonies analysed will be presented.