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Relationship between hematological characteristics and granulocyte-macrophage colony formation (CFU-GM) in MDS
Third International Cytokine patients
level
in
the
serum
of
AML and
Symposium on Myelodysplastic Syndromes MDS
LORELLA DEPAOLI, ALESSANDRO LEVIS, LUIGI RESEGOTTI Department of Haematology, Molinette Hospital, Torino, Italy The serum levels of ILZ,IL3,GM-CSF,G-CSF,Epo and TNF have been measured in 44 patients with AML, 28 patients with MD'S (11 RA,8 RAEB,SCMML) and in 27 healthy volontiers and correlations between cytokine level and several haematological parameters were tested by statistical methods. The mean cytokine values in the various groups of subjects were as follows: RAEB CMML Normal AML RA P 0.926 0.27 IL2 0.359 0.389 0.435 0.245 15.04 14.07 23.19 18.64 35.87 0.05 IL3 10.07 23.62 11.09 6.86 12.35 0.03 GM-C% G-CSF 35.55 170.15 29.88 34.50 50.21 0.05 148.16 68.59 467.65 220.00 101.12 0.000 Epo 17.74 20.00 16.35 32.84 TNF 6.84 0.003 Serum levels of IL3,GM-CSF,G-CSF and Epo were significantly higher in AML patients than in normal subjects,whereas such a difference was not found between patients with MDS and controls. No coorrelation was found between serum cytokine level and number of blasts both in bone marrow and in blood. A significant inverse correlation was found between serum Epo level and marrow erythroblasts in MDS but not in AML. These findings suggest that the role of regulatory hemopoietic factors may be different in AML and in MDS and therefore that between these processes qualitative beside quantitative differences exist in the biology of the neoplastic stem cell
Prediction treatment syndromes
Treatment with the combination of granulocyte-CSF (G-CSF) and erythropoietin (epo) may improve the anaemia in around 40% of patients with MDS. The high cost of such mtment encourage a search for clinical variables that may predict a response to treatment. ResuIts of two clinical phase II trials were pooled to constitute a basis for a decision model. Patients with MIX and significant an& wae included. G-CSF (0.2 to 5 pg/kg/day, s.c.) and epo (60 to 300 U/kg/day, s.c.) were given in increasing doses. The combination was given foa at Ieast 3 months. Minimal criteria for response was an increase in hemoglobin with at least 15 giI or a decrease in transfusion need of >50% Results: 83 evaluable patients (27 RA, 28 RAW, 23 RAEB, 5 RAJZB-t) were included in the study. 41% of the patients showed an erythroid response. The re se rate did not differ significantly between the two studies. Two vanaJr es were significandy aaak%ed with a clinical response: Transf.
need
FAB
noordU/month CMOUA
subgroup, age, time from count and karyotype
granulocyte
22Uhno&
~100 un
cO.OOO1(Fisher) ‘. ~0.0001 (Frshe 1
diagnosis to treatment, were not significantly
pre-Wearient associated with
response to treatment. Transfusion need and S-epo were combined in a crosstable showing response rates to G-CSF and epo in different subgroups of MIX. S-CIJO 5ooUfl Transf.
aelatialmhip benmtalogicrl ch8racterimticsl mnd grump ropbage colony foYmmta ‘on (Cm-Qn) in nDs
of response to G-CSF and epo for the anaemia of myelodysplastic (MDS).
EVAHELLSTR6M-LINDBERG,ROBERTNEGRIN.RICHARDSTEIN,SANFORD KRANTZ.lAMES VARDIMAN, AKIN 6ST AND PETER GREENBERKDeptof Hacmatology, Huddinge University Hospital, Sweden. Stanford University Medical Center, CA and Vsndtrbilt Medical Cauer, TN, Dept of Pathology, Chicago Medical Center, IL, USA, and Karolin* Hospital, Stockho& Swaten.
Swum~po
Spontaneous cytokine product ion irk aplastic anemia and refractory anrmla M Koike, T Ishiyama and N Tsuruoka. De artment of Hematology, Showa Univer
33% (&m)
8% (25 pts) Transf. w 38% (16pts) Conclusion: This predictive model may be useful for identifying MDS patients with different probabilities of responding to G-CSF and epo.
M.
GARCIA,
DeputPent Valencia,
C.F.
SAHI,
of Semetology. SPAIX.
F.
ARRIAGA, lioepital
P. LOPIZ, universitario
M.A.
SASZ.
La
Pe.
froa -blasts proportion and PA3 claesification, the relationship between in vitro CFD-GN results and other hematologieal parameters in IIDS is ill-defined. The main aim of this study u8c1 to asmees in 61 patienta with Xl%8 the Apart
possible relation&ip between multiple hematological characteristics in peripheral blood (PB) and bone marrow (BX) and tbe nuder of clusterm (S-SO cells) and coloniee (SO cells) in tbe in vitro marrow CPU-GM assay (s-i-molid agar culture). IUI abnormal culture grauth pattern was evident in 7% of the patients. The nus@er of clusters was directly related to &solute UBC (~=0.03), PSUI (~=0.02), immature myeloid premuso rs (PrO.02) and monocyte (-0.01) countm, proportion of bluat celle in PB (pPO.02). and proportion of nmocyte precursora (PtO.01) and blasts (P=O.OOl) in BK. RAGBT and CHt4L had a higher nuatber of cheers tbn RA (-0.03; P10.07), lwbs (P=O.O02; P=O*O2) and RAEB (pPO.01; pPO.04). The nomber of clusters was Iore cmnly normal in RA+RARS than in RMB*~BT+IIBK: (-0.04). There was also a strong and direct relationship between the number of colonies and the number of UBCS (P=o.o07), smd nmamytee (-0.02) in PB. The proportion of patients shoving abnormal nwabere of colonies, specially lower n-6, increased ae the blast cell percentages in PB (PpO.06) or BI( (P=O.O06) increased. The nus&er of colonies was laar in RSBthan in RA (P-0.045), and nornvll numbers of colonis were freqoently encountered in m than in V (~11.046). our study strongly suggest that in vitro culture of myeloid progenitors clo#rly parallels the in vivo capacity of differentiation and proliferation of myeloid precursors in 81~s patients. It should be of greet interest to test if cN-GH asaay could serve for predicting the in vivo therapeutic affect of hematopoietic growth factors in ZIDS.
level
in
the
serum
of
AML and
Symposium on Myelodysplastic Syndromes MDS
LORELLA DEPAOLI, ALESSANDRO LEVIS, LUIGI RESEGOTTI Department of Haematology, Molinette Hospital, Torino, Italy The serum levels of ILZ,IL3,GM-CSF,G-CSF,Epo and TNF have been measured in 44 patients with AML, 28 patients with MD'S (11 RA,8 RAEB,SCMML) and in 27 healthy volontiers and correlations between cytokine level and several haematological parameters were tested by statistical methods. The mean cytokine values in the various groups of subjects were as follows: RAEB CMML Normal AML RA P 0.926 0.27 IL2 0.359 0.389 0.435 0.245 15.04 14.07 23.19 18.64 35.87 0.05 IL3 10.07 23.62 11.09 6.86 12.35 0.03 GM-C% G-CSF 35.55 170.15 29.88 34.50 50.21 0.05 148.16 68.59 467.65 220.00 101.12 0.000 Epo 17.74 20.00 16.35 32.84 TNF 6.84 0.003 Serum levels of IL3,GM-CSF,G-CSF and Epo were significantly higher in AML patients than in normal subjects,whereas such a difference was not found between patients with MDS and controls. No coorrelation was found between serum cytokine level and number of blasts both in bone marrow and in blood. A significant inverse correlation was found between serum Epo level and marrow erythroblasts in MDS but not in AML. These findings suggest that the role of regulatory hemopoietic factors may be different in AML and in MDS and therefore that between these processes qualitative beside quantitative differences exist in the biology of the neoplastic stem cell
Prediction treatment syndromes
Treatment with the combination of granulocyte-CSF (G-CSF) and erythropoietin (epo) may improve the anaemia in around 40% of patients with MDS. The high cost of such mtment encourage a search for clinical variables that may predict a response to treatment. ResuIts of two clinical phase II trials were pooled to constitute a basis for a decision model. Patients with MIX and significant an& wae included. G-CSF (0.2 to 5 pg/kg/day, s.c.) and epo (60 to 300 U/kg/day, s.c.) were given in increasing doses. The combination was given foa at Ieast 3 months. Minimal criteria for response was an increase in hemoglobin with at least 15 giI or a decrease in transfusion need of >50% Results: 83 evaluable patients (27 RA, 28 RAW, 23 RAEB, 5 RAJZB-t) were included in the study. 41% of the patients showed an erythroid response. The re se rate did not differ significantly between the two studies. Two vanaJr es were significandy aaak%ed with a clinical response: Transf.
need
FAB
noordU/month CMOUA
subgroup, age, time from count and karyotype
granulocyte
22Uhno&
~100 un
cO.OOO1(Fisher) ‘. ~0.0001 (Frshe 1
diagnosis to treatment, were not significantly
pre-Wearient associated with
response to treatment. Transfusion need and S-epo were combined in a crosstable showing response rates to G-CSF and epo in different subgroups of MIX. S-CIJO 5ooUfl Transf.
aelatialmhip benmtalogicrl ch8racterimticsl mnd grump ropbage colony foYmmta ‘on (Cm-Qn) in nDs
of response to G-CSF and epo for the anaemia of myelodysplastic (MDS).
EVAHELLSTR6M-LINDBERG,ROBERTNEGRIN.RICHARDSTEIN,SANFORD KRANTZ.lAMES VARDIMAN, AKIN 6ST AND PETER GREENBERKDeptof Hacmatology, Huddinge University Hospital, Sweden. Stanford University Medical Center, CA and Vsndtrbilt Medical Cauer, TN, Dept of Pathology, Chicago Medical Center, IL, USA, and Karolin* Hospital, Stockho& Swaten.
Swum~po
Spontaneous cytokine product ion irk aplastic anemia and refractory anrmla M Koike, T Ishiyama and N Tsuruoka. De artment of Hematology, Showa Univer
33% (&m)
8% (25 pts) Transf. w 38% (16pts) Conclusion: This predictive model may be useful for identifying MDS patients with different probabilities of responding to G-CSF and epo.
M.
GARCIA,
DeputPent Valencia,
C.F.
SAHI,
of Semetology. SPAIX.
F.
ARRIAGA, lioepital
P. LOPIZ, universitario
M.A.
SASZ.
La
Pe.
froa -blasts proportion and PA3 claesification, the relationship between in vitro CFD-GN results and other hematologieal parameters in IIDS is ill-defined. The main aim of this study u8c1 to asmees in 61 patienta with Xl%8 the Apart
possible relation&ip between multiple hematological characteristics in peripheral blood (PB) and bone marrow (BX) and tbe nuder of clusterm (S-SO cells) and coloniee (SO cells) in tbe in vitro marrow CPU-GM assay (s-i-molid agar culture). IUI abnormal culture grauth pattern was evident in 7% of the patients. The nus@er of clusters was directly related to &solute UBC (~=0.03), PSUI (~=0.02), immature myeloid premuso rs (PrO.02) and monocyte (-0.01) countm, proportion of bluat celle in PB (pPO.02). and proportion of nmocyte precursora (PtO.01) and blasts (P=O.OOl) in BK. RAGBT and CHt4L had a higher nuatber of cheers tbn RA (-0.03; P10.07), lwbs (P=O.O02; P=O*O2) and RAEB (pPO.01; pPO.04). The nomber of clusters was Iore cmnly normal in RA+RARS than in RMB*~BT+IIBK: (-0.04). There was also a strong and direct relationship between the number of colonies and the number of UBCS (P=o.o07), smd nmamytee (-0.02) in PB. The proportion of patients shoving abnormal nwabere of colonies, specially lower n-6, increased ae the blast cell percentages in PB (PpO.06) or BI( (P=O.O06) increased. The nus&er of colonies was laar in RSBthan in RA (P-0.045), and nornvll numbers of colonis were freqoently encountered in m than in V (~11.046). our study strongly suggest that in vitro culture of myeloid progenitors clo#rly parallels the in vivo capacity of differentiation and proliferation of myeloid precursors in 81~s patients. It should be of greet interest to test if cN-GH asaay could serve for predicting the in vivo therapeutic affect of hematopoietic growth factors in ZIDS.