In vivo mobilization of karyotipically normal peripheral blood progenitor cells (pbpc) in high-risk myelodysplastic syndromes

L. Celesti, A. Deiana, E. Lemia, G. Fueazza, M. Sessareao, M. Podestà, F. Frassoni, M. Valboncsi, A. M. Carella

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Abstract

Patients with myeiodysplastic syndrome (MDS) with double or complex cylogenetic abnormalities have the worst prognosis. Autografting has been attempted in selected patients but in the majority of them there is no evidence that MDS is cured. The obstacles to more widespread use of autotransplants comprise the problem of providing grafts of progenitor cells which are predominantly, if not completely, disease-free. Our group previously reported that mobilization of Ph'-ncgalive progenitors is possible in a significant number of Ph'-positive ALL (Brit.J Haematol. 1995: 889-535) and CML patients (Bone Marrow Transplant. 1993: 12-267). In this pilot study we employed the same approach in patients with RAEB-l. secondary AMI (sAML) and therapy-related AML (tAML). All patients had double or complex cylogenetic abnormalities in marrow cells before mobilization therapy and none of them received previous chemotherapy. Eleven patients with a median age of 50 years (range. 22 to 68) entered our pilot study. The mobilization protocol consisted of ICE protocol (5 patients) and mini-ICE protocol (6 patients). From day +8 G-CSF (5u/kgttay) was administered daily until the total neutrophil count was greater tlian 1.0 \ 109/1 for three consecutive days. Leukophoreses were performed when the wbc exceeded IxlO9/! and the appearance in the PB of CD34+ve cells. Ail II patients completed the mobilization protocol and no patient died of the mobilizing procedure. Karyorype analysis was possible in all patients on all collections. No cylogenetic abnormalities were found in repeated sampling, in 6 of the 11 patients. Adeguate CFU-GM (>2xJOVkg) and CD34+ cells (>2xl()6/kg) were obtained in 7/11 and 9/11 patients, respectively. To date, four patients, who had entirely karyotypically normal PBPC collections, underwent aulografting. High-dose therapy consisted of idarubicin. etoposide and single-dose total body irradiation (IVT protocol). G-CSF was given at 5mg/kg/day from day +8 Evidence of marrow engraft me n l (ANCX).5xl09/l and platelets >25xl09/l) was attained at 9-17 days and 8-106 days, respectively. One patient is in complete hemàtological and cylogenetic remission 11 months after autografting. Three patients showed cytogenetic remission in the marrow at discharge but relapsed within two and six months after transplant: all of them died of refractory leukemia. In conclusion, our preliminary data in these selected high-risk MDS patients suggest that peripheral rmobilization of diploid cells is feasible.

Original languageEnglish
Pages (from-to)832
Number of pages1
JournalExperimental Hematology
Volume25
Issue number8
Publication statusPublished - 1997

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Myelodysplastic Syndromes
Blood Cells
Stem Cells
Bone Marrow
Autologous Transplantation
Granulocyte Colony-Stimulating Factor
Transplants
Idarubicin
Refractory Anemia with Excess of Blasts
Granulocyte-Macrophage Progenitor Cells
Whole-Body Irradiation
Autografts
Etoposide
Diploidy
Cytogenetics

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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In vivo mobilization of karyotipically normal peripheral blood progenitor cells (pbpc) in high-risk myelodysplastic syndromes. / Celesti, L.; Deiana, A.; Lemia, E.; Fueazza, G.; Sessareao, M.; Podestà, M.; Frassoni, F.; Valboncsi, M.; Carella, A. M.

In: Experimental Hematology, Vol. 25, No. 8, 1997, p. 832.

Research output: Contribution to journalArticle

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abstract = "Patients with myeiodysplastic syndrome (MDS) with double or complex cylogenetic abnormalities have the worst prognosis. Autografting has been attempted in selected patients but in the majority of them there is no evidence that MDS is cured. The obstacles to more widespread use of autotransplants comprise the problem of providing grafts of progenitor cells which are predominantly, if not completely, disease-free. Our group previously reported that mobilization of Ph'-ncgalive progenitors is possible in a significant number of Ph'-positive ALL (Brit.J Haematol. 1995: 889-535) and CML patients (Bone Marrow Transplant. 1993: 12-267). In this pilot study we employed the same approach in patients with RAEB-l. secondary AMI (sAML) and therapy-related AML (tAML). All patients had double or complex cylogenetic abnormalities in marrow cells before mobilization therapy and none of them received previous chemotherapy. Eleven patients with a median age of 50 years (range. 22 to 68) entered our pilot study. The mobilization protocol consisted of ICE protocol (5 patients) and mini-ICE protocol (6 patients). From day +8 G-CSF (5u/kgttay) was administered daily until the total neutrophil count was greater tlian 1.0 \ 109/1 for three consecutive days. Leukophoreses were performed when the wbc exceeded IxlO9/! and the appearance in the PB of CD34+ve cells. Ail II patients completed the mobilization protocol and no patient died of the mobilizing procedure. Karyorype analysis was possible in all patients on all collections. No cylogenetic abnormalities were found in repeated sampling, in 6 of the 11 patients. Adeguate CFU-GM (>2xJOVkg) and CD34+ cells (>2xl()6/kg) were obtained in 7/11 and 9/11 patients, respectively. To date, four patients, who had entirely karyotypically normal PBPC collections, underwent aulografting. High-dose therapy consisted of idarubicin. etoposide and single-dose total body irradiation (IVT protocol). G-CSF was given at 5mg/kg/day from day +8 Evidence of marrow engraft me n l (ANCX).5xl09/l and platelets >25xl09/l) was attained at 9-17 days and 8-106 days, respectively. One patient is in complete hem{\`a}tological and cylogenetic remission 11 months after autografting. Three patients showed cytogenetic remission in the marrow at discharge but relapsed within two and six months after transplant: all of them died of refractory leukemia. In conclusion, our preliminary data in these selected high-risk MDS patients suggest that peripheral rmobilization of diploid cells is feasible.",
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AU - Celesti, L.

AU - Deiana, A.

AU - Lemia, E.

AU - Fueazza, G.

AU - Sessareao, M.

AU - Podestà, M.

AU - Frassoni, F.

AU - Valboncsi, M.

AU - Carella, A. M.

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