Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia

A. Bacigalupo, M. T. Van Lint, M. Valbonesi, G. Lercari, P. Carlier, T. Lamparelli, F. Gualandi, D. Occhini, S. Bregante, A. Valeriani, G. Piaggio, A. Pitto, F. Benvenuto, O. Figari, G. De Stefano, A. Caimo, M. Sessarego

Research output: Contribution to journalArticle

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Abstract

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 μg/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 108/kg; CD34+ cells 6 x 106/kg; colony-forming unit- granulocyte macrophage 38 x 104/kg, and CD3+ cells 449 x 106/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 109/L and platelet counts of 30 x 109/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.

Original languageEnglish
Pages (from-to)353-357
Number of pages5
JournalBlood
Volume88
Issue number1
Publication statusPublished - Jul 1 1996

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Thiotepa
Transplants
Granulocyte Colony-Stimulating Factor
Cyclophosphamide
Blood Cells
Leukemia
Blood
Cells
Grafts
Tissue Donors
Graft vs Host Disease
Platelets
Stem cells
Antigens
Macrophages
Histocompatibility Antigens Class II
Polymorphism
Leukapheresis
Lymphoid Leukemia
Recurrence

ASJC Scopus subject areas

  • Hematology

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Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. / Bacigalupo, A.; Van Lint, M. T.; Valbonesi, M.; Lercari, G.; Carlier, P.; Lamparelli, T.; Gualandi, F.; Occhini, D.; Bregante, S.; Valeriani, A.; Piaggio, G.; Pitto, A.; Benvenuto, F.; Figari, O.; De Stefano, G.; Caimo, A.; Sessarego, M.

In: Blood, Vol. 88, No. 1, 01.07.1996, p. 353-357.

Research output: Contribution to journalArticle

Bacigalupo, A, Van Lint, MT, Valbonesi, M, Lercari, G, Carlier, P, Lamparelli, T, Gualandi, F, Occhini, D, Bregante, S, Valeriani, A, Piaggio, G, Pitto, A, Benvenuto, F, Figari, O, De Stefano, G, Caimo, A & Sessarego, M 1996, 'Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia', Blood, vol. 88, no. 1, pp. 353-357.
Bacigalupo, A. ; Van Lint, M. T. ; Valbonesi, M. ; Lercari, G. ; Carlier, P. ; Lamparelli, T. ; Gualandi, F. ; Occhini, D. ; Bregante, S. ; Valeriani, A. ; Piaggio, G. ; Pitto, A. ; Benvenuto, F. ; Figari, O. ; De Stefano, G. ; Caimo, A. ; Sessarego, M. / Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. In: Blood. 1996 ; Vol. 88, No. 1. pp. 353-357.
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abstract = "Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 μg/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 108/kg; CD34+ cells 6 x 106/kg; colony-forming unit- granulocyte macrophage 38 x 104/kg, and CD3+ cells 449 x 106/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 109/L and platelet counts of 30 x 109/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29{\%}, the actuarial relapse rate 22{\%}. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57{\%}. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.",
author = "A. Bacigalupo and {Van Lint}, {M. T.} and M. Valbonesi and G. Lercari and P. Carlier and T. Lamparelli and F. Gualandi and D. Occhini and S. Bregante and A. Valeriani and G. Piaggio and A. Pitto and F. Benvenuto and O. Figari and {De Stefano}, G. and A. Caimo and M. Sessarego",
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T1 - Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia

AU - Bacigalupo, A.

AU - Van Lint, M. T.

AU - Valbonesi, M.

AU - Lercari, G.

AU - Carlier, P.

AU - Lamparelli, T.

AU - Gualandi, F.

AU - Occhini, D.

AU - Bregante, S.

AU - Valeriani, A.

AU - Piaggio, G.

AU - Pitto, A.

AU - Benvenuto, F.

AU - Figari, O.

AU - De Stefano, G.

AU - Caimo, A.

AU - Sessarego, M.

PY - 1996/7/1

Y1 - 1996/7/1

N2 - Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 μg/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 108/kg; CD34+ cells 6 x 106/kg; colony-forming unit- granulocyte macrophage 38 x 104/kg, and CD3+ cells 449 x 106/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 109/L and platelet counts of 30 x 109/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.

AB - Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 μg/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 108/kg; CD34+ cells 6 x 106/kg; colony-forming unit- granulocyte macrophage 38 x 104/kg, and CD3+ cells 449 x 106/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 109/L and platelet counts of 30 x 109/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.

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