Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis

Marina Podestà, Giovanna Piaggio, Mario Sessarego, Anna Pitto, Osvaldo Figari, Monica Soracco, Angelo M. Carella, Anna Dejana, Vittorio Rosti, Giuseppina Fugazza, Giovanbattista Ravera, Enrica Lerma, Mario Cazzola, Andrea Bacigalupo, Francesco Frassoni

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Abstract

Objective. In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myelo-reductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome. Materials and Methods. We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85%- 100% Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC). Results. Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70%-100% to 0%-25% in the majority of patients (78%). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0% and 20% at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100% Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term- culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p <0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p <0.03). Conclusion. We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival. (C) 2000 International Society for Experimental Hematology.

Original languageEnglish
Pages (from-to)210-215
Number of pages6
JournalExperimental Hematology
Volume28
Issue number2
DOIs
Publication statusPublished - Feb 2000

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Autologous Transplantation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Stem Cells
Cytogenetics
Blood Cells
Cell Culture Techniques
Recurrence
Cytogenetic Analysis
Clinical Protocols
Bone Marrow Cells

Keywords

  • Autografting
  • Chronic myeloid leukemia
  • Long-term culture-initiating cell

ASJC Scopus subject areas

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

Cite this

Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis. / Podestà, Marina; Piaggio, Giovanna; Sessarego, Mario; Pitto, Anna; Figari, Osvaldo; Soracco, Monica; Carella, Angelo M.; Dejana, Anna; Rosti, Vittorio; Fugazza, Giuseppina; Ravera, Giovanbattista; Lerma, Enrica; Cazzola, Mario; Bacigalupo, Andrea; Frassoni, Francesco.

In: Experimental Hematology, Vol. 28, No. 2, 02.2000, p. 210-215.

Research output: Contribution to journalArticle

Podestà, Marina ; Piaggio, Giovanna ; Sessarego, Mario ; Pitto, Anna ; Figari, Osvaldo ; Soracco, Monica ; Carella, Angelo M. ; Dejana, Anna ; Rosti, Vittorio ; Fugazza, Giuseppina ; Ravera, Giovanbattista ; Lerma, Enrica ; Cazzola, Mario ; Bacigalupo, Andrea ; Frassoni, Francesco. / Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis. In: Experimental Hematology. 2000 ; Vol. 28, No. 2. pp. 210-215.
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title = "Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis",
abstract = "Objective. In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myelo-reductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome. Materials and Methods. We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85{\%}- 100{\%} Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC). Results. Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70{\%}-100{\%} to 0{\%}-25{\%} in the majority of patients (78{\%}). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0{\%} and 20{\%} at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100{\%} Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term- culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p <0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p <0.03). Conclusion. We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival. (C) 2000 International Society for Experimental Hematology.",
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author = "Marina Podest{\`a} and Giovanna Piaggio and Mario Sessarego and Anna Pitto and Osvaldo Figari and Monica Soracco and Carella, {Angelo M.} and Anna Dejana and Vittorio Rosti and Giuseppina Fugazza and Giovanbattista Ravera and Enrica Lerma and Mario Cazzola and Andrea Bacigalupo and Francesco Frassoni",
year = "2000",
month = "2",
doi = "10.1016/S0301-472X(99)00147-2",
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TY - JOUR

T1 - Autografting with Ph-negative progenitors in patients at diagnosis of chronic myeloid leukemia induces a prolonged prevalence of Ph-negative hemopoiesis

AU - Podestà, Marina

AU - Piaggio, Giovanna

AU - Sessarego, Mario

AU - Pitto, Anna

AU - Figari, Osvaldo

AU - Soracco, Monica

AU - Carella, Angelo M.

AU - Dejana, Anna

AU - Rosti, Vittorio

AU - Fugazza, Giuseppina

AU - Ravera, Giovanbattista

AU - Lerma, Enrica

AU - Cazzola, Mario

AU - Bacigalupo, Andrea

AU - Frassoni, Francesco

PY - 2000/2

Y1 - 2000/2

N2 - Objective. In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myelo-reductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome. Materials and Methods. We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85%- 100% Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC). Results. Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70%-100% to 0%-25% in the majority of patients (78%). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0% and 20% at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100% Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term- culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p <0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p <0.03). Conclusion. We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival. (C) 2000 International Society for Experimental Hematology.

AB - Objective. In many patients with chronic myeloid leukemia (CML), a residual population of primitive normal (Ph-negative) progenitors persists despite the marked expansion of the leukemic (Ph-positive) clone. These cells may be found in the blood of patients studied soon after diagnosis or during the period of endogenous hematopoietic recovery that follows myelo-reductive therapy. Based on those observations, we have developed a clinical protocol that allows collection of Ph-negative peripheral blood progenitor cells (PBPC) with transplantable hematopoietic regenerative potential. The aim of this study is to examine changes that occur in the percentage of Ph-negative- and Ph-positive-committed progenitor cells and to determine the relationship between changes and clinical outcome. Materials and Methods. We followed 15 patients with CML, mobilized and autografted soon after diagnosis with 85%- 100% Ph-negative PBPC for a median time of 28 months (range 18-50) after transplant. At 6 months, 1 year, 2 years, and last follow-up, cytogenetic analyses were performed on fresh bone marrow cells and on colony-forming cells (CFC). Results. Autologous transplantation induces a reduction in the proportion of Ph-positive CFC, from 70%-100% to 0%-25% in the majority of patients (78%). After autografting, 8 of 15 patients achieved a long-lasting cytogenetic remission (median, 24 months; range, 21-43) with a Ph-positivity ranging between 0% and 20% at the level of mature mononuclear cells and colony-forming cells (CFC). In some patients, the majority of CFC remained Ph-negative, whereas the majority of the mature cells were Ph-positive. Other patients (5/15) developed cytogenetic relapse (100% Ph-positive), although they were in hematological remission. We found that detection of Ph-positive long-term- culture initiating cells (LTC-IC) in the marrow at diagnosis was the only factor significantly associated with recurrence of the disease (p <0.01); on the other hand, the number of Ph-negative LTC-IC infused showed a significant correlation with a better outcome (p <0.03). Conclusion. We have shown that a prolonged period of complete or almost complete Ph-negative hemopoiesis can be achieved in patients with CML who undergo autografting with Ph-negative progenitors. Longer follow-up study will be needed to assess whether these changes are associated with improved survival. (C) 2000 International Society for Experimental Hematology.

KW - Autografting

KW - Chronic myeloid leukemia

KW - Long-term culture-initiating cell

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