scholarly journals Mobilization of hematopoietic progenitor cells for autologous transportation: consensus recommendations

2016 ◽  
Vol 62 (suppl 1) ◽  
pp. 10-15 ◽  
Author(s):  
Fernando Barroso Duarte ◽  
Benedito de Pina Almeida Prado ◽  
Garles Miller Matias Vieira ◽  
Luciano J. Costa
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Blood Circulation ◽  
Progenitor Cell ◽  
National Health System ◽  
Hematopoietic Progenitor Cell ◽  
Cell Transplant ◽  
Hematopoietic Progenitor ◽  
Term Survival

SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

The occurrence of idiopathic secondary post-transplant thrombocytopenia and the kinetics of platelet recovery predict survival in patients undergoing autologous hematopoietic progenitor cell transplantation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7109-7109
Author(s):  
E. Waller ◽  
M. J. Ninan ◽  
J. Roback ◽  
M. Arellano ◽  
C. Flowers
Keyword(s):  
Cell Transplantation ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Partial Recovery ◽  
Hematopoietic Progenitor ◽  
Term Survival ◽  
Platelet Recovery ◽  
Post Transplant ◽  
Platelet Counts

7109 Background: The frequency and clinical significance of secondary thrombocytopenia following initial engraftment in autologous hematopoietic progenitor cell transplantation (HPCT) is unknown. Methods: An IRB-approved retrospective study of thrombopoiesis in 359 patients transplanted with autologous blood (97%) or marrow (3%) who achieved transfusion-independent platelet engraftment to >50,000/mcL. Idiopathic secondary post-transplant thrombocytopenia (ISPT) was defined as >50% decline in blood platelets to <100,000/mcL in the absence of relapse or sepsis. Results: 62 of 359 study subjects (17%) met the criteria for ISPT within the first 100 days post-transplant. Patients with ISPT had more rapid platelet engraftment (17 + 5 days) versus non-ISPT patients (18 + 18 days; p=0.002) and partial recovery of platelet counts (median 96K/mcL) by day 75 post-transplant. The median survival for the entire population was 6.2 years with shorter survival in AML (1.3 years), breast cancer (6.2 years) and myeloma (5.5 years) than lymphoma patients (median not reached). Co- variates associated with post-transplant death (p<0.1) were entered into a multivariable logistic regression analysis stratified by cancer diagnosis at the time of transplant. Three factors were independently associated with worse survival: the number of prior chemotherapy regimens, failure to achieve a normal platelet counts post-transplant, and the occurrence of ISPT. A prognostic score was developed based upon the occurrence of ISPT and post-transplant platelet counts of <150,000/mcL. Survival of patients with both factors (n=25) was poor (15% alive at 5 years); patients with one factor (n=145) had 49% 5-year survival; patients with 0 factors (n=189) had 72% 5-year survival. Patients who failed to achieve a normal post-transplant platelet count received significantly fewer CD34+ cells/kg (P<0.001), while patients with ISPT received fewer CD34+CD38- cells/kg (P=0.001). Conclusion: ISPT reflects poor engraftment with long-term-repopulating CD34+ CD38- stem cells. The quantity and quality of autologous HPC in the graft are important prognostic variables for long-term survival. No significant financial relationships to disclose.

PTX-sensitive signals in bone marrow homing of fetal and adult hematopoietic progenitor cells

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2299-2306 ◽  
Author(s):  
Halvard Bonig ◽  
Gregory V. Priestley ◽  
Lina M. Nilsson ◽  
Yi Jiang ◽  
Thalia Papayannopoulou
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Fetal Liver ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Short Term ◽  
Migratory Capacity ◽  
Gi Protein

Abstract Several examples suggest a relationship between in vitro migratory capacity and bone marrow (BM) homing. Pertussis toxin (PTX) is a potent inhibitor of serpentine receptor–associated inhibitory trimeric guanidine nucleotide binding (Gi) protein signals. As such, it blocks hematopoietic progenitor cell migration in vitro, but contrary to expectation, no effects on BM homing were observed in previous studies. We therefore re-examined the effect of PTX on homing of murine BM and fetal liver (FL). We found that BM homing of PTX-incubated progenitor cells (colony-forming cells in culture [CFU-Cs]) from BM or FL in irradiated and nonirradiated recipients was reduced by more than 75%, with a concomitant increase in circulating CFU-Cs in peripheral blood. Additional studies confirmed the functional significance of this reduction in homing: PTX-treated cells did not provide radioprotection, and their short-term engraftment in BM and spleen was drastically reduced. Furthermore, several approaches show that cell-intrinsic rather than host-derived mechanisms are responsible for the PTX-induced homing defect. In summary, we show that Gi protein signals are required for BM homing and, as such, provide a new example of the association between BM homing and in vitro migration. Moreover, our data suggest that the behavior of hematopoietic progenitors in obeying Gi signaling does not diverge from that of mature leukocytes.

scholarly journals Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2074-2081 ◽  
Author(s):  
U Duhrsen ◽  
JL Villeval ◽  
J Boyd ◽  
G Kannourakis ◽  
G Morstyn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Stimulating Factor

Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte- macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.

scholarly journals Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3159-3167 ◽  
Author(s):  
RA Briddell ◽  
VC Broudy ◽  
E Bruno ◽  
JE Brandt ◽  
EF Srour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cells ◽  
Cloning Efficiency ◽  
Cell Cloning ◽  
Hematopoietic Progenitor ◽  
Kit Ligand ◽  
Hla Dr

A mouse antihuman monoclonal IgG2a antibody, termed stem cell receptor- 1 (SR-1), specific for a determinant of the c-kit ligand receptor (KR), was used as an immunologic probe to analyze KR expression by human bone marrow hematopoietic progenitor cells. Monoclonal antibodies to CD34 and HLA-DR were used in a multicolor staining protocol in conjunction with SR-1 to further define the phenotypes of various classes of hematopoietic progenitor cells. Expression of KR (SR-1+) on hematopoietic progenitor cells identified subpopulations of cells expressing CD34 (CD34+). While one-half of the CD34- and HLA-DR- expressing cells (CD34+ HLA-DR+) expressed the KR (SR-1+), one-third of the CD34+ cells that lacked HLA-DR expression (CD34+ HLA-DR-) were SR- 1+. The CD34+ HLA-DR+ SR-1+ cell population contained the vast majority of the more differentiated progenitor cells, including the colony- forming unit (CFU) granulocyte-macrophage; burst-forming unit- erythrocyte; CFU-granulocyte, erythrocyte, macrophage, megakaryocyte; and the CFU-megakaryocyte. The overall progenitor cell cloning efficiency of this subpopulation was greater than 31%. By contrast, the CD34+ HLA-DR- SR-1+ cell population contained fewer of these more differentiated progenitor cells but exclusively contained the more primitive progenitor cells, the BFU-megakaryocyte, high proliferative potential-colony-forming cell, and long-term bone marrow culture- initiating cell. The overall progenitor cell cloning efficiency of this subpopulation was greater than 7%. Both the CD34+ HLA-DR- and CD34+ HLA- DR+ cell subpopulations lacking KR expression contained few assayable hematopoietic progenitor cells. Long-term bone marrow cultures initiated with CD34+ HLA-DR- SR-1+ but not CD34+ HLA-DR- SR-1- cells, which were repeatedly supplemented with c-kit ligand (KL) and interleukin-3, generated assayable progenitor cells of at least 2 lineages for 10 weeks. These experiments demonstrate the expression of the KR throughout the hierarchy of human hematopoietic progenitor cell development. We conclude from our data that the KL and KR play a pivotal role in cytokine regulation of both the primitive and more differentiated human hematopoietic progenitor cells.

scholarly journals Hematopoietic progenitor cell regulation by CD4+CD25+ T cells

Blood ◽  
2010 ◽  
Vol 115 (23) ◽  
pp. 4934-4943 ◽  
Author(s):  
Maite Urbieta ◽  
Isabel Barao ◽  
Monica Jones ◽  
Roland Jurecic ◽  
Angela Panoskaltsis-Mortari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Activity ◽  
Innate Immune ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem

Abstract CD4+CD25+FoxP3+ regulatory T cells (Tregs) possess the capacity to modulate both adaptive and innate immune responses. We hypothesized that Tregs could regulate hematopoiesis based on cytokine effector molecules they can produce. The studies here demonstrate that Tregs can affect the differentiation of myeloid progenitor cells. In vitro findings demonstrated the ability of Tregs to inhibit the differentiation of interleukin-3 (IL-3)/stem cell factor (colony-forming unit [CFU]-IL3)–driven progenitor cells. Inhibitory effects were mediated by a pathway requiring cell-cell contact, major histocompatibility complex class II expression on marrow cells, and transforming growth factor-β. Importantly, depletion of Tregs in situ resulted in enhanced CFU-IL3 levels after bone marrow transplantation. Cotransplantation of CD4+FoxP3+gfp Tregs together with bone marrow was found to diminish CFU-IL3 responses after transplantation. To address the consequence of transplanted Tregs on differentiated progeny from these CFU 2 weeks after hematopoietic stem cell transplantation, peripheral blood complete blood counts were performed and examined for polymorphonuclear leukocyte content. Recipients of cotransplanted Tregs exhibited diminished neutrophil counts. Together, these findings illustrate that both recipient and donor Tregs can influence hematopoietic progenitor cell activity after transplantation and that these cells can alter responses outside the adaptive and innate immune systems.

scholarly journals Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 2074-2081 ◽  
Author(s):  
U Duhrsen ◽  
JL Villeval ◽  
J Boyd ◽  
G Kannourakis ◽  
G Morstyn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Progenitor ◽  
Stimulating Factor

Abstract Hematopoietic progenitor cell levels were monitored in the peripheral blood and bone marrow of 30 cancer patients receiving recombinant human granulocyte-colony stimulating-factor (rG-CSF) in a phase I/II clinical trial. The absolute number of circulating progenitor cells of granulocyte-macrophage, erythroid, and megakaryocyte lineages showed a dose-related increase up to 100-fold after four days of treatment with rG-CSF and often remained elevated two days after the cessation of therapy. The relative frequency of different types of progenitor cells in peripheral blood remained unchanged. The frequency of progenitor cells in the marrow was variable after rG-CSF treatment but in most patients was slightly decreased. The responsiveness of bone marrow progenitor cells to stimulation in vitro by rG-CSF and granulocyte- macrophage colony-stimulating factor did not change significantly during rG-CSF treatment. In patients nine days after treatment with melphalan and then rG-CSF, progenitor cell levels were very low with doses of rG-CSF at or below 10 micrograms/kg/d, but equaled or exceeded pretreatment values when 30 or 60 micrograms/kg/d of rG-CSF was given.

scholarly journals Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3159-3167 ◽  
Author(s):  
RA Briddell ◽  
VC Broudy ◽  
E Bruno ◽  
JE Brandt ◽  
EF Srour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cells ◽  
Cloning Efficiency ◽  
Cell Cloning ◽  
Hematopoietic Progenitor ◽  
Kit Ligand ◽  
Hla Dr

Abstract A mouse antihuman monoclonal IgG2a antibody, termed stem cell receptor- 1 (SR-1), specific for a determinant of the c-kit ligand receptor (KR), was used as an immunologic probe to analyze KR expression by human bone marrow hematopoietic progenitor cells. Monoclonal antibodies to CD34 and HLA-DR were used in a multicolor staining protocol in conjunction with SR-1 to further define the phenotypes of various classes of hematopoietic progenitor cells. Expression of KR (SR-1+) on hematopoietic progenitor cells identified subpopulations of cells expressing CD34 (CD34+). While one-half of the CD34- and HLA-DR- expressing cells (CD34+ HLA-DR+) expressed the KR (SR-1+), one-third of the CD34+ cells that lacked HLA-DR expression (CD34+ HLA-DR-) were SR- 1+. The CD34+ HLA-DR+ SR-1+ cell population contained the vast majority of the more differentiated progenitor cells, including the colony- forming unit (CFU) granulocyte-macrophage; burst-forming unit- erythrocyte; CFU-granulocyte, erythrocyte, macrophage, megakaryocyte; and the CFU-megakaryocyte. The overall progenitor cell cloning efficiency of this subpopulation was greater than 31%. By contrast, the CD34+ HLA-DR- SR-1+ cell population contained fewer of these more differentiated progenitor cells but exclusively contained the more primitive progenitor cells, the BFU-megakaryocyte, high proliferative potential-colony-forming cell, and long-term bone marrow culture- initiating cell. The overall progenitor cell cloning efficiency of this subpopulation was greater than 7%. Both the CD34+ HLA-DR- and CD34+ HLA- DR+ cell subpopulations lacking KR expression contained few assayable hematopoietic progenitor cells. Long-term bone marrow cultures initiated with CD34+ HLA-DR- SR-1+ but not CD34+ HLA-DR- SR-1- cells, which were repeatedly supplemented with c-kit ligand (KL) and interleukin-3, generated assayable progenitor cells of at least 2 lineages for 10 weeks. These experiments demonstrate the expression of the KR throughout the hierarchy of human hematopoietic progenitor cell development. We conclude from our data that the KL and KR play a pivotal role in cytokine regulation of both the primitive and more differentiated human hematopoietic progenitor cells.

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