scholarly journals Hematopoietic progenitor cell mobilization is more robust in healthy African American compared to Caucasian donors and is not affected by the presence of sickle cell trait

Transfusion ◽  
2016 ◽  
Vol 56 (5) ◽  
pp. 1058-1065 ◽  
Author(s):  
Sandhya R. Panch ◽  
Yu Ying Yau ◽  
Courtney D. Fitzhugh ◽  
Matthew M. Hsieh ◽  
John F. Tisdale ◽  
...  
Keyword(s):  
African American ◽  
Sickle Cell ◽  
Progenitor Cell ◽  
Sickle Cell Trait ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Cell Mobilization

Hematopoietic Progenitor Cell Transplantation from Parental Donors for Children with Sickle Cell Anemia and Stroke.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3393-3393
Author(s):  
Paul Woodard ◽  
Gregory Hale ◽  
Wing Leung ◽  
Raymond Barfield ◽  
Kimberly Kasow ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Progenitor Cell ◽  
Chronic Gvhd ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Pilot Studies ◽  
Cd34 Cells

Although allogeneic hematopoietic progenitor cell transplantation (HPCT) can be curative for sickle cell anemia (SCA), most patients lack an HLA matched sibling donor or matched unrelated donor. A 2002 multidisciplinary conference held at St. Jude Children’s Research Hospital reached consensus that pilot studies using parental donors were reasonable and ethical. Subsequently, eight children with a history of clinically overt stroke were transplanted on two sequential pilot studies. Peripheral blood progenitor cells were obtained from parents with sickle cell trait. Conditioning was i.v. busulfan (targeted to Css 900 ng/ml) q 6 hours x 4 days, fludarabine 150–200 mg/m2, and OKT3/methylprednisolone and infusion of CD34+ HPCT for 3 patients. Five patients received i.v. busulfan (targeted to Css 900 ng/ml) x 4 days, cyclophosphamide 200 mg/kg, thiotepa 10 mg/kg, OKT3/methylprednisolone, and infusion of both CD34+ cells and CD3+ cells with a fixed T-cell addback of 1.0–1.5 x 105 CD3+ cells/kg. Six children received pre-transplant immunosuppression with hydroxyurea and azathioprine. The median follow-up of eight patients is 1.4 years (range 2 months–4 years). Five of eight had durable donor engraftment,4 of whom are alive and free of SCA post-HPCT. Rejection occurred in 4 patients and was successfully reversed with additional CD34+ cells in one of three patients. GVHD occurred in patients receiving a fixed T-cell addback or DLI: two patients had grade II acute graft-versus-host disease (aGVHD), one grade III aGVHD, and three patients developed chronic GVHD, including a fatal case of bronchiolitis obliterans organizing pneumonia (BOOP) and fungal sepsis. One engrafted patient developed medulloblastoma 2 years post-HPCT and is in remission after treatment. Further investigation revealed that this child inherited a novel germline p53 mutation. In this preliminary experience, haploidentical HPCT for children with SCA and stroke was associated with significant graft rejection and chronic GVHD. The addition of pre-transplant hydroxyurea and azathioprine, increased intensity of conditioning, and the use of T-cell addback to the graft did not improve engraftment in the second cohort. While offering the possibility of cure, haploidentical HPCT for SCA as performed in this experience is associated with significant toxicity and should only be pursued in the context of a rigorously designed and controlled prospective clinical trial.

scholarly journals S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2478-2488 ◽  
Author(s):  
Karin Golan ◽  
Yaron Vagima ◽  
Aya Ludin ◽  
Tomer Itkin ◽  
Shiri Cohen-Gur ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Ros Signaling ◽  
Sphingosine 1 Phosphate ◽  
Cell Mobilization ◽  
Elevated Rate

Abstract The mechanisms of hematopoietic progenitor cell egress and clinical mobilization are not fully understood. Herein, we report that in vivo desensitization of Sphingosine-1-phosphate (S1P) receptors by FTY720 as well as disruption of S1P gradient toward the blood, reduced steady state egress of immature progenitors and primitive Sca-1+/c-Kit+/Lin− (SKL) cells via inhibition of SDF-1 release. Administration of AMD3100 or G-CSF to mice with deficiencies in either S1P production or its receptor S1P1, or pretreated with FTY720, also resulted in reduced stem and progenitor cell mobilization. Mice injected with AMD3100 or G-CSF demonstrated transient increased S1P levels in the blood mediated via mTOR signaling, as well as an elevated rate of immature c-Kit+/Lin− cells expressing surface S1P1 in the bone marrow (BM). Importantly, we found that S1P induced SDF-1 secretion from BM stromal cells including Nestin+ mesenchymal stem cells via reactive oxygen species (ROS) signaling. Moreover, elevated ROS production by hematopoietic progenitor cells is also regulated by S1P. Our findings reveal that the S1P/S1P1 axis regulates progenitor cell egress and mobilization via activation of ROS signaling on both hematopoietic progenitors and BM stromal cells, and SDF-1 release. The dynamic cross-talk between S1P and SDF-1 integrates BM stromal cells and hematopoeitic progenitor cell motility.

scholarly journals Plerixafor Overcomes the Adverse Effect of Diabetes on Hematopoietic Progenitor Cell Mobilization

2013 ◽  
Vol 19 (2) ◽  
pp. S192-S193
Author(s):  
Chunzhi Xia ◽  
Xiaobo Zhong ◽  
Dhakal Binod ◽  
Jonathan Thompson ◽  
Timothy Fenske ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Cell Mobilization
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