Cotransplantation of ex vivo–expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2764-2767 ◽  
Author(s):  
Lynne M. Ball ◽  
Maria Ester Bernardo ◽  
Helene Roelofs ◽  
Arjan Lankester ◽  
Angela Cometa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Increased Risk

Haploidentical hematopoietic stem-cell transplantation (HSCT) is associated with an increased risk of graft failure. Adult bone marrow–derived mesenchymal stromal cells (MSCs) have been shown to support in vivo normal hematopoiesis and to display potent immune suppressive effects. We cotransplanted donor MSCs in 14 children undergoing transplantation of HLA-disparate CD34+ cells from a relative. While we observed a graft failure rate of 15% in 47 historic controls, all patients given MSCs showed sustained hematopoietic engraftment without any adverse reaction. In particular, children given MSCs did not experience more infections compared with controls. These data suggest that MSCs, possibly thanks to their potent immunosuppressive effect on alloreactive host T lymphocytes escaping the preparative regimen, reduce the risk of graft failure in haploidentical HSC transplant recipients.

Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6123-6132 ◽  
Author(s):  
Richard K. Burt ◽  
Robert M. Craig ◽  
Francesca Milanetti ◽  
Kathleen Quigley ◽  
Paula Gozdziak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Crohn Disease ◽  
Ex Vivo ◽  
Activity Index ◽  
Clinical Relapse ◽  
Hematopoietic Stem

Abstract We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti–tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34+ selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.

scholarly journals SECOND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES

2019 ◽  
Vol 64 (1) ◽  
pp. 35-48
Author(s):  
L. A. Kuzmina ◽  
Z. V. Konova ◽  
E. N. Parovichnikova ◽  
M. Y. Drokov ◽  
V. A. Vasilyeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem

Background.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a standard treatment for many patients with hematological malignancies. Complications of allo-HSCT are frequently associated either with a relapse of the underlying disease or a graft failure. Second transplantation can be offered to selected patients and is seen as the only curative option. In this paper, we report the experience of managing 24 such patients, all of whom underwent a second allo-HSCT.Patients and methods.The research involved 24 patients (12 males/12 females) suffering from acute myeloid leukemia (AML, n = 14), acute lymphoblastic leukemia (ALL, n = 4), myeloproliferative disease (MPD, n = 3) and myelodysplastic syndrome (MDS, n = 3). The patients’ age ranged from 18 to 56 years, with the median age being 32 years. All the patients underwent a second allo-HSCT due to the disease relapse (n = 11) or graft failure (n = 13). 12 patients underwent a second allo-HSCT within the period of less than 6 months after the first allo-HSCT.Results.Following the second allo-HSCT, engraftment occurred in 18/24 (75 %) patients, while 3 patients demonstrated graft failure and 3 — disease progression. Out of 18 patients having engrafted, 9 (50%) died during the first 100 days after allo-HSCT as a result of severe infections or visceral toxicity. 3 more lethal outcomes were recorded in later periods due to the disease progression. The overall mortality rate after the second allo-HSCT equalled 61.5 %. The median overall survival (OS) and disease-free survival (DFS) rates were 13.5 months and 10.59 months, respectively. Three-year OS and DFS were 38.5 % and 27.6 % respectively. Significant differences in terms of OS were detected for patients with a longer interval (>6 months) between the first and second allo-HSCT. The change of a donor was not associated with a better clinical outcome.

scholarly journals Parvovirus B19-Associated Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 26 (3) ◽  
pp. S344
Author(s):  
Nabila Rattani ◽  
Christina Matheny ◽  
Erica Garcia-Frausto ◽  
Michael J. Eckrich ◽  
Lisa Madden ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Failure ◽  
Parvovirus B19 ◽  
Hematopoietic Stem

scholarly journals Clonal hematopoiesis in donors and long-term survivors of related allogeneic hematopoietic stem cell transplantation

Blood ◽  
2020 ◽  
Vol 135 (18) ◽  
pp. 1548-1559 ◽  
Author(s):  
Steffen Boettcher ◽  
C. Matthias Wilk ◽  
Jochen Singer ◽  
Fabian Beier ◽  
Elodie Burcklen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Increased Risk ◽  
Long Term Survivors

Abstract Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested ∼20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.

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