scholarly journals THE INDUCTION OF GRAFT VERSUS HOST DISEASE IN MICE TREATED WITH CYCLOPHOSPHAMIDE

1968 ◽  
Vol 128 (2) ◽  
pp. 277-291 ◽  
Author(s):  
Albert H. Owens ◽  
George W. Santos
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Severe Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Experimental Systems ◽  
Adult Mice ◽  
Competent Cells

In these studies adult mice treated with cyclophosphamide and foreign immunologically competent cells developed a graft versus host disease which outwardly resembled that encountered in other experimental systems. Progressively larger doses of cyclophosphamide produced an increasingly severe disease whereas comparable doses of mechlorethamine were ineffective. Increasingly larger cell inocula from parental, allogeneic, and xenogeneic donors resulted in a correspondingly more severe disease. Nucleated cells obtained from the peripheral blood were found to be the most potent inducers of this syndrome, while cells from the spleen, bone marrow, and thymus displayed lesser degrees of reactivity in that order. No such graft versus host disease occurred in mice given saline, lysed, or heat-killed cells in place of viable foreign cells. Neither did the disorder develop when comparable inocula of isogeneic cells were used.

Does Donor Epstein-Barr Virus (EBV) Seropositivity Affect Recipient's Risk of Graft Versus Host Disease (GVHD) in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5766-5766
Author(s):  
Erden Atilla ◽  
Esmanur Kaplan ◽  
Pinar Ataca Atilla ◽  
Selami Kocak Toprak ◽  
Pervin Topcuoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction: EBV seropositivity in general population is 80%. Reactivation of latent infection in pre-transplant seropositive patients causes post-transplant lenfoproliferative disease (PTLD) following Allo-HSCT. The effect of donor EBV positivity on recipient's risk of graft versus host disease is not clear. Our aim is to present EBV seroprevalence and PTLD incidence as well as demonstrating the relation of EBV seropositivity with GVHD. Patients and Methods: A total of 364 allogeneic stem cell transplant recipients and donors were evaluated retrospectively from 2006 to 2015. During Allo-HSCT preparation procedures all recipients and donors were serologically tested. EBV specific IgG (VCA-IgG, EBNAIgG, EA-IgG) and IgM (VCA-IgM) antibodies were determined by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). All patients were followed for reactivation. Results: EBV IgG positivity was detected in 338 of recipients (92.8%) and 283 of donors (77.7%). There was no statistically difference detected between related or unrelated transplants. The mean age was 37 (range 16-67). 217 recipients were male (60%). 295 (81%) patients were transplanted for malign hematological diseases. The majority of patients were grafted from full-matched related donors (258, 71%). The most common source of stem cell was peripheral blood in 299 patients (82%) followed by bone-marrow in 56 patients (15%), bone-marrow plus peripheral blood in 9 patients (3%). 273 (75%) patients received myeloablative conditioning regimen. All patients received prophylactic acyclovir (in related transplants 400mg 3 times daily, in un-related transplants 800mg 3 times daily) starting from conditioning and up to three months posttranplant period. One pretransplant seropositive 26 year-old aplastic anemia patient had PTLD with EBV IgM positivity within 3 months posttransplant. He received 4 cycles of rituximab and prednisolone and achieved complete response. Three patients had EBV IgM positivity in posttransplant 4, 9 and 24th months with symptoms of infectious mononucleosis. The seropositivity resolved without treatment. Acute GVHD developed in 223 patients (61%) whereas chronic GVHD was detected in 285 (78%) of patients. The incidence of acute GVHD was similar when donor was EBV seropositive compared to seronegative (78% vs 22%, p=0.72). Chronic GVHD incidence was similar between donor EBV seropositive group compared to seronegative group (80% vs 20%, P=0.199). Conclusion: EBV seropositivity is common detected in 92.8% of our allo-HSCT recipient cohort. Donor EBV status did not have an effect on developing acute or chronic GVHD. Disclosures No relevant conflicts of interest to declare.

Increased Donor CD86+CD14+ Cells in the Bone Marrow and Peripheral Blood of Patients With Chronic Graft-Versus-Host Disease

2008 ◽  
Vol 85 (12) ◽  
pp. 1826-1832 ◽  
Author(s):  
Mario Arpinati ◽  
Gabriella Chirumbolo ◽  
Giulia Marzocchi ◽  
Michele Baccarani ◽  
Damiano Rondelli
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Bone Marrow NK1.1− and NK1.1+ T Cells Reciprocally Regulate Acute Graft versus Host Disease

1999 ◽  
Vol 189 (7) ◽  
pp. 1073-1081 ◽  
Author(s):  
Defu Zeng ◽  
David Lewis ◽  
Sussan Dejbakhsh-Jones ◽  
Fengshuo Lan ◽  
Marcos García-Ojeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
T Cell Subsets ◽  
Host Disease ◽  
Graft Versus Host ◽  
Ifn Γ

Sorted CD4+ and CD8+ T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2b) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell–depleted donor marrow cells, into lethally irradiated BALB/c (H-2d) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1+ T cells represented <1% of all T cells in the blood and ∼30% of T cells in the marrow, the capacity of sorted marrow NK1.1− CD4+ and CD8+ T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1+ T cells suppressed GVHD. The marrow NK1.1+ T cells secreted high levels of both interferon γ (IFN-γ) and interleukin 4 (IL-4), and the NK1.1− T cells secreted high levels of IFN-γ with little IL-4. Marrow NK1.1+ T cells obtained from IL-4−/− rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1− and NK1.1+ T cell subsets via their differential production of cytokines.

Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 415-419 ◽  
Author(s):  
Mary E. D. Flowers ◽  
Pablo M. Parker ◽  
Laura J. Johnston ◽  
Alice V. B. Matos ◽  
Barry Storer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Cumulative Incidence ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Long Term Follow Up

Abstract In a previous multicenter phase III trial comparing peripheral blood stem cell transplantation (PBSCT) to bone marrow transplantation (BMT) from HLA-matched related donors, we found no statistically significant difference in the cumulative incidence of clinical extensive chronic graft-versus-host disease (GVHD) in the 2 groups. We have analyzed the results in more detail to determine whether the clinical characteristics of chronic GVHD after PBSCT might be distinct from those that occur after BMT. Clinical extensive chronic GVHD developed in 39 of 63 recipients of PBSCs and in 32 of 63 BM recipients who were alive and free of malignancy at day 100 after the transplantation. No significant differences were found in the time and type of onset of clinical extensive chronic GVHD or in the frequency of complications associated with severe morbidity. Involvement of skin and female genital tract was more frequent in PBSC recipients than in BM recipients. The cumulative incidence of chronic GVHD at 3 years was similar in the 2 groups, but the number of successive treatments needed to control chronic GVHD was higher after PBSCT than after BMT (P = .03), and the duration of glucocorticoid treatment was longer after PBSCT compared to BMT (P = .03). These results suggest that chronic GVHD after PBSCT may be more protracted and less responsive to current treatment than chronic GVHD after BMT. Assessment of the overall benefits of PBSCT compared to BMT will require continued long-term follow up of morbidity associated with chronic GVHD.

scholarly journals Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2773-2779 ◽  
Author(s):  
PJ van Dijken ◽  
J Wimperis ◽  
JM Crawford ◽  
JL Ferrara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Cell Compartment ◽  
Host Disease ◽  
Murine Bone Marrow ◽  
Graft Versus Host ◽  
Stem Cell Compartment

Abstract We have examined the effect of graft-versus-host disease (GVHD) on the reconstitution of donor hematopoiesis in a murine bone marrow transplant (BMT) model of GVHD to minor histocompatibility antigens. GVHD had no effect on peripheral blood counts, which normalized by 1 month after BMT, and did not affect numbers of hematopoietic progenitors in the BM, which remained decreased in all transplant recipients. Donor stem cells (colony-forming unit-spleen day 8) and stem cell self-renewal remained low in all mice for 5 months after transplant, but GVHD further damaged the stem cell compartment. Peripheral counts 1 month after transplant were supported by increased numbers of stem cells in cycle and increased splenic hematopoiesis. However, GVHD altered the pattern of extramedullary hematopoiesis, causing dramatically decreased activity in the spleen and increased activity in the liver. We conclude that GVHD further decreases hematopoietic reserve and causes damage to the donor stem cell compartment during hematopoietic reconstitution after transplant, despite unaffected progenitor frequencies and peripheral blood counts.

scholarly journals Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2773-2779
Author(s):  
PJ van Dijken ◽  
J Wimperis ◽  
JM Crawford ◽  
JL Ferrara
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Cell Compartment ◽  
Host Disease ◽  
Murine Bone Marrow ◽  
Graft Versus Host ◽  
Stem Cell Compartment

We have examined the effect of graft-versus-host disease (GVHD) on the reconstitution of donor hematopoiesis in a murine bone marrow transplant (BMT) model of GVHD to minor histocompatibility antigens. GVHD had no effect on peripheral blood counts, which normalized by 1 month after BMT, and did not affect numbers of hematopoietic progenitors in the BM, which remained decreased in all transplant recipients. Donor stem cells (colony-forming unit-spleen day 8) and stem cell self-renewal remained low in all mice for 5 months after transplant, but GVHD further damaged the stem cell compartment. Peripheral counts 1 month after transplant were supported by increased numbers of stem cells in cycle and increased splenic hematopoiesis. However, GVHD altered the pattern of extramedullary hematopoiesis, causing dramatically decreased activity in the spleen and increased activity in the liver. We conclude that GVHD further decreases hematopoietic reserve and causes damage to the donor stem cell compartment during hematopoietic reconstitution after transplant, despite unaffected progenitor frequencies and peripheral blood counts.

Comparative Analysis of Clinical Outcomes between Unrelated Donor Peripheral Blood Stem Cell Transplantation and Bone Marrow Transplantation for Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5275-5275
Author(s):  
Zhiping Fan ◽  
Qifa Liu ◽  
Kai Yang ◽  
Jing Sun ◽  
Dan Xu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
T Cell Reconstitution

Abstract Objective To evaluate hematopoietic reconstitution, immune reconstitution, infection, incidence of graft-versus-host disease (GVHD) and other complications between unrelated donor peripheral blood stem cell (PBSC) transplantation and bone marrow (BM) transplantation. Methods The clinical results in 21 patients receiving a PBSC graft mobilized by granulocyte colony stimulating factor (G-CSF) from unrelated donors were compared to 32 patients receiving unrelated BM transplants. Results The PBSC graft contained significantly more nucleated cells (P=0.000), and resulted in a significantly shorter time-to-neutrophil (12.43±3.67 versus 16.16±2.99 days) and platelet engraftment (14.67±6.19 versus 21.23±8.25 days), compared to the BM group (P=0.000, 0.003, respectively). T cell reconstitution between the two groups differed little after transplantation. The incidences of early-stage infection were 42.86% and 53.13% (not significant [NS]) in the PBSC and BM groups, respectively. Probabilities of acute graft-versus-host disease (aGVHD) were 61.90% and 71.88% (NS), of grades III to IV aGVHD 23.81% and 15.63% (NS) and of chronic GVHD 47.06% and 43.48% (NS) in the PBSC and BM groups, respectively. The probabilities of relapse were 6.90% and 12.50% (NS) in the PBSC and BM groups, respectively. The 2-year disease free survival (DFS) rates of the two groups were (50.14±12.00) % and (59.81±8.99) %( NS), respectively. Conclusion G-CSF-mobilized PBSCs engraft rapidly in unrelated donor recipients compared to conventional BM, but T cell reconstitution and the incidence of infection between the two groups differed little. There were no significant differences of the incidence and severity of aGVHD and cGVHD, and 2-year DFS rates between the two groups.

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