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

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.

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2773-2779 ◽  
Author(s):  
PJ van Dijken ◽  
J Wimperis ◽  
JM Crawford ◽  
JL Ferrara

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.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5766-5766
Author(s):  
Erden Atilla ◽  
Esmanur Kaplan ◽  
Pinar Ataca Atilla ◽  
Selami Kocak Toprak ◽  
Pervin Topcuoglu ◽  
...  

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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5275-5275
Author(s):  
Zhiping Fan ◽  
Qifa Liu ◽  
Kai Yang ◽  
Jing Sun ◽  
Dan Xu ◽  
...  

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.


Blood ◽  
1969 ◽  
Vol 33 (6) ◽  
pp. 859-864 ◽  
Author(s):  
J. M. HURST ◽  
M. S. TURNER ◽  
J. M. YOFFEY ◽  
L. G. LAJTHA

Abstract As assessed by its spleen colony-forming ability, the stem cell content of bone marrow from mice recovering from hypoxia increases with the duration of erythropoietic depression, and is directly proportional to the number of marrow lymphocytes.


Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 798-805 ◽  
Author(s):  
BR Blazar ◽  
DL Thiele ◽  
DA Vallera

Abstract Incubation of murine bone marrow and splenocytes with the dipeptide methyl ester, L-leucyl-L-leucine methyl ester (Leu-Leu-OMe), which results in the selective depletion of cytotoxic T cells and their precursors, natural killer cells, and monocytes, completely protected 30 recipients of fully allogeneic donor grafts from lethal graft-versus- host disease (GVHD). These results were comparable with those obtained in 30 recipients of anti-Thy 1.2 plus complement (C')-treated donor marrow. However, in contrast to antibody- and C'-dependent T-cell depletion, which reduces the level of donor cell engraftment in our model system, we did not observe such effects using Leu-Leu-OMe marrow pretreatment. As compared with the 24 H-2 typed recipients of anti-Thy 1.2 + C'-treated donor grafts, the 29 H-2 typed recipients of Leu-Leu- OMe-treated donor grafts had significantly (P less than .001) higher percentages of donor cells (mean = 93% v 74%) and significantly (P less than .001) lower percentages of host cells (mean = 6% v 15%) posttransplantation. In vitro limiting dilution assay (LDA) was performed to assess the comparative efficacy of cytolytic T-lymphocyte (CTL) precursor depletion by Leu-Leu-OMe or anti-Thy 1.2 + C' pretreatment. We observed greater levels of CTL precursor depletion in Leu-Leu-OMe treated as compared with anti-Thy 1.2 + C'-treated bone marrow plus spleen cells (BMS) obtained from nontransplanted mice. This suggests that the in vivo results cannot simply be attributed to a less efficacious functional inactivation of cytolytic T-cell precursors by Leu-Leu-OMe treatment as compared with anti-Thy 1.2 + C' treatment. Immunoreconstitution was similar in recipients of Leu-Leu-OMe-treated grafts and anti-Thy 1.2 + C'-treated grafts 100 days posttransplant. In our opinion, Leu-Leu-OMe marrow pretreatment deserves further investigation as a methodology to achieve GVHD prevention without significantly reducing the propensity toward host cell repopulation.


Sign in / Sign up

Export Citation Format

Share Document