Skin aGVHD Research Articles

Study of the Relationship between Granulocyte Colony-Stimulating Factor Together with Type 2 Dendritic Cells in Donor Grafts and the Allogeneic Hematopoietic Stem Cell Transplantation.

ObjectiveTo evaluate the influence of granulocyte colony-stimulating factor (G-CSF)on the quantity, ratio of dendritic cell(DC)1 and DC2 in peripheral blood (PB)and bone marrow(BM);To assess the influence of G-CSF on the cell composition of grafts (included the DC subsets) and the curative effect following Allogeneic hematopoietic stem cell transplantation (Allo-HSCT).MethodsBy FACS, the quantity, ratio of DC1 and DC2 were detected by 11 donors in granulocyte colony-stimulating factor mobilization peripheral blood hematopoietic stem cell(G-PBSC) graft, 20 donors in G-BM graft, 8 donors in primed PB, and 10 normal individuals in primed BM respectively.ResultDC2 count in BM (from a mean of 14.37×106/L to 29.68×106/L P=0.013) was increased by G-CSF treatment with 10ug/kg per day for 5 days, whereas BM DC1 count did not change. The ratio of DC2 to DC1 was significantly higher in donor BM with G-CSF (1.83±0.81) than in resting unprimed BM (1.12±0.32)(P=0.013).The number of PB DC2 (26.76×106/L) and the ratio of DC2 to DC1 (2.02± 1.43) was selectively increased in normal donor treated with G-CSF, but a similar to number of DC1.The absolute numbers of MNC, CD34+, CD3+, CD3+CD4+ or CD3+CD8+ cells contained in G-BM allograft were higher 1 to 2 times than those in BM allograft(P<0.05), but were comparable with those in G-PBSC allograft.The median time of neutrophil engraftment in G-BMT group(13 days) was longer 1day than that in peripheral blood hematopoietic stem cell transplantation (PBSCT)group (12 days);The median time of platelet engraftment in G-BMT group was comparable with that in PBSCT group, but was earlier 4 days than that in BMT group (P=0.039).PLT transfusion was significantly reduced in recipients of G-BM graft (50u) compared to BM (140u)(P=0.002); RBC transfusion did not differ between G-BMT and PBSCT or BMT;Median time to hospital discharge after transplantation was significantly reduced in patients receiving G-BM graft compared to BM (P=0.004).The incidence of gradesII~IV and III~IV aGVHD was respectively higher and lower in the G-BMT (31.6%OE14.5%) group than in the PBSCT (25% OE 20%) group, was lower than in the BMT group (50.1% OE33 .4%).The incidence rate of aGVHD in higher DC2 infusion group was 61.5% (lower DC2 infusion group:83.3%), the emergence time of aGVHD was 22days(18days).Similarly, the incidence rate of gradesII~IVand III~IV aGVHD in higher infusion group was 23.08% and 15.38%(lower infusion group: 66.67% and 33.33%).ConclusionThe number of PB and BM DC2 were selectively increased in normal donor treated with G-CSF but not PB or BM DC1.G-PBSC graft used for allogeneic transplantation contained more DC2 counts than resting BM but a similar to number of DC1.Compared to G-BMT, patients receiving G-BMT had prompt engraftment of platelet, lower platelet transfusion requirements, and shorted average length of stay.There was a incidence of less skin, liver or gut aGVHD, and less grades II~IV or III~IVaGVHD in the G-BMT group than in the BMT group.There was a tendency of rapid engraftment and decreased incidence or severity of aGVHD in the higher DC2 infusion group.

Human Herpesvirus 6 Variant B Infection in Adult Patients after Unrelated Cord Blood Transplantation

Human herpesvirus 6 variant B (HHV-6B) infection was studied in 23 adult patients who underwent cord blood transplantation (CBT). HHV-6B DNA was detected by quantitative polymerase chain reaction analysis after CBT in the sera from 15 patients (65%) at day 14 or 15 (week 2), from 16 patients (70%) at day 21 or 22 (week 3), and from 3 patients (13%) at day 28 or 29 (week 4). HHV-6B DNAemia was found in none of the 20 patients examined at day 7 or 8 (week 1). The overall incidence of HHV-6B DNAemia reached 87% (20 of 23 patients). This incidence was much higher than after unrelated bone marrow transplantation (19%, P < .0001). In CBT patients, positive HHV-6B DNAemia at week 3 was significantly associated with early skin rash (88% versus 14%, P < .005) and grade II-IV acute graft-versus-host disease (aGVHD) (69% versus 14%, P < .05). In contrast, positive HHV-6B DNAemia at week 2 was associated with neither skin rash nor aGVHD. Prospective large-scale studies are needed to determine the role of HHV-6 infection in CBT patients.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. A single centre descriptive study. Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.

Molecular Analysis of T-Cell Repertoire in Patients with Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

Complementarity-determining region (CDR3) size spectratyping has often been used to analyze the clonal expansion of T-cells. CDR3 size spectratyping has been useful in the analysis of the oligoclonal expansion of T-cells in virus infection, graft-versus-leukemia effect (GVL), graft-versus-host disease (GVHD), and immune reconstitution of T-cells after allogeneic stem cell transplantation (allo-SCT). We analyzed 26 T cell receptor (TCR)-β-chain subfamilies (VB) in 25 patients who underwent allo-SCT. Fifteen of these patients developed acute GVHD (aGVHD). Many TCR-VB were skewed in the early stage. In these TCR-VB subfamilies, VB6 was most often skewed at the time of skin aGVHD. We then analyzed the average score of the complexity of 26 TCR-VB spectratypings in patients with or without cGVHD. The patients who developed chronic GVHD (cGVHD) had a lower average score of TCR-VB complexity than that of patients without cGVHD (P = 0.010). In particular, the patients who developed the quiescent type and de novo type of cGVHD from 4 months after allo- SCT had a lower average score of TCR-VB complexity at 3 months than that of the patients who had no cGVHD (P = 0.0055). These results suggest that we might be able to consider a possible development of cGVHD by analyzing TCR-VB spectratyping after allo-SCT.

Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite

Objectives: To investigate mycophenolate mofetil (MMF) plasma levels and impact on acute graft versus host disease (aGvHD) after stem cell transplantation (SCT). Methods: SCT patients (n = 14) with aGvHD (≥ II) receiving MMF (1–3 g/d) in addition to cyclosporine, prednisolone, and methotrexate for aGvHD prophylaxis were investigated. Plasma levels of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were determined by high-performance liquid chromatography. Results: Overall median steady state pre-dose plasma MPA concentration was 0.47 mg/L and increased within 75 min after administration to 1.64 mg/L. In comparison to patients with skin aGvHD, patients with gut aGvHD had lower MPA concentrations, both pre-dose (p = 0.16) and after 75 min, ( p = 0.02). All 7 patients with skin aGvHD but only 2 patients with gut aGvHD responded to MMF. Overall, the pre-dose plasma MPA concentration was significantly ( p = 0.007) greater in responders ( n = 9) than in non-responders ( n = 5). Conclusion: MMF seems to be an effective treatment for aGvHD in SCT patients particular in those patients without gut involvement.

Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation.

Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p < 0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.