Tehran University Medical Journal

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Interest in umbilical cord blood as an alternative source of hematopietic stem cells is growing rapidly. Umbilical cord blood offers the clinician a source of hematopoietic stem cells that are readily available and rarely contaminated by latent viruses. Moreover, the collection of umbilical cord blood poses no risk to the donor. There is no need for general anesthesia or blood replacement and the procedure causes no discomfort. Current clinical experience suggests that the incidence of GVHD in umbilical cord blood transplantation is low. These results and associated laboratory findings pose intriguing possibilities for the future of umbilical cord blood stem cells in the setting of unrelated donor transplantation. There are other intriguing possibilities for example cord blood may be an optimal source of pluripotential stem cells for use in genetherapy.

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Background: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease (aGVHD). The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after BMT would be extremely valuable. By serially measuring serum levels of soluble IL-2 receptor (sIL-2R), IL-18 and following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to aGVHD as complication of the transplantation and determine useful markers for aGVHD predictors.

Materials and Methods: Serum sIL-2R, IL-18, and levels were measured by sandwich ELISA in 219 sera samples from 39 patients (with hematological disorders before and after allogeneic BMT) and 28 controls. All patients received BMT from HLA-identical siblings.

Results: 25 patients developed aGVHD and serum levels of sIL-2 R and IL-18 , in sera drawn before transplantation , in patients with acute graft-versus-host disease (aGVHD +) , were increased in comparison of patients without acute graft-versus-host disease (aGVHD ¯) and control group and there wasn’t any significant differences in serum levels of sIL-2 R and IL-18 in aGVHD ¯ patients and controls. Serum level of IL-18, in aGVHD+ patients, was increased during day 3 - 24 after BMT, and there was a significant difference in patients with GVHD 0 – GVHD III. In majority of patients with acute GVHD (60 %) , the peak levels of IL-18 and IL-2R was achieved on day 10 after BMT and the rise in sIL-2R and IL-18 preceded of clinical signs of GVHD (mean day 15 after BMT). Level of IL-18 in patients with aGVHD had strongly correlated with the severity of aGVHD on Day 10 after BMT. IL-18 level mean (before BMT), in patients who received Busulfan and Fludarabin to treat aGVHD, was lower than in patients who received Busulfan - Endoxan, or Cyclophosphamide.

Conclusion: Our data concluded that IL-18 plays an important role in the development of aGVHD and IL-18 level might be an indicator for aGVHD, reflecting the severity of the disease. These findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be useful predictor of aGVHD.

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Background: Human Cytomegalovirus (HCMV) infections are a significant challenge in patients with Hematopoietic Cell Transplant (HCT). Acute Graft vs. Host (GVHD) is recognized as a predisposing factor for increased incidence of HCMV reactivation. Availability of rapid and accurate tests for HCMV detection in HCT recipients is of foremost importance in developing countries, such as Iran.
Methods: A total of 201 peripheral blood leukocyte (PBL) and plasma specimens from 26 allogeneic HCT recipients were examined for HCMV DNA by polymerase chain reaction (PCR) assay. Densitometric analysis of 257bp PCR products from clinical samples and 101-106 "cloned plasmid" per µg DNA containing a HCMV specific fragment were analyzed using LabWorks software (v3.0.02). Optical density of amplicons was plotted, and calculated HCMV viral loads were compared with the patients' antigenemia results.
Results: HCMV viral loads ranged between <102 to 1.35×102 copies per µg DNA among 7 HCT patients. In addition, 14 episodes of positive antigenemia assay in 7 patients in which peak HCMV load were compared with GVHD grade II-IV patients. Significant correlation was also detected between HCMV DNA load in PBL and plasma samples, as well as HCMV DNA load in PBL samples and antigenemia results. Receiver–Operating Characteristic analysis determined that 2,200 HCMV copies in PBL samples as the threshold value for initiation of Ganciclovir therapy.
Conclusion: This report shows that rapid and sensitive assays, like quantitative PCR, are extremely valuable for detection of active HCMV infection, and life-threatening HCMV disease in HCT recipients during the post transplant period. Furthermore, high HCMV DNA load among GVHD grade II-IV patients confirms the high risk of HCMV reactivation among these HCT recipients. Tests such as quantitative PCR also helps physicians initiate timely preemptive therapy and for a shorter period, which may lead to better clinical outcome in HCMV-infected transplant patients.