الفهرس 
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Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many disorders, such as hematologic and oncologic malignancies as well as immunologic and metabolic disorders.
Unfortunately, cure is often hampered by some complications such as relapse of the underlying disease, graft-versus-host disease, or severe opportunistic infections, which account for the majority of deaths after HSCT.
Despite considerable progress in the management of these complications, infections remain an important cause of post-transplant morbidity and mortality, mainly after allogeneic HSCT.
Specific immune defects are associated with each of the different stages of transplantation, which put patients at risk of developing different types of infections.
In the pretransplantation period: baseline host status, medication therapy, pre-existing neutropenia or compromised barrier defences lead to infections at this stage. So before transplantation, screening is needed to identify potential infectious agents that may put the patient at risk following the immunosuppression that precedes the transplantation.
After the transplantation: Immunologic recovery occurs in three distinct phases, during which the pathogens causing opportunistic infections can differ.
The first is the aplastic phase (preengraftment period, approximately 0-30 d posttransplantation): Following the conditioning regimen until neutrophil recovery from the donated marrow.
The second phase (postengraftment period, approximately 30-100 d posttransplantation): Corresponds to the period from initial marrow engraftment to at least the third or fourth month, and is characterised by the resolution of neutropenia.
The third phase is considered to be the late posttransplantation period: This phase begins at day 100 and continues until the BMT recipient stops all immunosuppressive medication for GVHD, which is approximately 18-36 months post transplantation.
So the speed of immune recovery after allo-SCT is of central importance to overcome infectious complications and relapse.
Of the innate effector cells, NK cellularity recovers to normal levels within 1–2 months following HSCT, irrespective of any transplant related factors. Concomitant recovery in NK cellularity and cytotoxic activity has been demonstrated in haploidentical transplantation.
Also, neutrophil recovery occurs early and precedes monocytes and tissue macrophages. However, unlike NK cells, cellular recovery of myeloid cells is influenced by transplant-related factors such as stem cell source and GVHD, and their functional recovery does not parallel recovery in cellularity.
Like other innate effector cells, DCs recover early following HSCT, especially after matched sibling and nonmyeloablative allogeneic HSCT.
While the innate immune cells are rapidly reconstituted (within weeks), the adaptive part of the immune system requires months or even years to be fully recovered.
In general, B-cell reconstitution precedes T-cell recovery and recapitulates B-cell ontogeny in the absence of GVHD. B-cell numbers start to normalize by 3 months post transplantation, while B-cell function may take as long as 2 years to do.
On the other hand, T-cell recovery does not recapitulate cellular ontogeny. Thymic-independent peripheral expansion of memory T cells derived from progenitor cells within the graft precedes central or thymic dependent expansion of naı¨ve T cells causing an inversion of the CD4:CD8 ratio and a decreased pool of naı¨ve T cells with diverse TCR repertoires.
Despite successful homing and engraftment of stem cells ,immune reconstitution may not achieve functional maturation after HSCT because the process of IR is adversely affected by disease-, patient-, and transplant-related factors including patient age; underlying disease and disease status; transplant type (autologous vs. allogeneic), preparative regimen (myeloablative vs. nonmyeloablative), and stem cell source; major histocompatibility complex (HLA) disparity resulting in GVHD; and infection. These factors culminate to blunt immune responses and to increase susceptibility to infection and disease relapse.
Because HSCT creates a dynamic chimera involving the transplanted donor cells and the recipient cells. Chimerism tests on the patient’s blood or bone marrow determine how much is derived from the donor and how much is residual recipient material. For this reason, an accurate assessment of chimerism in the patient’s blood or bone marrow provides critical information on the progress of engraftment, and serves as a key element in predicting rejection and relapse. Also more detailed information about immune reconstitution can be gathered by examining T and B lymphocytes and neutrophils separately.
Over the last two decades, remarkable progress to enhance immune recovery following HSCT has been achieved & success in immunotherapy continues to evolve. Obvious targets for immunotherapy include immune effector cells themselves, their targets, or the responses they elicit. Other potential cellular targets include hematopoietic stem and progenitor cells and mesenchymal stem cells. Like their cellular targets, soluble mediators such as cytokines and novel factors like heat-shock proteins (HSPs) and TLR agonists have also been used to affect immune responses. Finally, combinations of these cellular and soluble forms of immunotherapy are currently being explored to promote desirable responses or to avoid undesirable ones in the HSCT recipient.
Also, revaccination of allogeneic HSCT recipients is a simple and effective strategy to reverse the loss of the vaccine response after HSCT.
Passive antibody prophylaxis with IVIG is used in some centers to prevent and to treat infections following HSC transplantation. While other centers do not recommend them to be used.