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Strategies for immune reconstitution following allogeneic hematopoietic cell transplantation

Marcel RM van den Brink, MD, PhD
Jarrod A Dudakov, PhD
Section Editor
Robert S Negrin, MD
Deputy Editor
Alan G Rosmarin, MD


Allogeneic hematopoietic cell transplantation (HCT) is an important and potentially curative treatment option for a wide variety of malignant and nonmalignant diseases. Paradoxically, cytoreductive conditioning regimens designed to allow for successful allogeneic HCT are also detrimental to recovery of the immune system in general, and the production of lymphocytes in particular.

Delayed recovery of the immune system is associated with a high degree of morbidity and mortality [1-3]. Post-transplant immune depletion is particularly striking within the T cell compartment, which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Preclinical and clinical studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency.

Immune reconstitution following allogeneic HCT will be discussed here. Immunization following HCT and other supportive care issues surrounding HCT are presented separately. (See "Immunizations in hematopoietic cell transplant candidates and recipients" and "Hematopoietic support after hematopoietic cell transplantation" and "Management of the hematopoietic cell transplant recipient in the immediate post-transplant period".)

The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, umbilical cord blood). Otherwise, the source of such cells will be specified (eg, peripheral blood progenitor cell transplantation).


A critical component of allogeneic HCT is the administration of chemotherapy and/or radiation therapy as a conditioning (or preparative) regimen with the goal of providing adequate immunosuppression to prevent rejection of the transplanted graft. Both alkylating chemotherapeutics and irradiation target highly proliferative cells [4-6], including developing and naïve lymphocytes [1]. As a result, following transplant, there is severe depletion of all hematopoietic cells of the immune system, especially lymphocytes. (See "Preparative regimens for hematopoietic cell transplantation".)

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Literature review current through: Oct 2017. | This topic last updated: Jun 27, 2016.
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