CHAPTER 94: Hematopoietic Stem Cell Transplantation and Graft-Versus-Host Disease

KEY POINTS

• The complications of hematopoietic stem cell transplantation generally relate to the consequences of the cytoreductive therapy, infections, and in the case of allogeneic transplants, immunosuppression and development of graft-versus-host disease.

• Graft-versus-host disease remains one of the most important complications of allogeneic transplantation.

• Stem cell transplant recipients may require admission to the intensive care unit for close monitoring for volume and electrolyte issues, vasopressor or renal support, and mechanical ventilation.

• The approach to the diagnosis and management of infectious disorders in the stem cell transplant recipient is dependent on the underlying disease and prior therapy, timing of the infection relative to the transplant, the type of transplant, the patient's immunologic history and comorbidities.

• Pulmonary complications develop in up to 60% of allogeneic transplant recipients and are the immediate cause of death in approximately half of the cases.

• Major noninfectious pulmonary complications in the early transplant period include idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, and periengraftment respiratory distress syndrome; bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia occur later.

• Despite advances in supportive care in the intensive care unit, the mortality rate of allogeneic transplant recipients who develop respiratory failure and multiple organ failure remains extremely high.

INTRODUCTION

Hematopoietic stem cell transplantation (HSCT) has become an expanding modality for the treatment of benign and malignant hematologic diseases. While HSCT has been shown to be of benefit in only a few nonhematologic malignant diseases such as relapsed testicular cancer and neuroendocrine tumors, it has been studied in clinical trials in a variety of others such as renal cell and breast cancer, without major efficacy.¹ In the area of benign diseases, it can restore hematopoiesis and/or immune function in congenital or acquired immune deficiency or marrow failure states. The most common diseases for which HSCT is performed are acute leukemia, myelodysplastic syndrome, Hodgkin and non-Hodgkin lymphomas, multiple myeloma, and less common disorders such as aplastic anemia.² Classical HSCT is a lifesaving procedure which utilizes high doses of chemotherapy and/or radiotherapy. In the case of malignant disease, it is a treatment modality which is used after at least one and often many courses of standard chemotherapy. Greater numbers of patients over a wide age range are undergoing transplantation as a part of their oncologic therapy, and more of these patients are becoming survivors.³

A stem cell transplant can be broken down into three components: the graft, the conditioning, and, in some types of transplant, the immunosuppression. There are two types of HSCT based on the source of the graft—“autologous”—when the stem cells are harvested from the patient at the time of blood count recovery after chemotherapy, or after receiving a white blood cell growth factor (granulocyte-colony stimulating factor [G-CSF]) or stem cell mobilizer (plerixafor)—which mobilizes bone marrow stem cells into the peripheral blood from which they can be collected by apheresis. The second type of stem cell transplant is “allogeneic” which ...