Page 1275 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

882 PART 7: Hematologic and Oncologic Disorders

TABLE 94-1 Reasons for Intensive Care Unit Admission of HSCT Recipients
HSCT
Respiratory insufficiency/failure
Infectious pneumonia
Noninfections lung injury syndromes—IPS, DAH, PERDS
Allogeneic Autologous
myeloablative, RIC myeloablative Pulmonary edema
Airway issues related to mucositis
Bronchiolitis obliterans
Unmodified TCD Unmodified Bronchiolitis obliterans organizing pneumonia
BM, PBSC, UCB BM, PBSC BM, PBSC Severe sepsis/septic shock
Hepatic failure
FIGURE 94-1. Types of hematopoietic stem cell transplantation. BM, bone marrow; Hepatic VOD
HSCT, hematopoietic stem cell transplantation; PBSC, peripheral blood stem cells; RIC, reduced GVHD
intensity conditioning; TCD, T-cell depleted; UCB, umbilical cord blood. Renal complications
Gastrointestinal hemorrhage
GVHD
can be obtained directly from the bone marrow by performing many Neurological complications
aspirations from the posterior iliac crests under general anesthesia, Intracranial hemorrhage
by apheresis of stem cells mobilized from the bone marrow into the Seizure
peripheral blood after administering G-CSF or stem cell mobilizer to
the donor, or in the form of umbilical cord blood stem cells which were DAH, diffuse alveolar hemorrhage; GVHD, graft-versus-host disease; IPS, idiopathic pneumonia syndrome;
harvested from the placenta at the time of a birth. In an autologous PERDS, periengraftment respiratory distress syndrome; VOD, venoocclusive disease.
transplant, the stem cells are only used to rescue the bone marrow
from the damage caused by the chemotherapy, radiotherapy, and/
or antibody therapy given just prior to the stem cell infusion to treat The third component of the allogeneic stem cell transplant is the
the malignancy. Stem cells in an allogeneic stem cell transplant immunosuppression (this treatment is not needed for an autologous
rescue the bone marrow from treatment damage with cells that are free transplant because the patient would be receiving their own cells back).
of disease. In addition, some of these stem cells, as well as the lym- Since the allogeneic transplant patient is receiving both new bone
phoid cells that accompany the stem cells, develop into a new immune marrow stem cells and cells to generate a new immune system, the latter
system, which may provide a biologic effect (allo effect) against the cells from the donor must be kept under control with immunosuppres-
tumor referred to as the graft-versus-leukemia or graft-versus-tumor sive drugs until they become acclimated to living in the patient.
effect (GvT). ABO incompatibility between the patient and the donor In summary, HSCT involves the use of chemotherapy, radiotherapy,
requires manipulation of the graft prior to infusion with red cell or or biologic therapy known as the conditioning, followed by infusion
plasma depletion. A limited number of allogeneic transplant centers of stem cells to (a) rescue the bone marrow from the consequences of
perform CD34+ selection of stem cells to remove many of the accessory the therapy and (b) in the case of allogeneic HSCT, to provide a new
cells (such as lymphocytes) prior to their infusion. Such manipulation immune system and hence, hopefully, a biologic effect against any
of the graft may be referred to as CD34+ selection or T-cell depletion residual disease. The most potentially complicated transplant is the
(TCD). The removal of T lymphocytes reduces the risk of GVHD, one myeloablative allogeneic HSCT. The complications of HSCT generally
of the major complications of allogeneic stem cell transplantation (see relate to consequences of the cytoreductive therapy (the condition-
the section “Graft-Versus-Host Disease”). ing), infections, and in the case of allogeneic HSCT, immunosuppres-
The second component of a transplant is the “conditioning,” which is sion and development of GVHD (see the section “Graft-Versus-Host
the treatment that prepares the patient for transplantation and gener- Disease”). Certain types of transplants can be expected to result in more
ally incudes chemotherapy, radiotherapy, and/or antibody therapy. The complications than others—these include allogeneic HSCTs which use
conditioning is administered to treat any disease which may remain mismatched volunteer donors or cord blood as the source of the graft,
following standard chemotherapy used by the general oncologist to patients with relapsed/refractory disease at the time of transplant, and
treat the disease. There are at least two forms of conditioning regimens. patients with end-organ dysfunction pretransplant.
Myeloablative conditioning is the classical form. The intensity of this Although HSCT can be lifesaving, the vulnerable condition of the
conditioning is such that the hematopoietic system would not be patient generated by the conditioning and/or immunosuppression can
expected to recover, or would take a very prolonged time to recover, also make it a “life-threatening” procedure. Furthermore, a proportion
without being rescued by the infusion of the stem cells. The very pro- of these patients will require transfer to the intensive care unit (ICU) for
longed period of pancytopenia, in such a setting, places the patient at more advanced level of care than can be provided on a bone marrow
high risk of life-threatening infections or bleeding and ultimately death. transplant ward. The reasons for ICU admission of HSCT recipients are
A newer type of transplant, developed over the past decade, utilizes shown in Table 94-1. ICU-directed care may include close monitoring
nonmyeloablative conditioning. In this case, the chemotherapy and for volume and electrolyte issues, vasopressor support, hemodialysis,
radiotherapy used in the conditioning is generally less intensive and is and mechanical ventilation. The reported rates of ICU admission for
not expected to destroy the bone marrow, but rather may provide some autologous and allogeneic HSCT recipients have ranged from 5% to
treatment of the tumor, will make some space in the marrow for the new approximately 60%. 6-14 Although HSCT patients may require ICU care
stem cells, and suppresses the patient’s immune system so that the stem at any time during their transplant course, the highest incidence is in the
cells and new immune system can grow. This nonmyeloablative type of peritransplant period. ICU admission beyond the first month posttrans-
transplant is used in large part for the immunologic effect of an alloge- plant is generally related to infection but may also relate to the long-term
neic stem cell transplant. The intensity of this conditioning is milder complications of transplantation.
than the myeloablative conditioning, and the patient’s marrow would
be expected to recover even if the transplant failed. These regimens COMPLICATIONS OF THE CONDITIONING REGIMEN
have caused less early posttransplant morbidity and mortality and have
extended the age of eligibility for allogeneic HSCT to patients in their The conditioning prepares the patient for the transplant. The agents used
seventies, and to patients with medical comorbidities that previously most frequently in conditioning for HSCT are listed in Table 94-2, along
would have precluded them from a transplant. with their major toxicities. Most are alkylating agents with their major

section07.indd 882 1/21/2015 7:43:03 AM