Abstract
In the past two decades, major improvements in antibiotics and other elements of supportive
care have decreased the number and severity of complications of hematopoietic stem
cell transplantation (HSCT). Despite these improvements, many subpopulations of transplant
patients still have a significant morbidity and mortality. It is becoming increasingly
clear that medical science does not have a good understanding of the pathophysiology
of many of the common, potentially fatal complications in patients currently undergoing
HSCT. As the mechanisms of these complications are subjected to increasingly more
rigorous scrutiny, it is becoming clear that many of these complications are intimately
connected one to another and are not isolated clinical disorders as previously thought.
One hypothesis that can explain the close relationship between them is that most of
the severe complications of HSCT are the result of a systemic inflammatory disorder
that has escaped biologic control, an inflammatory process begun by the preparative
regimen and perhaps added to by intercurrent infections, tumor cell death and other
as yet unidentified stimuli (transfusions, medications?). If this is true, this syndrome
would have many similarities with the multiple organ dysfunction syndrome (MODS) seen
in critically ill nontransplant patients. As such, this hypothesis has two significant
corollaries: (a) That looking for or empirically treating for a reversible organ specific cause of single organ dysfunction during
HSCT (such as infectious pneumonia, intracranial hemorrhage, or acute infectious hepatitis)
in any given patient is unlikely to be rewarding as the defect causing the organ dysfunction
is often systemic at the time of its presentation, and (b) that MODS is the dose-limiting
toxicity of our current preparative regimens, suggesting that when we understand its
pathopysiology and develop therapies for MODS we will be able to escalate their intensity
and, by doing so, cure more patients of their malignancy. Manipulation of the hemostatic
system may prove to be one of these therapies, but there is little doubt that other
interventions designed to modulate the inflammatory process will prove to be even
more useful in this syndrome. Using the defintions of organ dysfunction outlined in
this article, we can provide a basis for clinical monitoring of patients today and
for use in interventional clinical trials in the future.
Keywords:
Hematopoietic stem cell transplantation - HSCT - multiple organ dysfunction syndrome
- MODS - malignancies - infection - medications
