The number of autologous periperal blood progenitor cell (PBPC)
transplants performed annually has increased dramatically over the
past decade. Autologous PBPC transplants have quickly moved from the
exclusive province of the academic medical center to part of the
armamentarium of the practicing community oncologist.
Three technical developments have facilitated the widespread
application of this technology in the community setting. First,
increased familiarity with standardized conditioning regimens has
made the toxicity of high-dose chemotherapy predictable. Second,
the use of cytokine-mobilized peripheral blood stem cells (PBSCs)
that contain larger numbers of CD34+ cells, compared to bone marrow
autologous grafts, has shortened the period of post-transplant
neutropenia.[2,3] Third, the development of effective, standard
supportive care measures for the transplant maneuver has permitted
patients to be managed in the outpatient setting throughout the
administration of their conditioning regimen, as well as during the
post-transplant recovery phase.
Economic Forces That Support Outpatient Transplants
The article by Dix and Geller reviews the technical advances and
logistic infrastructure in supportive care that have helped make
outpatient transplants possible. Clinical outcomes related to the
complications of transplantation appear to be similar when comparing
inpatient and outpatient transplant models. A major impetus for
the shift toward outpatient transplants is economictransplant
centers negotiate with third-party insurers for global
case-rate contracts that pay a fixed reimbursement for
the transplant procedure. The increasing number of academic and
private practice centers that offer transplant services has increased
competition for these contracts, leading to decreases in the
reimbursement that the transplant center receives from third-party insurers.
In order to decrease the cost of caring for patients in the hospital
during the transplant maneuver, transplant centers have adapted by
delivering some, or all, of their care in the outpatient setting.
Successful transplant centers have integrated care across inpatient,
outpatient, and in-home settings to preserve optimal clinical
outcomes while reducing hospital days. The challenge for the next
decade will be to find the appropriate mix of these
different care settings.
The article by Dix and Geller describes three models of outpatient
care. In the early discharge model, patients are
discharged from the inpatient setting at the completion of high-dose
chemotherapy. In the delayed admission model, patients
receive both high-dose conditioning chemotherapy and the autologous
transplant in the outpatient setting. Patients are admitted to the
hospital if they develop significant mucositis, enteritis, or
neutropenic fever. In the comprehensive outpatient model
championed by the authors, patients are supported throughout the
entire transplant maneuver in the outpatient setting. Each model has
resulted in decreased hospitalization rates and median lengths of
stay, as compared with historical cohorts of patients transplanted
and supported throughout the period of neutropenia in the hospital setting.[4,6]
The economic consequences of the comprehensive outpatient care model
are best illustrated in the authors Figure
3. In traditional hospital-based transplant models, 75% of the
total revenue from managed care contracts went to the hospital, with
25% of the revenue supporting the costs of outpatient carea
reflection of the relative distribution of resources across inpatient
and outpatient settings. In the model described by Dix and Geller,
hospital charges for inpatient care comprised only 4% of the total
cost, with all hospital-related charges comprising only 20% of the
total. In a study by Rizzo et al, 17 patients undergoing a transplant
incurred only 29% of their charges in an inpatient facility.
The comprehensive outpatient care model thus represents a shift of
revenue from the hospital inpatient service to outpatient clinics,
practitioners, pharmacies, and laboratories. While the total cost of
the autologous transplant maneuver remains approximately $30,000 to
$60,000,[6-8] revenue in the comprehensive outpatient care model
mainly supports the payment of the transplant team salaries,
outpatient pharmacy, home health care personnel, and outpatient
facilities. The transplant center assumes control over cost and
revenue distribution, as opposed to directing most of the clinical
revenue to the inpatient facility. As a result, the transplant center
is able to efficiently allocate resources to provide the personnel
needed to ensure that patients remain safe while recovering from
neutropenia, mucositis, and enteritis as outpatients.
Of note, in the model described by Dix and Geller, transplant nurses
expend a significant amount of effort to maintain contact with
patients through telephone calls and by initiating and coordinating
home health care services that are not directly reimbursable, yet are
critical to maintaining positive clinical outcomes and patient satisfaction.
Potential Disadvantages of Outpatient Transplant Models
Although the comprehensive outpatient care model has advantages from
the standpoint of decreasing overall resource utilization and
efficiently integrating clinical care across inpatient and outpatient
settings, this approach does have inherent disadvantages. Some
patients may prefer to stay at home during much, if not all, of the
transplant maneuver. However, many patients do not live within the
requisite 30-minute driving radius of the transplant center, and must
stay in local hotels during their outpatient transplant,
thus mitigating the advantage of remaining in their own domicile
during the transplant.
In addition, patients may spend much of their day in the clinic
receiving treatment or undergoing various diagnostic tests. For
example, for the outpatient, the administration of high-dose
conditioning therapy may require an appointment lasting more than 12
hours, thereby limiting the relative advantage to staying at
home during this phase of the transplant maneuver. The patient
and caregiver must also get to and from the clinic, as well as to the
laboratories performing various diagnostic tests.
Thus, the outpatient transplant models shift a significant amount of
responsibility for management of complications of high-dose therapy
and autologous PBPC transplantation onto the patient and
caregiver(s). This cost shifting may have a significant
economic impact on the patient and caregiver that is difficult to measure.[4,9]
Another significant limitation to outpatient care models is the
management of enteritis and mucositis in the conditioning and
immediate post-transplant phase. The article by Dix and Geller
describes the management of nausea and vomiting using a combination
of granisetron (Kytril) and dexamethasone and a patient-controlled
patient-activated intermittent (BAD) pump that delivers
regulated doses of a mixture of Benadryl, Ativan, and dexamethasone
during the conditioning regimen. Analogous to patient-controlled
analgesia, by using the BAD pump, patients can anticipate and treat
nausea before it leads to significant emesis. The future use of new
agents, such as keratinocyte growth factor, may further decrease
the enteral toxicity related to the conditioning regimen, thus
further reducing the need to hospitalize patients for significant
mucositis and enteritis.
Outpatient Allogeneic Transplants
The future of autologous transplantation is firmly placed in the
outpatient setting. The comprehensive outpatient care model described
by Dix and Geller represents the practical integration of many
incremental advances in supportive care that have been made over the
past decade. A challenge for the future will be whether a similar
approach can be generally applied to the management of patients
undergoing allogeneic transplantation.
In general, the mucosal toxicity of total-body irradiation, coupled
with the post-transplant administration of methotrexate, has required
significant amounts of parenteral narcotics for pain control, as well
as parenteral nutrition. With new allogeneic transplant strategies
employing megadoses of donor hematopoietic progenitor
cells and avoiding the need for post-transplant
immunosuppression, full outpatient allogeneic transplants are
However, the cost savings that are achieved for high-risk patients
undergoing outpatient transplantation most likely will be modest, due
to the probability of hospital admissions for treatment-related
complications. Such an outpatient approach to allogeneic
transplantation will require a redoubling of staff resources to help
manage patients who are at risk for life-threatening opportunistic
infections and graft vs host disease, which is not generally seen in
autologous transplant recipients.
Whether it is safe for neutropenic, allogeneic transplant recipients
to be maintained outside of a relatively protected, high-efficiency
particulate air (HEPA)filtered environment remains unclear. The
successful management of allogeneic transplant recipients in the
outpatient setting will ultimately require new strategies to enhance
immune reconstitution in these patients.
1. Bensinger WI, Buckner CD: Preparative regimes, in Thomas E, Blume
K, Forman S (eds): Hematopoietic Cell Transplantation, pp 123-134.
Malden, Massachusetts, Blackwell Scientific, 1999.
2. Duncan N, Hewetson M, Powles R, et al: An economic evaluation of
peripheral blood stem cell transplantation as an alternative to
autologous bone marrow transplantation in multiple myeloma. Bone
Marrow Transplant 18:1175-1178, 1996.
3. Smith T, Hillner BE, Schmitz N, et al: Economic analysis of a
randomized clinical trial to compare filgrastim-mobilized
peripheral-blood progenitor-cell transplantation and autologous bone
marrow transplantation in patients with Hodgkins and
non-Hodgkins lymphoma. J Clin Oncol 15:5-10, 1997.
4. Rizzo JD, Vogelsang GB, Krumm S, et al: Outpatient-based bone
marrow transplantation for hematologic malignancies: Cost saving or
cost shifting? J Clin Oncol 17:2811-2818, 1999.
5. Beatty P: Clinical and managed-care issues in blood and marrow
transplantation for hematologic diseases. Exp Hematol 25:1195-1208, 1998.
6. Meisenberg B, Ferran K, Hollenbach K, et al: Reduced charges and
costs associated with outpatient autologous stem cell
transplantation. Bone Marrow Transplant 21:927-932, 1998.
7. Woronoff-Lemsi M, Arveux P, Limat S, et al: Cost-comparative study
of autologous peripheral blood progenitor cells (PBPC) and bone
marrow (ABM) transplantations for non-Hodgkins lymphoma
patients. Bone Marrow Transplant 20:975-982, 1997.
8. Yoder L: Costs and outcomes of a military bone marrow transplant
program. Mil Med 163:661-6666, 1998.
9. Freeman M, Vose J, Bennett C, et al: Costs of care associated with
high-dose therapy and autologous transplantation for
non-Hodgkins lymphoma: Results from the University of
Nebraska Medical Center 1989 to 1995. Bone Marrow Transplant
10. Farrell C, Rex K, Kaufman S, et al: Effects of keratinocyte
growth factor in the squamous epithelium of the upper aerodigestive
tract of normal and irradiated mice. Int J Radiat Biol 75:609-620, 1999.
11. Bachar-Lustig E, Rachamim N, Li HW, et al: Megadose of T
cell-depleted bone marrow overcomes MHC barriers in sublethally
irradiated mice. Nat Med 1:1268-1273, 1995.
12. Aversa F, Tabilo A, Velardi A, et al: Treatment of high-risk
acute leukemia with T-cell depleted stem cells from related donors
with one fully mismatched HLA haplotype. N Engl J Med 339:1186-1193, 1998.