Advances in the field of blood and marrow transplantation (BMT) leading to decreased morbidity and mortality have facilitated a shift in care of the transplant patient from the hospital to the outpatient clinic. One major factor that has facilitated this shift is the increased use of peripheral blood–derived stem cells (PBSCs) instead of bone marrow–derived stem cells as autologous rescue following administration of high-dose chemotherapy.
The use of PBSCs is associated with shorter periods of neutropenia and thrombocytopenia, as well as potentially less severe regimen-related toxicities.[2-4] In addition, improvements in supportive care strategies, including antibiotic algorithms for prophylaxis and treatment, antiemetic regimens, and transfusion protocols, have allowed patients to be cared for safely in the outpatient setting.
The potential advantages of outpatient care for BMT patients include improved patient satisfaction and quality of life by allowing them to remain in their home environment or in a nearby hotel. In addition, the elimination of a prolonged hospital stay may potentially decrease the convalescent period by keeping the patient more active and responsible during the transplant process. Published data in cancer patients support these potential advantages of outpatient care during BMT.[6,7]
Despite the potential impact of outpatient care on quality of life, thus far, the primary end points evaluated have been safety, feasibility, and pharmacoeconomics.[8,9] Numerous studies have documented the safety and feasibility of outpatient care during or after administration of high-dose chemotherapy with autologous PBSC rescue.[10-14] In terms of pharmacoeconomics, autologous BMT has traditionally been an expensive procedure, with historical costs exceeding $100,000 per patient. Attempts to decrease this cost have been fueled by the general pressure to decrease health care costs and the increasing use of global-fee contracts for BMT, in which the provider assumes the financial risk for all BMT services.[15,16]
Establishment of an outpatient component of care early in the BMT process requires prudent patient selection, intensive planning and education, trained staff, and appropriately equipped facilities. This review will address the logistic requirements and published outcomes for various outpatient BMT care models.
Three models of outpatient care have been described in the literature and are represented schematically in Figure 1.
Early Discharge Model
The first outpatient care model described, the early discharge model, was implemented by Peters et al at Duke University. In this program, high-dose chemotherapy is administered on the hospital BMT unit. After the completion of high-dose chemotherapy and stabilization of gastrointestinal toxicities, patients are discharged to the outpatient BMT clinic and followed on a daily basis.
During this period of intensive outpatient visits, patients are readmitted to the inpatient BMT unit only if they develop such complications as neutropenic fever, refractory gastrointestinal toxicities, or other clinical scenarios that cannot be managed in the outpatient setting. By implementing this approach, Peters et al reported a reduction in BMT-associated hospital stays from 24.5 to 7 days.
Delayed Admission Model
Another model described less extensively in the literature, but used in numerous autologous transplant centers, is the delayed admission model of Weaver et al. In this model, high-dose chemotherapy is administered in the outpatient setting, and patients are then admitted to the hospital for supportive care management.
Although the delayed admission approach can decrease the duration of hospitalization as compared to the traditional inpatient model, patients generally require 2 weeks of hospitalization during the supportive care period. For example, although the delayed admission model is referred to as an outpatient BMT program, Weaver et al reported that 96% of 80 patients with lymphoma undergoing autologous transplantation required hospitalization for a median of 14 days.
Total Outpatient Model
Recently, a more extensive approach to outpatient care has been described, which can be defined as a total, or comprehensive, outpatient model.[12-14] In this model, both high-dose chemotherapy administration and supportive care management are conducted in the outpatient setting, with patients hospitalized for complications that cannot be managed in the clinic or at home.
Of the three outpatient models, the total outpatient approach is associated with the shortest duration of hospitalization, but it is the most labor intensive for the outpatient BMT clinic. The comprehensive outpatient care model requires extensive coordination and implementation of resources, often including the establishment of specialty designated outpatient clinics and home health care programs.
Providing care to the BMT patient in the outpatient setting requires the availability and establishment of numerous facility and staff resources. The extent to which certain resources are needed depends on the established outpatient care model. Essential resources for every model include a designated outpatient and inpatient care facility.
Most outpatient programs have an equipped outpatient facility that operates during regular business or extended hours. The mechanisms used to provide after-hours or weekend care vary among centers, however. Options implemented include extended clinic hours or direct admission to the hospital for any complications occurring after hours. Another option that may minimize hospitalization is the establishment of a hospital-based outpatient treatment room for weekend and emergency visits. Provision of after-hours care may also depend on the level of home health care nursing and infusion services available.
The availability of dedicated, specialized staff is crucial to the success of an outpatient BMT program. Essential staff members include inpatient and outpatient BMT-trained nurses, pharmacy services specializing in high-dose therapy, laboratory and blood-banking support, medical and surgical consultants, and hematopoietic cell therapy support services.
In addition to these essential staff members, which are common to all outpatient models, other personnel have been added or adapted within various centers based on need and available resources. For example, the level of home health care involvement among outpatient BMT programs ranges from minimal to extensive. The model of Peters et al provides only minimal home health care support and, at one point, used home health care professionals primarily for ambulatory pump needs.
In contrast, the model of Geller et al integrates BMT-designated home health care nursing staff into the daily care of the patient. In this model, the BMT home health care staff consists of inpatient BMT nurses who rotate weekly. During the home health care week, their only responsibility is to answer telephone calls, make home visits for initial assessments and follow-up care, and provide primary nursing care to patients seen in the weekend outpatient BMT clinic.
Complete integration of home health care into the outpatient BMT program can expand the comprehensiveness of the program and help eliminate the need for short hospital stays to initiate intravenous antibiotics for a first neutropenic febrile episode. However, in other models with less home health care involvement or prolonged clinic hours, patients may be admitted to the hospital for evaluation and initiation of intravenous antibiotics.[10,11]
Before determining the appropriateness of outpatient care, the BMT candidate first undergoes the routine pre-BMT evaluation to determine eligibility. This evaluation includes an assessment of clinical eligibility based on disease restaging, organ function, and performance status, as well as a psychosocial assessment and investigation of insurance coverage.
1. Statistical Center of the International Bone Marrow Transplant Registry and Autologous Blood and Marrow Transplant Registry: Autologous Blood and Marrow Transplant Newsletter. December 1998.
2. Hartmann O, Le Corroller AG, Blaise D, et al: Peripheral blood stem cell and bone marrow transplantation for solid tumors and lymphomas: Hematologic recovery and costs: A randomized, controlled trial. Ann Intern Med 126:600-607, 1997.
3. Schmitz N, Linch DC, Dreger P, et al: Randomized trial of filgrastim-mobilized peripheral blood progenitor cell transplantation vs autologous bone-marrow transplantation in lymphoma patients. Lancet 347:353-357, 1996.
4. Beyer J, Schwella N, Zingsem J, et al: Hematopoietic rescue after high-dose chemotherapy using autologous peripheral-blood progenitor cells or bone marrow: Randomized comparison. J Clin Oncol 13:1328-1335, 1995.
5. Burns JM, Tierney DK, Long GD, et al: Critical pathway for administering high-dose chemotherapy followed by peripheral blood stem cell rescue in the outpatient setting. Oncol Nurs Forum 22:1219-1224, 1995.
6. Daniels LE: Developing a home chemotherapy service. Int J Palliative Nurs 1:81-85, 1995.
7. Deber RB, Kraetschmer N, Irvine J: What role do patients wish to play in treatment decision making? Arch Intern Med 156:1414-1416, 1996.
8. Smith TJ, Hilner 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 Hodgkin’s and non-Hodgkin’s lymphoma. J Clin Oncol 15:5-10, 1997.
9. Gilbert CJ: Peripheral blood progenitor cell transplantation for breast cancer: Pharmacoeconomic considerations. Pharmacotherapy 16:101S-108S, 1996.
10. Peters WP, Ross M, Vredenburgh JJ, et al: The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer. Semin Oncol 21(suppl 7):25-31, 1994.
11. Weaver CH, Schwartzberg L, Zhen B, et al: High-dose chemotherapy and peripheral blood stem cell infusion in patients with non-Hodgkin’s lymphoma: Results of outpatient treatment in community cancer centers. Bone Marrow Transplant 20:753-760, 1997.
12. Meisenberg BR, Miller WE, McMillan R, et al: Outpatient high-dose chemotherapy with autologous stem-cell rescue for hematologic and nonhematologic malignancies. J Clin Oncol 15:11-17, 1997.
13. Gluck S, des Rochers C, Cano C, et al: High-dose chemotherapy followed by autologous blood cell transplantation: A safe and effective outpatient approach. Bone Marrow Transplant 20:431-434, 1997.
14. Geller RB, Dix SP, Belt RJ, et al: Minimum resource utilization for patients with breast cancer, lymphoma, or multiple myeloma undergoing mobilization and high-dose chemotherapy followed by peripheral blood stem cell transplants as outpatients (abstract). Blood 90:370a, 1997.
15. Yee GC: Peripheral blood progenitor cell transplantation: Economic issues. Pharmacotherapy 18(suppl 1):9S-16S, 1998.
16. Rizzo DJ, Vogelsang GB, Krumm S, et al: Outpatient BMT for hematologic malignancies: Cost-saving or cost-shifting? J Clin Oncol 17:2811-2818, 1997.
17. Trabert E: Outpatient bone marrow transplantation: Examining the impact on quality and cost of care. The oncology round table. Oncology Watch, vol 8, 1998.
18. Stetz KM, McDonald JC, Compton K: Needs and experiences of family caregivers during marrow transplantation. Oncol Nurs Forum 23:1422-1427, 1996.
19. Compton K, McDonald JC, Stetz KM: Understanding the caring relationship during marrow transplantation: Family caregivers and health-care professionals. Oncol Nurs Forum 23:1428-1432, 1996.
20. McDonald JC, Stetz KM, Compton K: Educational interventions for family caregivers during marrow transplantation. Oncol Nurs Forum 23: 1432-1439, 1996.
21. Sharma N, Hendrix L, O’Connell K, et al: Obstacles to performing high-dose therapy with peripheral blood stem cell rescue in the outpatient setting (abstract). Blood 90(suppl 1):116a, 1997.
22. Stadtmauer EA, Schneider CJ, Silberstein LE: Peripheral blood progenitor cell generation and harvesting. Semin Oncol 22:291-300, 1995.
23. Bensinger WI, Longin K, Appelbaum F, et al: Peripheral blood stem cells collected after recombinant granulocyte colony-stimulating factor (rhG-CSF): An analysis of factors correlating with the tempo of engraftment after transplantation. Br J Haematol 87:825-831, 1994.
24. Gianni AM, Siena S, Bregni M, et al: Granulocyte-macrophage colony-stimulating factor to harvest circulating hematopoietic stem cells for autotransplantation. Lancet 9:580-583, 1989.
25. Brugger W, Birken R, Berta H, et al: Peripheral blood progenitor cells mobilized by chemotherapy plus G-CSF accelerate both neutrophil and platelet recovery after high-dose VP16, ifosfamide, and cisplatin. Br J Haematol 84:402, 1993.
26. Elias AD, Ayash L, Anderson KC, et al: Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer. Blood 79:3036-3044, 1992.
27. Demirer T, Rowley S, Buckner CD, et al: Peripheral blood stem-cell collection after paclitaxel, cyclophosphamide, and recombinant human granulocyte colony-stimulating factor in patients with breast and ovarian cancer. J Clin Oncol 13:1714-1719, 1995.
28. Jagannath S, Dicke KA, Armitage JO, et al: High-dose cyclophosphamide, carmustine, and etoposide and autologous bone marrow transplantation for patients with advanced Hodgkin’s disease. Ann Intern Med 104:163-168, 1986.
29. Peters WP, Ross M, Vredenburgh JJ, et al: High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. J Clin Oncol 11:1132-1143, 1993.
30. Philip T, Guglielmi C, Hagenbeek A, et al: Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 333:1540-1545, 1995.
31. Antman K, Ayashl, Elias A, et al: A phase II study of high-dose cyclophosphamide, thiotepa, and carboplatin with autologous marrow support in women with measurable advanced breast cancer responding to standard-dose therapy. J Clin Oncol 10:102-110, 1992.
32. Bensinger WI, Buckner CD: Preparative regimens, in Forman SJ, Thomas ED, Blume KG (eds): Hematopoietic Cell Transplantation, 2nd ed, pp 123-134. Malden, Massachusetts, Blackwell Scientific, 1999.
33. Weaver CH, Schwartzberg LS, Hainsworth J, et al: Treatment-related mortality in 1000 consecutive patients receiving high-dose chemotherapy and peripheral blood progenitor cell transplantation in community cancer centers. Bone Marrow Transplant 19:671-678, 1997.
34. Davis TL: Peripheral blood progenitor cell transplantation: Impact on the pharmacy workload and budget. Pharmacotherapy 18(suppl 1):24S-29S, 1998.
35. Weaver CH, West WH, Schwartzberg LS, et al: Induction, mobilization of peripheral blood stem cells (PBSC), high-dose chemotherapy, and PBSC infusion in patients with untreated stage IV breast cancer: Outcomes by intent to treat analyses. Bone Marrow Transplant 19:661-670, 1999.
36. Barbounis V, Koumakis G, Vassilo-manolakis M, et al: A phase II study of ondansetron as antiemetic prophylaxis in patients receiving high-dose polychemotherapy and stem cell transplantation. Support Care Cancer 3:301-306, 1995.
37. Okamoto S, Takahaski S, Tanosaki R, et al: Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: A prospective randomized study. Bone Marrow Transplant 17:679-683, 1996.
38. Gilbert CJ, Ohly KV, Rosner G, et al: Randomized, double-blind comparison of a prochlorperazine-based vs a metoclopramide-based antiemetic regimen in patients undergoing autologous bone marrow transplantation. Cancer 76:2330-2337, 1995.
39. Miyahara TT, Dix SP, Devine SP, et al: Evaluation of supportive care guidelines for monitoring breast cancer bone marrow transplant (BMT) patients in the outpatient setting (abstract). Blood 86(suppl 1):213a, 1995.
40. Frakes LA, Brehm TL, Kosty MP, et al: An all oral antiemetic regimen for patients undergoing high-dose chemotherapy with peripheral blood stem cell transplant. Bone Marrow Transplant 20:473-478, 1997.
41. Shepherd JD, Pringle LE, Barnett MJ, et al: Mesna vs hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 9:2016-2020, 1991.
42. Dix SP, Cord MK, Howard SJ, et al: Safety and efficacy of a continuous infusion, patient controlled antiemetic pump to facilitate outpatient administration of high-dose chemotherapy. Bone Marrow Transplant 24(5):561-566, 1999.
43. Gilbert C, Meisenberg B, Vredenburgh J, et al: Sequential prophylactic oral and empiric once-daily parenteral antibiotics for neutropenia and fever after high-dose chemotherapy and autologous bone marrow support. J Clin Oncol 12:1005-1011, 1994.
44. Meisenberg B, Gollard R, Brehm T, et al: Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue. Support Care Cancer 4:364-369, 1996.
45. McGuire TR, Tarantolo S, Reed E: Peripheral blood progenitor cells: Enabling outpatient transplantation. Pharmacotherapy 18:17S-23S, 1998.
46. Dix SP, Geller RB, Barnhart CS, et al: Single-agent trovafloxacin vs quinoline and cephalexin as anti-bacterial prophylaxis during BMT (abstract). Blood 92(suppl 1):332b, 1998.
47. Vose JM, Reed EC, Pippert GC, et al: Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: A randomized trial. J Clin Oncol 11:1306-1310, 1993.
48. Dickson TC: Clinical pathway nutrition management for outpatient bone marrow transplantation. J Am Diet Assoc 97:61-63, 1997.
49. Charuhas PM, Fosberg KL, Bruemmer B, et al: A double-blind randomized trial comparing outpatient parenteral nutrition with intravenous hydration: Effect on resumption of oral intake after marrow transplantation. J Parenter Enteral Nutr 21:157-161, 1997.
50. Ruiz-Arguelles G, et al: Non-cryopreserved peripheral blood stem cells autotransplants for hematological malignancies can be performed entirely on an outpatient basis. Am J Hematol 58:161-164, 1998.
51. Meisenberg B, et al: Reduced charges and costs associated with outpatient autologous stem cell transplantation. Bone Marrow Transplant 21:927-932, 1998.
52. Bennett CL, Armitage JL, Armitage GO, et al: Costs of care and outcomes for high-dose therapy and autologous transplantation for lymphoid malignancies: Results from the University of Nebraska 1987 through 1991. J Clin Oncol 13:969-973, 1995.
53. Dix SP, Simonich HA, Craycraft L, et al: Resource allocation for outpatient BMT programs utilizing case-rate managed care contracts (abstract). Blood 92(suppl 1):279a, 1998.
54. Chao NJ, Tierney K, Bloom JR, et al: Dynamic assessment of quality of life after autologous bone marrow transplantation. Blood 80:825-830, 1992.
55. Andrykowski MA, Bruehl S, Bardy MJ, et al: Physical and psychosocial status of adults 1 year after bone marrow transplantation: A prospective study. Bone Marrow Transplant 15:837-844, 1995.
56. McQuellon RP, Craven B, Russell GB, et al: Quality of life in breast cancer patients before and after autologous bone marrow transplantation. Bone Marrow Transplant 18:579-584, 1996.
57. McQuellon RP, Russell GB, Rambo TD: Quality of life and psychological distress of bone marrow transplant recipients: The “time trajectory” to recovery over the first year. Bone Marrow Transplant 21:477-486, 1998.
58. Lawrence CC, Gilbert CJ, Peters WP Evaluation of symptom distress in a bone marrow transplant outpatient environment. Ann Pharmacother 30:941-945, 1996.