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High-Dose Chemotherapy With Autologous Stem Cell Rescue in the Outpatient Setting

High-Dose Chemotherapy With Autologous Stem Cell Rescue in the Outpatient Setting

Outpatient bone marrow transplant (BMT) strategies, as reviewed by Dix and Geller, have evolved for various reasons—from social to medical. If high-dose approaches are to become a viable treatment for common cancers, such as breast cancer, the refinement of transplants to a “kinder and gentler” approach is essential.

Preference for Outpatient Treatment

The outpatient BMT approach was developed primarily to support the patient’s preference to be outside the hospital. Many patients find their time in the hospital to be one of the most

burdensome portions of traditional inpatient-based stem-cell transplant procedures. Patients will tolerate the chemotherapy, extensive monitoring, and antibiotic treatment, but prefer the privacy, personal dignity, and freedom afforded by an outpatient BMT approach.

Patients undergoing a stem-cell transplant tend to be very sophisticated, learn a great deal about their disease and treatment, and prefer to be intensively involved in the therapeutic decisions and provisions of their care. In addition, the patient’s family often feels much more empowered in an outpatient setting, where they sense a greater involvement.

The Caregiver’s Role

There is little doubt that the caregiver’s abilities are a critical component of a successful outpatient BMT approach. While some clinicians have found this to be limiting, in our experience, nearly every family, regardless of socioeconomic background, was capable of providing adequate caregiver support—if prepared in advance and well trained. Furthermore, when patients learn early on that they will soon be in need of a caregiver, they often show a remarkable ability to arrange satisfactory coverage. Indeed, the commitment of individuals and their family and friends is often a major determinant of the general well being of the patient, as well as the success of the transplant procedure.

Outpatient vs Inpatient Setting

Indeed, in our hands, the patient’s quality of life in the outpatient setting appears to be far superior to that in the traditional inpatient approach. Perhaps one of the most intriguing difficulties encountered among the now thousands of outpatient transplant patients is that they often do not want to be readmitted to the hospital, preferring instead to manage their symptoms and discomfort (if any) by themselves or their caregiver—even if they are quite symptomatic. Their satisfaction with their medical care is higher when performed in the outpatient arena than when confined to a hospital bed.

Of interest, one of the major concerns of physicians about the outpatient transplant approach is the perceived potential risk for the patient. Traditionally, patients have been hospitalized, and the wisdom of having aggressively treated patients who were febrile and neutropenic as outpatients raised concern for some physicians. However, when outpatient transplant programs are carefully established and managed, the patient’s risk is minimal. In fact, for many institutions, the outpatient transplant program represents one of the lowest-risk propositions for a hospital. We have found our infectious risks to be substantially lower among outpatients compared to inpatient treatment for matched patients.[1]

Optimal Outpatient BMT Programs

Perhaps the most critical element of the outpatient BMT strategy is the development of the integrated inpatient-outpatient team. A major determinant of success is the ability to offer 24-hour, 7-day coverage that provides the patient with a secure environment.

Many decisions regarding the particular characteristics of an outpatient BMT program are related to the logistic and financial considerations that help optimize the program for the patient. For example, in our program, we have minimized the use of home health care personnel since finding that the daily cost associated with its use generally outweighs its cost-effectiveness. Most of this care either can be rendered by the caregiver, or is of such a nature that it can be most efficiently provided in the outpatient clinic by a dedicated team member.

We have utilized a nearby apartment or hotel as a patient residence during outpatient BMT treatment and have generally not used the patient’s home. A major consideration for not employing a home-based treatment strategy relates to the transportation policies of most emergency medical technician (EMT) teams. If the BMT patient becomes critically ill and ambulance transport is required, the patient generally will be taken to the nearest hospital. However, for patients in the midst of a transplant procedure, the EMT’s designated hospital may not be the hospital in which the patient is undergoing the procedure. The critical early hours after an emergency event weigh importantly in our recommendation for housing the patient nearby the primary transplant center. Further, the home environment often places the patient back into his or her home role, potentially presenting additional stress.

The success of an outpatient BMT approach has been facilitated by the prophylaxis against neutropenic infection to minimize hospitalization. Contemporary oral antibiotic programs have been particularly useful, and in our program, readmissions for febrile events are now rare. Our decision to admit or closely observe patients during the initiation of antibiotic therapy is based on our desire to carefully assess the early course of febrile, neutropenic patients.

Furthermore, because septic patients will generally display their most significant symptoms early in their course, we find that an observation period of 4 to 6 hours in the outpatient clinic or a brief overnight admission facilitates patient comfort and safety. This provides a means of observingr the patient but cost-effectively utilizes available personnel, clinic, and inpatient space.

Care should be taken in modifying the high-dose chemotherapy regimens in order to facilitate the outpatient approach. The underlying strategy of using dose-intensive therapy is aimed primarily at treating the disease. In our experience, even minor modifications in the treatment regimen may result in either significant modifications to efficacy or changes in the toxicity profile—both of which may profoundly affect outcome.

In our experience, the success of a treatment regimen is determined primarily by the amount of mucositis produced. The regimen of cyclophosphamide, Platinol, and BCNU (CPB) produces no mucositis.[2] In our program, this effect, among others, causes CPB to be a preferred approach for outpatient transplants for both breast cancer and lymphoma.

On the other hand, regimens containing thiotepa (Thioplex), mephalan (Alkeran), or other agents that produce mucositis, generally show inferior results in the outpatient setting. This is because the mucositis often requires admission for pain control, hyperalimentation for fluid and nutritional support, and parenteral antibiotics to treat the more serious infectious complications associated with mucosal breakdown.[3-7]

Conclusion

In conclusion, patient preference, generally superior medical results, and economics all favor outpatient BMT approaches

—William P. Peters, MD, PhD
—Roy B. Baynes, MD, PhD
—Lucy Cassells, MD
—Roger Dansey, MD
—Jared Klein, MD
—Caroline Hamm, MD
—Chachada Karanes, MD
—Steve Abella, MD

References

1. Gilbert C, Meisenberg B, Vredenburgh J, et al: Sequential prophylactic ciprofloxacin and rifampin and empiric once daily vancomycin and aminoglycoside for neutropenic fever after high-dose chemotherapy and autologous bone marrow support. J Clin Oncol 12(5):1005-1011, 1994.

2. Peters WP, Eder JP, Henner WD, et al: High-dose combination alkylating agents with autologous bone marro support: A phase I trial. J Clin Oncol 4(5): 646-654, 1986.

3. Epstein JB, Schubert MM: Oral mucositis in myelosuppressive cancer therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88(3):273-276, 1999.

4. Zander AR, Berger K, Kroger N, et al: High-dose chemotherapy with busulfan, cyclophosphamide, and etoposide as conditioning regimen for allogeneic bone marrow transplantation for patients with acute myeloid leukemia in first complete remission. Clin Cancer Res 3(12; pt 2):2671-2675, 1997.

5. Eisen D, Essell J, Broun ER: Oral cavitiy complications of bone marrow transplantation. Semin Cutan Med Surg 16(4):265-272, 1997.

6. Cony-Makhoul P, Marit G, Boiron JM, et al: Busulphan and melphalan prior to autologous transplantation for myeloid malignancies. Bone Marrow Transplant 16(1):69-70, 1995.

7. Carl W: Oral complications of local and systemic cancer treatment. Curr Opin Oncol 7(4):320-324, 1995.

 
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