Leukemia & Lymphoma, July 2015; 56(7): 2098–2104 © 2015 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2014.974039
ORIGINAL ARTICLE: CLINICAL
Early discharge after high dose chemotherapy is safe and feasible: a prospective evaluation of 6 years of home care Arno P. M. Mank, Charlot Schoonenberg, Kim Bleeker, Susanne Heijmenberg, Koen de Heer, Marinus H. J. van Oers & Marie José Kersten Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
Abstract A single-center, prospective, non-randomized clinical study was performed to examine the safety and feasibility of early discharge in patients undergoing consolidation chemotherapy for acute leukemia, or autologous stem cell transplant for lymphoma or multiple myeloma. Patients were discharged into ambulatory care the day after the last chemotherapy administration and were subsequently seen at the ambulatory care unit three times a week. One hundred and one of 224 patients were ineligible for the program, mostly because of their medical situation, the lack of a caregiver or the travel time to the hospital. The remaining 123 patients were able to spend more than 70% of the time at home. In 44% of cycles they were never readmitted. This study demonstrates the safety, feasibility and benefits of managing carefully selected patients. Patients and their caregivers felt safe and comfortable at home, and the vast majority preferred home care to in-hospital treatment. Keywords: Infectious complications, clinical results, chemotherapeutic approaches, ambulatory care, nursing
Introduction High dose chemotherapy with or without autologous stem cell transplant (SCT) is standard practice for many hematologic malignancies. The main risks of intensive chemotherapy, with its subsequent prolonged pancytopenia, are infectious complications and bleeding [1]. The toxicity and mortality associated with high dose chemotherapy have been reduced by several factors, such as the use of mobilized peripheral blood stem cells instead of bone marrow, improved prophylactic and empiric antibiotic regimens, and a more proactive management in preventing and treating opportunistic infections [2]. Although protective isolation to prevent infections has long been the accepted standard of care for these patients, the necessity of keeping patients in hospital after myelosuppressive
chemotherapy or SCT until full neutrophil recovery is under discussion [3]. Early discharge with ambulatory treatment has the potential to decrease patient exposure to multidrug-resistant organisms in the hospital and provide a more comfortable environment for patients and their family [4,5]. High dose chemotherapy with or without SCT furthermore is an expensive treatment, with hospital admission costs accounting for 58–78% of the total costs, implying that early discharge might lead to a substantial decrease in costs [6–9]. Over the last 20 years different models for outpatient treatment have been developed for selected patient groups. Patients were either visited and if necessary treated at home, or patients were seen in an ambulatory care setting in the hospital, in a separate unit or in a hotel accommodation connected to the hospital. However, most of these studies were performed in a single hematologic malignancy with only a limited number of patients [10–18]. In one study performed in patients undergoing autologous SCT, patients showed significantly higher scores for emotional well-being and global quality of life in the early discharge group [19]. We have previously defined requirements for eligibility for early discharge in different patient groups treated with high dose chemotherapy [20]. We found that relatively few complications were seen after consolidation chemotherapy for acute myeloid leukemia (AML)/high riskmyelodysplastic syndrome (HR-MDS) and after autologous SCT in patients with relapsed lymphoma or multiple myeloma (MM). We therefore considered those patients to be the most suitable candidates for early discharge and in the present study prospectively examined the safety of early discharge in this group. Our main motivation to develop an early discharge program was to provide patients with the possibility to spend the neutropenic phase at home and to facilitate more admissions to the hematology ward. Because of the acute side effects of high dose chemotherapy and the need for adequate hydration
Correspondence: Arno P. M. Mank, Department of Hematology, F6.166, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands. Tel: ⫹ 31205667905. Fax: ⫹ 31205669030. E-mail: [email protected] Received 13 January 2014; revised 31 August 2014; accepted 3 October 2014
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Early discharge is safe and feasible we decided to administer the high dose chemotherapy itself on an inpatient basis.
Patients and methods Study design This was a prospective, non-randomized, single center clinical study, with a study group (early discharge) and a control group (patients not eligible for early discharge, treated in the hospital).
Patients and requirements for early discharge and ambulatory care All consecutive patients admitted to the Hematology Department of the Academic Medical Center in Amsterdam (The Netherlands) between September 2005 and September 2011 with a hematologic malignancy (AML, HR-MDS, acute lymphoblastic leukemia [ALL], relapsed lymphoma or MM) undergoing treatment with high dose chemotherapy were considered for participation in the early discharge project. Patients were treated with high dose chemotherapy following national HOVON (Hemato-oncology Volwassenen Nederland) study protocols such as high dose cytarabine and high dose melphalan. Patients with acute leukemia were not eligible during the first induction cycle. Eligibility criteria for early discharge included: World Health Organization performance status (WHO PS) ⱕ 2 [21], travel time from home to the hospital less than 60 min, availability of an educated caregiver 24 h a day, and patient understanding and acceptance of the procedures. At the time of actual discharge into ambulatory care, the following additional eligibility criteria were checked: patients should have no fever, mucositis ⱖ Common Toxicology Criteria (CTC) grade 2 [22], uncontrolled diarrhea and/or vomiting, cardiac or respiratory distress or other uncontrolled symptoms. Furthermore, they should have adequate oral intake, and feel safe to leave the hospital. If early discharge was not possible, patients were included in the control group. The study was approved by the ethics committee. Patients gave written informed consent for collection of the clinical data.
Early discharge Before starting this project an ambulatory care unit was organized to provide assistance to up to four patients simultaneously. Specialized hematology nurses (C.S. and K.B.) were trained to educate the patients and caregivers, to check fulfillment of the eligibility criteria for early discharge and to perform the check-ups at the ambulatory care unit. Subsequently more hematology nurses were educated by training on-the-job. All eligible patients and their caregivers were informed about the procedures before making the choice between early discharge or hospital care. At home, patients were instructed to check their vital parameters including temperature, oral intake and body weight daily, and to contact and return to the hospital immediately in case of fever and/or other signs of infection, bleeding or any other complication. If necessary, patients could consult the hematology nursing staff or hematologists on call 24 h per day. Patients requiring intravenous (IV) antibiotics could not receive those at home and needed to be admitted.
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Patients were discharged into ambulatory care on the day following the last administration of chemotherapy or, in the case of autologous SCT, on the day after reinfusion of the autologous stem cells. Patients visited the ambulatory care unit (consisting of a dedicated room at the in-patient clinic) three times a week, for monitoring of vital signs such as weight, temperature, pulse and blood pressure. In addition, oral intake was evaluated, the mouth was inspected for signs of mucositis, and the central venous catheter (CVC) insertion site was inspected. The complete blood count was checked and platelet and red blood cell transfusions were given when required. Patients were seen by a physician at least weekly and more often if necessary, i.e. in the case of medical concerns. The specialized nurses did not have any medication prescription privileges. Visits to the unit, which is open from 8 a.m. to 4 p.m., generally took 1–2 h if no red blood cell or platelet transfusions were required. Registration was done using the same medical and nursing charts as for the in-hospital patients. Patients who were neutropenic and hospitalized were nursed preferably in a single room. Strict hygiene procedures including hand washing and especially the use of hand alcohol were followed by all personnel. Patients were discharged from ambulatory care or from the hospital to the outpatient department as soon as neutrophils had recovered to ⬎ 0.5 ⫻ 109/L and their clinical condition was considered to be satisfactory.
Infection prophylaxis and supportive care All patients, both ambulatory and in-hospital patients, were given the same infection prophylaxis, which was started on the first day of high dose chemotherapy and continued until neutrophil recovery. Gram negative prophylaxis consisted of ciprofloxacin 500 mg orally or 400 mg intravenously IV twice daily; or, if ciprofloxacin-resistant gram negative bacteria were present in the surveillance cultures, colistin orally 200 mg four times daily and cotrimoxazole 960 mg twice daily. Gram positive prophylaxis consisted of oral feneticilline 250 mg orally or penicillin 1 million units IV four times daily from day 7 after the start of chemotherapy or day 1 after autologous SCT. In a case of penicillin allergy, clarithromycin 500 mg twice daily was prescribed. Antifungal prophylaxis consisted of amphotericin B oral suspension 500 mg four times daily [23]. Surveillance cultures of the throat, nose and perineum were done weekly.
Indications for readmission Patients were readmitted in the case of a temperature ⱖ 38.5°C, uncontrolled nausea, vomiting or diarrhea, mucositis grade ⱖ 2, requirement of total parenteral nutrition (TPN), hemodynamic instability, pneumonia, cardiac and/or respiratory distress or any other situation which could not be handled at home. If necessary, a hospital bed was always available. In the event of fever, patients were fully evaluated by a physician. Blood cultures were taken both from a peripheral vein and from the CVC. Other appropriate cultures were taken on indication, and a chest X-ray was performed.
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As soon as readmitted patients no longer required intravenous antibiotics and had recovered, they could be discharged into ambulatory care again.
reason not to discharge patients, because of inadequate oral intake and pain management.
Patient satisfaction Empiric antibiotic regimen In the case of fever, patients were treated empirically with vancomycin 1000 mg IV twice daily and ceftazidime 1000 mg IV three times daily, or with other antibiotics based on results of the surveillance cultures. Patients with persistent fever for more than 72 h despite IV antibiotics underwent evaluation for invasive aspergillosis by high resolution computed tomography (CT) scan and galactomannan antigen testing in serum. If abnormalities were found, a bronchoalveolar lavage was performed for galactomannan antigen testing and culture of the bronchoalveolar fluid.
The first 90 patients who participated in the early discharge group were invited to complete an anonymous questionnaire after completion of the whole procedure. On a psychometric 5-point symmetric scale, patients specified their level of agreement or disagreement with a series of 21 statements, also used in the quality of life measurement in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale [27]. Four statements reflecting the topics logistics, information giving, communication and patient perception were added.
Statistical methods Definitions and diagnostic criteria Neutropenia was defined as an absolute neutrophil count (ANC) ⬍ 0.5 ⫻ 109 /L. Fever was defined as a single temperature of ⱖ 38.5°C not related to transfusion or drug administration [24]. Episodes of neutropenic fever (NF) were classified into four groups: (1) fever of unknown origin (FUO): fever without signs and symptoms of inflammation at anatomic sites and no identification or recovery of pathogens; (2) clinically documented infection (CDI): fever with signs and symptoms of inflammation at anatomic sites, without documentation of a pathogenic microorganism (e.g. pneumonia); (3) microbiologically documented infection (MDI) with or without bacteremia: this group included infections with coagulase-negative Staphylococcus (CNS), in which case at least two positive blood cultures were required; (4) invasive pulmonary aspergillosis (IPA), further classified according to the revised European Organisation for Research and Treatment of Cancer and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria as proven, probable or possible IPA [25]. The severity of oral mucositis was graded according to the National Cancer Institute Common Toxicity Criteria version 3.0, from 0 (no symptoms) to 4 (necrosis and/or alimentation not possible) [26]. A score of 2 or more was considered to be a
The following factors were prospectively evaluated and descriptively analyzed for early discharge versus hospital care: number of days until neutrophil recovery, readmission rate, number of days in hospital, incidence of fever and infection, performance status, mucositis, nutrition status, weight difference between start and end of treatment, number of platelet and erythrocyte transfusions, and patient satisfaction. All analyses were carried out using SPSS version 18 (SPSS Inc., Chicago, IL).
Results Two hundred and twenty-four patients undergoing two hundred and eighty-three cycles of high dose chemotherapy were included in the study, of whom 107 patients underwent autologous SCT. One hundred and twenty-three patients (167 cycles) including 50 patients treated with SCT were included in the early discharge group, and 101 patients (116 cycles) including 57 patients treated with SCT were included in the hospital group. The most common reasons for ineligibility for the early discharge program were: medically unfit (63 cycles; mostly because of fever), logistic reasons (lack of a caregiver, long travel time to hospital) and patient preference (53 cycles) (Figure 1).
Figure 1. Eligibility for early discharge program.
Early discharge is safe and feasible
Baseline characteristics Patient characteristics including diagnosis and treatment are described in Table I, with AML/HR-MDS being the most frequent diagnosis. There was no difference in the male to female ratio between both groups, but there was a difference in age, with a higher median age in the hospital group: 57 years (range 19–72) vs. 49 years (range 18–68) in the early discharge group. The included treatment modalities also showed differences. Seventy-five percent of all patients treated with BEAM (BCNU, etoposide, Ara-C, melphalan) (n ⫽ 36) and 93% of all patients treated with high dose chemotherapy for (relapsed) NHL (n ⫽ 44) were included in the early discharge group, whereas only 32% of all patients treated with high dose melphalan (HDM) for MM (n ⫽ 71) were treated in the early discharge group (Table I).
Readmission rate In 73 (44%) of the 167 cycles included in the early discharge group, patients were never readmitted. Of the 108 readmissions, 82 were single readmissions; in 10 cycles patients were readmitted twice and two patients had to be readmitted three times. Fever was the most frequent reason for readmission (58%), followed by mucositis, diarrhea and respiratory distress. In 15% of the readmissions there were multiple reasons for readmission. The median duration of readmission was 6 days (range 1–22). The highest risk was observed following consolidation treatment for AML (72%) and following BEAM/autologous SCT (70%).
Outcome variables (mucositis, weight loss, fever and infections) In Table II the outcome variables, including fever and infection, are summarized for patients treated in the early discharge group. Because of the differences in diagnosis and treatment in the early discharge group versus the hospital group and the difference in age, we decided not to directly compare those parameters between the groups. Table I. Patient characteristics, diagnosis and treatment*.
Patients Male (%) Median age (years, range) Diagnosis AML/HR-MDS NHL MM ALL Lymphoma Cycles (total number of cycles) Consolidation AML/HR MDS ALL high dose chemotherapy NHL high dose chemotherapy BEAM, autologous SCT High dose melphalan, autoSCT
Early discharge group
Hospital group
123 73 (59.3) 49 (18–68)
101 54 (53.5) 57 (19–72)
38/10 34 24 13 4 167 57 19 41 27 23
40/6 8 44 1 2 116 54 2 3 9 48
AML, acute myeloid leukemia; HR-MDS, high risk myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; MM, multiple myeloma; ALL, acute lymphoblastic leukemia; SCT, stem cell transplant. *Chemotherapy regimens: Consolidation AML/HR MDS: daunorubicine, cytarabine, HD cytarabine, etoposide, mitoxantrone ALL: vincristine, daunorubicine, methotrexate, asparaginase NHL: cytarabine, cisplatin, ifosfamide, methotrexate, etoposide (VP16) BEAM: Carmustine (BCNU), etoposide (VP16), cytarabine, melphalan High Dose Melphalan: melphalan.
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The total number of patient days in the early discharge group was 2812, with a median of 14 days per cycle (range 6–40). The majority of patients needed platelet transfusions (84%) and/or red blood cell transfusions (79%). In 62% of the cycles, one or more febrile episodes occurred. In approximately two-thirds of the febrile episodes, the febrile episode was classified as FUO. An overview of the different micro-organisms that were identified is shown in Table II. The 27 gram-positive isolates included 19 coagulase negative staphylococci (70%) and two Streptococcus mitis. The gram-negative isolates included Escherichia coli (four) and Pantoea species (one). In 10 cases a possible IPA and in four cases a probable IPA was diagnosed; no proven IPA was diagnosed. The median number of days IV antibiotics were required was 3 days, with a range of 0–32 days. Two patients from the early discharge group had to be admitted temporarily to the intensive care unit (ICU); both recovered fully. One patient who was first admitted to the hematology ward had to be transferred to the ICU for 48 h because of hemodynamic instability following a CNS bacteremia. The second patient was transferred to the ICU because of a severe anaphylactic reaction following a platelet transfusion at the ambulatory care unit and could be discharged within 24 h. No deaths occurred in the early discharge group, whereas three patients died of treatment-related complications in the hospital group. Table II. Outcome variables in the ambulatory care group. Total number of cycles of therapy in 167 ambulatory care Total number of days in ambulatory care 2812 Median number of days in ambulatory care (range) 14 (6–40) 460 (16.4) Total number of days with PS ⱖ 2 (%) 143 (5.1) Total number of days with mucositis ⱖ grade 2 (%) Total number of days with no oral intake (%) 82 (2.9) Total number of days requiring TPN (%) 78 (2.8) Median weight change in kg (range) 1.4 (⫺ 9.0–9.0) Total number of cycles requiring platelet 140 (83.8) transfusions (%) Total number of cycles requiring red blood cell 132 (79.0) transfusions (%) Fever Cycles with fever (%) 103 (61.7) Consolidation AML/MDS (%) 42 (73.7) ALL intensive (%) 9 (47.4) NHL intensive (%) 23 (43.9) Autologous SCT after HDM (%) 11 (52.2) Autologous SCT after BEAM (%) 18 (66.7) 491 (17.4) Total number of days with fever ⱖ 38.5°C (%) Episodes and classification of neutropenic fever 110 FUO 62 MDI 37 27 Gram⫹ isolates CNS 19 7 Gram⫺ isolates Anaerobic isolates 3 CDI 3 IPA proven/probable/possible 0/4/10 Total numbers of days IV antibiotics were 812 (28.8) required (%) Median number of days on IV antibiotics (range) 3 (0–32) PS, performance status; TPN, total parenteral nutrition; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ALL, acute lymphoblastic leukemia; NHL, non-Hodgkin lymphoma; SCT, stem cell transplant; HDM, high dose melphalan; BEAM, BCNU, VP16, cytarabine, melphalan; FUO, fever of unknown origin; MDI, microbiologically documented infection; CNS, coagulase-negative Staphylococcus; CDI, clinically documented infection; IPA, invasive pulmonary aspergillosis; IV, intravenous.
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Discussion
Use of hospital beds and costs Early discharge of patients to ambulatory care treatment resulted in an increased capacity for admissions of the hematology ward. Given the median duration of admission for high dose chemotherapy of 22 days per cycle for patients in the hospital group versus a median of 14 days of admission for patients in the early discharge group, theoretically 92 extra patients could be admitted in the study period, leading to fewer patient refusals. In the hospital group, the total costs of hospital admission were calculated at €991 820 (2020 days of admission at €491 per day). The cumulative admission costs for the 2812 patient days in the ambulatory care group were considerably lower at €505 184 (783 days of admission at €491 per day; 182 days of day care at €423 per day and 673 regular visits to the ambulatory care unit at €65 per visit).
Patient satisfaction Sixty-four patients out of the first 90 patients in the study (71%) sent back the questionnaire. Four of the answers reflecting the topics logistics, information giving, communication and patient perception are shown in Figure 2. The results of the other questions pertaining to the early discharge program are shown in Table III. All patients felt safe at home regarding the risk of infections, and did not regret the decision to be treated at home. All patients, except for one, were positive about the logistics of ambulatory care. However, 15% of the patients and their caregivers felt it to be somewhat burdensome to come to the hospital for a check-up three times per week. Except for one patient, all patients would again choose ambulatory care if necessary, and would recommend it to fellow patients.
In this prospective study of patients with AML, ALL, lymphoma and MM receiving high dose chemotherapy with or without autologous stem cell support, we examined whether early discharge into ambulatory care is a safe and more patient-friendly alternative for hospital care. Patients included in the early discharge arm were able to spend more than 70% of the days they would otherwise have spent in the hospital at home. Although readmission was necessary in 56% of the cycles, which is comparable to experience with early discharge in other studies [9–11,14–16], none of the patients had life-threatening complications and there was no treatment-related mortality in the early discharge group. Several outcome variables, such as the number of days with fever, mucositis, weight loss and use of TPN, appeared to be more favorable in patients treated in the ambulatory care setting versus patients who stayed in hospital. However, since this was not a randomized trial, there were some striking differences in the patient and treatment characteristics between the groups. Patients in the early discharge group were younger and were more often diagnosed with (relapsed) non-Hodgkin lymphoma (NHL) and ALL, whereas in the hospital group patients were older and were more often diagnosed with MM, suggesting differences in baseline characteristics of the patients, and in potential toxicity of the different chemotherapy regimens. The strict and cautious selection of the patients is of major importance for the favorable results of our program, but also implies that by definition the more fit patients were selected for early discharge. No comprehensive calculation of all the costs in terms of diagnostic procedures, laboratory services, medication, blood products and overhead costs was performed, since
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I felt save at home and also felt to be less at risk for infections
The organization and logistics concerning the ambulatory care were well organized 80
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0 It was hard for me to come to the hospital for a check-up 3 times weekly Not at all
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Figure 2. Patient satisfaction: statements reflecting the topics.
Very much
Early discharge is safe and feasible
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Table III. Patient satisfaction (n ⫽ 64). Not at all A little bit Somewhat Quite a bit Very much Missing Ambulatory care is a good alternative for staying in hospital A check-up three times weekly was frequent enough to feel safe at home I felt safe at home and also felt less at risk of infections Discharge to ambulatory care was too early for me It was hard for me to come to hospital for a check-up three times weekly I had faith in the nurses who cared for me when I came in for check-ups During check-ups communication regarding the situation at home was satisfactory It was a burden for my caregiver to accompany me to hospital three times weekly There was ample opportunity to get an answer to my questions from my doctor and nurses There was sufficient contact with the doctor during the ambulatory care program Information giving concerning the ambulatory care program was well organized The organization and logistics concerning ambulatory care were well organized The waiting period during check-ups was long I was sufficiently prepared on what to do in an unexpected situation like fever and have also acted that way When telephone contact was necessary the responses were clarifying/ sufficient The physical burden for the caregiver(s) was hard to manage The psychological burden for the caregiver(s) was hard to manage The hygiene procedures at home were clear to me and easy to handle The risk of (possible) readmission is outweighed by the advantage of being at home I would recommend ambulatory care also to other patients If I had to undergo high dose chemotherapy again, I would again choose the ambulatory care program
they were expected to be similar for both groups. Still, it is clear that early discharge can be cost-effective, as the largest cost item is the cost of admission. Moreover, early discharge resulted in the ability to admit more patients to the ward. Importantly, results of the patient survey showed that patients feel safe, confident and comfortable at home and that the vast majority would again choose ambulatory care if necessary, or would recommend it to other patients. We would like to emphasize that it is of pivotal importance that the team of physicians and nurses is well trained and experienced in order to be able to educate and support both patients and their caregivers. Caregivers considered it to be a great responsibility to care for their spouses/family members and this requires a good support system for the caregivers. In conclusion, we were able to demonstrate that early discharge into ambulatory care of patients treated with high dose chemotherapy with or without autologous SCT is feasible and safe, if careful selection and follow-up of patients is guaranteed. Furthermore, early discharge is a cost-saving procedure, which can increase the capacity for admissions of a hematology department, and it is also greatly appreciated by most patients.
Acknowledgements The authors would like to thank the patients and caregivers who participated in this study, and the nurses and doctors who cared for the patients. Bart Biemond, hematologist, is acknowledged for critically reading the manuscript. Hans van der Lelie, former staff member of the Department of Hematology at the Academic Medical Center, is acknowledged for
– – 1/1.6 54/84.4 16/25.0 – –
3/4.7 3/4.7 1/1.6 5/7.8 25/39.1 2/3.1 –
– 3/4.7 6/9.4 3/4.7 14/21.9 3/4.7 2/3.1
21/32.8 37/57.8 35/54.7 1/1.6 5/7.8 27/42.2 35/54.7
40/62.5 21/32.8 21/32.8 1/1.6 3/4.7 32/50.0 27/42.2
– – – – 1/1.6 – –
13/20.3
18/28.1
18/28.1
14/21.9
1/1.6
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2/3.1
–
4/6.3
28/43.8
30/46.9
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2/3.1
1/1.6
8/12.5
26/40.6
27/42.2
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–
–
5/7.8
25/39.1
34/53.1
–
2/3.1
1/1.6
5/7.8
27/42.2
29/45.3
–
16/25.0 –
19/29.7 1/1.6
15/23.4 8/12.5
7/10.9 38/59.4
7/10.9 16/25.0
– 1/1.6
–
–
7/10.9
40/62.5
14/21.9
3/4.7
20/31.3 8/12.5 – 6/9.4
18/28.1 19/29.7 2/3.1 2/3.1
12/18.8 21/32.8 3/4.7 8/12.5
10/15.6 12/18.8 35/54.7 19/29.7
2/3.1 2/3.1 24/37.5 27/42.2
2/3.1 2/3.1 – 2/3.1
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2/3.1 –
1/1.6 1/1.6
16/25.0 10/15.6
45/70.3 51/79.7
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his strong belief in this project and for providing the basis for ambulatory care at our hospital. Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
References [1] Meyers JD. Infection in bone marrow transplant recipients. Am J Med 1986;81:27–38. [2] Bodey GP. The treatment of febrile neutropenia: from the dark ages to the present. Support Care Cancer 1997;5:351–357. [3] Tiel van FH, Harbers MM, Kessels AG, et al. Home care versus hospital care of patients with haematological malignancies and chemotherapy-induced cytopenia. Ann Oncol 2005;16:195–205. [4] Moores KG. Safe and effective outpatient treatment of adults with chemotherapy-induced neutropenic fever. Am J Health Syst Pharm 2007;64:717–722. [5] Lee SJ, Klar N, Weeks JC, et al. Predicting costs of stem-cell transplantation. J Clin Oncol 2000;18:64–71. [6] Uyl-de Groot CA , Gelderblom-den Hartog J, Huijgens PC, et al. Costs of diagnosis, treatment, and follow up of patients with acute myeloid leukemia in the Netherlands. J Hematother Stem Cell Res 2001;10:187–192. [7] Rizzo JD, Vogelsang GB, Krumm S, et al. Outpatient-based bone marrow transplantation for hematologic malignancies: cost saving or cost shifting? J Clin Oncol 1999;17:2811–2818. [8] de Lalla F. Outpatient therapy for febrile neutropenia: clinical and economic implications. Pharmacoeconomics 2003;21:397–413. [9] Jones JA , Qazilbash MH, Shih YC, et a. In-hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies: clinical and economic outcomes from the Nationwide Inpatient Sample. Cancer 2008;112:1096–1105. [10] Girmenia C, Alimena G, Latagliata R, et al. Out-patient management of acute myeloid leukemia after consolidation chemotherapy. Role of a hematologic emergency unit. Haematologica 1999;84:814–819. [11] Herrmann RP, Trent M, Cooney J, et al. Infections in patients managed at home during autologous stem cell transplantation
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for lymphoma and multiple myeloma. Bone Marrow Transplant 1999;24:1213–1217. [12] Svahn BM, Remberger M, Myrbäck KE, et al. Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood 2002;100:4317–4324. [13] Fernández-Avilés F, Carreras E, Urbano-Ispizua A . Case-control comparison of at-home to total hospital care for autologous stemcell transplantation for hematologic malignancies. J Clin Oncol 2006;24:4855–4861. [14] Møller T, Nielsen OJ,Welinder P, et al. Safe and feasible out patient treatment following induction and consolidation chemotherapy for patients with acute leukaemia. Eur J Haematol 2010;84:316–322 [15] Jagannath S, Vesole DH, Zhang M, et al. Feasibility and costeffectiveness of outpatient autotransplants in multiple myeloma. Bone Marrow Transplant 1997;20:445–450. [16] Morabito F, Martino M, Stelitano C, et al. Feasibility of a mixed inpatient-outpatient model of peripheral blood stem cell transplantation for multiple myeloma. Haematologica 2002;87: 1192–1199. [17] Naithani R, Kumar R, Mahapatra M, et al. Early discharge from hospital after consolidation chemotherapy in acute myeloid leukemia in remission: febrile neutropenic episodes and their outcome in a resource poor setting. Haematologica 2008;93:1416–1418. [18] Sive J, Ardeshna KM, Cheesman S, et al. Hotel-based ambulatory care for complex cancer patients: a review of the University Hospital experience. Leuk Lymphoma 2012;53:2397–2404. [19] Summers N, Dawe U, Stewart DA . A comparison of inpatient and outpatient ASCT. Bone Marrow Transplant 2000;26:389–395. [20] Mank A , Van der Lelie J, de Vos R, et al. Safe early discharge for patients undergoing high dose chemotherapy with or without stem cell transplantation: a prospective analysis of clinical variables
predictive for complications after treatment. J Clin Nurs 2011;20: 388–395. [21] van Campen C, Sixma H, Friele RD, et al. Quality of care and patient satisfaction:a review of measuring instruments. Med Care Res Rev 1995;52:109–133. [22] Donnelly JP, Muus P, Schattenberg A , et al. A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. Bone Marrow Transplant 1992;9:409–413. [23] Dykewicz C ; Centers for Disease Control and Prevention (U.S.); Infectious Diseases Society of America; American Society of Blood and Marrow Transplantation. Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis 2001;33:139–144. [24] Hughes WT, Armstrong D, Bodey GP, et al. Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34:730–751. [25] de Pauw B, Walsh TJ, Donnelly JP, et al.; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–1821. [26] National Cancer Institute. Common Terminology Criteria for Adverse Events v.3.0 (CTCAE). Available from: https:// ced4xbn2cbj5hh2iop.sec.amc.nl/protocolDevelopment/electronic_ applications/ctc.htm [27] McQuellon RP, Russell GB, Cella DF, et al. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant 1997;19:357–368.
ORIGINAL ARTICLE: CLINICAL
Early discharge after high dose chemotherapy is safe and feasible: a prospective evaluation of 6 years of home care Arno P. M. Mank, Charlot Schoonenberg, Kim Bleeker, Susanne Heijmenberg, Koen de Heer, Marinus H. J. van Oers & Marie José Kersten Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
Abstract A single-center, prospective, non-randomized clinical study was performed to examine the safety and feasibility of early discharge in patients undergoing consolidation chemotherapy for acute leukemia, or autologous stem cell transplant for lymphoma or multiple myeloma. Patients were discharged into ambulatory care the day after the last chemotherapy administration and were subsequently seen at the ambulatory care unit three times a week. One hundred and one of 224 patients were ineligible for the program, mostly because of their medical situation, the lack of a caregiver or the travel time to the hospital. The remaining 123 patients were able to spend more than 70% of the time at home. In 44% of cycles they were never readmitted. This study demonstrates the safety, feasibility and benefits of managing carefully selected patients. Patients and their caregivers felt safe and comfortable at home, and the vast majority preferred home care to in-hospital treatment. Keywords: Infectious complications, clinical results, chemotherapeutic approaches, ambulatory care, nursing
Introduction High dose chemotherapy with or without autologous stem cell transplant (SCT) is standard practice for many hematologic malignancies. The main risks of intensive chemotherapy, with its subsequent prolonged pancytopenia, are infectious complications and bleeding [1]. The toxicity and mortality associated with high dose chemotherapy have been reduced by several factors, such as the use of mobilized peripheral blood stem cells instead of bone marrow, improved prophylactic and empiric antibiotic regimens, and a more proactive management in preventing and treating opportunistic infections [2]. Although protective isolation to prevent infections has long been the accepted standard of care for these patients, the necessity of keeping patients in hospital after myelosuppressive
chemotherapy or SCT until full neutrophil recovery is under discussion [3]. Early discharge with ambulatory treatment has the potential to decrease patient exposure to multidrug-resistant organisms in the hospital and provide a more comfortable environment for patients and their family [4,5]. High dose chemotherapy with or without SCT furthermore is an expensive treatment, with hospital admission costs accounting for 58–78% of the total costs, implying that early discharge might lead to a substantial decrease in costs [6–9]. Over the last 20 years different models for outpatient treatment have been developed for selected patient groups. Patients were either visited and if necessary treated at home, or patients were seen in an ambulatory care setting in the hospital, in a separate unit or in a hotel accommodation connected to the hospital. However, most of these studies were performed in a single hematologic malignancy with only a limited number of patients [10–18]. In one study performed in patients undergoing autologous SCT, patients showed significantly higher scores for emotional well-being and global quality of life in the early discharge group [19]. We have previously defined requirements for eligibility for early discharge in different patient groups treated with high dose chemotherapy [20]. We found that relatively few complications were seen after consolidation chemotherapy for acute myeloid leukemia (AML)/high riskmyelodysplastic syndrome (HR-MDS) and after autologous SCT in patients with relapsed lymphoma or multiple myeloma (MM). We therefore considered those patients to be the most suitable candidates for early discharge and in the present study prospectively examined the safety of early discharge in this group. Our main motivation to develop an early discharge program was to provide patients with the possibility to spend the neutropenic phase at home and to facilitate more admissions to the hematology ward. Because of the acute side effects of high dose chemotherapy and the need for adequate hydration
Correspondence: Arno P. M. Mank, Department of Hematology, F6.166, Academic Medical Center, PO Box 22700, 1100 DE Amsterdam, The Netherlands. Tel: ⫹ 31205667905. Fax: ⫹ 31205669030. E-mail: [email protected] Received 13 January 2014; revised 31 August 2014; accepted 3 October 2014
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Early discharge is safe and feasible we decided to administer the high dose chemotherapy itself on an inpatient basis.
Patients and methods Study design This was a prospective, non-randomized, single center clinical study, with a study group (early discharge) and a control group (patients not eligible for early discharge, treated in the hospital).
Patients and requirements for early discharge and ambulatory care All consecutive patients admitted to the Hematology Department of the Academic Medical Center in Amsterdam (The Netherlands) between September 2005 and September 2011 with a hematologic malignancy (AML, HR-MDS, acute lymphoblastic leukemia [ALL], relapsed lymphoma or MM) undergoing treatment with high dose chemotherapy were considered for participation in the early discharge project. Patients were treated with high dose chemotherapy following national HOVON (Hemato-oncology Volwassenen Nederland) study protocols such as high dose cytarabine and high dose melphalan. Patients with acute leukemia were not eligible during the first induction cycle. Eligibility criteria for early discharge included: World Health Organization performance status (WHO PS) ⱕ 2 [21], travel time from home to the hospital less than 60 min, availability of an educated caregiver 24 h a day, and patient understanding and acceptance of the procedures. At the time of actual discharge into ambulatory care, the following additional eligibility criteria were checked: patients should have no fever, mucositis ⱖ Common Toxicology Criteria (CTC) grade 2 [22], uncontrolled diarrhea and/or vomiting, cardiac or respiratory distress or other uncontrolled symptoms. Furthermore, they should have adequate oral intake, and feel safe to leave the hospital. If early discharge was not possible, patients were included in the control group. The study was approved by the ethics committee. Patients gave written informed consent for collection of the clinical data.
Early discharge Before starting this project an ambulatory care unit was organized to provide assistance to up to four patients simultaneously. Specialized hematology nurses (C.S. and K.B.) were trained to educate the patients and caregivers, to check fulfillment of the eligibility criteria for early discharge and to perform the check-ups at the ambulatory care unit. Subsequently more hematology nurses were educated by training on-the-job. All eligible patients and their caregivers were informed about the procedures before making the choice between early discharge or hospital care. At home, patients were instructed to check their vital parameters including temperature, oral intake and body weight daily, and to contact and return to the hospital immediately in case of fever and/or other signs of infection, bleeding or any other complication. If necessary, patients could consult the hematology nursing staff or hematologists on call 24 h per day. Patients requiring intravenous (IV) antibiotics could not receive those at home and needed to be admitted.
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Patients were discharged into ambulatory care on the day following the last administration of chemotherapy or, in the case of autologous SCT, on the day after reinfusion of the autologous stem cells. Patients visited the ambulatory care unit (consisting of a dedicated room at the in-patient clinic) three times a week, for monitoring of vital signs such as weight, temperature, pulse and blood pressure. In addition, oral intake was evaluated, the mouth was inspected for signs of mucositis, and the central venous catheter (CVC) insertion site was inspected. The complete blood count was checked and platelet and red blood cell transfusions were given when required. Patients were seen by a physician at least weekly and more often if necessary, i.e. in the case of medical concerns. The specialized nurses did not have any medication prescription privileges. Visits to the unit, which is open from 8 a.m. to 4 p.m., generally took 1–2 h if no red blood cell or platelet transfusions were required. Registration was done using the same medical and nursing charts as for the in-hospital patients. Patients who were neutropenic and hospitalized were nursed preferably in a single room. Strict hygiene procedures including hand washing and especially the use of hand alcohol were followed by all personnel. Patients were discharged from ambulatory care or from the hospital to the outpatient department as soon as neutrophils had recovered to ⬎ 0.5 ⫻ 109/L and their clinical condition was considered to be satisfactory.
Infection prophylaxis and supportive care All patients, both ambulatory and in-hospital patients, were given the same infection prophylaxis, which was started on the first day of high dose chemotherapy and continued until neutrophil recovery. Gram negative prophylaxis consisted of ciprofloxacin 500 mg orally or 400 mg intravenously IV twice daily; or, if ciprofloxacin-resistant gram negative bacteria were present in the surveillance cultures, colistin orally 200 mg four times daily and cotrimoxazole 960 mg twice daily. Gram positive prophylaxis consisted of oral feneticilline 250 mg orally or penicillin 1 million units IV four times daily from day 7 after the start of chemotherapy or day 1 after autologous SCT. In a case of penicillin allergy, clarithromycin 500 mg twice daily was prescribed. Antifungal prophylaxis consisted of amphotericin B oral suspension 500 mg four times daily [23]. Surveillance cultures of the throat, nose and perineum were done weekly.
Indications for readmission Patients were readmitted in the case of a temperature ⱖ 38.5°C, uncontrolled nausea, vomiting or diarrhea, mucositis grade ⱖ 2, requirement of total parenteral nutrition (TPN), hemodynamic instability, pneumonia, cardiac and/or respiratory distress or any other situation which could not be handled at home. If necessary, a hospital bed was always available. In the event of fever, patients were fully evaluated by a physician. Blood cultures were taken both from a peripheral vein and from the CVC. Other appropriate cultures were taken on indication, and a chest X-ray was performed.
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As soon as readmitted patients no longer required intravenous antibiotics and had recovered, they could be discharged into ambulatory care again.
reason not to discharge patients, because of inadequate oral intake and pain management.
Patient satisfaction Empiric antibiotic regimen In the case of fever, patients were treated empirically with vancomycin 1000 mg IV twice daily and ceftazidime 1000 mg IV three times daily, or with other antibiotics based on results of the surveillance cultures. Patients with persistent fever for more than 72 h despite IV antibiotics underwent evaluation for invasive aspergillosis by high resolution computed tomography (CT) scan and galactomannan antigen testing in serum. If abnormalities were found, a bronchoalveolar lavage was performed for galactomannan antigen testing and culture of the bronchoalveolar fluid.
The first 90 patients who participated in the early discharge group were invited to complete an anonymous questionnaire after completion of the whole procedure. On a psychometric 5-point symmetric scale, patients specified their level of agreement or disagreement with a series of 21 statements, also used in the quality of life measurement in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale [27]. Four statements reflecting the topics logistics, information giving, communication and patient perception were added.
Statistical methods Definitions and diagnostic criteria Neutropenia was defined as an absolute neutrophil count (ANC) ⬍ 0.5 ⫻ 109 /L. Fever was defined as a single temperature of ⱖ 38.5°C not related to transfusion or drug administration [24]. Episodes of neutropenic fever (NF) were classified into four groups: (1) fever of unknown origin (FUO): fever without signs and symptoms of inflammation at anatomic sites and no identification or recovery of pathogens; (2) clinically documented infection (CDI): fever with signs and symptoms of inflammation at anatomic sites, without documentation of a pathogenic microorganism (e.g. pneumonia); (3) microbiologically documented infection (MDI) with or without bacteremia: this group included infections with coagulase-negative Staphylococcus (CNS), in which case at least two positive blood cultures were required; (4) invasive pulmonary aspergillosis (IPA), further classified according to the revised European Organisation for Research and Treatment of Cancer and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria as proven, probable or possible IPA [25]. The severity of oral mucositis was graded according to the National Cancer Institute Common Toxicity Criteria version 3.0, from 0 (no symptoms) to 4 (necrosis and/or alimentation not possible) [26]. A score of 2 or more was considered to be a
The following factors were prospectively evaluated and descriptively analyzed for early discharge versus hospital care: number of days until neutrophil recovery, readmission rate, number of days in hospital, incidence of fever and infection, performance status, mucositis, nutrition status, weight difference between start and end of treatment, number of platelet and erythrocyte transfusions, and patient satisfaction. All analyses were carried out using SPSS version 18 (SPSS Inc., Chicago, IL).
Results Two hundred and twenty-four patients undergoing two hundred and eighty-three cycles of high dose chemotherapy were included in the study, of whom 107 patients underwent autologous SCT. One hundred and twenty-three patients (167 cycles) including 50 patients treated with SCT were included in the early discharge group, and 101 patients (116 cycles) including 57 patients treated with SCT were included in the hospital group. The most common reasons for ineligibility for the early discharge program were: medically unfit (63 cycles; mostly because of fever), logistic reasons (lack of a caregiver, long travel time to hospital) and patient preference (53 cycles) (Figure 1).
Figure 1. Eligibility for early discharge program.
Early discharge is safe and feasible
Baseline characteristics Patient characteristics including diagnosis and treatment are described in Table I, with AML/HR-MDS being the most frequent diagnosis. There was no difference in the male to female ratio between both groups, but there was a difference in age, with a higher median age in the hospital group: 57 years (range 19–72) vs. 49 years (range 18–68) in the early discharge group. The included treatment modalities also showed differences. Seventy-five percent of all patients treated with BEAM (BCNU, etoposide, Ara-C, melphalan) (n ⫽ 36) and 93% of all patients treated with high dose chemotherapy for (relapsed) NHL (n ⫽ 44) were included in the early discharge group, whereas only 32% of all patients treated with high dose melphalan (HDM) for MM (n ⫽ 71) were treated in the early discharge group (Table I).
Readmission rate In 73 (44%) of the 167 cycles included in the early discharge group, patients were never readmitted. Of the 108 readmissions, 82 were single readmissions; in 10 cycles patients were readmitted twice and two patients had to be readmitted three times. Fever was the most frequent reason for readmission (58%), followed by mucositis, diarrhea and respiratory distress. In 15% of the readmissions there were multiple reasons for readmission. The median duration of readmission was 6 days (range 1–22). The highest risk was observed following consolidation treatment for AML (72%) and following BEAM/autologous SCT (70%).
Outcome variables (mucositis, weight loss, fever and infections) In Table II the outcome variables, including fever and infection, are summarized for patients treated in the early discharge group. Because of the differences in diagnosis and treatment in the early discharge group versus the hospital group and the difference in age, we decided not to directly compare those parameters between the groups. Table I. Patient characteristics, diagnosis and treatment*.
Patients Male (%) Median age (years, range) Diagnosis AML/HR-MDS NHL MM ALL Lymphoma Cycles (total number of cycles) Consolidation AML/HR MDS ALL high dose chemotherapy NHL high dose chemotherapy BEAM, autologous SCT High dose melphalan, autoSCT
Early discharge group
Hospital group
123 73 (59.3) 49 (18–68)
101 54 (53.5) 57 (19–72)
38/10 34 24 13 4 167 57 19 41 27 23
40/6 8 44 1 2 116 54 2 3 9 48
AML, acute myeloid leukemia; HR-MDS, high risk myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; MM, multiple myeloma; ALL, acute lymphoblastic leukemia; SCT, stem cell transplant. *Chemotherapy regimens: Consolidation AML/HR MDS: daunorubicine, cytarabine, HD cytarabine, etoposide, mitoxantrone ALL: vincristine, daunorubicine, methotrexate, asparaginase NHL: cytarabine, cisplatin, ifosfamide, methotrexate, etoposide (VP16) BEAM: Carmustine (BCNU), etoposide (VP16), cytarabine, melphalan High Dose Melphalan: melphalan.
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The total number of patient days in the early discharge group was 2812, with a median of 14 days per cycle (range 6–40). The majority of patients needed platelet transfusions (84%) and/or red blood cell transfusions (79%). In 62% of the cycles, one or more febrile episodes occurred. In approximately two-thirds of the febrile episodes, the febrile episode was classified as FUO. An overview of the different micro-organisms that were identified is shown in Table II. The 27 gram-positive isolates included 19 coagulase negative staphylococci (70%) and two Streptococcus mitis. The gram-negative isolates included Escherichia coli (four) and Pantoea species (one). In 10 cases a possible IPA and in four cases a probable IPA was diagnosed; no proven IPA was diagnosed. The median number of days IV antibiotics were required was 3 days, with a range of 0–32 days. Two patients from the early discharge group had to be admitted temporarily to the intensive care unit (ICU); both recovered fully. One patient who was first admitted to the hematology ward had to be transferred to the ICU for 48 h because of hemodynamic instability following a CNS bacteremia. The second patient was transferred to the ICU because of a severe anaphylactic reaction following a platelet transfusion at the ambulatory care unit and could be discharged within 24 h. No deaths occurred in the early discharge group, whereas three patients died of treatment-related complications in the hospital group. Table II. Outcome variables in the ambulatory care group. Total number of cycles of therapy in 167 ambulatory care Total number of days in ambulatory care 2812 Median number of days in ambulatory care (range) 14 (6–40) 460 (16.4) Total number of days with PS ⱖ 2 (%) 143 (5.1) Total number of days with mucositis ⱖ grade 2 (%) Total number of days with no oral intake (%) 82 (2.9) Total number of days requiring TPN (%) 78 (2.8) Median weight change in kg (range) 1.4 (⫺ 9.0–9.0) Total number of cycles requiring platelet 140 (83.8) transfusions (%) Total number of cycles requiring red blood cell 132 (79.0) transfusions (%) Fever Cycles with fever (%) 103 (61.7) Consolidation AML/MDS (%) 42 (73.7) ALL intensive (%) 9 (47.4) NHL intensive (%) 23 (43.9) Autologous SCT after HDM (%) 11 (52.2) Autologous SCT after BEAM (%) 18 (66.7) 491 (17.4) Total number of days with fever ⱖ 38.5°C (%) Episodes and classification of neutropenic fever 110 FUO 62 MDI 37 27 Gram⫹ isolates CNS 19 7 Gram⫺ isolates Anaerobic isolates 3 CDI 3 IPA proven/probable/possible 0/4/10 Total numbers of days IV antibiotics were 812 (28.8) required (%) Median number of days on IV antibiotics (range) 3 (0–32) PS, performance status; TPN, total parenteral nutrition; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ALL, acute lymphoblastic leukemia; NHL, non-Hodgkin lymphoma; SCT, stem cell transplant; HDM, high dose melphalan; BEAM, BCNU, VP16, cytarabine, melphalan; FUO, fever of unknown origin; MDI, microbiologically documented infection; CNS, coagulase-negative Staphylococcus; CDI, clinically documented infection; IPA, invasive pulmonary aspergillosis; IV, intravenous.
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Discussion
Use of hospital beds and costs Early discharge of patients to ambulatory care treatment resulted in an increased capacity for admissions of the hematology ward. Given the median duration of admission for high dose chemotherapy of 22 days per cycle for patients in the hospital group versus a median of 14 days of admission for patients in the early discharge group, theoretically 92 extra patients could be admitted in the study period, leading to fewer patient refusals. In the hospital group, the total costs of hospital admission were calculated at €991 820 (2020 days of admission at €491 per day). The cumulative admission costs for the 2812 patient days in the ambulatory care group were considerably lower at €505 184 (783 days of admission at €491 per day; 182 days of day care at €423 per day and 673 regular visits to the ambulatory care unit at €65 per visit).
Patient satisfaction Sixty-four patients out of the first 90 patients in the study (71%) sent back the questionnaire. Four of the answers reflecting the topics logistics, information giving, communication and patient perception are shown in Figure 2. The results of the other questions pertaining to the early discharge program are shown in Table III. All patients felt safe at home regarding the risk of infections, and did not regret the decision to be treated at home. All patients, except for one, were positive about the logistics of ambulatory care. However, 15% of the patients and their caregivers felt it to be somewhat burdensome to come to the hospital for a check-up three times per week. Except for one patient, all patients would again choose ambulatory care if necessary, and would recommend it to fellow patients.
In this prospective study of patients with AML, ALL, lymphoma and MM receiving high dose chemotherapy with or without autologous stem cell support, we examined whether early discharge into ambulatory care is a safe and more patient-friendly alternative for hospital care. Patients included in the early discharge arm were able to spend more than 70% of the days they would otherwise have spent in the hospital at home. Although readmission was necessary in 56% of the cycles, which is comparable to experience with early discharge in other studies [9–11,14–16], none of the patients had life-threatening complications and there was no treatment-related mortality in the early discharge group. Several outcome variables, such as the number of days with fever, mucositis, weight loss and use of TPN, appeared to be more favorable in patients treated in the ambulatory care setting versus patients who stayed in hospital. However, since this was not a randomized trial, there were some striking differences in the patient and treatment characteristics between the groups. Patients in the early discharge group were younger and were more often diagnosed with (relapsed) non-Hodgkin lymphoma (NHL) and ALL, whereas in the hospital group patients were older and were more often diagnosed with MM, suggesting differences in baseline characteristics of the patients, and in potential toxicity of the different chemotherapy regimens. The strict and cautious selection of the patients is of major importance for the favorable results of our program, but also implies that by definition the more fit patients were selected for early discharge. No comprehensive calculation of all the costs in terms of diagnostic procedures, laboratory services, medication, blood products and overhead costs was performed, since
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Figure 2. Patient satisfaction: statements reflecting the topics.
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Table III. Patient satisfaction (n ⫽ 64). Not at all A little bit Somewhat Quite a bit Very much Missing Ambulatory care is a good alternative for staying in hospital A check-up three times weekly was frequent enough to feel safe at home I felt safe at home and also felt less at risk of infections Discharge to ambulatory care was too early for me It was hard for me to come to hospital for a check-up three times weekly I had faith in the nurses who cared for me when I came in for check-ups During check-ups communication regarding the situation at home was satisfactory It was a burden for my caregiver to accompany me to hospital three times weekly There was ample opportunity to get an answer to my questions from my doctor and nurses There was sufficient contact with the doctor during the ambulatory care program Information giving concerning the ambulatory care program was well organized The organization and logistics concerning ambulatory care were well organized The waiting period during check-ups was long I was sufficiently prepared on what to do in an unexpected situation like fever and have also acted that way When telephone contact was necessary the responses were clarifying/ sufficient The physical burden for the caregiver(s) was hard to manage The psychological burden for the caregiver(s) was hard to manage The hygiene procedures at home were clear to me and easy to handle The risk of (possible) readmission is outweighed by the advantage of being at home I would recommend ambulatory care also to other patients If I had to undergo high dose chemotherapy again, I would again choose the ambulatory care program
they were expected to be similar for both groups. Still, it is clear that early discharge can be cost-effective, as the largest cost item is the cost of admission. Moreover, early discharge resulted in the ability to admit more patients to the ward. Importantly, results of the patient survey showed that patients feel safe, confident and comfortable at home and that the vast majority would again choose ambulatory care if necessary, or would recommend it to other patients. We would like to emphasize that it is of pivotal importance that the team of physicians and nurses is well trained and experienced in order to be able to educate and support both patients and their caregivers. Caregivers considered it to be a great responsibility to care for their spouses/family members and this requires a good support system for the caregivers. In conclusion, we were able to demonstrate that early discharge into ambulatory care of patients treated with high dose chemotherapy with or without autologous SCT is feasible and safe, if careful selection and follow-up of patients is guaranteed. Furthermore, early discharge is a cost-saving procedure, which can increase the capacity for admissions of a hematology department, and it is also greatly appreciated by most patients.
Acknowledgements The authors would like to thank the patients and caregivers who participated in this study, and the nurses and doctors who cared for the patients. Bart Biemond, hematologist, is acknowledged for critically reading the manuscript. Hans van der Lelie, former staff member of the Department of Hematology at the Academic Medical Center, is acknowledged for
– – 1/1.6 54/84.4 16/25.0 – –
3/4.7 3/4.7 1/1.6 5/7.8 25/39.1 2/3.1 –
– 3/4.7 6/9.4 3/4.7 14/21.9 3/4.7 2/3.1
21/32.8 37/57.8 35/54.7 1/1.6 5/7.8 27/42.2 35/54.7
40/62.5 21/32.8 21/32.8 1/1.6 3/4.7 32/50.0 27/42.2
– – – – 1/1.6 – –
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18/28.1
18/28.1
14/21.9
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30/46.9
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20/31.3 8/12.5 – 6/9.4
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1/1.6 1/1.6
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his strong belief in this project and for providing the basis for ambulatory care at our hospital. Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.
References [1] Meyers JD. Infection in bone marrow transplant recipients. Am J Med 1986;81:27–38. [2] Bodey GP. The treatment of febrile neutropenia: from the dark ages to the present. Support Care Cancer 1997;5:351–357. [3] Tiel van FH, Harbers MM, Kessels AG, et al. Home care versus hospital care of patients with haematological malignancies and chemotherapy-induced cytopenia. Ann Oncol 2005;16:195–205. [4] Moores KG. Safe and effective outpatient treatment of adults with chemotherapy-induced neutropenic fever. Am J Health Syst Pharm 2007;64:717–722. [5] Lee SJ, Klar N, Weeks JC, et al. Predicting costs of stem-cell transplantation. J Clin Oncol 2000;18:64–71. [6] Uyl-de Groot CA , Gelderblom-den Hartog J, Huijgens PC, et al. Costs of diagnosis, treatment, and follow up of patients with acute myeloid leukemia in the Netherlands. J Hematother Stem Cell Res 2001;10:187–192. [7] Rizzo JD, Vogelsang GB, Krumm S, et al. Outpatient-based bone marrow transplantation for hematologic malignancies: cost saving or cost shifting? J Clin Oncol 1999;17:2811–2818. [8] de Lalla F. Outpatient therapy for febrile neutropenia: clinical and economic implications. Pharmacoeconomics 2003;21:397–413. [9] Jones JA , Qazilbash MH, Shih YC, et a. In-hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies: clinical and economic outcomes from the Nationwide Inpatient Sample. Cancer 2008;112:1096–1105. [10] Girmenia C, Alimena G, Latagliata R, et al. Out-patient management of acute myeloid leukemia after consolidation chemotherapy. Role of a hematologic emergency unit. Haematologica 1999;84:814–819. [11] Herrmann RP, Trent M, Cooney J, et al. Infections in patients managed at home during autologous stem cell transplantation
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for lymphoma and multiple myeloma. Bone Marrow Transplant 1999;24:1213–1217. [12] Svahn BM, Remberger M, Myrbäck KE, et al. Home care during the pancytopenic phase after allogeneic hematopoietic stem cell transplantation is advantageous compared with hospital care. Blood 2002;100:4317–4324. [13] Fernández-Avilés F, Carreras E, Urbano-Ispizua A . Case-control comparison of at-home to total hospital care for autologous stemcell transplantation for hematologic malignancies. J Clin Oncol 2006;24:4855–4861. [14] Møller T, Nielsen OJ,Welinder P, et al. Safe and feasible out patient treatment following induction and consolidation chemotherapy for patients with acute leukaemia. Eur J Haematol 2010;84:316–322 [15] Jagannath S, Vesole DH, Zhang M, et al. Feasibility and costeffectiveness of outpatient autotransplants in multiple myeloma. Bone Marrow Transplant 1997;20:445–450. [16] Morabito F, Martino M, Stelitano C, et al. Feasibility of a mixed inpatient-outpatient model of peripheral blood stem cell transplantation for multiple myeloma. Haematologica 2002;87: 1192–1199. [17] Naithani R, Kumar R, Mahapatra M, et al. Early discharge from hospital after consolidation chemotherapy in acute myeloid leukemia in remission: febrile neutropenic episodes and their outcome in a resource poor setting. Haematologica 2008;93:1416–1418. [18] Sive J, Ardeshna KM, Cheesman S, et al. Hotel-based ambulatory care for complex cancer patients: a review of the University Hospital experience. Leuk Lymphoma 2012;53:2397–2404. [19] Summers N, Dawe U, Stewart DA . A comparison of inpatient and outpatient ASCT. Bone Marrow Transplant 2000;26:389–395. [20] Mank A , Van der Lelie J, de Vos R, et al. Safe early discharge for patients undergoing high dose chemotherapy with or without stem cell transplantation: a prospective analysis of clinical variables
predictive for complications after treatment. J Clin Nurs 2011;20: 388–395. [21] van Campen C, Sixma H, Friele RD, et al. Quality of care and patient satisfaction:a review of measuring instruments. Med Care Res Rev 1995;52:109–133. [22] Donnelly JP, Muus P, Schattenberg A , et al. A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients. Bone Marrow Transplant 1992;9:409–413. [23] Dykewicz C ; Centers for Disease Control and Prevention (U.S.); Infectious Diseases Society of America; American Society of Blood and Marrow Transplantation. Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis 2001;33:139–144. [24] Hughes WT, Armstrong D, Bodey GP, et al. Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002;34:730–751. [25] de Pauw B, Walsh TJ, Donnelly JP, et al.; European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008;46:1813–1821. [26] National Cancer Institute. Common Terminology Criteria for Adverse Events v.3.0 (CTCAE). Available from: https:// ced4xbn2cbj5hh2iop.sec.amc.nl/protocolDevelopment/electronic_ applications/ctc.htm [27] McQuellon RP, Russell GB, Cella DF, et al. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant 1997;19:357–368.
