Bone Marrow Transplantation (2014) 49, 1345–1346 © 2014 Macmillan Publishers Limited All rights reserved 0268-3369/14 www.nature.com/bmt

LETTER TO THE EDITOR

Hospital admissions following outpatient administration of high-dose melphalan and autologous SCT for AL amyloidosis Bone Marrow Transplantation (2014) 49, 1345–1346; doi:10.1038/ bmt.2014.132; published online 23 June 2014

The use of intensive clinic support to permit outpatient high-dose chemotherapy with autologous SCT (HDC/SCT) has been described in the literature for two decades. This approach has the theoretical advantages of reducing cost and also reducing the incidence of iatrogenic infections acquired in the hospital environment. In one of the first reports using this approach, Peters et al.1 found that ~ 70% of 92 breast cancer patients treated with HDC/SCT as outpatients required either no hospital admission or brief admissions of 1–4 days, resulting in a 50% reduction in cost compared to the traditional inpatient approach. Prophylactic antibiotics facilitate the outpatient management of myelosuppressed patients treated with HDC/SCT, although in one study 26% of patients were readmitted to the hospital for fever or infection despite treament with prophylactic ciprofloxacin and rifampin.2 In that study, 62% of the patients developed febrile neutropenia following HDC/SCT, but in most cases this was managed with empiric antibiotics as an outpatient; there was one death (0.7%) from invasive aspergillosis. Interestingly, FernandezAviles et al.3 developed an ‘at-home’ program for patients with hematologic malignancies undergoing HDC/SCT that utilized prophylactic ceftriaxone and treatment of febrile neutropenia with pipercillin-tazobactam. Compared with a control group of individually matched patients treated with conventional hospitalbased care, this intervention resulted in a lower rate (76 vs 96%) and shorter duration (median 2 vs 6 days) of febrile neutropenia, a hospital readmission rate of only 8%, a reduction of 19 days of hospitalization per patient, and a cost savings of ~ 50%. Our institutional experience is unusual in that the majority of patients undergoing HDC/SCT have AL amyloidosis and are treated with a high-dose melphalan conditioning regimen. All phases of treatment, including stem cell mobilization, stem cell collection, administration of high-dose melphalan and stem cell infusion and post-SCT management, are performed in the outpatient clinic.4 Patients were screened for treatment with HDM/SCT according to the inclusion criteria of specific clinical trials or institutional eligibility requirements, which have been reported in our previous reports.5 PBSCs were collected by leukapheresis after mobilization with G-CSF as previously reported. The dose of i.v. melphalan ranged from 140 to 200 mg/m2. Patients with severe cardiac involvement, Mayo clinic cardiac biomarker stage III and NYHA class III/IV congestive heart failure were hospitalized for cardiac monitoring during stem cell collection to rule out cardiac arrhythmias with G-CSF-associated fluid retention, and if none were observed, HDM/SCT was administered as outpatient. All patients were evaluated daily, including weekends, in the outpatient infusion clinic (day-hospital) by an infusion nurse, stem cell transplant nurse practitioner, hematology trainee and transplant attending physician. All patients received prophylactic antimicrobials including fluoroquinolone antibacterial, fluconazole antifungal and acyclovir antiviral medications. All patients

received a delayed antiemetic regimen with granisetron, lorazepam, prochlorperazine and dexamethasone for 6 days after SCT. Daily G-CSF was given at 5 mcg/kg/day starting D+1 until neutrophil engraftment. Patients were assessed daily for the need of transfusions, medications and i.v. fluids. Social support was provided to patients and caregivers by social worker, weekly support group meetings and visits with psychiatrists as needed. All patients were given an incentive spirometer to perform daily. Here, we examine variables related to hospital admissions and readmissions in patients with AL amyloidosis undergoing highdose melphalan and autologous SCT (HDM/SCT) at our institution. This project was undertaken as a quality improvement initiative, to identify factors that might be modifiable to improve outpatient care, management and outcomes. A retrospective review was conducted of all patients with AL amyloidosis undergoing HDM/SCT between January 2011 and December 2013. During this period, 70 patients with AL amyloidosis underwent HDM/SCT. All 70 patients began HDM/ SCT treatment protocols as outpatients. Of these, 79% (55/70) were admitted to the hospital within 30 days of stem cell infusion. The median day of admission was day +7, and the median duration of hospitalization was 5 days. Febrile neutropenia was the most common reason for hospitalization (33%, 18/55). Other reasons included fatigue (27%, 15/55), diarrhea (24%, 13/55), hypotension (22%, 12/55) and nausea/vomiting (20%, 11/55). Of the patients treated with 200 mg/m2 of melphalan, 81% (38/47) required hospitalization within 30 days, and of the patients treated with 140 mg/m2 of melphalan, 74% (17/23) required hospitalization within 30 days (P = 0.37). The 30-day TRM was 1% (1/70); the cause of death was respiratory failure from influenza A infection. Other variables examined are included in Table 1.

Table 1.

Patients with AL amyloidosis patients undergoing HDM/SCT

Variables Rate of admission Median day of admission Median days of hospitalization (range) Mean days of fever 4100.4° F Mean days of i.v. antibiotics Causes of hospitalization Febrile neutropenia Fatigue Diarrhea Hypotension Nausea/vomiting Mucositis

Admission within 30 days

Readmission within 30 days

79% (55/70) D+7 5 (1–37)

33% (18/55) D+13 4 (1–94)

1

1

4

1

33% 27% 24% 22% 20% 15%

(18/55) (15/55) (13/55) (12/55) (11/55) (8/55)

0% 11% 33% 17% 17% 11%

(0/18) (2/18) (6/18) (3/18) (3/18) (2/18)

Letter to the Editor

1346 Of the 55 patients who were admitted within 30 days of HDM/ SCT, there was a readmission rate of 33% (18/55), occurring on median day +13, and with a median duration of 4 days. Reasons for readmission included diarrhea (33%, 6/18), nausea/vomiting (17%, 3/18), hypotension (17%, 3/18) and mucositis (11%, 2/18). There were no readmissions for febrile neutropenia. Thus, in a population of patients with an underlying plasma cell dyscrasia associated with multiorgan dysfunction, this review is consistent with prior reports of low TRM, as reported by our group.6 Of note, we could not identify specific features of organ involvement that predicted hospitalization in this small retrospective chart review (data not shown). Nonetheless, 79% of patients require one hospitalization in the early post-transplant period. Only 25% of patients required more than one hospitalization. For the first hospitalization, febrile neutropenia was the most common reason for hospitalization, while persistent gastrointestinal complications of chemotherapy was the most common reason for readmission. To reduce initial hospitalization, outpatient management of febrile neutropenia could be considered, though most patients in this population do not meet IDSA criteria for lowrisk.7 To reduce readmission rates, more aggressive management of GI symptoms could be considered, though it is already our practice to use i.v. fluids, antiemetics and antimotility agents. On the basis of these data of the quality improvement project, no changes are being recommended going forward for outpatient HDM/SCT for AL amyloidosis. CONFLICT OF INTEREST The authors declare no conflict of interest.

Bone Marrow Transplantation (2014) 1345 – 1346

B Freeman, D Brauneis, DC Seldin, K Quillen, JM Sloan, AS Renteria, AC Shelton, T Teschner, KT Finn and V Sanchorawala Stem Cell Transplantation Program, Section of Hematology/ Oncology, Boston Medical Center, Boston, MA, USA E-mail: [email protected] REFERENCES 1 Peters WP, Ross M, Vredenburgh JJ, Hussein A, Rubin P, Dukelow K et al. The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer. Semin Oncol 1994; 21: 25–31. 2 Meisenberg B, Gollard R, Brehm T, McMillan R, Miller W. Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue. Support Care Cancer 1996; 4: 364–369. 3 Fernandez-Aviles F, Carreras E, Urbano-Ispizua A, Rovira M, Martinez C, Gaya A et al. Case-control comparison of at-home to total hospital care for autologous stem-cell transplantation for hematologic malignancies. J Clin Oncol 2006; 24: 4855–4861. 4 Cibeira MT, Sanchorawala V, Seldin DC, Quillen K, Berk JL, Dember LM et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 2011; 118: 4346–4352. 5 Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med 2004; 140: 85–93. 6 Tsai SB, Seldin DC, Quillen K, Berk JL, Ruberg FL, Meier-Ewert H et al. High-dose melphalan and stem cell transplantation for patients with AL amyloidosis: trends in treatment-related mortality over the past 17 years at a single referral center. Blood 2012; 120: 4445–4446. 7 Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of America. Clin Infect Dis 2011; 52: e56–e93.

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Hospital admissions following outpatient administration of high-dose melphalan and autologous SCT for AL amyloidosis.

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