Outpatient BEAM Using Daily Etoposide and Cytarabine with Autologous Hematopoietic Stem Cell Transplantation for Lymphoma Is Feasible and Decreases Inpatient Length of Stay
Authors: Cazeau Naomi , Cavalier Kathleen , Bhatt Valkal , McElrath Courtney , Lestrange Nicole , Lachaud-Richard Margot , Inumerables Faye , Andrejko Marci , Batalha Jason , Cohen Abigail , Cortes Melissa , Kiss Christina , Palumbo Dayna , Landau Heather J , Lahoud Oscar B , Dahi Parastoo B. , Scordo Michael , Sauter Craig S. , Giralt Sergio A. , Shah Gunjan L. 
Published: November 2019

Introduction:
High dose therapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous hematopoietic stem cell transplantation (AHCT) is the most common consolidation therapy for chemosensitive patients with relapsed/refractory Non-Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL) in the US. Inpatient hospitalization is usually required due to the twice daily dosing of etoposide and cytarabine, and patients remain admitted until neutrophil recovery. Utilizing our outpatient transplant program, we aimed to evaluate the feasibility and safety of outpatient BEAM with AHCT using daily dosed etoposide and cytarabine to enhance the patient experience and improve inpatient resource utilization.
Methods:
We performed a retrospective evaluation of patients treated in the outpatient setting at Memorial Sloan Kettering Cancer Center. Patients were eligible for outpatient AHCT if they did not have a clinical indication for inpatient continuous monitoring. Patients received BEAM conditioning consisting of carmustine on day -6 (300mg/m2), etoposide daily from day -5 through day -2 (200mg/m2/dose), cytarabine daily from day -5 through day -2 (400mg/m2/dose), and melphalan on day -1 (140mg/m2). AHCT on day 0, pegfilgrastim on Day +1, and supportive care were performed as per standard of care and institutional guidelines. Patients were seen daily by an advanced practice provider and HCT attending. Notably, service guidelines were revised to include a delayed emesis prophylactic regimen of oral dexamethasone (2mg bid) and lorazepam (0.5mg TID) from D+1 through D+7, which was initiated after the first three patients were treated. Patients were transfused packed red blood cells (pRBC) for hemoglobin <7g/dl and platelets for <20K/mcl.
Results:
From October 2018 to July of 2019, 13 patients (Hodgkin's lymphoma (n=5), mantle cell lymphoma (n=4), diffuse large B-cell lymphoma (n=2), T-cell lymphoma (n=2), and grey zone lymphoma (n=1)) were treated. The median age was 40 years (range 26-71), and the majority were male (69%). Median cell dose infused was 5.89 CD34+ cells/kg (range 2.53-10.66). Two patients received cell infusions over 2 days, and three patients received washed cell infusion products.
Two patients completed transplant entirely outpatient; the remainder required hospitalization during their transplant course. Reasons for admission included neutropenic fever (n=4), nausea (n=2), tachycardia (n=2), hypoxia (n=1), and other (n=2). Patients were admitted on a median of Day +6 (range Day+1 - Day+11) and remained inpatient for a median of 4 days (range 3-14). Eight patients (62%) returned to the outpatient stem cell transplant clinic for management prior to day 30. One patient was re-hospitalized prior to day 30. The median number of hospital days saved was 13 days/per patient. In total, 170 hospital days were saved with this regimen.
Engraftment and toxicities were similar to inpatient administration. Neutrophil engraftment occurred at a median of Day+9 (range 8-11) with a median of 6 days of ANC<500 (IQR 8-11). Platelets comprised most of the transfusion support required, with a median of 4 platelet (range 2-8) and 2 pRBC (range 0-2) transfusions per patient. Grade 2 or higher diarrhea occurred for a median of 3.5 days (range 3-11) with 38% not having any diarrhea. A small percentage of patients required additional antiemetics outside the standard of care (23%). The median weight lost per patient was 2.5kg (range 0 - 10.3kg). Patients received intravenous fluid support with a median of 5 normal saline boluses (range 1-10). All patients maintained normal serum creatinine peri-transplant, with a median maximum serum creatinine of 0.9mg/dl (range 0.7-1.1). Six patients (46%) had engraftment syndrome. All patients were alive with a median follow-up of 91 days (range: 29-205).
Conclusion:
We found that BEAM followed by AHCT using daily dosed etoposide and cytarabine is feasible and safe for the outpatient setting with tolerability matching that of the traditional inpatient BEAM regimen. Moreover, this treatment method has the potential to reduce a considerable number of inpatient hospital days, while still safely maintaining a threshold for toxicity requiring inpatient admission.

Disclosures
Bhatt: Incyte: Consultancy. Landau:Pfizer: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria. Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Sauter:Juno Therapeutics: Consultancy, Research Funding; Kite/Gilead: Consultancy; Precision Biosciences: Consultancy; Genmab: Consultancy; Spectrum Pharmaceuticals: Consultancy; GSK: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Sanofi-Genzyme: Consultancy, Research Funding. Giralt:Celgene: Consultancy, Research Funding; Takeda: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Shah:Amgen: Research Funding; Janssen: Research Funding.