Mini BEAM with Full-Dose of Melphalan (beaM) As a Conditioning Regimen for High Risk Patients with NHL Undergoing Autologous SCT

When considering ASCT for high risk NHL patients with dose-related toxicity concerns, choosing an appropriate conditioning chemotherapy regimen that is both safe and effective presents a challenge. ASCT in elderly population is a feasible and safe procedure, but characterized by higher transplant related mortality compared to younger population. Reports on ASCT in patients with PTLD are rare and limited to case reports without clear understanding of the impact ASCT has on the function of the transplanted organ. Initial outcomes of patients with amyloidosis undergoing ASCT have been marred by significant toxicity, particularly driven by cardiac damage due to amyloid.

As such we sought to improve the overall outcomes of our select patients by allowing them to proceed with ASCT, while attempting to reduce toxicity of the conditioning regimen. We used a modified mini-BEAM as conditioning regimen with full dose of melphalan (140mg/m²). This dose was also used due to its efficacy as conditioning regimen in patients with multiple myeloma undergoing ASCT who are elderly or have kidney impairment.

6 patients treated at our center received mini BEAM with full dose melphalan (beaM) as conditioning regimen before ASCT. Patients' characteristics are summarized in Table 1. Two had relapsed PTLD post cardiac transplant (including one with multiply relapsed PTCL), two had Waldenström macroglobulinemia and kidney amyloidosis, one had relapsed DLBCL and one had ALK- ALCL. Treatment prior to ASCT is also listed in Table 1. Conditioning regimen was as follows: carmustine 60mg/m² on day -6, etoposide 75mg/m² on days -5 to -2, cytarabine 100mg/m² on days -5 to -2 and melphalan 140 mg/m² on day -1. Stem cell infusion was performed on day 0.

Stem cell mobilization was performed with filgrastim and plerixafor and was successful in all 6 patients with a median of 1.5 apheresis sessions (range 1-3). Median number of stem cells collected was 6.2 x10⁶/kg (range 3.12 - 12.51 x10⁶/kg).

Post ASCT complications included one septic shock with lethal outcome for patient 6 due to MDR E. coli infection. Other side effects (≥grade 3) were: febrile neutropenia (n=2), non-infectious diarrhea (n=3), mucositis (n=1), cellulitis (n=1), seizure in a patient with previous seizure disorder (n=1), C. difficile infection (n=1), pneumonia (n=1), acute kidney injury (n=1), transaminitis (n=1), urinary tract infection (n=1) and HHV6 infection (n=1). Median time to neutrophil engraftment was 12 days (range 9-18) and median time to platelet engraftment was 20.5 days (18-23).

Outcomes of patients before and after ASCT are summarized in Table 1. Both patients with PTLD achieved CR to pralatrexate and R-EPOCH respectively and are in remission 499 and 531 days following transplant. WM/amyloidosis patients achieved VGPR for their amyloidosis and one is in CR with respect to his lymphoma. Their last follow up was 399 and 308 days following transplant. Patient with DLBCL relapsed 364 days after transplantation and patient with ALCL died from MDR E. Coli sepsis 10 days following transplant.

Mini-BEAM with full-dose of melphalan (beaM) is a safe and efficacious regimen that can be used in select lymphoma patients, particularly those with relapsed PTLD, and patients who are elderly or have impaired organ function.

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