Comparison of Toxicity and Outcomes of BCNU-Containing Conditioning Regimens Vs LACE in Lymphoma Transplants: A Retrospective Multicenter Analysis
Authors: Khattry Navin , Jain Reetu , Thippeswamy Ravi , Gore Adwaita , Bhosale Bharat , Jeevangi Nandish , Kannan Sadhana , Joshi Amit , Nair Reena , Saikia Tapan 
Published: October 2019

Abstract
Abstract 2023

Introduction:
BCNU – containing regimens (CBV and BEAM) are commonly used in lymphoma transplants. LACE (lomustine-200 mg/ m2 × 1d, etoposide 1000mg/ m2 x1d, ara-c 2000 mg/m2x 2d and cyclophosphamide 1800mg/ m2 for 3d) is an effective and well tolerated regimen reported by few centers. We retrospectively compared the two types of conditioning regimens for toxicity, efficacy and outcome.

Methods:
One hundred and fifty five patients Hodgkin's disease (HD) and Non Hodgkin's lymphoma (NHL) with primary refractory or relapsed disease from August 1994- May 2011 were included in this study from 3 transplant centers in Mumbai, India. Seventy-nine patients received BEAM or CBV and 76 LACE. One-hundred two patients had HD (BEAM/CBV-50, LACE-52) while 52 had NHL (BEAM/CBV-28, LACE- 24).Stem cell source was peripheral blood (PBSC) in all but one patient in LACE group and 68 patients in BEAM/CBV group. Oral mucositis was graded by WHO criteria while all other toxicities by common toxicity criteria version-3. Total Parenteral Nutrition (TPN) was used in patients with poor oral intake. Neutrophil engraftment (NE) was defined as first day of ANC > 0.5 × 109/L and platelet engraftment (PE) as first of seven days of unsupported platelet count > 20 × 109/L. Sinusoidal Obstruction Syndrome (SOS) of the liver was recorded according to Seattle criteria. Categorical data was analyzed using chi-square while continuous data with Mann Whitney Test. Overall survival (OS) and progression-free survival (PFS) was analyzed using Kaplan Meier survival analysis.

Results:
The median age at transplant was comparable (BEAM/CBV-25 year, LACE-23 year). Eleven patients in BEAM/CBV group had chemotherapy refractory disease compared to 6 in LACE at the time of transplant (P=0.106).The median serum albumin level (BEAM/CBV -3.9 gm/dl, LACE- 3.9 gm/dl) at the time of diagnosis were comparable. Incidence of grade 3 and 4 oral mucositis was higher in BEAM/CBV compared to LACE group (45 % vs 10%; P<0.001). Thirty-six (47%) patients in LACE group did not develop any grade of oral mucositis (P=0.001).The maximum grade and duration of diarrhea were comparable. More patients in BEAM/CBV group required parenteral nutrition (66% vs 33%; P=0.00004) and for longer duration (10 vs 9 days; P=0.003). No patient in LACE developed SOS compared to 5 in BEAM/CBV (P=0.05). Transplant related mortality was higher in BEAM/CBV (16 % vs 6%; P=0.063). The median CD 34 cell count of the stem cell graft was comparable (BEAM/CBV- 2.6 × 106/kg, LACE-5.9 × 106/kg; P=0.259), however more patients in the LACE group received PBSC grafts (BEAM/CBV-86%, LACE-98%; P=0.01). The median days to neutrophil engraftment (10 vs 11; P=0.014) and platelet engraftment (13 vs 15; P=0.006) were shorter in LACE. Median duration of hospitalization was less in LACE (3.3 vs 4 weeks P=0.016). At 2.5 years, OS (BEAM/CBV −58.5%, LACE −71%) and PFS (BEAM/CBV-50%, LACE-33%) were comparable, though in HD subgroup, OS was superior with LACE (BEAM-58%, LACE-85%; P=0.028).

Conclusion:
In our retrospective multicenter analysis LACE is a better tolerated regimen with lesser toxicity, earlier engraftment and comparable survival rates. Randomized trials comparing it with BCNU- containing regimens are needed.

Disclosures:
No relevant conflicts of interest to declare.