Comparison of Toxicity and Outcomes of BCNU-Containing Conditioning Regimens Vs LACE in Lymphoma Transplants: A Retrospective Multicenter Analysis

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.

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.

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).

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.

No relevant conflicts of interest to declare.