Long Term Outcomes of Autologous Hematopoietic Cell Transplant (AHCT) Following Thiotepa-Based High-Dose Therapy (HDT) in Patients with Non-Hodgkin Lymphoma (NHL)

There is little consensus regarding the optimal conditioning regimen for AHCT for NHL. Thiotepa is an alkylating agent with anti-lymphoma properties, but it has limited data as a conditioning agent for AHCT in adult NHL. We report here long-term results of our institutional experience in NHL receiving AHCT following HDT with etoposide, cyclophosphamide and thiotepa (VP-16/CY/TT). Patients received etoposide 1800mg/m2 IV x 1 dose, cyclophosphamide (50mg/kg/dose IV x 3-4 doses), and thiotepa (250mg/m2/dose – 300mg/m2/dose x 3 doses). Forty-three patients were consented and enrolled from November 1997 to June 2009. Disease characteristics are described in Table 1. Peripheral blood stem cell mobilization utilized cyclophosphamide and filgrastim. All patients received antibacterial, antiviral (acyclovir), and antifungal (fluconazole) prophylaxis along with filgrastim support after stem cell infusion.  Median follow up for surviving patients was 4.7 years (range 0.26 years to 15.85 years). Median time to neutrophil and platelet engraftment was 13 and 21 days, respectively. Significant regimen-related toxicities included mucositis (51%), neutropenic fever (72%), diarrhea (26%), and pneumonia (9%). No CNS failures were reported. Secondary malignancies occurred in 3 patients (7%) – two of which were soft tissue sarcomas and one MDS/AML. Progression free survival (PFS) and overall survival (OS) at 5 years was 53% (39% - 71%) and 73% (60% - 89%), respectively. Relapse rates at day +100 and 5 years were 9.4% (95% CI: 2.9% – 20.4%) and 40.1% (95% CI: 24.7% - 55.1%), respectively. Cumulative incidence of non-relapse mortality at day +100 and 5 years was 4.7% (95% CI: 0.8% - 14.0%) and 7% (95% CI: 1.8% - 17.4%), respectively. VP-16/Cy/TT is a well-tolerated conditioning regimen for patients with NHL, with promising long term progression-free and overall survival rates.

Table 1. Baseline Demographics

Characteristics	N=43
Median age, years (range)	55 (27-69)
Male gender, n (%)	22 (51%)
Diagnosis (%)
Diffuse Large B-cell Lymphoma (DLBCL) Follicular Lymphoma Transformed follicular lymphoma Mantle Cell Lymphoma T-cell NHL	23 (54%) 7 (16%) 2 (5%) 4 (9%) 7 (16%)
Bone Marrow Involvement	10 (23%)
CNS Involvement	2 (5%)
Stage
Early Stage (1&2) Advanced Stage (3&4) Missing	14 (32%) 27 (63%) 2 (5%)
IPI
Low (0-1) Intermediate (2-3) High (4-5) Unknown	17 (40%) 23 (54%) 2 (5%) 1 (2%)
Prior therapies, median (range)	2 (1-4)
Remission status before transplant
Complete Remission 1 Complete Remission 2 Complete Remission 3 Partial Remission	8 (19%) 17 (40%) 2 (5%) 16 (37%)
Autologous stem cell source (%)
Peripheral Blood Bone Marrow Both	35 (81%) 4 (9%) 4 (9%)
Karnofsky Performance Status, median (range)	90 (80-100)
Median CD34 cell dose infused  (106 cells/kg recipient), (range)	5.3 (1.8-10.5)