Dose Adjusted IV Busulfan/Cyclophosphamide (BU/CY) and Autologous (AU) Stem Cell Transplantation (SCT) for Recurrent Lymphoma.

The optimal preparative therapy for AuSCT for lymphoma is unknown. High dose Bu/CY is a generally well tolerated, and an effective regimen for allogeneic SCT for hematologic malignancy (HM), and autologous SCT for myeloid malignancies. It has, however, been less well studied for lymphoid malignancies. IV busulfan has largely replaced oral busulfan because of more predictable pharmacokinetics, and ease of administration. We have treated 46 patients (pts) with recurrent, chemosensitive lymphoma or lymphoma in which an initial complete remission was not achieved with the Bu/CY regimen and AuSCT from 2001 – 2004. 4 pts had AIDS related NHL (ARL). Patients had received a median of two chemoradiotherapeutic regimens prior to SCT. Diagnoses were indolent NHL (n = 12), aggressive NHL (n = 28) and Hodgkin’s disease (n = 6). IV busulfan was given at a dose of 0.8 mg/kg (based on actual or ideal body weight (IBW) whichever was less) every six hours for 16 doses (for patients < 50 years of age), or 14 doses (for patients = 50 years of age) on days -7 through -4. IV cyclophosphamide 60 mg/kg (based on a wt half way between actual and IBW for patients > 20% IBW) was given on days −3 and −2. AuSCT was performed on day 0. Additional autologous bone marrow was infused in pts who had less than 2 x 10⁶/ kg CD 34+ progenitor cells (n = 2). Median (range) patient age was 56 (24–78) years. Four pts were = 70 years old at the time of transplant. Median (range) times to ANC = 0.5 and platelets = 20k were 10 (8–12) and 12 (8–64) days, respectively. Regimen related toxicities (according to the Bearman toxicity scale) included grade II-III mucosal toxicity (n = 7), hepatic VOD (n = 1), and grade II GI toxicity (n = 7). Documented infection occurred in 16 (35%) pts. Two pts (4.4%) died before day 100 from non-relapse causes (progressive pulmonary toxicity (n = 1), recurrence of melanoma (n = 1). Late (= day 100) non-relapse mortality (NRM) occurred in two pts (respiratory failure, (n = 1); hepatic VOD (n = 1). Overall NRM was 8.7% (4/46 patients). No NRM occurred in pts with ARL or pts > 70 yrs. Fourteen of 40 pts with NHL have had relapse/progression. Three of six pts with HD have had relapse/progression. Actuarial progression free survival (PFS) and overall survival (OS) probabilities are 67% and 100% at 32 mos for pts with indolent NHL and 44% and 79% at 25 mos for pts with aggressive NHL, respectively. High dose IV Bu/CY as preparation for AuSCT, with dose reduction of IV busulfan to 14 mg/kg for patients = 50 years is well tolerated and is associated with favorable PFS and OS probabilities. The regimen has also been well tolerated in pts over the age of 70 with no life threatening or fatal toxicities in this subgroup.