Andy I. Chen

Long-Term Results Of Autologous Hematopoietic Cell Transplantation For Peripheral T Cell Lymphoma: The Stanford Experience

The peripheral T cell lymphomas (PTCL) carry a worse prognosis compared to B cell non-Hodgkin lymphoma. There is no uniform standard therapy for PTCL, and autologous hematopoietic cell transplant (AHCT) is often offered as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We conducted a retrospective review of patients who underwent AHCT for PTCL from 1989 to 2006. Fifty-three cases were identified consisting of systemic anaplastic large cell (n = 18), PTCL unspecified (n = 17), angioimmunoblastic (n = 9), nasal type extranodal NK/T (n = 7), hepatosplenic (n = 2), and adult T cell leukemia/lymphoma (n = 1). Fifteen patients were transplanted in first complete or partial response (CR1/PR1), 32 in second or beyond CR or PR (CR2/PR2+), and 11 with primary refractory disease (REF). With a median follow-up was 5 years (range: 1.0-11.5), the 5-year progression-free survival (PFS) and overall survival (OS) were 25% and 48%, respectively. Disease status at AHCT had a significant impact on PFS and OS. The 5-year PFS for patients in CR1/PR1, CR2/PR2+, and REF was 51%, 12%, and 0%, respectively, and the corresponding figures for OS were 76%, 40%, and 30%, respectively. The pretransplant factors that impacted survival were disease status and the number of prior regimens. Histology, age, sex, stage, B symptoms, bone marrow involvement, and duration of first response did not significantly affect PFS or OS. Based on these results, AHCT as consolidation therapy in first complete or partial response may offer a durable survival benefit. However, AHCT with conventional salvage chemotherapy has minimal durable benefit in patients with relapsed or refractory PTCL, and thus novel strategies and/or allogeneic HCT should be more aggressively explored in lieu of AHCT for relapsed/ refractory PTCL.

Tandem chemo-mobilization followed by high-dose melphalan and carmustine with single autologous hematopoietic cell transplantation for multiple myeloma.

Single autologous hematopoietic cell transplant (AHCT) with high-dose melphalan prolongs survival in patients with multiple myeloma but is not curative. We conducted a study of intensive single AHCT using tandem chemo-mobilization with CY and etoposide followed by high-dose conditioning with melphalan 200u2009mg/m2 plus carmustine 15u2009mg/kg. One hundred and eighteen patients in first consolidation (CON1) and 58 patients in relapse (REL) were transplanted using this intensified approach. Disease response improved from 32% very good PR (VGPR)+CR pre-mobilization to 76% VGPR+CR post transplant in CON1. With a median follow-up of 4.7 years, the median EFS was 2.8 years, and the median OS was 5.1 years in CON1. OS from time of transplant was significantly shorter for REL (3.4 years) compared with CON1 (5.1 years; P=0.02). However, OS from time of diagnosis was similar in REL (6.1 years) and CON1 (6.0 years; P=0.80). The 100-day non-relapse mortality in the CON1 and REL groups was 0% and 7%, respectively. In summary, intensified single AHCT with tandem chemo-mobilization and augmented high-dose therapy is feasible in multiple myeloma and leads to high-quality response rates.

Chromosome 1 Abnormalities Predict Shortened Progression Free and OverallSurvival in Patients with High Risk Multiple Myeloma Undergoing AutologousHematopoietic Cell Transplantation, a Retrospective Analysis

Abnormalities of chromosome (ch)1 have been shown to be significant adverse prognostic factors in multiple myeloma (MM) but they have not yet been systematically studied in patients undergoing autologous hematopoietic cell transplantation (auto-HCT). The aim of this study was to determine whether patients with high-risk MM and ch1 abnormalities (1q gain, 1p deletion, translocations of ch1) constitute a highest risk group compared to a contemporaneous cohort of high-risk MM patients without ch1 abnormalities. 232 patients (169 induction, 63 salvage) with MM and at least one recognized high-risk feature met criteria for inclusion. The presence of a ch1 abnormality (n=15) was highly significant in patients undergoing salvage autologous HCT (n=6) for predicting shorter PFS (p<0.001; HR= 22.93; 95% CI: 4.94- 106.48), and OS (p = 0.0002; HR= 21.22; 95% CI: 1.18-14.98). Median PFS and OS for those with a ch1 abnormality and del 13q (n=7) were 4.76 and 9.43 months, with ch1 abnormality and no del 13q (n=8) were 16.79 and 35.22 months respectively, and for those Without cytogenetic abnormalities, 24.44 and 57.03 months respectively. Based upon the impact of ch1 abnormalities on auto-HCT outcomes in this study, further investigation in larger series is warranted.