Prospective Clinical Study of High Dose Chemotherapy Followed By Peripheral Blood Stem Cell Transplantation for Relapsed or Refractory HIV-Associated Lymphoma

Introduction:

Even in the era of combined antiretroviral therapy, HIV-associated lymphoma is a complication with poor prognosis. The relapse rate of HIV-associated lymphoma is generally high and the outcome of the conventional therapy for relapsed or refractory disease is very poor. The recent reports showed the efficacy of autologous stem cell transplantation (ASCT) following high-dose therapy.

However, not all patients can be successfully treated with salvage chemotherapy and proceed to ASCT.

We conducted a single-arm multicenter phase 2 study for patients with relapsed or refractory HIV-associated lymphoma to assess the safety and efficacy of ASCT by an intention-to-treat analysis.

The primary objective of this study was to evaluate survival rate and engraftment at day 100 post stem cell transplant. The secondary objectives were to analyze overall survival at 1 year (1yr-OS) and 2 years (2yrs-OS), and progression free survival at 1 year (1yr-PFS) and 2 years (2yrs-PFS).

Patient and Methods:

We enrolled patients over 20 and less than 66 years old who were diagnosed relapsed or refractory HIV-associated lymphoma. Patients were treated with 1-4 courses of standard ICE +/- R or ESHAP +/- R regimen with a collection of autologous stem cells in-between. Patients who achieved partial remission or better with >2.0 million/kg of CD34 positive cell, proceeded to ASCT. Conditioning treatment for ASCT consisted of ranimustine 300mg/m2 on day -6, etoposide 200mg/m2 day -5 to -3, cytarabine 200mg/m2 day -5 to -3, and L-PAM 140mg/m2 on day -2.

Results:

Fourteen patients were enrolled from 3 institutions. All patients were male and the median age was 42.4 years old. The initial diagnosis was 10 of diffuse large B cell lymphoma, 2 of plasmablastic lymphoma, 1 of Burkitt lymphoma, and 1 of other. Five of 14 patients achieved partial remission or better after the standard salvage treatment (35.7%), and proceeded to ASCT. All of 5 patients achieved engraftment and alive at day 100 of ASCT. Kaplan-Meier survival analysis for 5 transplanted patients showed that 1yr- and 2yr-OS were 40%, and 1yr- and 2yr-PFS were 40%.

Grade 2 or 3 adverse events were reported in 4 patients (diarrhea: n=4, mucositis: n=3). No therapy related death was reported.

Conclusion:

ASCT for relapsed or refractory HIV-associated lymphoma is a safe and effective treatment strategy. However, the eligibility for ASCT was only one-thirds of relapsed/refractory patients, because of the low response rate of standard salvage chemotherapy. To improve the outcome, further study of effective salvage strategy is needed.