Prophylactic growth factor-primed donor lymphocyte infusion using cells reserved at the time of transplantation after allogeneic peripheral blood stem cell transplantation in patients with high-risk hematologic malignancies

Sang-Kyun Sohn, Jin-Tae Jung, Dong-Hwan Kim, Nan-Young Lee, Kwang-Woon Seo, Yee-Soo Chae, Soung-Won Park, Jong-Gwang Kim, Jang-Soo Suh, Kyu-Bo Lee
Cancer 2002 January 1, 94 (1): 18-24

BACKGROUND: Standard allogeneic bone marrow transplantation (BMT) offers only a small chance of cure for most adult patients with advanced hematologic malignancies. The authors postulated that allogeneic peripheral blood stem cell transplantation (PBSCT) followed by prophylactic growth factor-primed donor lymphocyte infusion (DLI) with cells reserved at harvest would maximize the graft-versus-tumor effects in patients with hematologic malignancies who had a high risk of recurrence.

METHODS: Seventeen patients with hematologic malignancies who had a high risk of recurrence were allocated on an intent-to-treat basis to allogeneic PBSCT from human leukocyte antigen-matched sibling donors followed by prophylactic growth factor-primed DLI of cells reserved at harvest for transplantation.

RESULTS: The median age was 37 years (range, 19-56 years). All donors underwent two or more apheresis procedures. The median numbers of mononuclear cells (MNCs), CD34 positive (CD34+) cells, and CD3+ cells, respectively, that were collected for 17 donors were 9.0 x 10(8) MNCs/kg (range, 4.9-14.4 x 10(8) MNCs/kg), 13.0 x 10(6) CD34+ cells/kg (range, 2.4-75.2 x 10(6) CD34+ cells/kg), and 5.8 x 10(8) CD3+ cells/kg (range, 3.3-9.9 x 10(8) CD3+ cells/kg) for a mean number of 2.35 apheresis procedures (range, 2.0-4.0 procedures). The median numbers of MNCs and CD3+ cells that were cryopreserved were 2.1 x 10(8) MNCs/kg (range, 0.0-4.4 x 10(8) MNCs/kg) and 1.4 x 10(8) CD3+ cells/kg (range, 0.0-3.5 x 10(8) CD3+ cells/kg). Seven of 17 patients received additional PBSCs, with a median of 5.0 x 10(7) CD3+ cells/kg (range, 3.0-9.9 CD3+ cells/kg) between Day 41 and Day 120. The reasons for inability to administer additional PBSCs in 10 patients included early death (n = 4 patients), severe graft-versus-host disease (GVHD) (n = 3 patients), disease recurrence (n = 2 patients), and harvest failure (n = 1 patient). Of seven patients, two patients died of recurrence, and one died of cytomegalovirus pneumonitis. The surviving four patients were free of disease when last assessed (median follow-up, 597 days) but were suffering from chronic GVHD (one patient had limited GVHD, and three patients had extensive GVHD).

CONCLUSIONS: The authors suggest that allogeneic PBSCT with prophylactic growth factor-primed DLI may be a potentially curative strategy for the treatment of hematologic malignancies in patients with a high risk of recurrence. Their approach may offer the additional advantage of collecting enough cells at harvest for the potential use of DLI, which is easy, convenient for donors, and cost effective.

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