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.
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.
Sohn
Sang-Kyun
SK
Department of Hematology/Oncology, Kyungpook National University Hospital, Taegu, Korea. sksohn@knu.ac.kr
Jung
Jin-Tae
JT
Kim
Dong-Hwan
DH
Lee
Nan-Young
NY
Seo
Kwang-Woon
KW
Chae
Yee-Soo
YS
Park
Soung-Won
SW
Kim
Jong-Gwang
JG
Suh
Jang-Soo
JS
Lee
Kyu-Bo
KB
D000328:Adult; D018952:Antigens, CD34; D017252:CD3 Complex; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D015925:Cryopreservation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells; D006801:Humans; D016219:Immunotherapy, Adoptive; D007937:Leukapheresis; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D010865:Pilot Projects; D016019:Survival Analysis; D020858:Tissue and Organ Harvesting / Q000379:methods*; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D017252:CD3 Complex; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor