Time-course of the recovery of cellular immune function after high-dose chemotherapy and peripheral blood progenitor cell transplantation for high-grade non-Hodgkin's lymphoma.
Chemotherapy induces high remission rates in high-grade lymphoma. However relapse remains a major problem. One approach to this is myeloablative chemotherapy with transplantation of autologous bone marrow or peripheral blood progenitor cells (PBPC). Immunological mechanisms have been suggested to play a role in the prevention of relapse after transplantation. We investigated the recovery of cellular immune functions after high-dose chemotherapy and PBPC transplantation in 5 patients with high grade non-Hodgkin's lymphoma. All patients showed rapid reconstitution of natural killer (NK) and inducible lymphokine-activated killer (LAK)-activity 10-14 days after transplantation. Four of 5 patients showed higher levels of LAK-generation in the post-transplant period compared with levels prior to myeloablative treatment. Absolute lymphocyte counts in peripheral blood reached 1.0 x 10(9)/l between days 10 and 13 with a predominance of CD8+ cells and an inversion of the CD4/CD8 ratio. Four of 5 patients had a transient increase in CD56+ and CD16+ cell counts post-transplant. No change in the proportion of CD25+ cells was noted. These results show that PBPC transplantation leads to a rapid recovery of cellular immune functions after myeloablative chemotherapy and provides evidence for an increased presence of LAK precursor cells early in the post-transplant period which can be activated by IL-2 to exert high levels of cytotoxicity.
Scheid
C
C
CRC Department of Immunology, Paterson Institute for Cancer Research, Manchester, UK.
Pettengell
R
R
Ghielmini
M
M
Radford
J A
JA
Morgenstern
G R
GR
Stern
P L
PL
Crowther
D
D
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000628:therapy; D002066:Busulfan / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007937:Leukapheresis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D011034:Podophyllotoxin / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002066:Busulfan; D011034:Podophyllotoxin; D015080:Mesna; D008558:Melphalan; D002330:Carmustine