Enhanced lymphocyte proliferation responses in pediatric patients early after myelosuppressive chemotherapy.
BACKGROUND
It has long been known that patients both after myelosuppressive chemotherapy (ChTh) and after myeloablative bone marrow transplantation (BMT) show a long lasting impairment of cellular immune functions. However, recent reports have revealed that early after BMT a passing state of augmented immune responsiveness exists. Adoptive T cell therapy in this period of lymphopenia-induced (homeostatic) proliferation has shown better results than in steady state in murine studies.


METHODS
To determine whether also early after myelosuppressive ChTh enhanced immune responses can be found, we have determined proliferation of peripheral blood lymphocytes and calcium influx and performed immunophenotyping in pediatric patients recovering from myelosuppressive ChTh in comparison to immunoreconstituted patients late after BMT.


RESULTS
The lymphocytes of the ChTh patients were found to proliferate vigorously in response to stimulation with a variety of antibodies and mitogens, while in the BMT patients any stimulation was severely reduced. The increase of intracellular calcium after stimulation was similar in both patient groups. ChTh patients showed an expansion of an activated "naive" phenotype (CD45RO- HLA-DR+) in both the CD4 and CD8 subsets. In contrast, BMT patients showed a prominent expansion of "memory type" T lymphocytes (CD45RO+ HLA-DR+).


CONCLUSIONS
Early after ChTh, a period of immunoaugmentation seems to exist. Whether this observation can be used clinically to increase cure rates remains to be elucidated.
Stachel
Daniel
D
Department of Pediatrics, Pediatric Hematology and Oncology, University of Erlangen-Nurnberg, Erlangen, Germany. Daniel.Stachel@kinder.imed.uni-erlangen.de
Fütterer
Agnes
A
Haas
Rainer J
RJ
Schmid
Irene
I
D015703:Antigens, CD / Q000378:metabolism; D016026:Bone Marrow Transplantation; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016853:Muromonab-CD3 / Q000494:pharmacology; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D015703:Antigens, CD; D016853:Muromonab-CD3; D010835:Phytohemagglutinins; D000001:Calcimycin; D002118:Calcium; D013936:Thymidine