G-CSF during large field radiotherapy reduces bone marrow recovery capacity.
OBJECTIVE
Side effects of chemo- and radiotherapy are granulo- and thrombocytopenia. However, the long-term effects of in vivo granulocyte-colony-stimulating factor (G-CSF) stimulation of the hematopoietic system during radiotherapy are not yet completely understood. In the present study, we sought to determine the bone marrow effect of G-CSF during radiotherapy.


METHODS
In a prospective, randomized clinical trial 10 patients (6 m, 4 f, 30-64 yrs, mean 50.6 yrs) were assigned to large field radiotherapy (RT). 7 patients (pat.) with non-Hodgkin lymphoma, one patient with Hodgkin's disease and 2 patients with small-cell carcinoma of the lung were included. The patients were randomized to either radiotherapy alone (group A) or radiotherapy with simultaneous G-CSF (group B) treatment and assessed for acute and late toxicity. Blood samples were drawn and analyzed before and after G-CSF stimulation. The mobilization effectivity of G-CSF on CD34 superset+ progenitor cells was measured using flow cytometry and colony forming units (CFU) testing on admission and during the complete follow-up period (1, 3 and 18 months post RTx).


RESULTS
Overall, 50 pat. were intended to be included to the protocol. However, the preliminary analysis revealed a significant decrease of thrombocytes and CD34 superset+ progenitor cells in the G-CSF treatment group. According to the study protocol further treatment was stopped. Peripheral leukocyte counts ranged between 2800 - 4375 /mul in 9/10 pat. In group B mean thrombocyte levels dropped below 30.000 mg/l and CD34 superset+ progenitor cells to 50% (interruption criteria, p<0.02, Student's t-test). Hemoglobin values did not vary. Differential blood smears showed differences in granulocyte counts and a higher proportion of neutrophils in group B. Lymphocyte counts of patients randomized to group A were significantly decreased when compared to group B. In group A, 3/5 pat. developed an overshooting reaction (4,7 x increase) after G-CSF-stimulation. In arm B circulating CD34 superset+ progenitor cells dropped. In arm A, 3/5 pat. had an initial overshoot reaction when compared to none in group B. CFU (> 40 cells) and cluster (4 -39 cells) showed considerable variations.


CONCLUSIONS
Our results demonstrate that simultaneous treatment with G-CSF during radiotherapy reduces the mobilization of CD34+ progenitor cells and exhaust the bone marrow capacity while peripheral leukocyte counts remain at baseline levels.
Pape
H
H
Klinik für Strahlentherapie und Radiologische Onkologie, Heinrich-Heine-Universität Duesseldorf, Moorenstrasse 5, D-40225 Duesseldorf, Germany. papeh@uni-duesseldorf.de
Orth
K
K
Heese
A
A
Heyll
A
A
Kobbe
G
G
Schmitt
G
G
Niederbichler
A D
AD
Peiper
M
M
Schwarz
A
A
Boelke
E
E
D000328:Adult; D018952:Antigens, CD34 / Q000528:radiation effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001491:Basophils / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D004307:Dose-Response Relationship, Radiation; D004804:Eosinophils / Q000166:cytology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007958:Leukocyte Count; D008175:Lung Neoplasms / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D011446:Prospective Studies; D013997:Time Factors; D014916:Whole-Body Irradiation; D014965:X-Rays
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor