High-dose hydroxyurea plus G-CSF mobilize BCR-ABL-negative progenitor cells (CFC, LTC-IC) into the blood of newly diagnosed CML patients at any time of hematopoietic regeneration.
The objective of this study was to analyze the mobilization kinetics of normal (BCR-ABL(neg)) and malignant (BCR-ABL(pos)) progenitor cells using a new, low toxic, out-patient-based mobilization regimen for Philadelphia chromosome-positive (Ph(pos)) chronic myelogenous leukemia (CML) patients. High doses of hydroxyurea (HD-HU, 3.5 g/m(2) per day, orally for 7 days) followed by granulocyte colony-stimulating factor (G-CSF) (10 microg/kg subcutaneously) were administered to 11 newly diagnosed CML patients. Each apheresis product (n = 30) was individually analyzed for the number and genotype of mature colony-forming cells (CFC) and primitive long-term culture initiating cells (LTC-IC), respectively, by reverse transcription polymerase chain reaction (RT-PCR) of individual colonies. Sufficient numbers of CD34(+) cells/kg bodyweight (BW) could easily be obtained in all patients (median, 15 x 10(6)/kg BW per patient) with a median number of three aphereses performed per patient (range 2-4). Almost each apheresis itself (25/30) contained > or =2 x 10(6) CD34(+) cells/kg BW. All patients with low and intermediate Sokal risk indices (9/11) mobilized primarily BCR-ABL(neg) LTC-IC (median 92%, range 47-100) and CFC (median 89%, range 57-100). Moreover, the mean percentage of BCR-ABL(neg) CFC and LTC-IC in the various apheresis products in these patients did not change throughout the entire time of hematopoietic regeneration. The toxicity of the mobilization procedure was low. Side effects were mild erythema in 8/11 and oral mucositis in 3/11 patients. Overall, the low toxicity of this regimen, together with the fact that sufficient BCR-ABL(neg) progenitors can be collected throughout the entire period of hematopoietic regeneration, renders this mobilization regimen particularly attractive for the collection of BCR-ABL(neg) progenitors in early chronic phase of Ph(pos) CML.
Petzer
Andreas L
AL
Universitätsklinik Innsbruck, Abteilung für Hämatologie & Onkologie, Innsbruck, Austria. andreas.petzer@uibk.ac.at
Hochenburger
Elmar
E
Haun
Margot
M
Duba
Hans Ch
HCh
Grünewald
Kurt
K
Hoflehner
Elisabeth
E
Sill
Heinz
H
Linkesch
Werner
W
Gastl
Günther
G
Gunsilius
Eberhard
E
D000328:Adult; D001781:Blood Component Removal / Q000592:standards; D004359:Drug Therapy, Combination; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014182:Transplantation, Autologous / Q000379:methods
D016179:Granulocyte Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl; D006918:Hydroxyurea