Mobilization of Philadelphia-negative peripheral blood mononuclear cells in chronic myeloid leukaemia using hydroxyurea and G-CSF (filgrastim).
A relatively simple and non-toxic out-patient-based regimen for the mobilization of Philadelphia-negative (Ph-ve) mononuclear cells in chronic myeloid leukaemia (CML) was evaluated in 10 patients, nine in stable chronic phase and one in accelerated phase. They received oral hydroxyurea at a mean dose of 3.5 g/m2 daily for 7 d, followed by 300 micrograms of G-CSF daily until the last day of harvesting. In the nine chronic-phase patients the mean number of days from the end of hydroxyurea to the commencement of harvesting was 14.5 (range 10-18). The patient in accelerated phase recovered and was harvested after 6 d. The mean number of aphereses performed was 3.4. Adequate numbers of stem cells were obtained in 9/10 patients judged by our usual criteria. Side-effects were mild in comparison to published intravenous schedules. No patients lost their hair. Five (50%) patients required admission with neutropenic fever which responded to antibiotics in all cases. Four (40%) patients developed a transient rash and four (40%) experienced mild oral mucostis. This level of toxicity enabled half of the patients to be treated entirely on an out-patient basis. The harvest products were analysed for cells belonging to the leukaemic clone by conventional cytogenetics, FISH and PCR. All were PCR positive. The mean Ph positivities by cytogenetics and FISH were comparable at 18.1% and 15% respectively. Half the patients had > 98% normal metaphases. We conclude that this approach is comparable in efficacy to published intravenous regimens and significantly less toxic. It can be safely used at diagnosis before interferon therapy commences.
Johnson
R J
RJ
General Infirmary at Leeds.
Owen
R G
RG
Child
J A
JA
Morgan
G J
GJ
Barnard
D L
DL
Dickinson
H
H
Ricketts
S
S
Rawstron
A
A
Evans
P
P
Woodhead
V
V
Major
K
K
Robinson
F
F
Smith
G M
GM
D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D000069585:Filgrastim; D016044:Fusion Proteins, bcr-abl / Q000032:analysis; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000473:pathology / Q000628:therapy*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000473:pathology / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl; D000069585:Filgrastim; D006918:Hydroxyurea