title: High-dose hydroxyurea and G-CSF to collect Philadelphia-negative cells in chronic myeloid leukemia: preliminary results.
abstract: Five patients with Ph+ chronic myeloid leukemia and no detectable diploid cells in the marrow received 6 g hydroxyurea twice daily for 7 days followed by G-CSF to harvest Ph-cells 1-84 months after diagnosis. Three were in first chronic phase, and two in accelerated phase. One stopped hydroxyurea after 4 doses due to intractable vomiting and was not apheresed, while two stopped hydroxyurea after 9 and 11 doses because of mucositis and skin rash. Two tolerated all doses; one with no significant side effects, and one with mucositis and painful plantar rash. The nadir leukocyte, neutrophil, and platelet counts were 0.4-0.8, 0-0.1, and 2-19 x 10(9)/L respectively. Apheresis was commenced when the leukocytes were 1.2-3.8 x 10(9)/L 9-10 days after starting G-CSF, and 6 aphereses were performed. Four collections were 100% Ph+, and two 22% and 90% Ph-. The total nucleated cell, CD34+/CD34-subset, CD34+/CD33+ subset, and CFU-GM yields per kg per collection were 0.48-2.38 (median 1.18) x 10(8), 0-0.48 (median 0.012) x 10(6), 0.028-10.19 (median 0.92) x 10(6), and 0.29-41.81 (median 21.78) x 10(4) respectively. We conclude that hydroxyurea in the dose we used is poorly tolerated, and is associated with significant adverse effects including severe myelosuppression. It is possible to harvest diploid cells during recovery, but achievement of Ph-negativity appears to be erratic and cell yields are poor.
authors.affiliation: Leukaemia Unit, Royal Marsden Hospital, Surrey, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mehta
authors.forename: R
authors.initials: R
authors.lastname: Powles
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: G J
authors.initials: GJ
authors.lastname: Swansbury
authors.forename: B
authors.initials: B
authors.lastname: Millar
authors.forename: V
authors.initials: V
authors.lastname: Shepherd
authors.forename: J
authors.initials: J
authors.lastname: Bell
authors.forename: T
authors.initials: T
authors.lastname: Min
authors.forename: S
authors.initials: S
authors.lastname: Cabral
authors.forename: J
authors.initials: J
authors.lastname: Treleaven
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002469:Cell Separation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged
chemical_list: D000970:Antineoplastic Agents; D016179:Granulocyte Colony-Stimulating Factor; D006918:Hydroxyurea