Treatment of chronic myeloid leukaemia in first chronic phase with idarubicin and cytarabine: mobilization of Philadelphia‐negative peripheral blood stem cells

Abstract

Summary. Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P ¼ 0 : 02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P ¼ 0 : 018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.

Autologous stem cell transplantation in chronic myeloid leukaemia using Philadelphia chromosome negative blood progenitors mobilised with hydroxyurea and G-CSF

“…These results are very similar to the data published using intravenous regimens such as ICE 21 (complete 31%, major 17%) and idarubicin/ cytarabine 20 (complete 43%, major 16% of individual harvests).…”

“…Direct comparison with other data from autotransplants using PhϪ PBSCs mobilised with intravenous chemotherapy is difficult as the data is still immature and relates to small numbers of patients. Chalmers et al 20 In conclusion, we have developed a method for PhϪ PBSC mobilisation in CML that appears to be less toxic than intravenous regimens. This regimen may therefore be an attractive alternative particularly as this procedure may best be carried out early in the disease process when toxic treatments are harder to justify.…”

“…It is clear that the results of stem cell mobilisation are superior when carried out earlier in the disease both in terms of the number of stem cells collected and the proportion of harvests that are PhϪ. 17,20 We have evaluated an oral regimen of hydroxyurea and G-CSF for collection of these cells in the early recovery phase after myelosuppression. The toxicity of the procedure, although not insignificant, was considerably less than that of published intravenous schedules 17,19,20 with one third of patients being treated entirely as outpatients, a median time to haematological recovery of 14 days and with no prolonged cytopenias or fatalities.…”

“…17,20 We have evaluated an oral regimen of hydroxyurea and G-CSF for collection of these cells in the early recovery phase after myelosuppression. The toxicity of the procedure, although not insignificant, was considerably less than that of published intravenous schedules 17,19,20 with one third of patients being treated entirely as outpatients, a median time to haematological recovery of 14 days and with no prolonged cytopenias or fatalities. This contrasts with intravenous mobilisation regimens such as idarubicin/cytarabine/etoposide (ICE) 21 and idarubicin/ cytarabine 20 which have a mortality of approximately 5% and a cytopenic period of at least 3 weeks for the majority of patients with occasional very protracted cytopenias.…”

Collection of Philadelphia-negative peripheral blood progenitor cells in unselected patients with chronic granulocytic leukaemia

“…Analysis of 30 metaphases cannot exclude a clone of up to 10% Ph-positive cells at the 95% confidence limit. 32 Other studies 13,26,31 are based on the analysis of 20 metaphases (clones of up to 14% Ph-positive cells cannot be excluded). Such variation in the number of metaphases examined could go some way towards explaining the apparently lower levels of completely Ph-negative collections in this study.…”