Outcome of peripheral blood stem cell mobilization in advanced phases of CML is dependent on the type of chemotherapy applied

Abstract

High-dose chemotherapy with autologous transplantation of in vivo purged PBSC is a novel investigational approach to treating chronic myelogenous leukemia (CML) patients not responsive to conventional therapy with interferon-alpha (IFN-alpha) and not eligible for allogeneic transplantation. PBSC mobilization using either '5+2/7+3'-type chemotherapy or 'mini-ICE/ ICE' chemotherapy was investigated in 43 patients with advanced phases of Philadelphia (Ph)-positive CML. Thirty patients were in late chronic phase (>12 months post diagnosis) and 13 patients in accelerated phase (AP) or blast crisis (BC). Contamination with Ph-positive cells was evaluated in harvests from 37/43 patients. The outcome of PBSC mobilization was dependent on the type of chemotherapy administered: a complete or major cytogenetic response (<35% Ph-positive metaphases) in leukapheresis collections was obtained in ten of 15 patients treated with 'mini-ICE/ICE' but in only three of 28 patients treated with '5 + 2/7 + 3' chemotherapy. One patient (1/43) in blast crisis died during mobilization therapy (2%). Twenty-five patients underwent PBSC transplantation and all of them engrafted successfully. Transplantation-related mortality was 0%. The data show that in advanced phases of CML the chance of harvesting Ph-negative peripheral blood stem cells depends on the type of chemotherapy used for mobilization.

Chemotherapy-induced mobilization of karyotypically normal PBSC for autografting in CML

“…Late chronic phase and AP/BC were refractory to '5 + 2/7 + 3' but were sensitive to 'mini-ICE/ICE' chemotherapy. 19 Table 5 illustrates that a CCR and MCR was observed in 13% of patients treated with '5 + 2/7 + 3' vs 69% in patients treated with 'mini-ICE/ICE' (P = 0.0011).…”

“…Pretransplant cytogenetic analysis has not been performed routinely due to the short interval between PBSC mobilization and transplantation. Median time to achieve a white blood cell (WBC) count of Ͼ1.0 × 10 9 /l was 12 days (range [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and to regenerate platelets to Ͼ50 × 10 9 /l was 20 days (range 10-123). Table 6 demonstrates hematopoietic recovery and toxicity following PBSC transplantation.…”

Mobilisation of haemopoietic progenitors in CML: a second course of intensive chemotherapy does not improve Ph-negativity in stem cell harvests

“…The median number of days with neutrophil counts below 0.5 × 10 9 /l was 19 after the first and 18 (14-36) days after the second cycle of induction chemotherapy. Platelet counts were below 20 × 10 9 /l for 13 (median, range 8-28) and 16 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) days, respectively, and below 50 × 10 9 /l for 17 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and 21 (14-37) days, respectively. Median numbers of platelet transfusions were three (1-16) and five (1-17), respectively, and those of red blood cell transfusions were six (range 2-17) after the first cycle and 10 (4-16) after the second.…”

“…A substantial portion of patients treated in this way revert, at least temporarily, to Ph-negative haemopoiesis. [9][10][11][12][13][14][15][16][17][18][19] The probability of reaching a major cytogenetic reponse after autoSCT may be related to the number of negative progenitors in the stem cell graft. 20 Generally, haemopoietic stem cells have been harvested in the early recovery phase after a single cycle of conventional intensive chemotherapy followed by G-CSF.…”

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

“…9,10 Furthermore, there is evidence that the chemotherapy regimen used for mobilisation may also influence the quality of the leukapheresis products. 9,11 Between 1994 and 2000, 91 CML patients were mobilised within two clinical trials of the East German Study Group Haematology/Oncology (OSHO). The initial trial, designed as a pilot study, included 20 patients in late chronic phase.…”