Factors influencing collection of peripheral blood progenitor cells following high‐dose cyclophosphamide and granulocyte colony‐stimulating factor in patients with multiple myeloma

Abstract

We treated 103 multiple myeloma (MM) patients with 7 g/m2 cyclophosphamide (Cy) followed by 300 μg G‐CSF/d to harvest peripheral blood progenitor cells (PBPC). PBPC autografts containing > 2.0 × 106 CD34+ cells per kg body weight were obtained at the first attempt from 90/100 evaluable patients. The most significant factor predicting impairment of PBPC collection was the duration of previous melphalan treatment (P < 0.0001). In multivariate discriminate analysis, treatment with melphalan during the most recent chemotherapy cycles prior to mobilization (P = 0.0727) and previous radiotherapy (P = 0.0628) had a marginally significant negative influence on the efficacy of PBPC collection. We found no reduced functional capacity of CD34+ cells to restore haemopoiesis after myeloablative treatment related to the duration of melphalan exposure. At the time of best response to conventional treatment, a median paraprotein reduction of 21% was achieved following high‐dose cyclophosphamide (HD‐Cy). Two heavily pretreated patients died and one patient developed pulmonary toxicity W.H.O. grade IV following HD‐Cy. Potential transplant candidates should undergo mobilization and harvesting of PBPC before melphalan‐containing treatment. Combinations of haemopoietic growth factors and their dose modifications should be investigated to improve PBPC collection, to allow a dosage reduction of the mobilization chemotherapy.

Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study

“…Thus, even if HGF could decrease the hematological toxicity of HDCYC, their use did not seem to change significantly this difference for the others. 29,32 As we observed, other parameters also involved in PBPC collection efficiency such as duration of therapy before HDCYC are important for HDCYC tolerance. Indeed, in a more recent study reporting results of total therapy, no death was observed after HDCYC 6 g/m 2 in newly diagnosed MM patients.…”

“…Indeed, comparative studies have reported that an increase in the CYC dose resulted in an increase in the number of PBPC harvested, irrespective of whether HGF were used or not. 28,29 In another study, patients treated with a lower dose of CYC had a less pronounced mobilization when compared with a high-dose CYC group. 30 Moreover, a significantly lower potentially malignant B cell content of autografts harvested after 7 g/m 2 is a further argument to prefer this dosage.…”

“…30 Moreover, a significantly lower potentially malignant B cell content of autografts harvested after 7 g/m 2 is a further argument to prefer this dosage. 29 In this setting another advantage of the administration of HDCYC at 7 g/m 2 is a further potential reduction of the tumor mass. 31 However, an increased dose for both better mobilization and in vivo purging efficacy is associated with an increased toxicity.…”

“…29 In this setting another advantage of the administration of HDCYC at 7 g/m 2 is a further potential reduction of the tumor mass. 31 However, an increased dose for both better mobilization and in vivo purging efficacy is associated with an increased toxicity. 28 In our study following HDCYC at 7 g/m 2 , toxic deaths related to infection were observed as recently reported by Goldsmidt et al 31 using the same dosage and by Jagannath et al 22 using HDCYC 6 g/m 2 , despite the use of HGF in all studies.…”

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging

“…20,21,25 Novel antiangiogenic treatment approaches are currently investigated and might be used in MM in the near future. 26,27 In fact, the successful treatment of MM patients with thalidomide that has antiangiogenic effects was shown by Singhal et al 11 Preclinical models show that antiangiogenic treatment and tumor cell directed treatment approaches might have synergistic effects.…”