Abstract
Background: High dose chemotherapy with autologous hematopoietic stem cell rescue has become one of the standard treatment options for many hematopoietic malignancies. Mobilization by granulocyte colony-stimulating factor (GCSF) with or without chemo priming and followed by peripheral blood stem cell (PBSC) collection is the preferred method to obtain progenitor cells. Successful mobilization and collection of stem cells is dependent upon a number of clinical factors including previous chemotherapy history and disease stage. One question concerns whether efficacy of mobilization and collection, as measured by the number of days or number of collections to reach a defined CD34 cell target dose, is an independent prognostic factor for autologous stem cell transplantation outcome.
Method: A total of 358 patients transplanted from January 2003 to December 2004 (201 males and 157 females, ages from 2.7 to 77.3 years old with median of 53 years of age) underwent autologous PBSC collection after mobilization with GCSF at 10 mcg/kg to 16mcg/kg with or without chemo priming. PBSC collections are typically initiated on day 5 post GCSF injection, or day 10 after chemo priming and GCSF injection without information about their absolute peripheral CD34 cell count. This retrospective study included patients with the following diagnoses: 45 (13%) acute Myelogenous leukemia (AML), 124 (35%) non-Hodgkin’s lymphoma (NHL) 33 (9%) Hodgkin’s disease (HD), 123 (34%) multiple myeloma (MM), and 33 (9%) solid tumors. All patients underwent 4 hours of daily PBSC collection with an average processed volume of 12 to 15 liters at average flow rate of 40ml to 60ml/minute (by Cobe Spectra, Gambro BCT, Denver, CO) until a minimum CD34 count of 2×106/kg of body weight with a target of CD34 cell count of 5×106/kg is reached. The mean number of collections to reach this minimum CD34 cell dose was 2.7 (median 1, range 1 to 14). Collected cells were cryopreserved and stored at −140°C in the vapor phase of a liquid nitrogen freezer prior to their transplantation. Patients received a median CD34 cell dose of 6.4×106/kg with range 2.0 to 67.6×106/kg for their transplants. Correlations were performed between PBSC mobilization/collection efficacy and transplantation outcomes.
Results: Both greater CD34 cell dose used in the transplant (r= −0.24, p<0.0001) and shorter number of days PBSC to reach the minimum 2×106/kg (r=0.10, p=0.06) fostered quicker engraftment. Regardless, most patients engrafted within a reasonable time, with outliers not explained by cell dose or days to collect 2×106 CD34 cells. There was only one graft failure. CD34 cell dose and number of days PBSC collection to reach the minimum 2×106/kg of CD34 cell dose did not independently affect the overall survival or disease-free-survival for this study population as a whole and per each diagnostic group. Patient age at transplantation did not confound the result.
Cyclophosphamide-based hematopoietic stem cell mobilization before autologous stem cell transplantation in newly diagnosed multiple myeloma