Intermediate Dose Cyclophosphamide Followed by Sequential GM-CSF and G-CSF: An Efficient and Predictable PBPC Mobilization Regimen for Autografting: A Single Center Study of Two Hundred and Thirty Patients.

Abstract

Collection of an optimal dose of peripheral blood progenitor cells (PBPC), eg, >5x106 CD34+ cells/kg, speeds engraftment after autologous bone marrow transplantation (ABMT). PBPC mobilization using high dose cyclophosphamide (Cy), eg 3–7gm/m2 and G-CSF typically produces a higher yield of PBPC than Cy or G-CSF alone, but WBC rebound following such regimens is often unpredictable, necessitating multiple assessments of blood WBC and CD34+ cell count, may require weekend leukapheresis (LP), and is associated with a high risk of febrile neutropenia. To minimize these problems while producing an adequate PBPC yield, we mobilized 230 unselected patients (pts) for ABMT using moderate dose Cy (1.5g/m2, day 1), followed by sequential administration of GM-CSF (500mcg/d, days 3–7) and G-CSF (5mcg/kg/d, day 8 until completion of LPs). This “CyGMG” regimen was based upon reports suggesting a synergy between GM-CSF and G-CSF. LP was initiated on day 11 irrespective of WBC or blood CD34+ cell count. Cy was administered on Friday (day 1) with LP starting on Monday (day 11 = LP day 1) and 20L LPs were performed for up to six days, thus avoiding weekend LP in most pts (median #LP = 3, range 1–6). Pt median age was 53 (range 19–78); 134 male, 96 female; diagnosis; myeloma (77), NHL (94), breast cancer (17), Hodgkin's disease (28), Testicular cancer (4), other (10). Median prior chemotherapy (CT) regimens = 2 (range 0–6). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of >2, or 5x106/CD34+ cells/kg on LP days 1–5 was 0.5, 0.77, 0.87, 0.91, 0.93, 0.87 and 0.25, 0.5, 0.65, 0.72, and 0.74 respectively. In addition, since 12/2003 when the collection target for pts with myeloma was increased to 10x106 CD34+ cells/kg, 76% of myeloma pts achieved this goal. Based on multivariate cox regression, diagnosis (myeloma vs other) and day 1 platelet (plt) count were significantly associated with achieving 2 or 5 x 106/CD34+ cells/kg and the above factors plus the # of prior CT regimens were associated with achieving 10x106/CD34+ cells/kg. However, (in contrast with a previous report) the day 1 plt count was not correlated with CD34+ cells/kg in the subgroup of myeloma pts (r=0.07, p=0.62). For non-myeloma pts a plt count >75,000 predicted achievement of 5x106 CD34+ cells/kg (2/17 pts with <75K plt vs 91/136 pts with >75K plt; p<.0001 by X2). Toxicities consisted mostly of mild bone pain and fevers, and 12 patients required hospital care during mobilization (not necessarily regimen related).Conclusion: This large series indicates that the above mobilization regimen (1) efficiently mobilizes adequate PBPC in the vast majority of an unselected population of pts for ABMT (including myeloma pts with a target dose of 10x106 CD34/kg), (2) obviates the need for WBC and peripheral blood CD34+ cell count monitoring before commencing LP and the need for weekend LP, and (3) is well tolerated by pts.