Cy/GM/G with scheduled LP commencement on Day 11 enables optimal CD34+ cell yields in most patients undergoing autologous transplantation, despite a low risk of FN and avoidance of weekend LP.

No 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.

We have previously reported that intermediate dose cyclophosphamide followed by sequential GM-CSF and G-CSF (iCy/GM/G) provides efficient mobilization for patients undergoing autografting. Furthermore, the predictable time course of mobilization with this regimen obviates the need for weekend leukaphereses (Blood 2003: 957a). Recently, the addition of rituximab to mobilization regimens for B-cell NHL has been shown to be effective at depleting contaminating B-cells from the leukapheresis product. However, the effect of rituximab administered for in-vivo purging, on mobilization and stem cell collection parameters is unclear. We compared leukapheresis (LP) yield parameters, and the time course of stem cell mobilization in 23 consecutive B-cell NHL patients mobilized with iCy/GM/G plus rituximab (group 1) with 27 consecutive B-cell NHL patients mobilized with the same regimen without rituximab (group 2). The iCy/GM/G regimen consisted of cyclophosphamide 1.5g/m2 (d1), GM-CSF 500 mcg/d (d 3–7), G-CSF (d 8 until completion of LP) 600mcg/d for weight ≤80kg, 960 mcg for weight > 80 kg. Rituxan was administered at 375mg/m2 as a single dose on d8. LP was begun on d 11 irrespective of WBC. D1 was usually a Friday in order to avoid weekend LP. Patients underwent up to 20 liter LP for ≤ 5 days (median =3, range 1–5 for both groups) with a target collection of > 5 x 10e6 CD34+ cells/kg. The groups were well matched for median age, gender, number of prior chemotherapy regimens (median=2 for both groups), prior pelvic XRT and histological subtype of B-NHL (p=NS in all cases). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of 2 x 10e6 CD34+ cells/kg on d 1–5 was 0.43, 0.70, 0.78, 0.84, 0.84 respectively for group 1 and 0.22, 0.69, 0.77, 0.84, 0.84 respectively for group 2. The corresponding probabilites of achieving 5 x 10e6 CD34+ cells/kg on d 1–5 were 0.22, 0.39, 0.57, 0.57, 0.57 (group 1) and 0.11, 0.30, 0.46, 0.59, 0.59 (group 2) (p=NS Log-rank test). Percentage of CD34+ cells in the LP product (LP CD34%) was measured daily. Maximums LP CD34% was seen on LP d1 for both groups with a fall on subsequent days (p=NS between groups 1 and 2). Toxicities experienced were generally mild consisting mostly of bone pain and fevers and were similar in both gropups. No patient required admission for febrile neutropenia. The number of CD34+ cells infused were similar for both groups (median 5.9 vs.5.7 x10e6 CD 34+ cells/kg). Median time to reach ANC > 500/mm3 and platelets > 20,000/mm3 were identical between groups 1 and 2 (d11 and d 10 respectively). These data show that the addition of rituximab administered on d 8 to the iCy/GM/G regimen in patients with B-NHL does not impair the yield of CD34+ cells, or the tolerability of the regimen. Furthermore, the time course of the mobilization and therefore the predictbility of the collection is not compromised. Maximum cumulative yield of CD34+ cells is achieved within 4 days of LP with no patient benefitting from a fifth day of collection. The additional cost and inconvenience of weekend leukapheresis can be avoided in all cases using this regimen.