Mobilisation of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin’s lymphomas and Hodgkin’s disease

Abstract

Summary:The transplantation of mobilised peripheral blood stem cells is associated with more rapid engraftment than marrow transplantation. We have previously reported that G-IVE (G-CSF, ifosphamide, VP-16, epirubicin) improves the yield of CD34 ؉ cells mobilised in patients with lymphoproliferative disorders compared with cyclophosphamide 3 g/m 2 and G-CSF (G/CYCLO). In this study we have extended these observations to a larger series of patients including different lymphoma subtypes. Ninety-seven patients undergoing stem cell mobilisation were studied. Forty-two patients with lymphoproliferative disorders received G-IVE for mobilisation and 55 patients G/CYCLO. The median number of mobilised CD34 ؉ cells per leucapheresis was significantly higher for those patients receiving G-IVE: 5.82 ؋ 10 6 /kg (0.19-36) compared with 1.2 ؋ 10 6 /kg (0.04-17), P Ͻ 0.001 which resulted in a significantly reduced number of leucapheresis procedures performed in the G-IVE group. When patients were analysed dependent on underlying disease G-IVE mobilised significantly more CD34 ؉ cells per leucapheresis for all lymphoma types reaching 8.41 ؋ 10 6 /kg (0.2-32) compared to 1.32 ؋ 10 6 /kg (0.06-17) for patients with highgrade NHL mobilised with G-IVE and C-GCSF respectively (P = 0.012). For patients with low-grade NHL 3.12 ؋ 10 6 /kg (0.10-24.39) compared to 1.08 ؋ 10 6 /kg (0.04-9.74) were collected (P = 0.04) and for patients with Hodgkin's disease 3.02 ؋ 10 6 /kg (1.48-36) and 1.04 ؋ 10 6 /kg (0.1-12.3) (P = 0.001). Mobilisation with G-IVE resulted in the achievement of clinically significant CD34 ؉ cell thresholds in a significantly higher proportion of patients compared to cyclophosphamide and G-CSF reaching Ͼ2.5 ؋ 10 6 /kg CD34 ؉ cells in 88% vs 62% (P = 0.004), Ͼ5 x 10 6 /kg in 67% vs 18% (P = 0.001) and Ͼ10 ؋ 10 6 /kg in 31% vs 14.5% (P = 0.05). Furthermore, an analysis of engraftment demonstrated that there was a significant reduction in the time to achieve platelet counts of Ͼ20 and Ͼ50 ؋ 10 9 /l in patients receiving each incremental dose of CD34 ؉ cells. We conclude that G-IVE mobilises significantly more CD34 ؉

Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF

“…17 Min et al 22 compared rhG-CSF starting on day 2 or 8 after infusion of CY in 30 patients, and they too found no difference between the two groups with regard to collection yield, toxicity or engraftment characteristics. Similarly, Haynes et al and McQuaker et al 18,19 reported the late administration of rhG-CSF after mobilization chemotherapy in patients with lymphomas. In both studies, patients achieved successful PBSC mobilization in terms of total CD34 þ cell yields.…”

“…It has to be noted that in most of these studies, the primary objective was not to evaluate 'late' administration of rhG-CSF. [16][17][18][19][20][21] These studies have evaluated the 'late' use of rhG-CSF (4 days after chemotherapy), at varied doses and schedules with comparable results with those obtained after starting rhG-CSF immediately after chemotherapy. 18,19,21 Mollee et al 16 compared CY þ rhG-CSF with CE þ rhG-CSF of 10 mg/kg once daily for PBSC mobilization in patients with lymphoma.…”

“…We may therefore speculate that this provided us with more consistent results compared with those studies reported previously using different doses, regimens and timing of rhG-CSF. [16][17][18][19][20][21][23][24][25] We concluded that PBSC mobilization after the 'late' use of rhG-CSF is an effective approach, and that in routine clinical practice the late use of rhG-CSF may therefore be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.…”

A European reference protocol for quality assessment and clinical validation of autologous haematopoietic blood progenitor and stem cell grafts

“…5,6,[26][27][28][29] We do not yet know the minimal safe number of CD34 ϩ cells needed for clinical engraftment of all lineages, as this may vary depending on the stem and progenitor cell subset composition in a given patient or autograft. [42][43][44][45][46] However, we do know that a graft content of more than 5-10 million Table 1a Overall median number of CD34 + cells from nine studies of haematological recovery following autologous stem cell reinfusion 26,28,[47][48][49][50][51][52][53][54] In a survey of 1600 patients from nine published papers, including a minimum of 50 patients each, it is concluded that the overall median time to ANC and platelet recovery is 11 days (2-93) and 11 days (0-1000ϩ), respectively. From 15 studies with information of reinfused low numbers (Table 1a and b), it is concluded that no definite lower level exists to document groups of patients at high risk for prolonged recovery, based on CD34 numbers below 1 million/kg, 55 48 From such data, it is obvious that we will never obtain an exact number of CD34 ϩ cells delineating an insufficient or safe graft.…”

High-dose chemotherapy and autologous peripheral blood stem cell transplantation in lymphoma without blood product support

“…A femoral Hickman line had been inserted for this purpose without complication. As our target number of CD34 + cells for autologous PBSC transplant is Ͼ5 × 10 6 /kg, 3 and because we wanted a higher CD34 + cell number in this patient to ensure rapid haemopoietic recovery, we repeated the PBSC mobilisation using IVE and G-CSF as previously described. 3 This resulted in the collection of 2.45 × 10 6 /kg CD34 + cells in a further three aphereses.…”