European data on stem cell mobilization with plerixafor in non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma patients. A subgroup analysis of the European Consortium of stem cell mobilization.

The effectiveness of the novel hematopoietic stem cell mobilizing agent plerixafor was evaluated in nationwide compassionate use programs in 13 European countries. A total of 580 poor mobilizers with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL) and multiple myeloma (MM) were enrolled. All patients received plerixafor plus granulocyte CSF with or without chemotherapy. Overall, the collection yield was significantly higher in MM patients (>2.0 × 10(6) CD34+ cells/kg: 81.6%; >5.0 × 10(6) CD34+ cells/kg: 32.0%) than in NHL patients (>2.0 × 10(6) CD34+ cells/kg: 64.8%; >5.0 × 10(6) CD34+ cells/kg: 12.6%; P<0.0001) and also significantly higher in HL patients (>2.0 × 10(6) CD34+ cells/kg: 81.5%; >5.0 × 10(6) CD34+ cells/kg: 22.2%) than in NHL patients (P=0.013). In a subgroup analysis, there were no significant differences in mobilization success comparing patients with diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. Our data emphasize the role of plerixafor in poor mobilizers, but further strategies to improve the apheresis yield especially in patients with NHL are required.

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA.

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16 mg/kg/day, with a subsequent dose increase in one case to 0.24 mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24 mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24 mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.

Plerixafor plus granulocyte CSF can mobilize hematopoietic stem cells from multiple myeloma and lymphoma patients failing previous mobilization attempts: EU compassionate use data.

Plerixafor was recently approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA) to enhance stem cell mobilization for autologous transplant in patients with lymphoma and multiple myeloma. In this study, we present the first European compassionate use experience in mobilization failures, patients who are hardest to remobilize but were not included in registration trials. A total of 56 consecutive patients from 15 centers in Spain and the United Kingdom were included: age 60 (33-69) years; 29 men (32 with myeloma and 24 with lymphoma); 2 lines of previous chemotherapy (1-10); 73 previously failed mobilization attempts with G-CSF (28), chemotherapy plus G-CSF (43) or G-CSF plus SCF(2). Overall, 71% of patients reached ≥ 10 CD34+ cells per µL with plerixafor on day 5 after a 7.6-fold expansion from day 4. A total of 42 patients (75%) collected ≥ 2 × 106, average 3.0 ± 1.7 (0.4-10.6) CD34+ cells per kg with plerixafor plus G-CSF. There were no severe drug-related adverse events. In all, 35 patients (63%) underwent transplant, receiving an average of 3.1±1.2 (1.9-7.7) × 106 CD34+ cells per kg. All patients engrafted neutrophils (day 12; 13.4 ± 0.8; 8-30) and platelets (day 15; 18.5 ± 2.4; 8-33). In our experience, plerixafor offers an effective alternative to collect sufficient CD34+ cells for autologous SCT from patients who fail conventional mobilization methods, with good tolerance and a high success rate.

Family donor care management: principles and recommendations.

The World Marrow Donor Association (WMDA) is an international organization fostering collaboration in clinical transplantation and promoting the interests of unrelated stem cell donors. The WMDA has developed standards for the recruitment, counseling, work-up and subsequent donations to protect the interests of donors. Although the care of family donors has been carefully considered and managed in transplant centers (TCs) internationally over numerous years (and increasingly TCs are facing accreditation programs, which address this issue) there is currently a lack of standardized guidelines for the management of family donors. The underlying principles of family donor care are in many ways identical to those concerning unrelated donors, although key ethical considerations differ. Although the WMDA is primarily involved in the field of unrelated donors, we believe that it is important to collaborate with those involved with family donors, to standardize the care. This document hopes to encourage increased collaboration between those caring for related and unrelated donors, and build on the extensive work, which has already been undertaken in this field to homogenize care. We recognize that there will be financial, regulatory and logistic differences in different countries and that the manner in which these principles are achieved may vary.

Ideal body weight correlates better with engraftment after PBSC autograft than actual body weight, but is under-estimated in myeloma patients possibly due to disease-related height loss.

Stem cell dose is important in determining rate of engraftment following autograft. We show closer correlation with haematopoietic reconstitution when the CD34+ cell dose is calculated using ideal (IBW) rather than actual (ABW) body weight in 218 patients receiving peripheral blood stem cell (PBSC) autograft for haematological malignancy. ABW was 21% greater than IBW thus the median CD34+ dose of 5.0 x 10(6)/kg (ABW) rose to 6.1 x 10(6)/kg when calculated by IBW. Neutrophils reached 0.5 x 10(9)/l in 11 days (range 8-21), while platelets reached 20 x 10(9)/l unsupported in 12 days (range 7-38). For both neutrophil and platelet engraftment, a greater inverse correlation was seen when IBW was used to calculate stem cell dose (r2=0.082 vs r2=0.104 for neutrophils and r2=0.085 vs r2=0.135 for platelets). Those non-myeloma patients who failed to achieve a CD34+ dose of 4 x 10(6) cells/kg by ABW but did so by IBW achieved neutrophil and platelet engraftment not significantly different from those who achieved that stem cell dose by both methods. This was not confirmed in patients treated for myeloma, possibly owing to inaccurate IBW in patients with skeletal height loss. We confirm that calculation of CD34+ cell dose by IBW safely predicts engraftment for patients with haematological malignancies other than myeloma undergoing PBSC autograft.