melphalan and plerixafor

Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's disease who demonstrated with previous mobilization failure. In this named patient program we report the Austrian experience in insufficiently mobilizing patients.. Twenty-seven patients from eight Austrian centers with a median (range) age of 58 (19-70) years (18 female, nine male) were included in the study. Plerixafor was limited to patients with previous stem cell mobilization failure and was given in the evening of Day 4 of G-CSF application.. A median increase of circulating CD34+ cells within 10 to 11 hours from administration of plerixafor by a factor of 4.7 over baseline was noted. Overall, 20 (74%) patients reached more than 10 × 10(6) CD34+ cells/L in the peripheral blood, resulting in 17 (63%) patients collecting at least 2 × 10(6) CD34+ cells/kg body weight (b.w.; median, 2.6 × 10(6) CD34+ cells/kg b.w.; range, 0.08 × 10(6) -8.07 × 10(6) ). Adverse events of plerixafor were mild to moderate and consisted of gastrointestinal side effects and local reactions at the injection site. Thirteen (48%) patients underwent autologous transplantation receiving a median of 2.93 × 10(6) CD34+ cells/kg (range, 1.46 × 10(6) -5.6 × 10(6) ) and showed a trilinear engraftment with a median neutrophil recovery on Day 12 and a platelet recovery on Day 14.. Our study confirms previous investigations showing that plerixafor in combination with G-CSF is an effective and well-tolerated mobilization regimen with the potential of successful stem cell collection in patients with previous mobilization failure.

Topics: Adolescent; Adult; Aged; Antigens, CD34; Austria; Benzylamines; Combined Modality Therapy; Cyclams; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Immunoglobulin G; Leukapheresis; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Receptors, CXCR4; Transplantation, Autologous; Young Adult

The introduction of plerixafor has enabled successful collection of stem cells in the majority of patients with lymphoma or myeloma in whom previous attempts at mobilization have failed. However, a proportion of patients have been shown to be resistant to this mobilization regimen. To identify the factors that impair stem cell mobilization and collection with plerixafor, we reviewed the data for 197 patients who had undergone mobilization with plerixafor and granulocyte-colony stimulating factor in Central Europe. Predictors of mobilization failure were evaluated using logistic regression analysis. Among the 197 patients mobilized, the target of ≥2.0 × 10(6) CD34+ cells/kg was collected from 133 (67.5%). Our analysis revealed that previous treatment with lenalidomide, bortezomib, melphalan, radiotherapy, or autologous stem cell transplantation and regimen of plerixafor use in combination with chemotherapy had no significant effect on the efficiency of collection. In contrast, an age ≥65 years (odds ratio 0.331, 95% CI: 0.112-0.977, P < 0.05), a diagnosis of non-Hodgkin's lymphoma (odds ratio 0.277, 95% CI: 0.124-0.622, P < 0.01), and treatment with ≥ four chemotherapy regimens (odds ratio 0.366, 95% CI: 0.167-0.799, P < 0.05) were associated significantly with failed mobilization. The rate of successful mobilizations was decreased in patients treated with purine analogues (odds ratio 0.323, 95% CI: 0.096-1.094, P = 0.07) but increased in female patients (odds ratio 1.961, CI: 0.943-4.080, P = 0.07). Patients who are characterized by the above negative features could benefit potentially from further improvement in the mobilization strategy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-HIV Agents; Antineoplastic Agents; Benzylamines; Boronic Acids; Bortezomib; Child; Cyclams; Europe; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Heterocyclic Compounds; Humans; Lenalidomide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Myeloablative Agonists; Prognosis; Pyrazines; Thalidomide; Transplantation, Autologous; Transplantation, Homologous

Topics: Aged; Algorithms; Antigens, CD34; Benzylamines; Cyclams; Female; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Retrospective Studies

Nearly half of AL amyloidosis patients have cardiac involvement, an independent predictor of poor prognosis. High-dose melphalan and autologous stem-cell transplantation (HDM/SCT) can induce complete hematologic responses and prolong survival in AL amyloidosis. Granulocyte colony-stimulating factor (G-CSF)-induced mobilization of peripheral blood stem cell (PBSC) in AL amyloidosis patients is associated with volume overload, arrhythmias and capillary leak syndrome. Plerixafor has a different mechanism of action and has non-overlapping toxicities with G-CSF. We describe our experience in five patients with AL amyloidosis and cardiac involvement who received plerixafor with G-CSF for PBSC mobilization. Median age was 56 years; two patients had undergone heart transplantation within the year prior to HDM/SCT. Three patients received plerixafor after an initial trial of mobilization with G-CSF alone. No patient had any significant toxicities during mobilization and PBSC collection. The median total yield of PBSCs collected was 5.9 × 10(6) CD34+ cells/kg; the median number of leukapheresis days was 2. Neutrophil engraftment after HDM/SCT occurred at a median of nine days, platelet engraftment at a median of 13 days. Plerixafor was effective and well tolerated when used upfront or as rescue for PBSC mobilization in AL amyloidosis patients with cardiac involvement.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Benzylamines; Cyclams; Female; Graft Survival; Granulocyte Colony-Stimulating Factor; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Remission Induction; Transplantation, Autologous

Topics: Antineoplastic Combined Chemotherapy Protocols; Benzylamines; Combined Modality Therapy; Cyclams; Dexamethasone; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Heterocyclic Compounds; Humans; Kidney Failure, Chronic; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Peripheral Blood Stem Cell Transplantation; Receptors, CXCR4; Renal Dialysis; Thalidomide; Transplantation Conditioning