Objectives: Several variables possibly affecting collection of peripheral hematopoietic stem/progenitor cells (PBSC) were evaluated: type of apheresis machine (Amicus version 2.5, Baxter vs Cobe Spectra version 7.0, Terumo BCT), venous access (peripheral vein vs central venous catheter, i.g. CVC), and apheresis regimen (standard vs large volume leukapheresis, i.g. SVL vs LVL) with the objective to increase collection effi cacy at the site. Background: Peripheral blood represents the currently preferred source of hematopoietic stem/progenitor cells (HSCs) for transplantation. Methods: Data regarding 169 collection procedures performed in healthy donors and patients between January 2008 and December 2011 at the Clinics of Haematology and Transfusiology in St Cyril and Method Hospital in Bratislava (Slovakia) were analysed. Results: With Cobe Spectra apheresis machine it was possible to process larger blood volumes per procedure with higher CD34+ cell collection effi ciency (p = 0.0229) and lower RBC contamination of the harvest than with Amicus (p = 0.0116). On the other hand, Amicus helped to limit PLT contamination of the harvest (p < 0.0001), thus minimizing post-procedural decrease in patient´s PLT count. The highest detected advantage of CVC usage was higher fl ow rate of procedure, thus processing larger blood volumes per unit of time. Interesting fi nding was the tendency to lower harvest PLT contamination (p = 0.054). When LVL was performed, signifi cantly higher HSCs yields were collected, even in "poor mobilizers" when the pre-run parameters were low. Conclusion: Management of PBSC collection requires a particular approach in each subject. Institutionally and individually optimized collection may help to improve the transplantation outcome and decrease the fi nancial costs (Tab. 8, Ref. 15). Text in PDF www.elis.sk.
Introduction:high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT) is widely used in the treatment of patients with haematological and non-haematological malignancies. One of the most common causes of mortality after HSCT is infection during the time of prolonged neutropenia. Prolonged neutropenia more than 7 days increase the risk of fungal infections and it is an indication for the use of antifungal prophylaxis. After hematopoietic SCT, G-CSF is commonly used to enhance stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal use of G-CSF after autoHSCT, most studies have been conducted on small numbers of patients and have varied significantly in patient’s demographics, G-CSF dosage regimen and other factors affecting outcomes. Objective:restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autoHSCT in patients with lymphoid malignancies. Methods: between January 2009 and July 2014, 117 patients with lymphoid malignancies who underwent autoHSCT in the Department of Hematology and Transfusion medicine in Bratislava were included. The patients were divided into two groups; in the first group (43 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied late (on day 6.-8.) after autoHSCT. In the second group (74 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied early (on day 3.-4.) after autoHSCT. All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. Patient’s demographics are shown in table 1. Statistical analysis was performed using SPSS statistical software v. 20, with significant Pvalue of 0.05 (two-tailed). Results: sever neutropenia (ANC < 0.5 x 109) and very severe neutropenia (ANC < 0.1 x 109) for more than 7 days were recorded as following: in the first group (delayed G-CSF), 34/42 (81%) and 25/41 (61%) patients respectively. In the second group (early G-CSF), 11/66 (17%) and 2/52 (4%) patients respectively (RR = 4.8, 95% CI = 2.7 to 8.4 and RR = 15, 95% CI = 3.9 to 63). Median time to engraftment of leukocytes above 1, granulocytes above 0.5, and 0.1 x 109/l was 6, 5, and 4 days for patients who received G-CSF early and 7, 7 and 5 days for patients who received G-CSF late (P <0001). The median duration of hospitalization was 19 (15-28) days in the first group and 16 (11-23) days in the second group (P = 0.001, 95% CI =2.02-4.17). There was no significant difference in the rate of febrile neutropenia in both groups (P = 0.53), but the rate of fungal infection and the use of HRCT scan of the lung was higher in the group of patients who received delayed G-CSF than early G-CSF (19% vs. 3%, P=0.005) and (23% vs. 6%, P=0.007) respectively. Conclusion:early application of G-CSF (3rd-4th day) after autologous HSCT accelerates engraftment, shorten the duration of neutropenia, reduce the risk of infectious complications (especially fungal infections), reduce the use of antimicrobial drugs, shorten the hospital stay and overall costs. Table.1 Delayed application of G-CSF Early application of G-CSF Patient N. 43 74 Age, m edian(range) 60 (39-67) years 59 (33-68) years P = 0.694 Sex P = 0.079 Male, N (%) 16 (37%) 40 (54%) Female, N (%) 27 (63%) 34 (46%) CD34+cells x106/kg, m edian(range) 2.5 (1.3-5.6) 2.3 (1.3-4.5) P = 0.138 Diagnosis P = 0.855 Multiple myeloma, N (%) 41 (95%) 72 (97%) NHL, N (%) 2 (5%) 2 (3%) ECOG performance status P = 0.221 0 35 (82%) 53 (72%) 1 7 (16%) 18 (24%) 2 1 (2%) 2 (3%) 3 0 0 4 0 1 (1%) Engraftment , median(range) Leu. > 1 x 109/l 7 (4-12) days 6 (3-9) days P ≤ 0,0001 Neut.> 0.5 x 109/l 7 (5-9) days 5 (3-7) days P ≤ 0,0001 Neut. > 0.1 x 109/l 5 (3-6) days 4 (2-6) days P ≤ 0,0001 Hospitalization, median(range) 19 (15-28) days 16 (11-23) days P= 0,001 Sever neutropenia ≥ 7 days, N (%) 34/42 (81%) 11/66 (17%) RR = 4.8, 95% CI = 2.7 to 8.4 Very sever neutropenia ≥ 7 days, N (%) 25/41 (61%) 2/52(4%) RR = 15, 95% CI = 3.9 to 63 Febrile neutropenia, N (%) 40 (93%) 64 (88%) P = 0.531 Invasive fungal infection, N (%) 8/43 (19%) 2/73 (3%) P = 0,005 HRCT scan use, N (%) 10 (23%) 4 (6%) P = 0.007 Cost 3582 (787-18187) Eur. 1408 (263-2143) Eur. P=0,041 Disclosures No relevant conflicts of interest to declare.
4385 Introduction: Successful autologous peripheral blood stem cell transplantation (aPBSCT) is critical for long-term survival and quality of life in patients with multiple myeloma (MM). Standard mobilization of PBSCs is in 15 to 20% of MM patients inefficient. Better mobilization response is achieved by adding plerixafor to current mobilization regimens. Based on studies it is possible to reduce these numbers to 2%. Methodology: During the period from 06/2009 to 08/2011 our department mobilized five patients with MM using plerixafor, of whom three were remobilized using standard G-CSF + plerixafor scheme (G+P) after a previous unsuccessful mobilization with cyclophosphamide + G-CSF (C+G). Two patients received plerixafor on demand in a failed first-line mobilization attempt (C+G+P). Comprehensive statistical analysis of products mobilized with plerixafor (8 products) versus products obtained using C+G regime alone (40 products) was performed comparing smears, colony forming-units (CFUs) and immunophenotype profile. Time to mobilization, pretreatment, used mobilization regime and adverse effects of plerixafor regimes were also analyzed. The ultimate goal of every mobilization - successful transplantation - was also described and analyzed comparing composition of transplanted products with engraftment of white blood cells (WBC), neutrophil granulocytes and platelets. Results: Analysis of the plerixafor group only: 1. Both mobilization strategies (second-line G+P and first-line C+G+P) allowed to collect enough CD34+ cells for one (3 patients) or two (2 patients) transplants. Failure to mobilize using plerixafor has not been recorded. 3 patients successfully received transplants. 2. Based on an analysis of risk factors for determining poor mobilizer 3 patients could be mobilized preemptively using G+P scheme preventing use of controversial cyclophosphamide. 3. Adverse effects were mild and mainly related to G-CSF. In one patient mobilization was stopped after collecting 2.45 ×106/kg because of anxiety. However, we were unable to definitely connect anxiety symptoms to plerixafor. 4. There was a statistically significant increase of leukocytes in peripheral blood observed after adding plerixafor. In 3 patients it allowed the CD34+ cells to rise above 20/μl. Comparative analysis of plerixafor group vs. group of patients mobilized with C+G: 1. Duration of cytopenia after transplantation was comparable and statistically not different. 2. Significantly higher numbers of CD19+ cells after plerixafor administration suggest a possible value of this drug in the treatment of diseases with this marker. 3. Significant reduction of toxic granulation after plerixafor administration may be a proof of lesser number of infectious complications. 4. Significantly lower numbers of younger cell forms and non-significantly higher numbers of mature cells in products mobilized with plerixafor prove a) no cytotoxic effect of plerixafor b) decreased regenerative potential of bone marrow in poor mobilizers even if chemotherapy is used. 5. Significantly lower numbers of CD34+ cells and CFUs in plerixafor mobilized products suggest a worse overall mobilization response in this group. However CFUs have shown to predict stem cells yield better than CD34+ cells alone. 6. The importance of a non-significant decrease in CD56+ cells in plerixafor mobilized products is unclear as co-expression of CD 38/56 does not show any differences. Conclusions: 1. Preemptive first line mobilization with G+P seems to be an important strategy in predicted poor mobilizers which would otherwise be mobilized with C+G(+P). This prevents possible neutropenia and its complications. On demand first line G+P seems to be a good choice in patients that are mobilized with growth factors only as there is no risk of neutropenia. 2. We highly recommend the investigation of CFUs which usually predict stem cells yield better than CD34+ cells alone and may allow transplantation even if CD34+ cells are low. 3. Because aPBSCT is a therapeutic modality with clear benefit for patients with MM, we highly recommend the use of plerixafor in all MM patients where it is impossible to collect sufficient stem cells. According to our investigation, we believe that plerixafor is only starting its career as a mobilization drug. Its most valuable potential may be in curative regimens of diseases which have affinity to bone marrow. Disclosures: No relevant conflicts of interest to declare.
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