scholarly journals High White Blood Cell Concentration in the Peripheral Blood Stem Cell Product Can Induce Seizures during Infusion of Autologous Peripheral Blood Stem Cells

2012 ◽  
Vol 18 (7) ◽  
pp. 1055-1060 ◽  
Author(s):  
Carlos Bachier ◽  
Josh Potter ◽  
Grant Potter ◽  
Rominna Sugay ◽  
Paul Shaughnessy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Blood Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Cell Concentration ◽  
Peripheral Blood Stem Cells ◽  
Stem Cell Product ◽  
Blood Stem Cells

Seizures During Infusion of Autologous Peripheral Blood Stem Cells Are Related to High White Blood Cell Concentration in the Peripheral Blood Stem Cell Product and Can Be Prevented by Dilution of Product with Autologous Plasma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4386-4386
Author(s):  
Carlos Bachier ◽  
Grant Potter ◽  
Joshua Potter ◽  
Charles F. LeMaistre ◽  
Paul Shaughnessy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Blood Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Cell Transplant ◽  
Autologous Plasma ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 4386 Seizures are rare during infusion of autologous peripheral blood stem cells (PBSC). We retrospectively analyzed 159 adult patients (pts.) collected consecutively between January 2006 and July 2009. Pts. were collected on either COBE Spectra (COBE) (n=85) or Fresenius AS 104 (Fresenius) (n=74) cell separators and mobilized with granulocyte colony stimulating factor (G-CSF) alone (n=47), G-CSF and Plerixafor (n=26), or G-CSF and chemotherapy (n=66). Pts. characteristics did not differ between the COBE and Fresenius cohorts, but there were differences in PBSC product (Table). Pts. collected with COBE had higher white blood cell (WBC) and total nucleated count (TNC) but lower mononuclear cell (MNC) percentage and cell viability than pts. collected with the Fresenius. Absolute CD34+ cells in the PBSC product, CD34+ cells / kg and total CD34+ cells / kg infused at transplant were not significantly different. CD34+ yields (calculated as the ratio of CD34+ cells /μl of the PBSC product to the patient's peripheral blood CD34+ cells / μl taken on the day of collection) were significantly higher on the COBE than Fresenius. No serious adverse events occurred during PBSC infusion except 3 of 159 pts. developed seizures during infusion of PBSC; all collected on the COBE and all three had product WBC > 590 × 103/μl (compared to a median of 163.3 × 103/ μl for all other products)(Figure). Evaluation of pts. did not identify abnormalities in imaging studies, cerebrospinal fluid analysis, electrolytes, or past history which might explain etiology of seizures. No significant difference in WBC or platelet engraftment was observed in pts. collected with COBE or Fresenius. We then prospectively correlated WBC counts midway and at the end of PBSC collections. Fourteen pts. had 15 apheresis using the Fresenius. Mid- and post-WBC concentrations were 64 +/− 23 × 103/μl and 69 +/− 20 × 103/μl, respectively. Fifty-one pts. had 66 apheresis using COBE, with WBC counts obtained midway and at the end of collection of 287 +/− 150 × 103/μl and 273 +/− 144 × 103/μl, respectively. Mid-WBC accurately correlated with WBC at the end of the collection in both the COBE and Fresenius cohorts (r2 = 0.940 and r2 = 0.904, respectively). Using this information, we prospectively evaluated 65 pts. who underwent 80 PBSC collections in anticipation of an autologous (n=44) or allogeneic (n=7) stem cell transplant between June 2009 and January 2010. Collections for these pts. were performed using the COBE (n=66) or the Fresenius (n=15). Mid-WBC were obtained and products with mid-collection WBC concentration > 450 × 103/uL (n=29) had additional autologous plasma collected at the time of collection for final product dilution to < 450 × 103/uL prior to cryopreservation. Pts weight, volume of PBSC product and CD34+ cells/kg infused did not differ between the pts who received diluted PBSC product and those who did not. There were also no differences in either ANC (12 ± 1.3 days vs. 11.5 ± 1.3 days, dilution vs. non-dilution, p = 0.760) or in platelet engraftment (18 ± 3.7 days vs. 16 ± 2.7 days, dilution vs. non-dilution, p = 0.561). No serious adverse infusion effects were observed in either group. In conclusion, high number of WBC in COBE collections is a possible cause of PBSC infusion related seizures. No seizures were observed after dilution of PBSC with high WBC concentration.TIENT AND PRODUCT CHARACTERISTICSCOBE (±SD)Fresenius (±SD)Number of Products165180Number of Patients8574Age at collection56 ± 1456 ± 15Weight at Collection (kg)82.7 ± 17.979.5 ± 15.9Collections / Patient2 ± 12 ± 1Blood Volume Processed at end of Collection (L)18.0 ± 2.418.1 ± 2.7(*)Product Volume (ml)241 ± 56.8402 ± 72.0Peripheral WBC (103/ μl)36.6 ± 18.933.3 ± 24.5(*)Product WBC(103/ μl)163.3 ± 136.055.8 ± 29.3(*)TNC (1010)3.51 ± 1.861.95 ± 1.19(*)MNC (1010)2.36 ± 1.191.60 ± 0.09(*)MNC (%)75.0 ± 23.385.0 ± 10.8Volume prior to freezing(ml)100 ± 54100 ± 32(*)Post Freeze Viability (%)70 ± 1475 ± 10Peripheral CD34+/ μl24.0 ± 43.825.3 ± 79.1(*)Product CD34+/μl726.7 ± 1325.9264.63 ± 781.0(*)Product / Peripheral CD34+24.87 ± 10.9010.91 ± 6.64Absolute Product CD34+ cells (108)1.77 ± 3.521.14 ± 3.35Product CD34+/kg (106)2.02 ± 4.671.39 ± 4.15Total CD34+ cells infused (106 / kg)3.85 ± 3.203.85 ± 2.24(*) = p values < 0.05 Disclosures: No relevant conflicts of interest to declare.

scholarly journals α4 integrin levels on mobilized peripheral blood stem cells predict rapidity of engraftment in patients receiving autologous stem cell transplantation

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2362-2365 ◽  
Author(s):  
Bernd Hartz ◽  
Thorsten Volkmann ◽  
Sebastian Irle ◽  
Cordula Loechelt ◽  
Andreas Neubauer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Peripheral Blood Stem Cells ◽  
Expression Levels ◽  
Blood Stem Cells ◽  
Mobilized Peripheral Blood

Abstract Rapidness of leukocyte engraftment in patients receiving peripheral blood stem cell transplantation is clinically important because the risk of fatal opportunistic infections increases with time to engraftment. Adhesion receptor molecules on hematopoietic stem cells (HSCs) have been shown to modulate homing and engraftment of HSCs. Therefore, we correlated expression levels of α4 (CD49d) and α6 (CD49f) integrins in the CD34+ HSC compartment with time to engraftment. Leukapheresis products from 103 patients were retrospectively analyzed for CD34, CD38, CD3, CD49f, and CD49d surface molecules by multiparameter flow cytometry. High expression levels of α4 integrin, but not α6 integrin on CD34+ cells, were associated with regular engraftment of leukocytes (days 8-19), whereas low surface expression correlated with delayed recovery (> 19 days; P < .0005). We show that α4 integrin expression levels on HSCs in leukapheresis products predict the engraftment capacity of mobilized peripheral blood stem cells in peripheral blood stem cell transplantation patients.

Peripheral Blood Stem-Cell Mobilisation and Autologous Stem Cell Transplantation In HIV-Related Malignancies.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4592-4592
Author(s):  
Marcus Hentrich ◽  
Xaver Schiel ◽  
Fuat Oduncu ◽  
Arthur Gerl ◽  
Clemens Scheidegger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Hiv Rna ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Neutrophil Engraftment

Abstract Abstract 4592 Introduction: Patients (pts) with HIV-infection are generally excluded from clinical trials that evaluate the role of high dose chemotherapy (HDCT) in malignant lymphoma or relapsed germ cell tumor (GCT). However, recent data indicate that HDCT followed by autologous peripheral blood stem cell transplantation (ASCT) may be effective in relapsed HIV-related lymphoma. Methods: This is an observational cohort study including patients with HIV-related lymphoma or HIV-related GCT who have peripheral blood stem cells mobilized by a combination of chemotherapy (CT) and G-CSF. Pts did or did not undergo consecutive ASCT. The primary outcome measure is feasibility. High-dose BEAM was used as a conditioning regimen in pts with HIV-related lymphoma while high-dose carboplatin/etoposide (CE) was chosen for pts with GCT. Results: From 07/05 to 03/10 peripheral blood stem cells (PBSC) were successfully harvested in 10 of 11 HIV-infected pts with diffuse large B-cell lymphoma (DLBCL) [n=4], Burkitt's lymphoma (BL) [n=3], plasmablastic lymphoma (PL) [n=2], Hodgkin lymphoma (HL) [n=1] and testicular GCT [n=1]. The mean number of collected stem cells was 15.7×106/kg CD34+ cells (range, 6.3 – 33). PBSC-mobilisation failed in one pt with relapsed BL. 7 of 11 pts were mobilized following salvage CT for DLBCL [n=4], BL [n=1], HL [n=1] or GCT [n=1] while 4 pts were under primary CT for BL or PL. So far, 5 of 10 pts received HDCT + ASCT. Pt 1 (44 yrs, CDC C3; HIV-RNA< 50 cop/ml at time of SCT) received HDCT as 3rd salvage therapy for DLBCL. A total of 9.2 × 106/kg CD34+ cells were transplanted. Neutrophil engraftment occurred on day +14. The pt achieved a partial remission but died of progressive lymphoma 6 months after ASCT. Pt 2 (60 yrs, CDC B3; HIV-RNA< 50/ml) underwent HDCT + ASCT (13.8 × 106/kg CD34+ cells) for a 1st relapse of HL. Neutrophil engraftment was observed on day +10. The pt is well and disease free 25 months after ASCT. Pt 3 (26 yrs, CDC C3, HIV-RNA< 50/ml), a hepatitis C co-infected haemophiliac, received HDCT + ASCT for refractory DLBCL but died of liver cirrhosis and neutropenic sepsis with multi-organ failure on day +16. Pt 4 (25 yrs, CDC A3, HIV-RNA< 50/ml) received 3 sequential courses of HD-CE followed by ASCT in 3-week intervals for a 3rd relapse of a nonseminomatous GCT. Neutrophil engraftment occurred on day +10, + 12 and +14, respectively. A complete remission (CR) was achieved. However, the pt suffered another relapse involving the central nervous system and died of progressive GCT 15 month after the 3rd transplant. Pt 5 (41 yrs, CDC C3, HIV-RNA 220/ml) underwent HDCT in 2nd complete remission after successful salvage-CT for a first sensitive relapse of DLBCL. A total of 12.9 × 106/kg CD34+ cells were transplanted. The pt is currently alive and neutropenic (day +3). ASCT was not performed in the other 6 pts because of refractory BL [n=1], ongoing first remission following induction CT for BL [n=2] and PL [n=2] and concomitant histoplasmosis necessitating antifungal therapy [n=1]. Conclusions: Successful mobilisation of PBSC is feasible in the majority of pts with HIV-related malignancies. ASCT seems effective in selected pts with chemo-sensitive relapse of malignant lymphoma or GCT. HIV-infected pts should no longer be excluded from HDCT-programs. Disclosures: No relevant conflicts of interest to declare.

Cryopreserved Allogeneic Peripheral Blood Stem Cells Result in Outcome Equivalent to Those of Fresh Infusions Enabling Rational Scheduling of Donations,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4052-4052
Author(s):  
Bhuvan Kishore ◽  
John Davis ◽  
Katayoun Rezvani ◽  
David Marin ◽  
Richard M Szydlo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Median Time ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Registry Data ◽  
Cumulative Probability ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Neutrophil Engraftment

Abstract Abstract 4052 Introduction: Donor stem cells are traditionally infused fresh into recipients in the setting of allogeneic hematopoietic stem cell transplantation (allo-SCT). In this study, we investigated outcomes of 133 sibling allografts using cryopreserved peripheral blood stem cells. We demonstrate that cryopreservation did not have a negative impact on engraftment when compared to data from the IBMTR/EBMT, Seattle and the Canadian registry studies. Non-relapse mortality (NRM) and overall survival (OS) were within acceptable limits. Patients and Methods: We identified all recipients of HLA-matched sibling peripheral stem cells cryopreserved for a minimum of 7 days, who underwent allo-SCT at Hammersmith Hospital from January 1998 until May 2011 (n = 133). The median age at allo-SCT of 78 (59 %) males and 55 (41 %) females was 48 (17 – 65) yrs. Thirty-five (26 %) were transplanted for CML (including accelerated and blast phase), 42 (31 %) for AML, 11 (8 %) for ALL, 14 (11 %) for myeloma and 13 (10%) for other causes. Fifty-six (42 %) had myeloablative and 77 (58 %) had reduced intensity conditioning, with 23 (17 %) having in vivo T-cell depletion with monoclonal anti-CD52 antibody (alemtuzumab). Using validated institutional protocols hematopoietic progenitor cell collections were cryopreserved on the day of collection or on following morning. Cells are were mixed with 10 % v/v dimethyl sulfoxide, frozen to -−00°C at a controlled rate and then transferred to vapor phase liquid nitrogen ≤ −150°C. Thawing and infusion of cells were performed in accordance with a standard protocol defining thawing temperature and the maximum time between thawing and infusion. Median CD-34+ cell dose infused was 9.83 × 106/kg (range 2.4 – 33 × 106/kg). All cryopreserved peripheral blood stem cell collections were infused into the recipients. Engraftment was defined as a peripheral absolute neutrophil count (ANC) of 0.5 × 109/L for 2 successive days and platelet count of > 50 × 109/L for 2 consecutive days, both without support. G-CSF was used only in delayed neutrophil engraftment (> 30 days). Results: Overall 125 (93 %) achieved neutrophil engraftment and median time to engraftment was 19 (range 10 – 42) days. Delayed neutrophil engraftment (>30 days) was present in 4 patients. Results are comparable to the registry data which showed neutrophil engraftment in a median of 14 – 19 days (Table 1). Cumulative probability of achieving ANC > of 0.5 × 109/L for the whole cohort was 94 % (88 – 95). Eight of the 133 patients who died early (< day 30) failed to achieve neutrophil engraftment prior to death. The causes of death were sepsis (n = 6), myocardial ischemia (n = 1) and renal failure (n = 1).Three recovered counts with G-CSF and one patient required stem cell rescue. One hundred and thirteen patients (84 %) recovered platelets to >50 × 109/L within a median time of 21 (range 0 – 240) days, which again is similar to registry data as shown in table 1. The cumulative probability of achieving platelets of 50 × 109/L was 84 % (77 – 88). Twenty patients (16 %) failed to achieve this threshold and causes were multiple. There was no association between CD34+ cell doses infused and delayed or non engraftment of platelets. The incidence of acute and chronic GvHD were 44 % (grade II-IV GvHD 31 %) and 30 % (50 % extensive) respectively. Day 100 NRM was 23 % and OS at 3 years was 50 %. Conclusion: This study provides evidence that cryopreservation and subsequent infusion of peripheral blood stem cell harvests is safe, ensures durable engraftment and is comparable to fresh stem cell infusions (Table 1). We do not routinely use growth factors to aid count recovery and as such the time to engraftment data is consistent. Cryopreservation importantly allows for flexibility in arranging admissions and scheduling regimens for both the donors and the transplant units. Although not observed in our cohort, there is a theoretical risk of not utilizing the cryopreserved cells, thus unnecessarily harvesting donors. One way to circumvent this possibility is by timing the collection close to the transplant. Disclosures: No relevant conflicts of interest to declare.

Ifosphamide, Etoposide and Epirubicin (IVE) Is an Effective Combined Salvage and Peripheral Blood Stem Cell Mobilisation Regimen for Transplant-Eligible Patients with Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2432-2432
Author(s):  
Mark J. Bishton ◽  
Richard Lush ◽  
Nigel H. Russell ◽  
Bronwen E. Shaw ◽  
Andrew P. Haynes
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Response Rates ◽  
Peripheral Blood Stem Cells ◽  
Stem Cell Mobilisation ◽  
Blood Stem Cells

Abstract Introduction: High-dose therapy with stem cell transplantation following salvage chemotherapy has an established role in the management of both Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL). Peripheral blood stem cells are preferred as their use gives more rapid haemopoietic engraftment with associated reductions in both antibiotic and blood product usage and reduced length of in-patient stay. There are several combination chemotherapy regimens currently in use for salvage treatment and PBSC mobilisation in patients with relapsed or refractory lymphoma. The combination of Ifosphamide 3g/m2/day D1-3, Etoposide 200mg/m2/day D1-3 & Epirubicin 50mg/m2 D1 (IVE) has shown a high response rate in patients with both relapsed or refractory NHL and HD, and we report our experience of the IVE regimen in lymphoma patients considered for transplantation. Methods: Eligible patients with relapsed or primary refractory/progressive lymphoma were treated with 1–3 cycles of IVE at 4 weekly intervals, with the intent to proceed to either autologous or allogeneic stem cell transplantation only if they demonstrated a response. Peripheral blood stem cells were collected following G-CSF support if prior bone marrow biopsy was clear of lymphoma, with a target of 5×106/kg CD34 +ve stem cells. Responses to treatment were assessed using standard CT criteria. Results: 143 patients (93 male 50 female) were treated, with a median age of 49.9 years (19.3–66.88). Histological sub-types of lymphoma included follicular (38 patients), diffuse large B cell (31), Hodgkin’s disease (29), transformed follicular (19), mantle cell (14), high grade T cell (10) and small lymphocytic (2). Grade IV neutropenia was seen in 113 patients (79.6%) and in 77/270 patient cycles intra-venous antibiotic treatment was required. Treatment in 10 patients, in 14 cycles, was thought to be complicated by Ifosphamide encephalopathy. A major response (CR/PR) to IVE was seen in 115 patients (80.4%), with response rates of 93.1% for HD and 78% for NHL. 130 patients proceeded to stem cell mobilisation (90.9%), with a median collection of 7.86×106/kg CD34+ stem cells. 129 mobilised in excess of 2×106/kg and 64 (50.7%) mobilised greater than 5×106/kg on their first collection. 128 patients went on to transplantation (104 autologous and 24 allogeneic), with an estimated overall survival (OS) of 53% and event free survival (EFS) of 42% at 5 years. Sub group analysis showed a 5 year OS and EFS in HD of 62% and 52% respectively, while NHL showed a 5 year OS of 50% and 39% respectively. Conclusions: We conclude that IVE is a very effective salvage protocol across a wide range of lymphomas, with response rates comparing very favourably with those seen in other regimens. It is also an excellent peripheral blood stem cell mobilising regimen with predictable kinetics, with a high number of patients progressing to stem cell transplantation. Furthermore it is well tolerated with little cardiac or renal toxicity and minimal encephalopathy.

Effects of cell concentration, time of fresh storage, and cryopreservation on peripheral blood stem cells

2021 ◽  
pp. 103298
Author(s):  
Anelise B. Araújo ◽  
Gabrielle D. Salton ◽  
Melissa H. Angeli ◽  
Juliana M. Furlan ◽  
Tissiana Schmalfuss ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Cell Concentration ◽  
Peripheral Blood Stem Cells ◽  
Concentration Time ◽  
Blood Stem Cells
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