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.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

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.

scholarly journals To Predict Success of Postapheresis Yield and Post–Autologous Transplant Engraftment Based on Preapheresis Peripheral Blood CD34+ Cell Counts: An Indian Scenario–Based Study

2021 ◽  
Author(s):  
Pinki Devi ◽  
Ganapathi Bhat ◽  
Harish S. Ahuja
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Introduction The use of hematopoietic stem cells for autologous and allogeneic transplantation has increased in the recent past significantly, due to introduction of newer chemotherapeutic drugs, immunological techniques, and better stem cell technology. Among the bone marrow and peripheral blood stem cells, collection of the latter being more convenient to the patient and associated with faster granulocyte and platelet engraftment has been known as preferred method for mobilization. Peripheral blood stem cells can be extracted from the autologous or allogeneic donor. Mobilization of the stem cells for autologous stem cell transplant is traditionally done using growth factors alone or in combination with chemotherapy, with or without an additional mobilizing agent. A significant number of hematological malignancy patients are poor mobilizers, (i.e., they are unable to achieve the minimal target cell dose during their first round of mobilization).Therefore, a prediction for a successful stem cell mobilization ideally should be made before initiating any apheresis procedure to spare those with a low rate of success from the risks associated with apheresis procedure. Preapheresis CD34 cell count can predict postapheresis yield and hence, can help to reduce the collection sessions. Reduction of apheresis sessions decreases the discomfort, inconvenience, time, and monetary expenses. Objectives This study was aimed to analyze preapheresis and postapheresis CD34+ cell counts. Materials and Methods Patients of any age and gender with diagnosis of hematological malignancies admitted for autologous stem cell transplantation for hematological malignancies (including Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma) and germ cell tumors in our institute from July 2008 to July 2016 were included in the study. The post-GCSF CBC, preapheresis CBC, CD34+ cell counts, and postapheresis CBC, CD34+ cell counts, mononuclear cell counts to predict the outcome of amount of yield. The effect on engraftment will be measured according to the defining criteria of achieving a sustained peripheral blood neutrophil count of >500 × 106/L (Wolff 2002) and a platelet count of more than >20 × 109/L (Teltschik et al. 2016) independent of platelet transfusion for at least 7 days. Collection of stem cells was done using apheresis machine (COBE SPECTRA). Complete peripheral blood counts using automated analyzers. Peripheral blood CD34 + cell counts and postapheresis CD34+ cell count using BD FACS CANTO II flow cytometer. To calculate postapheresis yield, the related CD34 count measured by flow cytometer was multiplied by the apheresis product volume and divided by the recipient’s body weight (kg). Number of CD34+ cells collected = (CD34 cell concentration in final product) × (final product volume). Results A total of 100 patients who underwent a total of 320 apheresis sessions were included in the study. There were 78 males and 22 females. We also found a significant correlation between preapheresis CD34 + cell count and postapheresis CD34 percentage on days 1, 2, and 3 of the apheresis sessions. In our study, to obtain more than 1.31 × 106 cells (median = 1.04, range: 0.15–4.70), an absolute count of pre apheresis CD34 + cells ≥14 cells would be necessary. A target of CD34 + cells ≥ 2 × 106/kg was obtained in majority of patients if a concentration of ≥25 CD34 + cells was present in postapheresis collection. Conclusion Compiling our results with the previous published data, we conclude that there is a strong correlation between preapheresis absolute CD34 + cell counts and postapheresis CD34 + cell count. Our study also suggests that the minimum absolute cell count of >10 cells/μL is required, to achieve a target of >2–5 × 106 cells for postapheresis yield.

scholarly journals Intrabone Injection of T-Cell Depleted Peripheral Blood Stem Cells from HLA-Haploidentical Donors to Reduce the Risk of Graft Rejection in Children

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1146-1146
Author(s):  
Luisa Strocchio ◽  
Marco Zecca ◽  
Patrizia Comoli ◽  
Perotti Cesare ◽  
Claudia Del Fante ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Stem Cell ◽  
T Cell ◽  
Graft Rejection ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Inoculum

Abstract Background. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment option for patients with malignant and non-malignant hematologic disorders lacking an HLA-compatible donor. Strategies for T-cell depletion (TCD) of the graft, such as positive selection of CD34+ cells, offer the potential to prevent acute and chronic graft-versus-host disease (GVHD). The risk of graft rejection associated with the extensive depletion of both T lymphocytes and accessory cells can be overcome by infusing a very high number (megadose) of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) (exceeding 10x106/kg recipient body weight) to overcome the HLA barrier (Aversa F. et al. Blood 1994). Moreover, the infusion of a megadose of CD34+ cells (higher than 20x106/kg and 12.4x106/kg, respectively) has been shown to result in faster immunological recovery and improved leukemia-free survival probability in children (Handgretinger R. et al. Bone Marrow Transplant 2001; Klingebiel T. et al. Blood 2010). Nevertheless, in the case of donors considered “poor mobilizers” (10-30% of cases), the threshold dose of CD34+ cells needed to ensure the inoculum of a megadose of stem cells might not be achieved. In the setting of cord blood (CB) transplantation, one of the strategies aimed at overcoming the problem of low cellularity is represented by the intrabone injection of CB stem cells, with good engraftment rates even in adult patients. We explored the same strategy in the context of T-cell depleted haplo-HSCT and low graft cellularity due to poor donor mobilization, ensuing in inadequate dose of CD34+cells available after positive selection TCD. Patients and methods. From September 2009 to April 2013, 11 pediatric patients affected by malignant or non-malignant hematological disorders (5 acute lymphoblastic leukemias, 1 acute myeloid leukemia, 1 myelodysplastic syndrome, 2 dyskeratosis congenita, 1 Fanconi anemia) received a T-cell depleted CD34+positively selected PBSC allograft from an HLA-haploidentical related donor. Due to the failure to achieve a target cell dose higher than 12x106 purified CD34+ cells/kg, part of the stem cell inoculum was infused as intrabone injection. The procedure was carried out at the patient bedside by multiple intrabone injections in the superior-posterior iliac crests under sedoanalgesia, as previously described (Frassoni F. et al. Lancet Oncol 2008). The median dose of CD34+ cells infused was 9x106/kg (range, 5-12) while the median number of CD3+ lymphocytes was 0.7x104/kg recipient body weight (range, 0.3-11). About one third of the stem cell inoculum, corresponding to a total volume of 20-40 ml, was given intrabone, while the remaining stem cell portion was infused intravenously. Results.No complication occurred during, or immediately after, the intrabone injection. Nine out of the 11 patients achieved a complete donor engraftment, while graft rejection occurred in 2 patients. The median time for neutrophil engraftment was 13.5 days (range, 12-20), while the median time for platelet recovery was 14 days (range, 13-24). One patient developed grade II acute GVHD and only 1 case of limited chronic GVHD was observed. No transplant-related deaths were observed. Conclusions. Our data suggest that, in the haplo-HSCT setting, the intrabone injection of positively selected CD34+ cells, can be safely used in cases of low graft cellularity due to poor donor mobilization, with the aim of minimizing the risk of graft rejection or poor engraftment. Our preliminary data need to be confirmed in larger series of patients and compared with those obtained with conventional intravenous administration of comparable dose of CD34+ cells. Disclosures No relevant conflicts of interest to declare.

Mobilisation and Harvest of Peripheral Blood Stem Cells from 187 Healthy Donors. A Comparison of Two Different Apheresis Machines and Three Apheresis Programs.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4115-4115
Author(s):  
Gunilla Kumlien ◽  
Gunilla Bergstrom ◽  
Amal Ayoub ◽  
Liisa Kanogo ◽  
Hans Hagglund
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Whitney Test ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Harvest ◽  
Platelet Depletion

Abstract Background: Between January 1995 and July 2004, mobilisation and harvest of peripheral blood stem cells for allogeneic transplantation was performed in 136 related and 51 unrelated healthy donors. Four related and one unrelated donor were harvested on two separate occasions after renewed G-CSF mobilisation. For logistic reasons, automated harvest programs were used until recently. Automated apheresis programs for peripheral blood stem cell harvest are less labour intensive but unfortunately also less efficient. One of the potential health hazards for donors is the depletion of platelets, thus it is essential to minimize platelet depletion. Method: Between 1995 and 1999 CS3000 (Baxter) cell separator with an automated stem cell harvest program was used. Since 1995 Cobe Spectra (Gambro) cell separator is used, initially with the automated program AutoPBSC and since March 2004 with the “manual” program MNC. The 187 medical reports were analysed retrospectively. Results: Median age was 40 years (range 14–71), median weight was 75 kg (range 42–130) and the male/female ratio was 1.3 (107/80). In a majority of donors (97%) antecubital veins were used as access to the circulation. In 4% of donors antecubital veins were unsuitable, and a femoral catheter was therefore employed. Donors were mobilised with G-CSF 10 ug/kg and harvested on days five and six. Transplantation dose was median 6,3 x 10(6) CD34+ cells/kg recipient (range 1,2–98,6). Harvest yield was median 5,8 x 10(6) CD34+ cells/kg donor (range 1,4–16,3). Donor platelet count after second apheresis was median 129 x 10(9)/L (range 57–268) (normal range 150–400). There were no significant differences regarding yield of CD34+ cells between male and female donors or between the two automated apheresis programs CS3000 and CobeSpectra AutoPBSC but the shift to CobeSpectra MNC-program led to a significantly increased yield only after six (three male and three female) donors (Mann-Whitney Test p<0,005) and median yield doubled to 10 x 10(6) CD34+ cells/kg donor. There was no significant difference between CS3000 and Cobe Spectra MNC regarding platelet depletion but Cobe Spectra AutoPBSC was significantly less platelet depleting compared both to CS3000 (Mann-Whitney Test p<0,001) and Cobe Spectra MNC (Mann-Witney Test p<0,001). Conclusion: No serious side effects were reported during G-CSF mobilisation or apheresis. Cobe Spectra MNC program is significantly more efficient regarding yield of CD34+ cells than the two automated programs. Cobe Spectra AutoPBSC is significantly less platelet depleting than both CS3000 and Cobe Spectra MNC.

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