Effect of the Adminstration of Rituximab between Mobilization Chemotherapy and Leukapheresis on Stem Cell Collection Parameters: A Study of Fifty NHL Patients Mobilized Using Intermediate Dose Cyclophosphamide and Sequential GM-CSF and G-CSF.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2874-2874
Author(s):  
Asad Bashey ◽  
Lin Liu ◽  
Anita Ihasz ◽  
Ewa Carrier ◽  
Januario Castro ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Time Course ◽  
Cumulative Probability ◽  
Gm Csf ◽  
Cd34 Cells ◽  
Group 2 ◽  
Stem Cell Collection ◽  
Intermediate Dose ◽  
Group 1

Abstract We have previously reported that intermediate dose cyclophosphamide followed by sequential GM-CSF and G-CSF (iCy/GM/G) provides efficient mobilization for patients undergoing autografting. Furthermore, the predictable time course of mobilization with this regimen obviates the need for weekend leukaphereses (Blood 2003: 957a). Recently, the addition of rituximab to mobilization regimens for B-cell NHL has been shown to be effective at depleting contaminating B-cells from the leukapheresis product. However, the effect of rituximab administered for in-vivo purging, on mobilization and stem cell collection parameters is unclear. We compared leukapheresis (LP) yield parameters, and the time course of stem cell mobilization in 23 consecutive B-cell NHL patients mobilized with iCy/GM/G plus rituximab (group 1) with 27 consecutive B-cell NHL patients mobilized with the same regimen without rituximab (group 2). The iCy/GM/G regimen consisted of cyclophosphamide 1.5g/m2 (d1), GM-CSF 500 mcg/d (d 3–7), G-CSF (d 8 until completion of LP) 600mcg/d for weight ≤80kg, 960 mcg for weight > 80 kg. Rituxan was administered at 375mg/m2 as a single dose on d8. LP was begun on d 11 irrespective of WBC. D1 was usually a Friday in order to avoid weekend LP. Patients underwent up to 20 liter LP for ≤ 5 days (median =3, range 1–5 for both groups) with a target collection of > 5 x 10e6 CD34+ cells/kg. The groups were well matched for median age, gender, number of prior chemotherapy regimens (median=2 for both groups), prior pelvic XRT and histological subtype of B-NHL (p=NS in all cases). The estimated (Kaplan-Meier) cumulative probability of achieving a target collection of 2 x 10e6 CD34+ cells/kg on d 1–5 was 0.43, 0.70, 0.78, 0.84, 0.84 respectively for group 1 and 0.22, 0.69, 0.77, 0.84, 0.84 respectively for group 2. The corresponding probabilites of achieving 5 x 10e6 CD34+ cells/kg on d 1–5 were 0.22, 0.39, 0.57, 0.57, 0.57 (group 1) and 0.11, 0.30, 0.46, 0.59, 0.59 (group 2) (p=NS Log-rank test). Percentage of CD34+ cells in the LP product (LP CD34%) was measured daily. Maximums LP CD34% was seen on LP d1 for both groups with a fall on subsequent days (p=NS between groups 1 and 2). Toxicities experienced were generally mild consisting mostly of bone pain and fevers and were similar in both gropups. No patient required admission for febrile neutropenia. The number of CD34+ cells infused were similar for both groups (median 5.9 vs.5.7 x10e6 CD 34+ cells/kg). Median time to reach ANC > 500/mm3 and platelets > 20,000/mm3 were identical between groups 1 and 2 (d11 and d 10 respectively). These data show that the addition of rituximab administered on d 8 to the iCy/GM/G regimen in patients with B-NHL does not impair the yield of CD34+ cells, or the tolerability of the regimen. Furthermore, the time course of the mobilization and therefore the predictbility of the collection is not compromised. Maximum cumulative yield of CD34+ cells is achieved within 4 days of LP with no patient benefitting from a fifth day of collection. The additional cost and inconvenience of weekend leukapheresis can be avoided in all cases using this regimen.

scholarly journals Non-Effectiveness of Using RICE Post RDHAP or RDHAP Post RICE after Failure of First Line Salvage Therapy in DLBCL Patients Who Are Eligible for ASCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4226-4226 ◽  
Author(s):  
Tony Ibrahim ◽  
Tarek Assi ◽  
Julien Lazarovici ◽  
Maxime Annereau ◽  
David Ghez ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Salvage Therapy ◽  
Research Funding ◽  
Primary Therapy ◽  
Second Line ◽  
First Line ◽  
Salvage Regimen ◽  
Group 2 ◽  
Group 1

Abstract Background: The treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) remains challenging. The use of salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in young and fit patients is considered the standard of care. RDHAP (rituximab, dexamethasone, high dose cytosine arabinoside and cisplatin) and RICE (rituximab, ifosfamide, carboplatin, and etoposide) are the two most commonly used salvage-regimens with comparable efficacy (CORAL study). However, nearly 40% of the patients do no respond to these regimens and subsequently they do not proceed to ASCT. There are no guidelines concerning the choice of a second-line salvage regimen. There are sparse data in the literature concerning the best choice if the first salvage regimen fails. The aim of our study was to investigate the potential role of a second salvage regimen, before intensification, by RICE or RDHAP in patients with DLBCL refractory to the first line salvage therapy by RDHAP or RICE, respectively. Methods: We retrospectively included all patients aged 18 years and above who had a relapsed or refractory DLBCL and who were eligible for an autologous stem cell transplant (ASCT) between the years 2008 and 2017. They should have had progressive or stable disease (PD/SD) following first-line salvage based on RICE (group 1) or RDHAP (group 2) and should have received a second-line salvage based on RDHAP or RICE, respectively. Patients who received carboplatin or oxaliplatin instead of cisplatin in the RDHAP protocol were also included. All cases were discussed at a tumor board and the revised International Working Group response criteria for Malignant lymphoma were used to assess the response to chemotherapy. Information were collected using electronic medical record. Ethics committee approval was not necessary. Results: 100 patients' medical files were reviewed, out of which 69 were excluded for the following reasons: 5 patients lacked necessary information; 13 patients were treated for a non-DLBCL; 30 patients could not receive second line salvage therapy because of deterioration of their performance status; 21 patients because they received a bridging therapy (other than RICE or RDHAP) before second line salvage therapy. The study included 31 patients with 19 (61.3%) males and 12 (38.7%) females. The median age was equal to 59 years (standard deviation 14). DLBCL was at the initial diagnosis in all but 6 patients in whom DLBCL developed after an indolent lymphoma (follicular lymphoma in 4 and marginal zone lymphoma in 2). 70% had germinal centre B-cell subtype, while 30% had activated B-cell subtype. 70% were refractory to the primary therapy (CR not attained on primary therapy or relapsed within 6 months) and 30% recurred after a CR lasting more than 6 months. All patients included in group 1 (n=5) have received cisplatin during the treatment with the RDHAP regimen. Among the 26 patients included in the second group, 19 (73.1%) have received cisplatin, 4 (15.4%) oxaliplatin, and 3 (11.5%) carboplatin in first line salvage. No patient in group 1 responded to RICE and eventually no patient proceeded to ASCT. In the second group, 2 patients (7.7%) deceased after the first cycle of RDHAP because of drug related toxicities (1 due to ifosfamide-induced encephalopathy and 1 due to septic choc following febrile neutropenia). Ten patients (38.5%) responded to RDHAP, in whom an ASCT was planned. However, 2 patients could not proceed to ASCT because of peripheral stem cell collection failure. After a median follow up of 8.7 months, the median progression free survival (PFS) of the 8 patients who proceeded to ASCT was 6.3 months (CI 95% 2.6-10.1). Only 1 patient had a tumor response lasting more than 30 months. No factor was found to be associated with PFS on cox regression analysis (which included age, sex, type of DLBCL, and refractory or recurrent status). Conclusion: There is little information regarding the effectiveness of a second-line salvage therapy in patients not responding to first line intensification. All except one patient either could not proceed to ASCT or had a limited response (less than 3 months) post ASCT. In addition, the toxicity was not negligible considering that 2 patients died because of drug related events. This study suggests that patients with DLBCL who failed to respond to first line salvage by RDHAP or RICE should be considered for investigational therapies rather than second line rescue. Disclosures Ribrag: pharmamar: Other: travel; MSD: Honoraria; BMS: Consultancy, Honoraria, Other: travel; Roche: Honoraria, Other: travel; Amgen: Research Funding; argenX: Research Funding; Servier: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; Incyte Corporation: Consultancy; Gilead: Consultancy, Honoraria; Infinity: Consultancy, Honoraria; epizyme: Consultancy, Honoraria.

scholarly journals Remobilization with G-CSF Is Less Effective Than the Initial Mobilization in Healthy Donors Undergoing Peripheral Blood Stem Cell Collection for Allogeneic Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 850-850
Author(s):  
Mark A Fiala ◽  
Soo Park ◽  
Camille N. Abboud ◽  
Amanda F. Cashen ◽  
Meagan Jacoby ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Graft Failure ◽  
Median Number ◽  
Cxcr4 Antagonist ◽  
Gm Csf ◽  
Cd34 Cells ◽  
The Mean ◽  
Group 2 ◽  
One Way Anova ◽  
Group 1

Abstract Background: The need to repeat peripheral blood stem cell (PBSC) mobilization and collection arises infrequently in healthy donors, but may be required due to insufficient initial collection, graft failure, or relapse of the recipient’s disease. Currently no published data exists on the efficacy of remobilization of healthy PBSC donors. Studies of remobilization in patients undergoing autologous transplantation (ASCT) have largely focused on the use of alternative mobilization agents such as chemotherapy or plerixafor. Boeve et al (Bone Marrow Transplant, 2004) reported that remobilization with G-CSF in patients undergoing ASCT who failed initial mobilization with G-CSF, resulted in higher numbers of CD34+ cells collected than the initial collection, though this required a doubling of the dose of G-CSF. Patients/Methods: We performed retrospective chart review of 977 consecutive adult (>18 yrs) donors who underwent apheresis for PBSC donation at Washington University School of Medicine from 1995 through 2013. We identified 66 donors who had undergone more than one mobilization. Two cohorts of donors were identified for analysis: Group 1 included donors mobilized initially and again subsequently with G-CSF (10 ug/kg/day), or GM-CSF (5 ug/kg/day) + G-CSF (10 ug/kg/day). Group 2 consisted of donors mobilized with a CXCR4 antagonist, plerixafor (240-320 ug/kg) or POL6326 (1000-2500 ug/kg), and subsequently were remobilized with G-CSF (10 ug/kg/day). Statistical Analysis: Spearman correlations were performed to analyze the relationship between peak peripheral blood (PB) CD34+/uL level; the number of CD34+ cells collected per kg (recipient weight); and the number of CD34+ cells per L of apheresis collected during initial mobilization (MOB1) and remobilization (MOB2); and the interval (days) between MOB1 and MOB2. One-way ANOVA with repeated measures analyses were performed to determine the relationship of PB CD34+/uL, CD34+/kg and CD34+/L during MOB1 and MOB2. Results: Group 1 included 30 donors. The median age was 49 years (range 18-75) and 15 were male. The median number of days between MOB1 and MOB2 was 140 (range 26-2238). All 30 donors were remobilized due to graft failure or relapse of the recipient’s disease. PB CD34+/uL, CD34+/kg and CD34+/L all correlated between MOB1 and MOB2. The mean PB CD34/uL at MOB1 was 69 compared to 37 at MOB2 (p= 0.029); the mean CD34/kg collected at MOB1 was 5.6x106 compared to 3.3x106 at MOB2 (p= 0.002); and the mean CD34/L collected at MOB1 was 24.0x106 compared to 17.6x106at MOB2 (p= 0.023). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 1. Group 2 included 32 donors. The median age was 51 years (range 21-67) and 18 were male. The median number of days between MOB1 and MOB2 was 20 (range 4-1123). 18 donors were remobilized due to mobilization failure, while 14 were remobilized due to graft failure or relapse of the recipient’s disease. The mean PB CD34/uL at MOB1 was 15 compared to 68 at MOB2 (p< 0.001); the mean CD34/kg collected at MOB1 was 2.5x106 compared to 7.1x106 at MOB2 (p< 0.001); and the mean CD34/L collected at MOB1 was 10.6x106 compared to 30.1x106at MOB2 (p< 0.001). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 2. Conclusion: Remobilization with G-CSF or GM-CSF and G-CSF after initial successful mobilization with the same regimen results in poorer mobilization while remobilization with G-CSF after initial mobilization with a CXCR4 antagonist results in dramatically improved mobilization. The reason for this remains unclear, but in this study the interval between collections was not associated with successful remobilization. Abstract 850. Table 1 Group 1 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 69 (13-417) 37 (1-115) F(1.0, 29.0) = 5.26, p= 0.029 r= 0.615, p< 0.001 CD34/kg (x106) 5.6 (0.8-13.8) 3.3 (0.3-10.6) F(1.0, 29.0) = 11.77, p= 0.002 r= 0.483, p= 0.007 CD34/L (x106) 24.0 (4.5-72.0) 17.6 (2.8-41.3) F(1.0, 29.0) = 5.74, p= 0.023 r= 0.566, p< 0.001 Abstract 850. Table 2 Group 2 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 15 (2-54) 68 (14-358) F(1.0, 31.0) = 23.16, p< 0.001 r= 0.433, p= 0.013 CD34/kg (x106) 2.5 (0.2-19.7) 7.1 (1.7-42.4) F(1.0, 31.0) = 33.84, p< 0.001 r= 0.769, p< 0.001 CD34/L (x106) 10.6 (1.4-67.1) 30.1 (6.0-165.0) F(1.0, 31.0) = 34.70, p< 0.001 r= 0.774, p< 0.001 Disclosures No relevant conflicts of interest to declare.

Imaging the Differential Engraftment of GFP-Expressing Spleen and Bone Marrow Cells in Various Organs after Reduced-Intensity Stem Cell Transplantation in Mice Model.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3228-3228
Author(s):  
Yuji Heike ◽  
Zhijian Yang ◽  
Huaiyu Ma ◽  
Robert Hoffmann ◽  
Yuriko Morita ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pelvic Bone ◽  
Donor Cells ◽  
Cd34 Cells ◽  
Group 2 ◽  
Reduced Intensity ◽  
Group 1

Abstract [Background] Reduced-intensity allogeneic stem cell transplantation is of critical importance in the treatment of hematological malignancies. The object of this experiment is to establish fludrabine-based reduced-intensity allogeneic stem cell transplantation model using donor cells labeled with GFP and image the engraftment process of donor cells in various organs. [Materials and Methods] GFP transgenic C57/BL6 mice (GFP-Tgm) were used as donors and C57/BL6 × DBA F1 mice (BDF1) were used as recipients. Recipient mice were pretreated with fludarabine (Flu) 150 mg/kg/day × 6 days i.p. and cyclophosphamide (CPA) 150 mg/kg/day × 2 days i.p. On day 0, 107 GFP splenocytes (Group 1) and GFP bone marrow cells (Group 2) were injected in the tail vein. Whole body and intravital imaging were used to visualize the migration of GFP-Tgm cells into various organs including the brain, femur, intestine, liver, lung, ovary, pelvic bone, ribs, skin, skull, spine, spleen and uterus on days-7 and -14. The macro images were obtained with the Olympus OV100 Small Animal Imaging System. GFP-Tgm cell migration, particularly CD34+ cells in the various organs was also analyzed by flow cytometry (FACS) using APC-labeled anti-CD34 monoclonal antibodies. [Results and Discussion] On day-7, the migration of donor GFP-Tgm cells in peripheral lymph nodes, intestine, lung, ovary, skin and uterus were detected in both groups. Migration of GFP-Tgm cells in the femur, pelvic bone, ribs and skull were clearly detected in Group 2, but not in Group 1. On day-14 GFP donor cells were imaged in the lung, ovary, skin and uterus both groups. However, GFP-Tgm cells were no longer imaged in the intestine in Group 2 except in Payer patches. In both groups the GFP-Tgm cells were strongly detected in the femur, pelvic bone, skull and spine on day-14. We also analyzed the migration of CD34+ GFP-Tgm cells by FACS analysis. On day-14, the percentage of GFP-Tgm cells in the bone marrow and spleen was, respectively, 14% and 53% in Group 1, and 10% and 13% in Group 2. The percentage of CD34+ GFP-Tgm cells among total CD34+ cells in the bone marrow was 10% in Group 1 and 14% in Group 2, and in the spleen was 24% and 19%, respectively. Those results suggested that in this model, donor bone marrow and spleen cells, but not purified CD34+ cells, have different engraftment kinetics in various organs including the intestine, which is a target organ for graft-versus host disease. These results clearly suggest that caution should be paid to evaluate engraftment kinetics of infused cells, at least in mice model.

CFU-GEMM Infused Influences Immunologic Recovery in Children Older Than 7 years After Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4483-4483
Author(s):  
Katarzyna Drabko ◽  
Marta Choma ◽  
Agnieszka Zaucha-Prazmo ◽  
Beata Wojcik ◽  
Dorota Winnicka ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Helper Cells ◽  
Suppressor Cells ◽  
T Helper ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Group 2 ◽  
Graft Quality ◽  
T Suppressor Cells ◽  
Group 1

Abstract Abstract 4483 Introduction Reconstitution of immunity is considered as one of the most important factors predicting outcome after hematopoietic stem cell transplantation (HSCT). Age of the recipient as well as graft quality reflect on this process however this influence is not completely understood yet. In this study we aimed to evaluate the influence of graft quality on recovery of lymphocyte subpopulation. Patients and Methods The total number of 63 patients who underwent allogeneic transplantation in one center between May 2002 and November 2008, were included into the study. Median age of the patient was 8,6 (range 0.2-18) yrs. Patients were divided into 2 age groups: group 1 (n=26) children age 0,2-7 and group 2 (n=37) children >7 yrs. In all cases quality of graft were assessed by counting WBC, CD34 cells and CFU-GEMM. 45 patients (21 in group 1 and 24 in group 2) were available for evaluation of immune reconstitution: in those patients the absolute number of lymphocytes CD3/CD19 (B) cells, CD3/CD4 (T helper) cell, CD3/CD8 (T suppressor) cells and CD3/CD16+56 (NK) cells were measured 3 and 6 months after transplantation. Results Younger children (group 1) received higher median number of transplanted nucleated cells (4.9×108 vs 2.5×108, p=0.008), CD34 cells (5.6×106 vs 2.1×106, p=0.02) and CFU-GEMM (2.25×104 vs 1.17×104, p=0.01) than older ones (group 2). No differences were found in absolute values of B, T-helper, T-suppressor and NK cells at 3 and 6 months after transplantation (Table 1). In older children (group 2), but not in younger ones, the number of GFU-GEMM transplanted negatively correlated with number of T-suppressor cells 3 months post HSCT (p<0,05; r=-0,7) and positively with number of T-helper cells 6 moths after HSCT (p<0,05; r=0,73). Conclusions Number of CFU-GEMM infused influences immunologic recovery in children older than 7 years after HSCT. Graft quality correlates with number of T-suppressor cells and T-helper cells during first 6 months after HSCT and these changes may contribute to post transplant complications. Supported by grant MNiSW of Poland N407 117 35 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Intracoronary Injection of Autologous CD34+ Cells Improves One-Year Left Ventricular Systolic Function in Patients with Diffuse Coronary Artery Disease and Preserved Cardiac Performance—A Randomized, Open-Label, Controlled Phase II Clinical Trial

2020 ◽  
Vol 9 (4) ◽  
pp. 1043 ◽  
Author(s):  
Pei-Hsun Sung ◽  
Yi-Chen Li ◽  
Mel S. Lee ◽  
Hao-Yi Hsiao ◽  
Ming-Chun Ma ◽  
...  
Keyword(s):  
Systolic Function ◽  
Coronary Intervention ◽  
Left Ventricular ◽  
Diffuse Coronary Artery Disease ◽  
Cd34 Cells ◽  
Group 2 ◽  
Artery Disease ◽  
One Year ◽  
Lv Systolic Function ◽  
Group 1

This phase II randomized controlled trial tested whether intracoronary autologous CD34+ cell therapy could further improve left ventricular (LV) systolic function in patients with diffuse coronary artery disease (CAD) with relatively preserved LV ejection fraction (defined as LVEF >40%) unsuitable for coronary intervention. Between December 2013 and November 2017, 60 consecutive patients were randomly allocated into group 1 (CD34+ cells, 3.0 × 107/vessel/n = 30) and group 2 (optimal medical therapy; n = 30). All patients were followed for one year, and preclinical and clinical parameters were compared between two groups. Three-dimensional echocardiography demonstrated no significant difference in LVEF between groups 1 and 2 (54.9% vs. 51.0%, respectively, p = 0.295) at 12 months. However, compared with baseline, 12-month LVEF was significantly increased in group 1 (p < 0.001) but not in group 2 (p = 0.297). From baseline, there were gradual increases in LVEF in group 1 compared to those in group 2 at 1-month, 3-months, 6-months and 12 months (+1.6%, +2.2%, +2.9% and +4.6% in the group 1 vs. −1.6%, −1.5%, −1.4% and −0.9% in the group 2; all p < 0.05). Additionally, one-year angiogenesis (2.8 ± 0.9 vs. 1.3 ± 1.1), angina (0.4 ± 0.8 vs. 1.8 ± 0.9) and HF (0.7 ± 0.8 vs. 1.8 ± 0.6) scores were significantly improved in group 1 compared to those in group 2 (all p < 0.001). In conclusion, autologous CD34+ cell therapy gradually and effectively improved LV systolic function in patients with diffuse CAD and preserved LVEF who were non-candidates for coronary intervention (Trial registration: ISRCTN26002902 on the website of ISRCTN registry).

The use of antiviral drug based on technologically processed antibodies to interferon-γ, CD4 receptor and histamine in the treatment of influenza in adults: results of a multicenter open-label randomized comparative trial with oseltamivir

2021 ◽  
Vol 19 (1) ◽  
pp. 39-57
Author(s):  
K.V. Zhdanov ◽  
◽  
R.F. Khamitov ◽  
V.V. Rafalsky ◽  
M.P. Mikhaylusova ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Open Label ◽  
Virus Elimination ◽  
Antiviral Immune Response ◽  
Cd4 Receptor ◽  
Antiviral Efficacy ◽  
Ifn Γ ◽  
Group 2 ◽  
Group 1

Objective. A multicenter open-label randomized controlled clinical trial was aimed to compare the efficacy of the study drug (SD) containing technologically processed affinity purified antibodies (high dilutions) to IFN-γ, CD4 receptor and histamine (Ergoferon) with oseltamivir, and evaluate the influence of SD on the antiviral immune response in adults with seasonal influenza. Patients and methods. 184 outpatients aged 18–70 with confirmed influenza of mild/moderate severity were included and randomized into 2 groups (in a 1:1 ratio). Patients received SD (Group 1, n = 92) or oseltamivir (Group 2, n = 92), according to the instructions for medical use for 5 days. As the primary endpoint, the percentage of patients with recovery/improvement was assessed (according to the data of the patient's diary on days 2–7 and according to the clinical examination on days 3 and 7). Additionally, the duration and severity of influenza symptoms, the percentage of patients with virus elimination (according to RT-PCR of nasopharyngeal samples), the percentage of patients with complications, the percentage of patients prescribed antipyretic drugs, the change in concentration of T cell (IL-2, IL-18, IFN-γ) and B cell antigen-specific (IL-4, IL-16) immune response regulators in serum, the leukocyte phenotypes on days 1, 3 and 7 were evaluated. Statistical analysis was performed using a “Non-Inferiority” design (or no less efficiency/safety). Intention-to-Treat (ITT) analysis data are presented. Results. According to patients’ self-assessment, 53.3% of patients in Group 1 recovered/improved on the 6th day in the morning and 65.2% – in the evening (vs. 53.3% and 57.6% in Group 2, respectively). There were 73.9% recovered/ improved patients on the 7th day in the morning (vs. 67.4% in Group 2). A generalized analysis showed that the treatment results in both groups were comparable (p < 0.0001). According to objective medical examination, 79.3% of patients in the SD group and 74.0% of patients in the Оseltamivir group recovered/improved on the 7th day (p < 0.0001). The antiviral efficacy of SD was not inferior to oseltamivir, which was confirmed by comparable periods of virus elimination, duration and severity of fever and other influenza symptoms. A moderate activating effect of SD on the immune system was evaluated. A significant, compared to oseltamivir, increase in the concentration of IL-2 and IL-4 on the 3rd day of treatment (p = 0.03 and p = 0.04 vs. the oseltamivir group), and IFN-γ on the 3rd and the 7th days (p = 0.012 and p < 0.0001, respectively, vs. the oseltamivir group). No stimulating effect of SD on the growth and differentiation of immune cells was found. Conclusion. SD is effective and safe in the treatment of patients with influenza. The therapeutic and antiviral efficacy of SD is comparable to that of oseltamivir. The antiviral activity of SD affects the interferon system and the concentration of the cytokines IL-2 and IL-4, regulators of the T and B cell immune response. At the same time, there is no significant stimulation of interferon production with further development of hyporeactivity. Key words: influenza, oseltamivir, therapy, cytokines, Еrgoferon

scholarly journals Kinetics of committed and primitive blood progenitor mobilization after chemotherapy and growth factor treatment and their use in autotransplants

Blood ◽  
1994 ◽  
Vol 83 (12) ◽  
pp. 3808-3814
Author(s):  
HJ Sutherland ◽  
CJ Eaves ◽  
PM Lansdorp ◽  
GL Phillips ◽  
DE Hogge
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Time Course ◽  
Recovery Phase ◽  
High Dose ◽  
Gm Csf ◽  
Cell Counts ◽  
Cd34 Cells

Peripheral blood cells (PBCs) collected by leukapheresis after progenitor mobilization with chemotherapy and growth factors have been used successfully to replace marrow autografts in protocols requiring stem-cell support. Moreover, such transplants are often associated with more rapid recovery of blood cell counts than is routinely achieved with bone marrow. While conditions that mobilize colony-forming cells (CFCs) into the circulation are becoming increasingly well characterized, little information is available as to how these or other mobilizing treatments may influence the release of more primitive cells into the peripheral blood. To quantitate the peripheral blood content of such cells, we used the long-term culture-initiating cell (LTC-IC) assay, which detects a cell type that is able to produce progeny CFCs after a minimum of 5 weeks in cultures containing marrow fibroblasts. In this report, we present the findings on 21 patients who were transplanted over a 7-year period at our institution with PBCs alone. PBCs were collected in steady-state (n = 6) or during the recovery phase after high-dose cyclophosphamide (Cy; n = 15, nine with and six without additional growth factor administration). PBCs collected from another 11 patients given granulocyte colony-stimulating factor (G-CSF) were transplanted together with autologous marrow. Time-course studies of nine patients after Cy +/- granulocyte-macrophage CSF (GM-CSF) showed that CD34+ cells, CFCs, and LTC-ICs fell from normal to undetectable levels after Cy, and increased at the time of white blood cell (WBC) recovery: LTC-ICs to a mean of sixfold and CFCs to a mean of 26-fold higher than normal. The mean number of CD34+ cells, CFCs, and LTC-ICs present in the PBC harvest was twofold to 10-fold higher after mobilization than in steady-state collections; however, more than 2-log interpatient variability was observed. After PBC transplantation, the median time to a WBC count more than 10(9)/L was 12 days; polymorphonuclear leukocyte (PMN) count more than 0.5 x 10(9)/L, 15 days; and platelet count more than 20 x 10(9)/L, 17 days, although patients who received fewer than 1.5 x 10(5) CFCs/kg had a more than 50% chance of delayed count recovery (> 28 days). Patients who received Cy + GM-CSF-stimulated PBCs had more rapid and consistent platelet recoveries as compared with other groups receiving Cy mobilized or steady-state PBCs alone, and a rapid WBC recovery after Cy predicted a rapid WBC recovery after transplantation.

scholarly journals Impact of Induction Treatment on Stem Cell Collection: A COVID Related Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4848-4848
Author(s):  
Brad Rybinski ◽  
Ashraf Z. Badros ◽  
Aaron P. Rapoport ◽  
Mehmet Hakan Kocoglu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Number Of Cycles ◽  
Time Required ◽  
Stem Cell Collection

Abstract Introduction: Standard induction therapy for multiple myeloma consists of 3-6 cycles of bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide and dexamethasone (KRd). Receiving greater than 6 cycles of a lenalidomide containing regimen is thought to negatively impact the ability to collect sufficient CD34+ stem cells for autologous stem cell transplant (Kumar, Dispenzieri et al. 2007, Bhutani, Zonder et al. 2013). Due to the COVID-19 pandemic, at least 20 patients at University of Maryland Greenebaum Comprehensive Cancer Center (UMGCC) had transplant postponed, potentially resulting in prolonged exposure to lenalidomide containing induction regimens. Here, in the context of modern stem cell mobilization methods, we describe a retrospective study that suggests prolonged induction does not inhibit adequate stem cell collection for transplant. Methods: By chart review, we identified 56 patients with multiple myeloma who received induction with VRd or KRd and underwent apheresis or stem cell transplant at UMGCC between 10/1/19 and 10/1/20. Patients were excluded if they received more than 2 cycles of a different induction regimen, had a past medical history of an inborn hematological disorder, or participated in a clinical trial of novel stem cell mobilization therapy. We defined 1 cycle of VRd or KRd as 1 cycle of "lenalidomide containing regimen". In accordance with routine clinical practice, we defined standard induction as having received 3-6 cycles of lenalidomide containing regimen and prolonged induction as having received 7 or more cycles. Results: 29 patients received standard induction (Standard induction cohort) and 27 received prolonged induction (Prolonged induction cohort) with lenalidomide containing regimens. The median number of cycles received by the Standard cohort was 6 (range 4-6), and the median number of cycles received by the Prolonged cohort was 8 (range 7-13). The frequency of KRd use was similar between patients who received standard induction and prolonged induction (27.58% vs. 25.93%, respectively). Standard induction and Prolonged induction cohorts were similar with respect to clinical characteristics (Fig 1), as well as the mobilization regimen used for stem cell collection (p = 0.6829). 55/56 patients collected sufficient stem cells for 1 transplant (≥ 4 x 10 6 CD34 cells/kg), and 40/56 patients collected sufficient cells for 2 transplants (≥ 8 x 10 6 CD34 cells/kg). There was no significant difference in the total CD34+ stem cells collected at completion of apheresis between standard and prolonged induction (10.41 and 10.45 x 10 6 CD34 cells/kg, respectively, p = 0.968, Fig 2). Furthermore, there was no significant correlation between the number of cycles of lenalidomide containing regimen a patient received and total CD34+ cells collected (R 2 = 0.0073, p = 0.5324). Although prolonged induction did not affect final stem yield, prolonged induction could increase the apheresis time required for adequate collection or result in more frequent need for plerixafor rescue. There was no significant difference in the total number of stem cells collected after day 1 of apheresis between patients who received standard or prolonged induction (8.72 vs. 7.96 x 10 6 cells/kg, respectively, p = 0.557). However, patients who received prolonged induction were more likely to require 2 days of apheresis (44% vs. 25%, p = 0.1625) and there was a trend toward significance in which patients who received prolonged induction underwent apheresis longer than patients who received standard induction (468 vs 382 minutes, respectively, p = 0.0928, Fig 3). In addition, longer apheresis time was associated with more cycles of lenalidomide containing regimen, which neared statistical significance (R 2 = 0.0624, p = 0.0658, Fig 4). There was no significant difference between standard and prolonged induction with respect to the frequency of plerixafor rescue. Conclusions: Prolonged induction with lenalidomide containing regimens does not impair adequate stem cell collection for autologous transplant. Prolonged induction may increase the apheresis time required to collect sufficient stem cells for transplant, but ultimately clinicians should be re-assured that extending induction when necessary is not likely to increase the risk of collection failure. Figure 1 Figure 1. Disclosures Badros: Janssen: Research Funding; J&J: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding.

scholarly journals Localised gastrointestinal diffuse large B cell lymphomas; Does surgical approach still exist?

2015 ◽  
Vol 6 (1) ◽  
pp. 10-17
Author(s):  
Abeer Ibrahim ◽  
Ali Zedan ◽  
Alia M. A. Attia
Keyword(s):  
B Cell ◽  
Surgical Approach ◽  
Gastric Lymphoma ◽  
B Cell Lymphoma ◽  
Anatomical Site ◽  
Intestinal Lymphoma ◽  
Significant Difference ◽  
Group 2 ◽  
Large B Cell ◽  
Group 1

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is the commonest pathological type of gastrointestinal lymphoma and its management was changed from surgery to combined chemoimmunotherapy in the last decade; however, this strategy is questionable, especially if rituximab is not available. Methods: Seventy-nine files were reviewed retrospectively. We divided the patients into two groups; group 1 included 37 patients who underwent surgery followed by chemotherapy and group 2 included 42 patients who received chemotherapy. The indication of surgery was mainly due to obstruction/perforation. We compared the outcomes of PFS and OS between the two groups and according to primary anatomical site. Results: We found that the outcomes for the surgery group before chemotherapy was superior to chemotherapy alone in terms of DFS, p = 0.012 and OS p = 0.037. But in the anatomical subgroups analysis, it did not show any significant difference in primary gastric lymphoma (PGL) regarding DFS and OS, p = 0.706, p = 0.858, respectively; On the contrary, we found significant improvement in PFS and OS, p = 0.032, p = 0.025, respectively, in primary intestinal lymphoma (PIL) favouring the use of the surgical approach. Conclusion Surgery is still an important strategy in the case of DLBCL in PIL intestinal lymphoma; however, in the case of PGL, the use of chemotherapy even without rituximab achieves similar results. Our conclusions are limited by the small numbers of the study

Optimization of Plerixafor Utilization Based on Peripheral Blood CD34+ Count for Autologous Peripheral Blood Stem-Cell Collection

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 41-41
Author(s):  
Gaurav K. Gupta ◽  
Sera Perreault ◽  
Stuart Seropian ◽  
Christopher A. Tormey ◽  
Jeanne E. Hendrickson
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Medical Center ◽  
Tertiary Care ◽  
Peripheral Blood Cd34 ◽  
Tertiary Care Medical Center ◽  
Group 2 ◽  
Group 1

Introduction: Peripheral CD34+ cells may be mobilized using filgrastim (G-CSF) alone or in combination with chemotherapy. However, some patients also require plerixafor, an inhibitor of C-X-C chemokine receptor type-4, for adequate mobilization. Given its cost, judicious utilization of plerixafor is warranted. Material and Methods: A retrospective analysis of autologous stem-cell mobilization was performed at a tertiary-care medical center in adult patients with multiple myeloma and lymphoma; here we will focus on the utility of repeat plerixafor dosing. Patients were mobilized at the treating physician's discretion with filgrastim plus plerixafor or chemotherapy plus filgrastim plus plerixafor. Collections were initiated once peripheral CD34+ counts reached 20/µL (or 10/µL if chemotherapy mobilized); plerixafor was administered if these counts were not reached after 4 or 8 days, respectively, of filgrastim treatment. Results: Patients with multiple myeloma (86) or lymphoma (30) were evaluated. One hundred five were mobilized by filgrastim plus plerixafor and 11 by chemotherapy plus filgrastim plus plerixafor. No patient that received plerixafor with a CD34+ count &lt;5/µL after chemotherapy mobilized the next day. The end collection goal was achieved in 86 (81.9%) of the filgrastim plus plerixafor group and 7 (63.6%) of the chemotherapy plus filgrastim plus plerixafor group. Patients given at least one dose of plerixafor were divided into groups based on collection goal, peripheral blood CD34+ cell count after 1 dose and the first day collection yield: Group 1) Goal of 3x10^6/kg and CD34+ count ≥ 30 cell/µL vs &lt; 30 cell/µL; Group 2) Goal of 6x10^6/kg and ≥ 50% of collection goal after 1 day of collection vs CD34+ count &lt; 50 cell/µL or &lt; 50% of collection goal. Forty of 42 (95%) patients in Group 1 with a CD34+ count ≥ 30 cell/µL achieved their end collection goal after one plerixafor dose. Eighteen of 19 (95%) patients in Group 1 with a CD34+ count &lt;30 cell/µL received a second dose of plerixafor and 8 (44.4%) achieved their end collection goal. Twenty-eight of 32 (87.5%) patients in Group 2 with ≥ 50% of collection goal achieved on the first day of collection reached their end collection goal after one plerixafor dose. Nine of 12 (75%) patients in Group 2 with a CD34+ count of &lt; 50 cells/µL or &lt;50% collection goal received an additional dose of plerixafor and 6 (66.7%) achieved their end collection goal. Conclusion: Based on these data, we have developed the following repeat plerixafor dosing algorithm: 1) for a collection goal is 3x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is &lt; 30 cell/µL, and 2) for a collection goal of 6x10^6/kg, administer a second dose of plerixafor if the CD34+ count on the first day of collection is &lt; 50 cell/µL or if the first day of collection yields &lt;50% of the end goal. This algorithm optimizes pharmacy, apheresis and stem cell processing resources. Disclosures No relevant conflicts of interest to declare.

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