scholarly journals Bone Marrow Harvest Volume and CD34+ Cell Count in Pediatric Sibling Donors: A Single Centre Retrospective Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1969-1969
Author(s):  
Awatif Alanazi ◽  
Amir Nadeem ◽  
Khawar Siddiqui ◽  
Mouhab Ayas ◽  
Ali Abdallah Ahmari ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Cell Count ◽  
P Value ◽  
Pediatric Age ◽  
Term Survival ◽  
Cell Dose ◽  
Cd34 Cells ◽  
Harvest Volume ◽  
The Impact

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment modality offering cure or long-term survival for many hematologic malignancies, and non-malignant diseases in children. HLA-matched siblings are considered the best donors because of reduced risks of transplant-related complications and better clinical outcome. According to the National Marrow Donor Program Guidelines, the maximum amount of bone marrow harvest is limited to 20ml/kg donor's body weight. The aim of this retrospective study was to assess the optimal bone marrow harvest volume in pediatric donors needed to obtain the desired CD34+ cell count. METHODS: We reviewed medical charts of 553 pediatric (age at harvest <18 years) sibling donors who were harvested for bone marrow from Jan 2007 to Dec 2017 at our institution for pediatric (age at infusion < 14 years) transplant naïve recipients in order to examine the volume harvested per donor's weight, the percentage of harvests that reached the minimum desired CD34+ cell count of ≥3.0X10^6 per Kg of recipient weight, harvest related hospitalization days and side effects related to the procedure and the impact of granulocyte-colony stimulating factor (GCSF) priming on CD34 count of harvested bone marrow. RESULTS: 288 out of 553 donors were male. 155 (28%) were below 5 years of age at harvest, 189 (34.2%) were between 5-10 and remaining 209 (37.8%) were 10 years and above, with a median of 8.4 years (range: 0.2-17.9). Primary indication for transplant among 131 (23.7%) of our pediatric recipients were Malignant Disorders, Non-Malignant Disorders in 214 (38.7%) and Primary Immunodeficiency and Histiocytic Disorders in 208 (37.6%). GCSF priming was carried out in 219 (39.6%) donors. The minimum desired CD34+ cell count of ≥3.0X10^6 per Kg of recipient weight was reached in 517 (93.5%) harvests. Post infusion Absolute Neutrophil Counts (ANC) recovery within Day+28 was recorded among 472 (85.4%) of the transplant naïve recipients, while in 72 (13%) cases ANC never recovered and in remaining 9 (1.6%) time to recovery was beyond Day+28. ANC recovery within Day+28 was significantly associated with CD34+ cell dose of ≥3.0X10^6 per Kg of recipient weight (n=441, 93.4% vs. 31, 6.6%; P-Value<0.001). Median CD34+ cells (X10^6) collected per Kg of donor weight were significantly higher among donors younger than 5 years of age when compared to those 10 and beyond (P-Value <0.001) with a median harvested volume of 13.7, 12.0 and 8.3 mL/Kg (P-Value<0.001, Table 1). On the same note, median CD34+ cells collected per donor weight were significantly higher among donors primed with GCSF in contrast to those who did not (6.02 X10^6 vs. 3.1 X10^6, P-value <0.001). 54 (9.8%) of our donors required PRBC transfusion; among whom 34 (63%) were below 5 years of age at harvest, 15 (27.8%) 5-10 years and remaining 5 (9.3%) were 10 and above (P-Value<0.001). 2 (0.5%) donors were hospitalized for four days, 12 (3.2%) for three, 201 (54.3%) for two and 155 (42%) for one day only. No significant side effects were noted among our donor population. CONCLUSION: Our study confirmed that CD34 cell count were significantly higher among younger donors. The use of Higher CD34 cell dose is significantly associated with engraftment. Priming with G-CSF had significant impact on CD34+ cell count. These large data confirm the suggestion that the volume of bone marrow harvested can be decreased among younger donors without significantly changing the overall CD34 cell count. Disclosures No relevant conflicts of interest to declare.

scholarly journals Do Changes in Transplant Practice Influence Risk of Therapy-Related Myelodysplasia/ Acute Myeloid Leukemia after Autologous Hematopoietic Cell Transplantation (aHCT) for Non-Hodgkin Lymphoma (NHL)?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 430-430 ◽  
Author(s):  
Can-Lan Sun ◽  
Jennifer Berano-Teh ◽  
Patrick Halliday ◽  
Lindsey Hageman ◽  
Maya Ramamurthy ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Risk Analysis ◽  
Cell Count ◽  
Cumulative Incidence ◽  
P Value ◽  
Competing Risk Analysis ◽  
Cell Dose ◽  
Cd34 Cells ◽  
The Impact

Abstract Background: t-MDS/AML is the leading cause of non-relapse mortality after aHCT for NHL. Older age at aHCT, exposure to total body irradiation (TBI), and low number of CD34+ cells infused are associated with an increased risk of developing t-MDS/AML. However, over the past decade, aHCT has been increasingly used for older patient populations (potential for increase in t-MDS/AML risk). On the other hand, use of TBI has declined and number of CD34+ cells infused has increased (potential for decrease in t-MDS/AML risk). The impact of these changes in aHCT clinical practice on t-MDS/AML risk has not been assessed, and is addressed here. Methods: Information regarding t-MDS/AML diagnosis was procured from medical records and California Cancer Registry to ensure near-complete capture of events. Competing risk analysis was used to describe the cumulative incidence of t-MDS/AML, and to evaluate the role of host and aHCT-related factors in the development of t-MDS/AML. In order to understand the impact of changing clinical practices, patients were classified into those transplanted in the early era (1986-2002) vs. recent era (2003-2009). Results: A total of 1,261 consecutive patients received aHCT for NHL between 1986 and 2009 at City of Hope, and were followed for development of t-MDS/AML until 12/31/2011. Median age at aHCT was 50y (range, 5-78). Compared with patients transplanted in early era, those transplanted in recent era were more likely to be ≥50y at aHCT (recent era: 65% vs early era: 44%, p<0.001); less likely to be conditioned with TBI (recent era: 17% vs. early era: 67%, p<0.001); but more likely to receive a larger CD34+ cell dose (>3x10(6)/Kg: recent era 18% vs. early era: 12%, p<0.0001). After a median follow-up of 4.8y (range, 0.02-24.6),78 patients developed t-MDS/AML, yielding a 15y cumulative incidence of 7.5%. The cumulative incidence of t-MDS/AML was higher among those ≥50y (10.0% vs. 5.3%, p=0.002), and among those exposed to TBI (8.8% vs. 5.2%, p=0.07). Taken together, older patients exposed to TBI had a significantly higher cumulative incidence of t-MDS/AML (10.9%), as compared with younger patients not exposed to TBI (2.3%, p<0.001, Figure). Furthermore, the cumulative incidence of t-MDS/AML was higher among those with a low CD34+ cell dose (<3x10(6)/Kg) (14.2%) vs. those with a high CD34+ cell dose (≥3x10(6)/Kg) infusion (4.3%, p<0.0001). Multivariable competing risk analysis (adjusted for era) demonstrated the independent and significant impact of older age (≥50y: HR=2.4, 95%CI, 1.5-3.9, p=0.0004 [ref grp: <50y]), exposure to TBI (HR=1.8, 95%CI, 1.1-3.1, p=0.02 [ref grp: no TBI]), and low CD34+ cell count (<3x10(6)/Kg, HR=3.3, 95%CI, 1.9-5.8, p<0.0001 [ref grp: ≥3x10(6)/Kg]) in increasing the risk of t-MDS/AML. The impact these findings in light of changing practices with time is detailed in Table and summarized here. Multivariable analysis (taking age at aHCT into account) demonstrated that the risk of t-MDS/AML was reduced by 50% among those transplanted in the recent era (HR=0.5, 95%CI, 0.3-0.9, p=0.03 [ref grp: early era]) (Model 1). However, inclusion of TBI and CD34+ cell count in the model abrogated the reduction in the risk of t-MDS/AML during the recent era (HR=0.97, 95%CI, 0.5-1.9, p=0.9, referent grp: early era) (Model 2). Conclusions: This large study spanning over 25y confirms the independent role of age at aHCT, TBI, and CD34+ cell count in t-MDS/AML risk. More importantly, the study delineates the risk of t-MDS/AML in the context of changes in clinical practice of aHCT for NHL, demonstrating a reduction in the incidence of t-MDS/AML (despite an increase in age limit for aHCT) that is likely due to the declining practice of using TBI and the ability to use a higher number of CD34+ cells for aHCT. Table Model 1 Model 2 Model 3 HR (95% CI), p-value HR (95% CI), p-value HR (95% CI), p-value Era of aHCT 1986-2002 1.0 1.0 1.0 2003-2009 0.54 (0.3-0.9), p=0.03 0.71 (0.4-1.3), p=0.3 0.97 (0.5-1.9) p=0.9 Age at aHCT <50y 1.0 1.0 1.0 ≥50y 2.09 (1.3-3.4), p=0.002 2.25 (1.4-3.6), p=0.0007 2.41 (1.5-3.9) p=0.0004 Conditioning with TBI No TBI 1.0 1.0 Yes TBI 1.80 (1.1-3.0), p=0.02 1.8 (1.1-3.1) p=0.02 CD 34 counts >3 1.0 ≤3 3.32 (1.9-5.8) p<0.001 missing 2.36 (1.2-4.5) p=0.01 Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Interaction of Stem Cells and Their Niche: Behavior and Gene Expression Profiles of CD34+/CD38− Cells upon Co-Cultivation with AFT024.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1281-1281
Author(s):  
Wolfgang Wagner ◽  
Rainer Saffrich ◽  
Ute Wirkner ◽  
Volker Eckstein ◽  
Jonathon Blake ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Differential Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Nuclear Antigen ◽  
Cd34 Cells ◽  
Differential Gene ◽  
The Impact

Abstract Cell-cell contact between stem cells and cellular determinants of the microenvironment plays an essential role in the regulation of self-renewal and differentiation. The stromal cell line derived from murine fetal liver (AFT024) has been shown to support maintenance of primitive human hematopoietic progenitor cells (HPC) in vitro. We have studied the interaction between HPC (defined as CD34+/CD38− umbilical cord blood cells) and AFT024 and the impact of co-cultivation on the behavior and gene expression of HPC. By time lapse microscopy the mobility and behavior of CD34+/CD38− cells were monitored. Approximately 30% of the CD34+/CD38− cells adhered to the cellular niche through an uropod. CD44 and CD34 were co-localized at the site of contact. Gene expression profiles of CD34+/CD38− cells were then compared upon co-cultivation either with or without AFT024. After cultivation for 16h, 20h, 48h or 72h the HPC were separated form the feeder layer cells by a second FAC-Sort. Differential gene expression was analyzed using our Human Genome cDNA Microarray of over 51,145 ESTs. Among the genes with the highest up-regulation in contact with AFT024 were several genes involved in cell adhesion, proliferation and DNA-modification including tubulin genes, ezrin, complement component 1 q subcomponent 1 (C1QR1), proto-oncogene proteins c-fos and v-fos, proliferating cell nuclear antigen (PCNA), HLA-DR, gamma-glutamyl hydrolase (GGH), minichromosome maintenance deficient 6 (MCM6), uracil-DNA glycolase (UNG) and DNA-methyltransferase 1 (DNMT1). In contrast, genes that were down-regulated after contact with AFT024 included collagenase type iv (MMP2), elastin (ELN) and hemoglobin genes. Differential expression of six genes was confirmed by RT-PCR. Other authors have reported on the differential gene expression profiles of CD34+ cells derived from the bone marrow versus those from G-CSF mobilized blood. As CD34+ cells from the bone marrow might represent cells exposed to the natural HPC niche we have then compared our findings with these experiments. In these comparisons we identified several overlapping genes that are involved in regulation of cell cycle and DNA repair including PCNA, DNMT1, MCM6, MCM2, CDC28 protein kinase regulatory subunit 1B (CKS1B), Topoisomerase II (TOP2a), DNA Ligase 1 (LIG1) and DNA mismatch repair protein MLH1. All these genes were up-regulated among CD34+/CD38− cells upon co-culture with AFT024, as well as among CD34+ cells derived from the bone marrow versus those from peripheral blood. Our studies support the hypothesis that intimate contact and adhesive interaction of HPC with their niche profoundly influenced their proliferative potential and their differentiation program.

Expression of Angiopoietins and Their Receptor Tie2 in the Bone Marrow of Patients with Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1894-1894
Author(s):  
Christoph Schliemann ◽  
Ralf Bieker ◽  
Teresa Padro ◽  
Torsten Kessler ◽  
Heike Hintelmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Term Survival ◽  
Bone Marrow Biopsies ◽  
Cox Regression Analysis ◽  
The Impact ◽  
Acute Myeloid

Abstract Angiopoietin-1 (Ang-1) and its natural antagonist Angiopoietin-2 (Ang-2), both ligands for the receptor tyrosine kinase Tie2, are known to play an essential role in normal and pathological angiogenesis. However, the importance of angiopoietin signaling in the pathophysiology of hematologic neoplasias such as acute myeloid leukemia (AML) remains to be elucidated. We investigated the expression of Ang-1, Ang-2 and Tie2 by immunohistochemical analyses in bone marrow biopsies of 64 adult patients with newly diagnosed AML and correlated angiogenic factor expression with clinicopathological variables and long-term survival. Expression of Ang-2 was significantly increased in the bone marrow of AML patients (median [interquartile ranges]: 4.7 [3.3 – 5.7] AU [arbitrary units]) as compared with 16 control patients (1.5 [1.5 – 1.8] AU; P < 0.0001). In contrast, Ang-1 expression levels in AML patients did not differ from those found in controls. Thus, we observed a reversal of the Ang-1 and Ang-2 expression balance in the neoplastic bone marrow (Ang-2:Ang-1 ratio: 1.73) as compared with normal bone marrow (0.51; P < 0.0001). Furthermore, the angiopoietin receptor Tie2 was significantly overexpressed in leukemic blasts (3.8 [2.8 – 4.9] AU vs. 1.8 [1.6 – 2.3] AU; P < 0.0001). Patients expressing high levels of Ang-2 showed significantly longer overall survival (OS) than those with low Ang-2 levels (52.7 vs. 14.7 months; P = 0.039). The impact of Ang-2 expression on OS was especially evident in AML patients simultaneously expressing low levels of Ang-1 (P = 0.0298). Multivariate Cox regression analysis revealed karyotype and Ang-2 expression as independent prognostic factors for OS (hazard ratio [CI]: 3.06 [1.39 – 6.70] and 0.31 [0.14 – 0.69], respectively; P < 0.01). In conclusion, these data provide evidence that the alteration of angiopoietin balance in favor of Ang-2 may play a critical role in the pathophysiology of AML. Furthermore, high pre-therapeutic bone marrow Ang-2 levels indicate a favorable prognosis in polychemotherapy treated AML by a yet unknown mechanism.

Factors Predicting PBPC Collections in Healthy Adolescents and Children with Solid Tumours.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5119-5119
Author(s):  
Susana Roncon ◽  
Isabel L. Barbosa ◽  
Sergio M. Lopes ◽  
Sara Ferreira ◽  
Alcina Avila ◽  
...  
Keyword(s):  
Cell Count ◽  
Ewing Sarcoma ◽  
Flow Cytometric Analysis ◽  
Cell Number ◽  
Solid Tumours ◽  
Healthy Adolescent ◽  
Central Lines ◽  
Minimum Requirement ◽  
Cell Dose ◽  
Cd34 Cells

Abstract G-CSF is used for mobilization of hematopoietic cells in healthy adolescent donors and pediatric patients. In both groups it is important to ascertain factors predicting the success of apheresis as well as the number of procedures to achieve the target CD34+ cell number for hematologic recovery. We retrospectively analyzed factors predicting the yield for a target CD34+ cell dose in10 healthy adolescent donors and 43 children with solid tumours who were enrolled in the transplantation program at our center from January 1996 to July 2007. The healthy adolescents (n=10) had a median age of 15 years (range 13–16) and body weight (bw) of 45 kg (range 20–74) and the children with solid tumours (n=42) (Neuroblastoma n=28, Ewing sarcoma n=7 and other solid tumours n=7) had a median age of 4 years (range 1–15) and bw of 17 kg (range 9 – 63). Mobilization regimen consisted of G-CSF in a dosage of 10 μg/kg per day, applied subcutaneously for 5 or 6 days. A pre-collection peripheral blood (PB) CD34+ count was performed in all children, by flow cytometric analysis. Standard volume apheresis was carried out using a Cobe Spectra blood cell separator, through peripheral veins in donors and central lines in patients. We estimated a minimum of 4 x106 and 2x106 CD34+ cells/kg bw receptor for successful engraftment for allogeneic and autologous transplant, respectively. The healthy adolescent donors had high number of PB CD34+ cells (median 62/μl, range 42 – 75) and the majority (7/10) only required a single apheresis to collect sufficient cells for their family related recipients. The neuroblastoma patients with >10/μl PB CD34+ cells collected in one day the target cell dose (median 4.6x106 CD34+ cells/kg, range 2.6 – 27.0). Those with <10/μl PB CD34+ cells underwent 2 apheresis and the majority reached the cell target. The majority of children with Ewing sarcoma and other solid tumours (9/14) also collected >2.0 x106 CD34+ cells/kg in 2 apheresis. In summary all the children with solid tumours received a single course of G-CSF and presented on the 5th day of mobilization a median PB CD34+ cell count of 9/μl (range 1–216). The majority (75%) collected >2.0 x106 CD34+ cells/kg and the remaining (25%) had <10/μl PB CD34+ cells and did not achieve this minimum requirement. We found a correlation between the PB CD34+cell count and the number of apheresis and CD34+ cells yielded both for the adolescent donors and children with solid tumours. Based on these results, a PB CD34+ cell count >10/μl was a good indicator for performing PBPC collections in paediatric patients from our institution.

Mobilization with Plerixafor (Mozobil ®)Plus G-CSF Results in Superior Day 1 Collection of CD34+ Cells Compared to Placebo Plus G-CSF: Results From Two Randomized Placebo-Controlled Trials in Patients with Multiple Myeloma or Non-Hodgkin's Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3224-3224 ◽  
Author(s):  
Brian J. Bolwell ◽  
Auayporn P. Nademanee ◽  
Patrick Stiff ◽  
Edward Stadtmauer ◽  
Richard T. Maziarz ◽  
...  
Keyword(s):  
Placebo Group ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Yield ◽  
P Value ◽  
Employment Equity ◽  
Advisory Committees ◽  
Cell Dose ◽  
Cd34 Cells ◽  
Equity Ownership

Abstract Abstract 3224 Poster Board III-161 Background While most centers use 2 × 106 CD34+ cells/kg as the minimal cell dose for autologous hematopoietic stem cell (HSC) transplantation (auto-HSCT), infusion of higher CD34+ cell dose is associated with better outcomes in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL). Recent evidence suggests a correlation between CD34+ cell yield on Day 1 of collection and total CD34+ cell yield as well as post-transplant outcomes. This analysis was designed to: 1) compare Day 1 collection between patients with NHL or MM mobilized with plerixafor plus G-CSF or placebo plus G-CSF; and 2) determine whether Day 1 CD34+ cell yields correlated with the total mobilization yield and number of apheresis days. Methods Data were obtained from two prospective, randomized, double-blind, placebo-controlled, phase 3 clinical trials that compared the safety and efficacy of plerixafor (0.24 mg/kg/day SQ) plus G-CSF (10 μg/kg/day) with placebo plus G-CSF for mobilization of HSC for auto-HSCT in patients with NHL (3101 Study) or MM (3102 Study). Pearson correlation coefficient was used to evaluate the association of day 1 CD34+ cell collection with total CD34+ cell yield and the number of days of apheresis. Results In the NHL trial, 150 patients were mobilized with plerixafor plus G-CSF and 148 patients underwent mobilization with placebo plus G-CSF. More than half the patients (55.3%) in the plerixafor group collected ≥2 × 106 CD34+ cells/kg on Day 1 of apheresis (Figure 1A). In contrast, 19.6% patients in the placebo group collected ≥ 2 × 106 CD34+ cells/kg on Day 1 of apheresis (p< 0.001). In the MM study, 148 patients were mobilized with plerixafor plus G-CSF and 154 patients were mobilized with placebo plus G-CSF. More than half the patients (52.7%) in the plerixafor group collected ≥6 × 106 CD34+ cells/kg on the first day of collection compared to only 16.9% patients in the placebo group (p<0.001; Figure 1B). There was a strong positive correlation between day 1 collection and the total CD34+ cell yield in patients with NHL (r= 0.86, p-value= <0.0001) or MM (r= 0.87, p-value= <0.0001) in both the plerixafor and placebo groups. For NHL patients, the median Day 1 collection was higher in the plerixafor group compared to the placebo group: 2.66 × 106 vs. 0.77 × 106 CD34+ cells/kg (p<0.001) and this translated into higher total CD34+ cell yields in the two groups respectively: 5.69 × 106 vs. 1.98 × 106 CD34+ cells/kg (p<0.001). Similarly, for MM patients, the median CD34+ cells/kg collected on Day 1 was higher in the plerixafor group compared to the placebo group: 7.01 × 106 vs. 2.29 × 106 CD34+ cells/kg (p<0.001) and this translated into better overall collection in the plerixafor vs. placebo groups: 10.96 × 106 vs. 6.18 × 106 CD34+ cells/kg (p<0.001). A negative correlation was observed between CD34+ cells collected on Day 1 and the number of days of apheresis performed in patients with NHL (r= -0.67, p-value=<0.0001) or MM (r= -0.50, p-value= <0.0001) in both the plerixafor and placebo groups. Consequently, better Day 1 collection in plerixafor-treated NHL or MM patients translated into significantly fewer apheresis days to achieve the target collection compared to placebo treated patients. Conclusions These data support previous reports demonstrating a strong correlation between day 1 CD34+ cell collection and total CD34+ cell yield and apheresis days. These data also demonstrate that addition of plerixafor to G-CSF allows significantly more patients to achieve the target cell collection within 1 day of apheresis compared to G-CSF alone. These findings support the observation that mobilization with plerixafor plus G-CSF reduces the number of apheresis days required to achieve the minimal or optimal cell dose to proceed to transplantation. Disclosures Bolwell: Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Nademanee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stiff:Genzyme Corp.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stadtmauer:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Maziarz:Genzyme Corp.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Micallef:Genzyme Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Marulkar:Genzyme Corporation: Employment, Equity Ownership. Gandhi:Genzyme Corporation: Employment, Equity Ownership. DiPersio:Genzyme: Honoraria.

Use of Plerixafor to Overcome Stem Cell Mobilization Failure: Long Term Follow up of Patients Proceeding to Transplant Using Plerixafor Mobilized Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4390-4390 ◽  
Author(s):  
Abhinav Deol ◽  
Judith Abrams ◽  
Ashiq Masood ◽  
Zaid Al-Kadhimi ◽  
Muneer H. Abidi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Cell Count ◽  
Peripheral Blood ◽  
Cd 34 ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Abstract 4390 Background: Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods: Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results: Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion: Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.

Impact of Cytopenia Following Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation Using Post-Transplant Cyclophoshamide

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2281-2281
Author(s):  
Villetard Ferdinand ◽  
Stefania Bramanti ◽  
Samia Harbi ◽  
Sabine Fürst ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Transplantation ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Risk Index ◽  
Conditioning Regimen ◽  
Post Transplantation ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
The Impact

Abstract Introduction Allogeneic transplantation from a haploidentical donor (HaploSCT) is an alternative strategy in the treatment of hematologic malignancies in absence of HLA-identical donor. Recent studies reported similar outcome after HaploSCT compared to HLA-identical transplantation in different settings (Bashey, JCO 2013; Wang, Blood 2015; Gosh, JCO 2016). Although survivals seemed promising after HaploSCT, hematopoietic recovery following such a mismatched transplantation could represent a limitation. Thus, our series aims to evaluate hematological recovery after HaploSCT using a post transplantation cyclophosphamide (PT-Cy) platform. Methods This retrospective monocentric study included consecutive patients with following criteria: adults with hematological malignancies; bone marrow or peripheral blood T-replete HaploSCT from 2011 to 2015; non-myeloablative (Baltimore approach) or reduced intensity conditioning (busulfan-based) regimen; PT-Cy as part of GVHD prophylaxis. Patients with primary graft failure were excluded. Absolute neutrophil count (ANC), red cells (RCT) or platelet transfusion (PT) requirements on day 30 (D30) and day 100 (D100) were analyzed among disease-free patients. We first separately evaluated the rate of patients with significant cytopenia in each lineage (defined by ANC < 1 G/L, RCT need, PT need) and searched for impact of pre-transplantation factors on cytopenia (multivariate analyses by binary logistic regression). Then, we evaluated outcome by D30- and D100-landmark analyses according to cytopenia. Results One hundred and forty six patients with a median age of 56 years (range: 19-73) were analyzed: 142 and 117 were evaluable at D30 (4 early deaths) and D100 (17 deaths, 11 relapses), respectively. At D30, 20% of patients had ANC<1G/L, 67% needed RCT and 63% needed PT. Corresponding values at D100 were 20%, 42% and 28%, respectively (Figure 1). At D30: the use of PBSC (HR 9.5, p=0.002) was significantly associated with ANC>1G/L at D30; the use of NMAC Baltimore schema (HR 0.3, p=0.012) and CD34+ cell dose > median (HR 0.4, p=0.041) decreased PT needs while hematopoietic cell transplantation comorbidity index (HCT-CI)≥3 (HR 3.3, p=0.004) was associated with PT needs; no factor was found to significantly influence RCT. At D100: Age>60 years (HR 2.4, p=0.045), female to male HaploSCT (HR 3.3, p=0.020) and HCT-CI≥3 (HR 3.7, p=0.006) were significantly associated with higher risk of RCT need; female to male HaploSCT (HR 3.6, p=0.015) and HCT-CI≥3 (HR 6.9, p=0.001) were associated with PT needs; no factor was found to significantly influence ANC. With a median follow up of 25 months (range: 5-55), cox multivariate model with adjustment by age (continuous), disease risk index (low/intermediate vs high/very high), HCT-CI (0-2 vs ≥3), conditioning regimen (baltimore vs. busulfan-based) and graft source (bone marrow vs PBSC) showed that ANC<1 G/L was strongly associated with higher NRM (HR 2.9, p=0.011) and shorter OS (HR 3.4, p<0.001), overcoming the impact of RCT and PT needs (Figure 2A and 2B). In contrast, D100 analysis showed that PT need was the most determinant factor of increased NRM (HR 13.7, p=0.013) and poor OS (HR 7.3, p=0.003), while both D100 ANC and RCT needs did not impact outcome (Figure 2C and 2D). Discussion We found that cytopenia remain a concern after HaploSCT, leading to increased NRM and OS. The absence of ANC>1G/L at D30 as well as the need of PT at D100 may be considered as a strong post transplantation factor predicting poor outcome. Some pre-transplantation factors of cytopenia have been identified, such as CD34+ cell dose, sex mismatch and graft source. Among them, some may help for donor selection while the optimal donor for HaploSCT is still unknown. Moreover, better neutrophil recovery at D30 is achieved with the use of PBSC. CD34+ optimal cell dose in this setting remains also to be determined. In addition, post transplantation events such GVHD and/or infections should be evaluate to explore their interactions with such cytopenia, aiming to develop early therapeutic interventions. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characterization of the Hematopoietic Supporting Activity of Osteoblasts Derived from Bone Marrow Mesenchymal Stromal Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4358-4358
Author(s):  
Manal Alsheikh ◽  
Roya Pasha ◽  
Nicolas Pineault
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Conflicts Of Interest ◽  
Soluble Factors ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
The Impact ◽  
Myeloid Progenitors

Abstract Osteoblasts (OST) found within the endosteal niche are important regulators of Hematopoietic Stem and Progenitor Cells (HSPC) under steady state and during hematopoietic reconstitution. OST are derived from mesenchymal stromal cells (MSC) following osteogenic differentiation. MSC and OST secrete a wide array of soluble factors that sustain hematopoiesis. Recently, we showed that media conditioned with OST derived from MSC (referred as M-OST) after 6 days of osteogenic differentiation were superior to MSC conditioned media (CM) for the expansion of cord blood (CB) progenitors, and CB cells expanded with M-OST CM supported a more robust engraftment of platelets in NSG mice after transplantation. These findings raised the possibility that M-OST could be superior to MSC for the ex vivoexpansion HSPC. In this study, we set out to test the hypothesis that the growth modulatory activity of M-OST would vary as a function of their maturation status. The objectives were to first monitor the impact of M-OST differentiation and maturation status on the expression of soluble factors that promote HSPC expansion and in second, to investigate the capacity of M-OST CMs prepared from M-OST at distinct stages of differentiation to support the expansion and differentiation of HSPCs in culture. M-OST at distinct stages of differentiation were derived by culturing bone marrow MSC in osteogenic medium for various length of time (3 to 21 days). All CB CD34+ enriched (92±7% purity) cell cultures were done with serum free media conditioned or not with MSC or M-OST and supplemented with cytokines SCF, TPO and FL. We first confirmed the progressive differentiation and maturation of M-OST as a function of osteogenic culture length, which was evident by the induction of the osteogenic transcription factors Osterix, Msx2 and Runx2 mRNAs, the gradual increase in osteopontin and alkaline phosphatase positive cells and quantitative increases in calcium deposit. Next, we investigated the expression in MSC and M-OSTs of genes known to collaborate for the expansion of HSPCs by Q-PCR. Transcript copy numbers for IGFBP-2 increased swiftly during osteogenic differentiation, peaking at day-3 (˃100-fold vs MSC, n=2) and returning below MSC level by day-21. In contrast, ANGPTL members (ANGPTL-1, -2, -3 and -5) remained superior in M-OSTs throughout osteogenic differentiation with expression levels peaking around day 6 (n=2). Next, we tested the capacity of media conditioned with primitive (day-3, -6), semi-mature (day-10, -14) and mature M-OST (day-21) to support the growth of CB cells. All M-OST CMs increased (p˂0.03) the growth of total nucleated cells (TNC) after 6 days of culture compared to non-conditioned medium used as control (mean 2.0-fold, n=4). Moreover, there was a positive correlation between cell growth and M-OST maturation status though differences between the different M-OST CMs tested were not significant. The capacity of M-OST CMs to increase (mean 2-fold, n=4) the expansion of CD34+ cells was also shared by all M-OST CMs (p˂0.05), as supported by significant increases with immature day-3 (mean ± SD of 18 ± 6, p˂0.02) and mature day-21 M-OST CMs (14 ± 5, p˂0.05) vs. control (8 ± 3, n=4). Conversely, expansions of TNC and CD34+ cells in MSC CM cultures were in-between that of control and M-OST CMs cultures. Interestingly, M-OST CMs also modulated the expansion of the HSPC compartment. Indeed, while the expansion of multipotent progenitors defined as CD34+CD45RA+ was promoted in control culture (ratio of 4.5 for CD34+CD45RA+/CD34+CD45RA- cells), M-OST CMs supported greater expansion of the more primitive CD34+CD45RA- HSPC subpopulation reducing the ratio to 3.3±0.4 for M-OST cultures (cumulative mean of 10 cultures, n=2). Moreover, the expansions of CD34+CD38- cells and of the long term HSC-enriched subpopulation (CD34+CD38-CD45RA-Thy1+) in M-OST CM cultures were respectively 2.7- and 2.8-fold greater than those measured in control cultures (n=2-4). Finally, the impact of M-OST CMs on the expansion of myeloid progenitors was investigated using a colony forming assay; expansion of myeloid progenitors were superior in all M-OST CM cultures (1.6±0.2 fold, n=2). In conclusion, our results demonstrate that M-OST rapidly acquire the expression of growth factors known to promote HSPC expansion. Moreover, the capacity of M-OST CMs to support the expansion of HSPCs appears to be a property shared by M-OST at various stages of maturation. Disclosures No relevant conflicts of interest to declare.

Abstract 15869: Off-Pump Coronary Artery Bypass Grafting is Associated With Higher Rate of Percutaneous Coronary Intervention at 8-Year Follow-Up

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Fabio Barili ◽  
Stefano Rosato ◽  
Paola D’Errigo ◽  
Alessandro Parolari ◽  
Lorenzo Menicanti ◽  
...  
Keyword(s):  
Risk Factor ◽  
Univariate Analysis ◽  
Hazard Ratio ◽  
P Value ◽  
Term Survival ◽  
Off Pump ◽  
Pump Cabg ◽  
The Impact

Introduction: The debate on the advantages and limitations of off-pump (OPCAB) vs on pump CABG has not still arrived to a conclusion and concerns still exist on graft patency. This study was designed to compare the impact on mortality and morbidity of OPCAB and on-pump CABG, with a specific focus on mid-term need for percutaneous cardiac intervention (PCI). Methods: The PRIORITY project was designed to evaluate the mid-long term outcomes of 2 large prospective multicenter cohort studies on CABG conducted between 2002-2004 and 2007-2008. Data on isolated CABG performed both on-pump and off-pump were derived from clinical dataset and linked to 2 administrative datasets. Time-to event analyses were performed in a competing risk framework to evaluate the potential role of surgical techniques on outcomes. Results: The population consisted of 11020 patients who underwent isolated CABG (27.2% OPCAB). Several risk factor but surgical technique independently affected in-hospital mortality. The incidence of postoperative PCI was significantly higher in OPCAB group (p<0.05) and the multivariate logistic regression demonstrated that on-pump CABG was the only factor that protects from PCI after surgery (OR 0.61). Although unadjusted long-term survival was significantly worst for OPCAB (Log-rank p-value 0.00), the adjustment for factors found significant in the univariate analysis did not confirm OPCAB as a risk factor for mortality (hazard ratio was 0.96 ± 0.05, p-value 0.407). On the contrary, the significantly better cumulative incidence function of hospitalization for PCI at follow-up (Gray test p-value 0.00) in the on-pump group was confirmed even by the adjustment for confounding factors (p-value 0.00, adjusted hazard ratio 0.70 ± 0.07) and hence OPCAB was demonstrated to be an independent risk factor for PCI with an hazard that is 42% higher than on-pump CABG. Conclusions: This study demonstrated that OPCAB did not affect short and long-term mortality. Nonetheless, it was a risk factor for re-hospitalization for PCI.

AB0336 IMPACT OF SUBJECTIVE INTOLERANCE TO METHOTREXATE ON THE QUALITY OF LIFE OF PATIENTS WITH RHEUMATOID ARTHRITIS: SIDE EFFECTS AND AVOIDANCE COPING STRATEGIES THROUGH SELF-ADMINISTRATION IN THE EVENING OR DURING THE WEEKEND

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1466.1-1467
Author(s):  
G. Cavalli ◽  
M. Biggioggero ◽  
A. Cariddi ◽  
G. De Luca ◽  
E. Agape ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Social Participation ◽  
Disease Duration ◽  
P Value ◽  
Self Administration ◽  
Cross Sectional ◽  
The Impact

Background:Methotrexate (MTX) represents theanchor drugfor the treatment of rheumatoid arthritis (RA), as well as other rheumatological diseases such as psoriatic arthritis (PsA) and spondyloarthritides (SpA). Despite consolidated clinical efficacy, the use of MTX suffers from relevant limitations. Common issues include subjective intolerance, nausea, malaise, and fatigue, which negatively impact on quality of life and work/social participation.Objectives:In this study, we evaluated the frequency with which patients on MTX therapy opt for self-administration over the weekend or in the evening hours, in order to minimize interference with daily activities, work productivity, and social participation.Methods:A cross-sectional, prospective study was performed in two tertiary referral Rheumatology clinics, which included consecutive patients with RA, PsA, or SpA on MTX therapy. Enrolled patients had not previously received instructions by their healthcare provider as to when during the week or day MTX ought to be administered, and were free to choose or change the weekday and time for self-administration. Data on the route and timing of MTX self-administration was collected using dedicated questionnaires, which included queries on the dose and route of administration, day of the week and time of self-administration, reasons for the patient’s choice, use of folic acid supplementation, and concomitant therapies. Statistical analyses were conducted using a chi-square test; a p-value <0.05 was considered significant.Results:A total of 275 consecutive patients treated with MTX were included, mostly with RA (86%). Patients had an average age of 59.8 years (SD 14.0) and an average disease duration of 134.5 months (SD 127.3). The average MTX dose was 15 mg/wk (SD 4.4); MTX was administered subcutaneously in 68.2% of cases, orally in 17.8%, and intramuscularly in 5%. Regarding the timing of MTX self-administration, 157 patients (57.1%) took MTX in the evening and 119 patients (44.3%) took it during the weekend; even among patients taking MTX in the evening, weekend administration was preferred (93/157, 59.2%, p <0.001). The most frequent reasons leading to MTX self-administration during the evening or weekend were gastrointestinal side effects/nausea (85% of cases), fatigue (63%), interference with work activities (36%) and interference with social activities (29%). Patients who opted for MTX self-administration in the evening or over the weekend were significantly younger (p <0.001), with no significant gender differences or disease duration.Conclusion:The majority of patients with inflammatory arthritis opt for self-administration of MTX in the evening (absolute majority) or during the weekend (relative majority). This choice is dictated by the need to avoid side effects and detrimental repercussions on the individual’s social or working life. The adoption of these strategies for minimizing the adverse effects of MTX is more frequent among younger patients, and provides an indirect, yet powerful indicator of the impact of MTX therapy on patients’ quality of life.Disclosure of Interests:Giulio Cavalli Consultant of: SOBI, Pfizer, Sanofi, Novartis, Paid instructor for: SOBI, Novartis, Speakers bureau: SOBI, Novartis, Martina Biggioggero: None declared, adriana cariddi: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Elena Agape: None declared, nicola boffini: None declared, Elena Baldissera Speakers bureau: Novartis, Pfizer, Roche, Alpha Sigma, Sanofi, Lorenzo Dagna: None declared, Ennio Giulio Favalli Consultant of: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie, Speakers bureau: Consultant and/or speaker for BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis, and Abbvie

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