scholarly journals 255: Correlation between infused mononuclear cells (MNC) and transplant outcome in pediatric cord blood transplantation (CBT). A study of 92 single CBT done at Children’s Memorial Hospital, Chicago, IL

2007 ◽  
Vol 13 (2) ◽  
pp. 93-94
Author(s):  
M. Merchant ◽  
M. Olszewski ◽  
W. Huang ◽  
R. Duerst ◽  
D. Jacobsohn ◽  
...  
Keyword(s):  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Memorial Hospital ◽  
Transplant Outcome ◽  
Blood Transplantation

Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1138-1141 ◽  
Author(s):  
Francesco Frassoni ◽  
Marina Podestà ◽  
Rita Maccario ◽  
Giovanna Giorgiani ◽  
Gabriele Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
Transplant Recipients ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an adult bone marrow (BM) transplant. We studied neutrophil and platelet recovery and, at a median time of approximately 1 year after transplantation, the frequency of colony-forming cells (CFCs) and long-term culture initiating cells (LTC-ICs) in the BM of the 2 groups. Recipients of BM transplants received 1-log more cells and had significantly faster neutrophil and platelet recovery. Conversely, the frequency of committed and early progenitors was significantly higher in the BM of children given CB cells compared with BM transplant recipients (median count of CFC/2 × 104 BM mononuclear cells, 20 versus 11, P = .007; median count of LTC-IC/106 BM mononuclear cells, 8.2 versus 0.2 P = .001). CB, but not adult BM stem cells, can better restore the host hematopoietic progenitor cell reservoir; the delayed engraftment after CB transplantation may reflect the difficulty of CB progenitors to reprogram themselves toward differentiation.

Early lymphocyte reconstitution is associated with improved transplant outcome after cord blood transplantation

Cytotherapy ◽  
2011 ◽  
Vol 13 (1) ◽  
pp. 78-82 ◽  
Author(s):  
Sara K. Tedeschi ◽  
Madan Jagasia ◽  
Brian G. Engelhardt ◽  
Jennifer Domm ◽  
Adetola A. Kassim ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Transplant Outcome ◽  
Blood Transplantation

Establishment of a Murine Model of Allogeneic Umbilical Cord Blood Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4600-4600
Author(s):  
Yi Wang ◽  
Wu Depei ◽  
Guanghua Chen ◽  
Aining Sun
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Umbilical Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Adult Mice ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

Abstract This study was undertaken to establish a murine model of unrelated allogeneic umbilical cord blood transplantation (UCBT). To investigate the potential possibility to reconstitute the immunohematopietic system in adult mice recipients across major histocompatibility complex by mixed 2 near term cord blood transplantation: 1×106 umbilical cord blood mononuclear cells from 20 day old C57BL/6 (H2b) pups and 1×106 umbilical cord blood mononuclear cells from 20 day old C3H (H2k) mixed pups delivered by cesarean were injected into lethally irradiated (8.0Gy) BALB/c (H2d) adult mice in the same time. After one month, anti-H2b and anti-H2k antibody were used to investigate donor chimera in recipients. Results showed that all of the control mice that reconstituted with only 1×106 umbilical cord blood mononuclear cells from 20-day-old C57BL/6 (H2b) pups died with in three weeks after radiation. 70% recipients that reconstituted with mixed umbilical cord blood mononuclear cells survived in the observation period of three months. Two donors mixed chimera was demonstrated by using anti-H2b and anti-H2k antibody in the same recipient. In vitro mixed lymphocyte response showed immune tolerance. The results confirmed that two kinds of umbilical cord blood can form mixed chimera in the same adult mice recipients. Mixed umbilical cord blood transplantation can reconstitute the immunohematopietic system in adult mice recipients without causing serious GVHD. This model may be suitable to address many questions raised in clinical mixed umbilical cord blood transplantation.

scholarly journals A Murine Model for Human Cord Blood Transplantation: Near-Term Fetal and Neonatal Peripheral Blood Cells Can Achieve Long-Term Bone Marrow Engraftment in Sublethally Irradiated Adult Recipients

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 1089-1099 ◽  
Author(s):  
Andromachi Scaradavou ◽  
Luis Isola ◽  
Pablo Rubinstein ◽  
Yelena Galperin ◽  
Vesna Najfeld ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Near Term ◽  
Ex Vivo Culture

Abstract The purposes of the research reported here were first to explore a murine model for human placental and umbilical cord blood transplantation and second to evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked with the human multiple drug resistance transgene (MDR1) were used for syngeneic transplants into sublethally irradiated adult mice. Donor cells were transplanted either fresh and untreated, or after ex vivo culture in the presence of the hematopoietic growth factors recombinant murine stem cell factor, recombinant human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal mouse mononuclear cells were cultured directly in methylcellulose with growth factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were first cultured in liquid medium for 3 to 8 days and then transferred to semisolid assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to 11.6-fold increase, and the numbers of colonies observed in methylcellulose were similar to those produced by fresh FNPB cells. Donor-type engraftment was demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1 transgene in the peripheral blood of all surviving animals (5 of 7 recipients of the fresh, and 3 of 8 recipients of the ex vivo–cultured cells) 2 to 4 months after transplantation. The proportion of donor leukocytes in the peripheral blood of the recipients (chimerism) was evaluated using fluorescence in situ hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from 2% to 26%. In addition, bone marrow cultures were obtained from two recipient animals: one had received fresh-untreated cells and was evaluated 8 months after transplant, the other had received ex vivo cultured cells and was tested 14 months after grafting. The derived hematopoietic colonies were tested by PCR and the transgene was detected, conclusively proving long-term engraftment of donor cells. These results indicate that FNPB transplants can be successfully performed in sublethally irradiated mice with and without ex vivo culture. Long-term donor-type engraftment with sustained chimerism has been demonstrated. Thus, murine neonatal blood grafts can be used as an animal model for cord blood transplantation for gene therapy studies where complete myeloablation is not desirable and partial replacement of defective marrow may be sufficient. Furthermore, the possibility of numerically expanding hematopoietic progenitor cells contained in neonatal blood without affecting their engraftment ability could facilitate use of cord blood grafts in adult recipients.

Differences in the Kinetics of Hematopoietic and Stem Cell (SC) Engraftment Following Murine Newborn/Cord Blood (NB) and Bone Marrow (BM) Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4949-4949
Author(s):  
Tao Du ◽  
George F. Atweh ◽  
Yelena Galperin ◽  
Rona Singer Weinberg
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Blood Transplantation ◽  
Cell Counts ◽  
Kinetics Of

Abstract Cord blood is being used at an increasing frequency as a source of stem and progenitor cells in human hematopoietic transplantation. However, very little is known about the kinetics of engraftment of cord blood relative to bone marrow derived stem cells. We have used a murine model of newborn/cord blood transplantation to address this question. Our studies demonstrated that murine NB can provide long-term engraftment in primary, secondary, and tertiary transplant recipients. Although NB engrafts more slowly than BM, at one year, engraftment was similar in both types of recipients. We compared the rate of recovery of blood counts, hematopoietic progenitor counts and putative stem cell [SC] counts (i.e. Sca-1+, c-kit+, Lin- cells) in recipients of NB and BM transplantation. Interestingly, the SC ratio in mononuclear cells from donor NB/donor BM was 3.25 ± 0.8 (range = 2.45 – 4.75, n=15). Similarly, donor NB mononuclear cells contained approximately 30% of the number of megakaryocytic progenitors, 12% of the myeloid progenitors and 5% of the erythroid progenitors of donor BM mononuclear cells. The repopulation kinetics in recipients of donor BM and NB transplantation were analyzed at regular intervals, up to 8 months after transplantation. During the first two weeks, NB recipients had lower hemoglobin, WBC and platelet counts than BM recipients. However, by 1 month, the hemoglobin and WBC counts were at similar levels in NB and BM recipients. In contrast, NB transplantation recipients required 2 to 3 months to achieve platelet counts similar to those in BM recipients. These results are reminiscent of the well-known delayed platelet recovery following human cord blood transplantation. Progenitor cell counts in the bone marrow of recipients paralleled the hematological recovery described above. At 2 weeks post-transplantation, progenitor counts of all lineages in NB recipients were 25 to 35% of those in BM recipients. By 1 month, erythroid and myeloid progenitor numbers were similar in NB and BM recipients. In contrast, the appearance of megakaryocytic progenitors was delayed following NB transplantation and did not reach the same level as BM recipients until about 2 months after transplantation. During recovery, the number of SC in the bone marrow of both types of recipients increased gradually over time. At one month after transplantation, the number of SC in BM recipients was significantly greater than that in NB recipients, with a ratio of 4.2 ± 0.2. This SC ratio decreased gradually during the next several months. At 2, 4, and 8 months following transplantation, the ratios of SC in BM recipients/NB recipients were 3.5 ± 0.4, 2.6 ± 0.5, and 2.2 ± 0.3, respectively (n=5). This gradual decrease in the ratio of BM/NB SC suggests that NB SC increase more rapidly than BM SC. In conclusion, these data demonstrate that the kinetics of hematopoietic and stem cell recovery following NB and BM transplantation are significantly different. Although hematopoietic recovery after NB transplantation is slow at first, final engraftment is similar following NB and BM transplantation. Furthermore, the number of SC in NB recipients increases at a faster rate than the number of SC in BM recipients. These differences in SC recovery may be a reflection of differences either in the homing capacity or in the functional maturity of NB relative to BM SC. Further investigation is required to distinguish between these two possibilities.

Rapid and Massive Expansion of Cord Blood Derived Cytokine Induced Killer (CIK) Cells: An Innovative Proposal for the Treatment of Leukemia Relapse after Cord Blood Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 723-723
Author(s):  
Martino Introna ◽  
Marta Franceschetti ◽  
Alice Ciocca ◽  
Gianmaria Borleri ◽  
Elena Conti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Cik Cells ◽  
Blood Transplantation

Abstract Cytokine induced killer cells (CIK) are CD3+/CD56+ T/NK cells with cytotoxic potential against leukemic and other tumor cells but not normal bone marrow in vitro and in vivo. They are expanded in vitro with rhIL-2 after stimulation of peripheral blood mononuclear cells with OKT3 and IFN-γ. We have shown in a recent phase I study that 107/kg allogeneic CIK cells can be safely given to patients relapsing after allogeneic bone marrow transplantation and show evidence of anti-leukemic activity in vivo with very little GVHD. Cord blood (CB) transplantation is progressively becoming an extensively used treatment for patients with malignant disorders. One major limitation of this procedure is the lack of donor derived cells to perform donor lymphocyte infusions in case of relapse. In order to be able therefore to extend the use of CIK cells to the CB transplantation setting, we have standardised a 21 days expansion protocol to produce CIK cells starting from very small amounts of nucleated cells isolated from cord blood. Using this protocol, 15x106 mononuclear cells (MNC) from CB containing a mean 0.3x106 CD3+/CD56+ yielded on average 805 x 106 MNC (50 fold expansion) containing 630 x106 CD3+/CD56+ cells (corresponding to a fold expansion of 1860 for CIK). In order to transfer the method to a clinical setting, we explored the possibility of expanding the residual cells recovered from the empty bags after CB transplantion. Three used CB bags were returned to the laboratory after transplantation and repeatedly washed. An average of 22 x106 nucleated cells could be recovered, yielding a mean 473 x106 CD3/CD56+ cells at the end of the culture period (1485 fold expansion of CIK cells). CIK cells generated from CB showed strong cytotoxic activity against a variety of tumor target cell lines including B and T lymphomas and myeloid leukemias (42–72% killing at a 30:1 E:T ratio). More importantly, they were cytotoxic against AML blasts isolated from 2 patients (41% lysis). During expansion CB derived CIK cells upregulated the NKG2D marker from a mean fluorescence intensity of 49 to 209. Furthermore they expressed perforin and granzyme molecules in >90% of cells. These observations open up the possibility of a future clinical application of this protocol, performed in GMP conditions. Patients relapsing following cord blood transplantation may be treated with CIK cells expanded from the same cord blood unit, where donors would not be anymore available for cell mediated immunotherapy.

Impact of Early Lymphocyte Recovery On Transplant Outcome After Cord Blood Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3386-3386
Author(s):  
Sara K Tedeschi ◽  
Brian Engelhardt ◽  
Waleed Khalaf ◽  
Janice Tracy ◽  
Jennifer Domm ◽  
...  
Keyword(s):  
Cord Blood ◽  
Nk Cells ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Rapid Recovery ◽  
Transplant Outcome ◽  
Blood Transplantation

Abstract Abstract 3386 Poster Board III-274 Background: Previous studies have shown that rapid recovery of the absolute lymphocyte count (ALC) is associated with improved transplant outcomes after related and unrelated donor allogeneic stem cell transplantation (allo-SCT). Natural killer (NK) cells are the first lymphocytes to recover after allo-SCT and comprise the majority of peripheral blood lymphocytes after transplantation. Rapid recovery of NK cells at 1 month post allo-SCT has been associated with rapid neutrophil and platelet engraftment and decreased non-relapse mortality. Studies have shown that prolonged T-cell lymphopenia and compensatory expansion of B and NK cells occurs early after cord blood transplantation (CBT). However, no consistent link has been reported between lymphocyte/NK cell recovery and transplant outcome after CBT. Methods: Records from 40 CBT patients at our institution (3/2006-6/2009) were reviewed to determine the impact of lymphocyte recovery on transplant outcome in an IRB-approved study. The ALC was calculated based on the total white cell count and automated differential. Common transplant outcome variables (graft failure, acute and chronic graft versus host disease [GVHD], relapse, non-relapse mortality [NRM] and survival) were studied in relation with ALC at 1, 2, 3 months post-CBT. ALC was analyzed as a continuous variable and also as a dichotomous variable with two distinct groups based on transplant associated outcomes. Results: The majority of patients (n=33, 83%) received CBT for hematological malignancies. The median age was 22 years (range: 0.6-64), and 24 (60%) were male. Disease status at transplantation included 29 (73%) high risk and 8 (20%) standard risk hematological malignancies. Conditioning consisted of myeloablative regimens in 28 (70%) (TBI=21, non-TBI=7). Fifty percent of patients received thymoglobulin with their conditioning regimen. All patients received calcineurin inhibitors and mycophenolate for GVHD prophylaxis. Nineteen patients (48%) received two cord blood units. The median nucleated cell dose was 4.1 × 10 7 cells/kg (range, 2.2-27.3). Five (13%) patients experienced graft failure. Acute GVHD (grade II-IV) occurred in 30 (75%) patients; chronic GVHD occurred in 15 of 31 patients (48%) surviving beyond 100 days. Six (15%) experienced relapse and 9 (23%) died from non-relapse causes. At the time of analysis, 26 patients (65%) were alive with a median follow-up for surviving patients of 422 days (range 51-1256). Patients with ALC<100/μl at 1 month post-CBT showed increased graft failure (4 of 10 vs. 1 of 29; p=0.011). Patients with ALC>150/μl at 1 month post-CBT had decreased NRM (0 vs. 37%±10%, p=0.011) and improved survival (46%± 32% vs. 41%±13%, p=0.013) (Figure 1). There was no impact of ALC at 1, 2, or 3 months post-CBT on relapse or acute or chronic GVHD. There was no relationship between age, type of conditioning regimen, disease risk, number of cord units (one vs. two) or nucleated cell dose on ALC recovery. Conclusion: Our results indicate that ALC 1 month post-CBT is a surrogate marker for engraftment, and that low ALC (<150/μl) identifies an “at-risk” population of patients after CBT. These results point to the importance of developing patient-specific strategies to improve outcomes in those who fail to achieve satisfactory lymphocyte counts in the first month post-CBT. A limitation of this study is the small sample size, and validation in larger prospective multicenter CBT studies is warranted. Disclosures: Jagasia: Genzyme: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document