scholarly journals Clinical Outcomes of Unrelated Umbilical Cord Blood Graft vs. Haploidentical Donor Transplantation: Critical Issues for an Adequate Comparison

2021 ◽  
Vol 8 ◽  
Author(s):  
Diana Vanegas ◽  
Laura Niño-Quiroga ◽  
Mauricio Chaparro ◽  
Bernardo Camacho-Rodríguez ◽  
Marcela Estupiñán ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Low Income ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Haploidentical Transplantation ◽  
Pediatric Transplantation ◽  
Number Of Patients ◽  
Alternative Donor

Unrelated umbilical cord blood (UCB) and haploidentical grafts have been used for allogeneic hematopoietic stem and progenitor cell (HSPC) transplantation in patients without a related or non-related human leukocyte antigen (HLA)-matched donor. The less stringent HLA-matching requirement in both sources raises an important possibility for patients in need of urgent transplantation to treat any hematological disease. Selection of the best alternative donor is a difficult task that will depend on donor criteria, center experience, patient disease conditions, and risk, among others. Most comparisons available in scientific publications between both graft sources are obtained from retrospective analysis in wide time windows and a heterogeneous number of patients, types of disease, disease stages, previous treatments, graft source, conditioning regimen, graft vs. host disease (GVHD) approach, and evaluable endpoints. There is also an evident impact of the economic traits since low-income countries must consider less expensive treatments to satisfy the needs of the patients in the most effective possible path. Therefore, haploidentical transplantation could be an appealing option, even though it has not been completely established if any chronic treatment derived from the procedure could become a higher cost. In Colombia, there is a huge experience in UCB transplantation especially in units of pediatric transplantation where benign indications are more common than in adults. Due to the availability of a public UCB bank and HLA high-resolution typing in Colombia, there is a wider inventory of cord blood donors. Unfortunately, we do not have an unrelated bone marrow donor registry, so UCB is an important source along with haploidentical transplantation to consider in decision-making. This minireview focuses on comparing the main issues associated with the use of both HSCP sources and provides tools for physicians who face the difficult decision between these alternative donor sources.

Analysis of Mismatched Umbilical Cord Blood Transplants for Adults Patients 45 Years or Older.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5067-5067
Author(s):  
Seah H. Lim ◽  
Willaim V. Esler ◽  
Yana Zhang ◽  
Jian Zhang ◽  
Colleen Burris ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Older Patients ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Secondary Aml ◽  
Leukemia Relapse ◽  
Older Populations

Abstract Although hematopoietic stem cell (HSC) transplants are curative for some patients with hematologic malignancies, they have been applied primarily to younger patients. Yet, hematologic malignancies are commoner in the older populations. Therefore, despite advances in HSC transplants, many patients, especially older patients, still die of their disease. Umbilical cord blood (UCB) transplants have been shown to produce comparable results to those obtained from unrelated bone marrow transplants for adults with hematologic malignancies. UCB transplants may be particularly suitable for older patients needing unrelated HSC transplants since the incidence of GVHD is lower despite the less stringent HLA-matching requirement. Furthermore, UCB procurement is fast and can be accomplished in two weeks. However, data on the applicability of UCB transplants in older adult patient is lacking. The outcome of 14 consecutive adult patients (9 males and 5 females), 45 years or older, needing HSC transplants but without matched sibling donors in a single institution was analyzed. The median age was 55.5 years (range 45–78). The median weight was 72 kg (range 60–105). The median CD34 cells infused were 2.3 x 105/kg. Four patients received one-antigen mismatched, five patients two-antigen mismatched and five patients three-antigen mismatched transplants. Conditioning regimens consisted of Bu/Cy with (n=5) or without (n=1) ATG, Flu/Mel (n=7) and BEAM (n=1). GVHD prophylaxis consisted of cyclosporin A and methylprednisone. Five patients received double UCB transplants. The diagnosis: AML (n =8; 2 untreated secondary AML, 2 primary refractory AML, 2 secondary AML in CR1, 1 secondary AML in CR2 and 1 AML in CR3 and has failed a previous autologous transplant), CML (n=3; 2 in BC and 1 in CP1), CLL (n =2; both with advanced refractory disease) and SAA due to Hep C (n=1). Despite the age of these patients, Grade I–II acute GVHD occured in 10 patients and Grade III–IV in only 2 patients. Three patients died, all from septicemia, before engraftment could be documented. Other deaths include severe GVHD (n=2), VOD (n=1), stroke (n=1), septicemia (n=1) and leukemia relapse (n=1). Five patients are alive and disease-free. As of August 1, 2007, the 5-year actuarial DFS and OS are both 31% for the group and 50% for those <65 years (Figure 1). All five patients >65 years died within 100 days of transplants. In conclusion, some older patients needing HSC transplants may benefit from mismatched UCB transplants if they are not candidates for autologous transplants and do not have HLA-matched siblings. Obviously longer follow-up is needed in these patients to better determine the long-term effect of this approach in older patients. However, further optimization of the conditioning regimen is needed for patients older than 65 years to reduce early TRM due to toxicities. Figure Figure

Alternative Donors (Umbilical Cord Blood and Haploidentical Donors) for Allogeneic Stem Cell Transplantation in Relapsed / Refractory Hodgkin Lymphoma: A Retrospective Analysis of the EBMT Lymphoma Working Party and the Spanish Group of Stem Cell Transplantation (GETH)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4399-4399 ◽  
Author(s):  
Carmen Martinez ◽  
Jorge Gayoso ◽  
Carmen Canals ◽  
Herve Finel ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Hematopoietic Stem ◽  
Number Of Patients

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

Negative Impact of KIR-Ligand Mismatch on Transplant-Related Mortality (TRM) in Umbilical Cord Blood Transplant (UCBT) Recipients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2041-2041 ◽  
Author(s):  
Claudio G. Brunstein ◽  
John E. Wagner ◽  
Daniel J. Weisdorf ◽  
Juliet N. Barker ◽  
Hariet Noreen ◽  
...  
Keyword(s):  
Beneficial Effect ◽  
Cord Blood ◽  
Nk Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Independent Predictor ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Myeloid Malignancy

Abstract Umbilical cord blood (UCB) is frequently considered as a suitable alternate source of hematopoietic stem cells (HSC) for both pediatric and adult patients who require HSC transplant for treatment of high-risk or relapsed hematologic malignancy. As mismatched killer Ig-like receptor ligands (KIR-L MM) has been associated with anti-host alloreactive natural killer (NK) cell activity and reduced risk of acute myeloid leukemia relapse in recipients of T-cell depleted haploidentical HSC, we hypothesized that GVL after UCBT may also be mediated by NK alloreactivity. We therefore assessed the effect of KIR-L MM in 243 recipients of UCB transplanted at the University of Minnesota between 1998 and 2004 for whom HLA-A, -B, -C and DRB1 typing was available for both patient and UCB unit(s). Median age, weight, and follow-up were 27 yrs (range, 0.2–69), 64.6 kg (range, 3.8–120.2), and 1.1 yr (range, 0.5–6.6), respectively. For recipients of double UCBT (n =106), we analyzed the KIR-L assignment of the engrafting unit only. KIR-L MM in the GVH direction was established using the algorithm of Ruggeri and Velardi and was found in 70 (29%) donor-recipient pairs. Probability of 2-year survival was 54% (95%CI: 42–66) vs. 47% (95%CI: 38–56) (p=0.88) in KIR-L MM vs. matched pairs, respectively. Intensity of the conditioning regimen was the only independent predictor of survival, with a RR of death 1.54 (95%CI: 1.07–2.22, p=0.02) for those who received a non-myeloablative conditioning. For the whole group, incidence of relapse at 1-yr was 17% (95%CI: 8–26) vs. 31% (95%CI: 24–38) (p=0.12); for myeloid malignancy patients, incidence of relapse at 1 year was 13% (95%CI:2–24) vs. 34% (95%CI:22–46)(p=0.10). Intensity of the conditioning regimen was the only independent predictor of relapse, with a RR 2.09 (95%CI: 1.31–3.35, p<0.01) for those who received a non-myeloablative conditioning. Incidence of graft failure and grade II–IV acute GVHD was 11% (95%CI: 3–18) vs. 10% (95%CI: 6–15) (p= 0.97) and 50% (95%CI: 37–63) vs. 50% (95%CI: 42–58) (p=0.67), respectively. Notably, the incidence of TRM was higher among recipients of KIR-L MM grafts [26% (95%CI: 15–26) vs. 13% (95%CI: 8–18), p=0.01]. KIR-L MM did not impact on outcome within the subgroups of patients based on conditioning, number UCB units (single vs. double), and those who had a myeloid malignancy (AML, CML or MDS). In multivariate analysis, a nucleated cell dose < 3.5 X 10E7/kg [RR 3.86 (95%CI: 1.84–8.12, p<0.01)] and KIR-L MM [RR 2.15 (95%CI: 1.15–4.01, p<0.01)] were independent predictors of increased TRM. In summary, in the setting of UCBT, KIR-L MM is associated with increased TRM with no obvious beneficial effect on engraftment, relapse risk or survival as previously demonstrated in recipients of TCD haploidentical HSC. Differences in NK cells reconstitution, presence of T-cells and/or use of immunosuppression may interfere with any potential beneficial effect alloreactive NK cells in the setting of UCBT. While additional studies are still needed, results to date fail to support a specific search for UCB units with a KIR-L MM.

Melphalan Containing Cytoreduction Results in a Good Overall Survival (OS) in Pediatric Patients with Relapse or Refractory AML Undergoing Unrelated Umbilical Cord Blood Transplantation (UCBT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3150-3150
Author(s):  
Vinod K. Prasad ◽  
Juan Wu ◽  
Paul L. Martin ◽  
Timothy A. Driscoll ◽  
Suhag H. Parikh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Pediatric Patients ◽  
Cord Blood Transplantation ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Refractory Aml

Abstract Children with AML unable to achieve remission after initial diagnosis or at relapse will not be cured by conventional therapy but may be salvaged by allogeneic hematopoietic stem cell transplantation. Those lacking a related donor may not survive the time that is required to find an unrelated adult donor. Banked, unrelated donor umbilical cord blood (UCB) increases access to transplant by providing a rapidly available source of allogeneic hematopoietic stem cells. Fifty-one pediatric patients with Relapse or Refractory AML were transplanted with Unrelated Cord Blood (UCB) between 1995 and 2005. By low resolution HLA-A and -B plus high-resolution DRB1 typing, UCB units were 3/6 (18%), 4/6 (45%), 5/6 (31%) or 6/6 (6%) matched. The median age was 8.4 years. Ethnic minorities comprised 35.3% of patients. Thirteen patients had received prior auto- or allo-transplants. The median total nucleated cell (TNC) dose infused was 4.4x107/kg. All patients received myeloablative regimens. Patients receiving Melphalan containing regimens (Bu/Mel/ATG or Flu/Mel/ATG or TBI/Mel/ATG) were grouped as Melphalan-Pos (n=33) and the rest as Melphalan-Neg (n=18). GVHD prophylaxis was Cyclosporine plus methylprednisone in 94.8%. Two groups were statistically similar for sex (p=0.69), age (p=0.1), ethnic minority (p=1), HLA matching (p=0.1), CMV status (p=0.68), and cell dose infused (p=0.35). The probabilities of overall survival (OS) were estimated by Kaplan-Meier analysis and compared using log-rank test. Three year probability of OS in Melphalan-Pos group was higher (36%) than the Melphalan-Neg (11%) group although the difference did not reach statistical significance. We restricted subsequent analyses to a subgroup of patients (n=28) who were transplanted between year 2000 and 2005 because the supportive care practices in our program regarding the use of voriconazole, granulocyte transfusions, early detection and treatment of CMV, and VOD prophylaxis and therapy had been standardized since 2000. The 3 year probability of overall survival for Melphalan-Pos patients (n=13) was significantly higher (54%) than the Melphalan-Neg (n=15) patients (7%) (p=0.023). AGVHD (Grade 2–4) was seen in 18% and CGVHD in 6% of patients. The causes of death in Melphalan-Pos vs. Melphalan-Neg patients were relapse (30% vs 46%), infection (8% vs 40%) and organ failure (8% vs 7%). Two Melphalan-Pos and one Melphalan-Neg patient developed graft failure. The median time to ANC > 500 was 21 and 28 days and to Platelet > 50K was 70 and 104 days in Melphalan-Pos and Melphalan-Neg groups, respectively. We conclude that for high risk pediatric patients with relapsed or refractory AML lacking a family donor, UCB transplantation following Melphalan containing cytoreduction results in cure in a significant number of patients.

scholarly journals Impacts of Total Body Irradiation in Allogeneic Umbilical Cord Blood Hematopoietic Stem Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4852-4852
Author(s):  
Jeffrey J. Pu ◽  
Kristin N. Berger ◽  
Hao Wang ◽  
Wei Fu ◽  
Elizabeth L Miller ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Conditioning Regimens ◽  
Total Body ◽  
Univariate Analyses

Abstract Background: Umbilical cord blood hematopoietic stem cell transplant (UCBT) has been practiced as an alternative source of hematopoietic stem cells for patients in need of transplantation. Double-units UCBT has been established as a means of achieving a cell dose of at least 2.5x10 7 nucleated cells per kilogram of body weight in adult recipients. The advantages of UCBT include its rapid availability, reduced stringency in terms of human leukocyte antigen (HLA) match requirements, and subsequent increase in access to transplants for racial minorities. Both related and unrelated UCBTs with single or double units have been performed with high rates of success in both pediatric and adult settings to treat a variety of medical conditions. Prior to undergoing UCBT, recipients must undergo a conditioning regimen to create space in the bone marrow, suppress the immune system to allow for donor stem cell engraftment, and reduce the tumor burden in cases of neoplastic disease. Total body irradiation (TBI) is commonly incorporated into conditioning regimens to enforce these efforts. Although intense myeloablation in general is associated with a lower risk of relapse and graft rejection, greater regimen intensity also leads to a higher rate of transplant related morbidity and mortality (TRM). Inclusion of TBI specifically in conditioning regimens has been shown to result in organ toxicity and subsequent malignant neoplasm. To help mitigate the risks of myeloablative conditioning (MAC) regimens, non-TBI and reduced-intensity conditioning (RIC) regimens have been investigated as a means of reducing TRM and increasing access of transplantation to patients with age disadvantages or significant comorbidities. Despite ongoing investigation, studies comparing conditioning regimens of UCBT, with and without TBI, remain limited. This study, using real-world data collected from 4 institutions, retrospectively analyzed the impact of TBI as part of MAC or RIC conditioning regimens in patients undergoing UCBT. Methods: This is a retrospective study that analyzed the outcomes of 136 patients receiving umbilical cord blood transplants at four institutions. Seventy-nine patients received myeloablative condition (MAC), in which 36 underwent TBI and 33 did not; 67 patients received reduced-intensity condition (RIC), in which 24 underwent TBI and 43 did not. Univariate and multivariate analyses were conducted to compare the outcomes and the post-transplant complications between patients who did and did not undergo TBI in MAC subgroup and RIC subgroup, respectively. Results: Characteristics of UCBT recipients who did and did not undergo TBI, stratified by conditioning regimen were compared with both multivariate and univariate analyses and didn't see significant difference. We didn't observe significant difference in GVHD and transplant-related infection incidence rates between patient subgroup that did and did not undergo TBI as part of their pre-UCBT conditioning regimen via both multivariate and univariate analyses. In RIC subgroup, the patients who underwent TBI appeared to have superior overall survival (adjusted hazard ratio [aHR]=0.25, 95% confidence interval [CI]: 0.09-0.66, p=0.005) (Figure 1), progression-free survival (aHR=0.26, 95% CI: 0.10-0.66, p=0.005) (Figure 2), and shorter time to neutrophil engraftment (aHR=6.26, 95% CI: 2.27 - 17.31, p=0.0004) (Figure 3). However, in MAC subgroup, there were no statistically significant difference between using and not using TBI. There were also no differences between the patients who either underwent or not underwent TBI in terms of acute or chronic GVHD rates or rates of transplant-related infections in both subgroups. Conclusion: Combining with RIC, TBI may improve OS, PFS, and neutrophil engraftment time. However, the incidences of other post-transplant complication were comparable between patients who underwent and did not undergo TBI as part of conditioning regimens during umbilical cord blood transplant. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Brain Sparing Conditioning Regimen and Umbilical Cord Blood Transplantation for Inherited High Risk Neurologic Metabolic Diseases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3009-3009
Author(s):  
Jakub Tolar ◽  
Pamala Jacobson ◽  
Lawrence Charnas ◽  
Paul J. Orchard
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Metabolic Diseases ◽  
Conditioning Regimen ◽  
High Risk Population ◽  
Hematopoietic Stem ◽  
Neurologic Function ◽  
The Brain

Abstract In addition to the well established role of hematopoietic stem cell transplantation (HSCT) in the treatment of malignancies, HSCT is utilized for a number of neurologic metabolic diseases (typically, enzyme deficiencies) due to the ability of donor graft to provide an ongoing source of enzyme that can be taken up by recipient’s cells. Many of these diseases damage the white matter of the brain, and after onset of symptoms are characteristically progressive and lethal. Major limitations to the success of HSCT as therapy for these diseases are graft failure and toxicity to the brain from conditioning, resulting in disease progression. Thus, we reasoned that it would be advantageous to develop a less intensive conditioning regimen that minimally contributed to central nervous system toxicity while providing sufficient immunosuppressive to permit engraftment from unrelated cord blood donors. We are testing a reduced intensity regimen including Campath 1H (1.5 mg/kg), clofarabine (200 mg/m2), melphalan (140 mg/m2), and low dose total body irradiation (200 cGy) for this patient population. To gain insight into the persistence of Campath 1H, we measured serum levels within 30 hours prior to the cord blood infusion. We report outcomes in three adults and three children: Diagnosis Age (years) UCB Graft; HLA match NC dose (×108/kg CD34+ dose (×106/kg) Campath 1H serum level* Donor Engraftment 1 MLD 44 dUCB; 4/6, 5/6 0.44 0.68 Undectectable 0% 2 ALD 9 dUCB; 5/6, 5/6 0.90 1.43 699 100% 3 ML 1 dUCB; 5/6, 5/6 1.43 3.04 1,575 100% 4 TS 1 sUCB; 6/6 0.97 1.33 2,250 100% 5 MLD 42 dUCB; 5/6, 6/6 0.76 0.94 2,728 60% 6 MLD 42 dUCB; 5/6, 5/6 0.22 0.24 Not done 100% Legend: MLD, metachromatic leukodystrophy; ALD, adrenoleukodystrophy; ML, mucolipidosis type II; TS, Tay-Sachs disease; NC, nucleated cell; dUCB, double unit umbilical cord blood; sUCB, single unit umbilical cord blood; ND, not detected; Eng, engraftment; HLA matching is reported for antigen level HLA-A, B and allele level DRB1. *Campath 1H levels (nanograms/mL) are reported as an average of two measurements of samples diluted 10x. Cumulative doses for both UCB units are shown. The most recent donor chimerism is reported. To decrease the risk of graft rejection and prevent graft versus host disease (GvHD) patients received cyclosporine and mycophenolate mofetil. Patient 2 developed grade II skin and gastrointestinal acute GvHD, treated successfully with systemic and topical steroids. All patients are alive; none experienced progressive deterioration of neurologic function in the peri-transplant period. Our data suggest that this conditioning regimen is minimally toxic to the brain. The two subjects with the lowest Campath 1H concentrations had autologous recovery (patient 1) and GvHD (patient 2), suggesting that in vivo T cell depletion with Campath 1H may be beneficial. These results suggest that novel modifications in the transplant process may provide opportunities to decrease neurologic toxicity and maintain optimal neurologic function in this high risk population.

High Impact of Matching Score On Different HSCT Outcomes After Single and Double Umbilical Cord Blood Transplantation for Hematological Malignancies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1992-1992
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Hélène Labussière-Wallet ◽  
Marie Y. Detrait ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematological Malignancies ◽  
Negative Impact ◽  
Hematopoietic Stem ◽  
Number Of Patients ◽  
Significant Negative Impact ◽  
Matching Score ◽  
The Impact

Abstract Abstract 1992 Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological malignancies for which umbilical cord blood (UCB) represents an alternative source of HSC. In order to overcome the low cellularity of one UCB unit, double (d) UCBT has been developed. The impact of different matching variables between UCB units and recipient including HLA, sex and ABO on the different transplantation outcomes are still unclear and not very well defined yet. On the other hand, a major focus in previous studies has been on cellularity with different thresholds, despite the heterogeneous pre-freezing and post-thawing counting techniques especially without any link to matching variables. In this study, we evaluated the impact of the different matching variables in addition to cellularity and other disease and patient characteristics on single(s) and double UCBT outcomes in pediatric and adult patients between 1998 and 2011. There were 53 adults (37 dUCBT and 16 sUCBT) with a median age of 36 years (18–64) and 48 children (3 dUCBT and 45 sUCBT) with a median age of 2 years (0–14) and a median follow-up of surviving patients of 24 months (1–85). The different patient, UCB, disease and HSCT characteristics have been analyzed and taken into account. The median number of pre-freezing and post-thawing cells was for 1) TNC: 3.3×107/kg (1.9–5.1) and 2.6×107 (1.5–4.6) in adults; 1.6×107 (0.5–4) and 1.18×107 (0.5–3) in children; 2) CD34: 1.89×105 (0.57–4.2) and 1.55×105 (0.5–4.1) in adults; 4×105 (0.6–19.3) and 2.8×105 (0.26–19) in children with a respective cells viability of 54% and 58%. We built a scoring scale that took into account the matching variables (sex, ABO and HLA) between UCB units and recipient and between UCB units each other in case of dUCBT. The median score was 3.8 (1–7) in adults and 3 (1–6) in children; the detailed score calculation method will be communicated later. We evaluated in multivariate analysis separately in adults and children, the impact of the matching score, cellularity, single or double UCBT, type of disease, disease status and conditioning on different HSCT outcomes. We found a positive impact of infused CD34 ≥1.55×105 on neutrophiles recovery in adults [HR=2.1 (1.16–3.8), p=0.015] and infused CD34 ≥2.8×105 on neutrophiles and platelets recovery [HR=2.5 (1.2–5), p=0.007 and HR= 4.4 (1.6–11.6), p=0.002 respectively] in children; no significant factor was observed on the cumulative incidence of acute GVHD≥grade II. In addition, we showed a significant negative impact of matching score > 3.8 on adults overall survival (OS) with a 3 years probability of 19% (6–60) vs. 57% (38–84) for those with score ≤3.8 [HR=3.9 (1.5–9.8), p=0.003]. Similarly, score >3.8 had a significant negative impact also on progression-free survival (PFS) only in adults with a 3 years probability of 13% (3–65) vs. 21% (5–94) for patients with a score ≤3.8 [HR=2.8 (1.01–8), p=0.04]. No significant factor was found to influence transplant related mortality. In conclusion, cell dose remains a significant impacting factor on short term transplantation outcome while the matching score appears to have a strong impact on adult long term outcomes mainly OS and PFS. These very promising results lead us to evaluate this score in larger number of patients for its validation and in order to include it in the UCB unit choice either in simple or double UCBT. Disclosures: Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Hoechst dye efflux reveals a novel CD7+CD34− lymphoid progenitor in human umbilical cord blood

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2125-2133 ◽  
Author(s):  
Robert W. Storms ◽  
Margaret A. Goodell ◽  
Alan Fisher ◽  
Richard C. Mulligan ◽  
Clay Smith
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Large Population ◽  
Lymphoid Cells ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract A novel Hoechst 33342 dye efflux assay was recently developed that identifies a population of hematopoietic cells termed side population (SP) cells. In the bone marrow of multiple species, including mice and primates, the SP is composed primarily of CD34−cells, yet has many of the functional properties of hematopoietic stem cells (HSCs). This report characterizes SP cells from human umbilical cord blood (UCB). The SP in unfractionated UCB was enriched for CD34+ cells but also contained a large population of CD34− cells, many of which were mature lymphocytes. SP cells isolated from UCB that had been depleted of lineage-committed cells (Lin− UCB) contained CD34+ and CD34− cells in approximately equivalent proportions. Similar to previous descriptions of human HSCs, the CD34+Lin− SP cells were CD38dimHLA-DRdimThy-1dimCD45RA−CD71−and were enriched for myelo-erythroid precursors. In contrast, the CD34−Lin− SP cells were CD38−HLA-DR−Thy-1−CD71−and failed to generate myelo-erythroid progeny in vitro. The majority of these cells were CD7+CD11b+CD45RA+, as might be expected of early lymphoid cells, but did not express other lymphoid markers. The CD7+CD34−Lin− UCB SP cells did not proliferate in simple suspension cultures but did differentiate into natural killer cells when cultured on stroma with various cytokines. In conclusion, the human Lin− UCB SP contains both CD34+ multipotential stem cells and a novel CD7+CD34−Lin− lymphoid progenitor. This observation adds to the growing body of evidence that CD34− progenitors exist in humans.

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