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

Adult Mismatched Umbilical Cord Blood Transplant Is Feasible in a Community Setting for an Unselected Group of High Risk Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5391-5391
Author(s):  
Seah H. Lim ◽  
William V. Esler ◽  
David Beggs ◽  
Colleen Burris ◽  
Yana Zhang ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Older Patients ◽  
Blast Crisis ◽  
Community Setting ◽  
Secondary Aml ◽  
Unselected Group ◽  
Very High

Abstract Conflicting results has been found on how the size of a transplant program affected the clinical outcome of hematopoietic stem cell transplant (HSCT). Some insurance carriers demand their clients to only receive HSCT in large centers, even if the service is available locally and the patients have to travel a long distance away from their home to receive the service at the approved program. Amarillo, Texas is 350 miles from Dallas and 600 miles from Houston. The HSCT program was established in Dec 2001. 18–25 transplants (autologous, allogeneic and umbilical cord blood (UCB) transplants) are performed a year. To determine whether a justification could be made to offer HSCT in a program that is small, new and community-based, we have analyzed the outcome of the adult mismatched umbilical cord blood transplants (UBCT) carried out on an unselected group of patients needing HSCT but without a matched sibling donor in our center in the last five years. Thirteen patients (8 males and 5 females) have undergone unrelated mismatched UBCT. The median age was high at 54 years (range 17 to 78). Four patients received reduced intensity conditioning regimen with Flu/Mel and 9 patients received the myelo-ablative regimen with Bu/Cy. Four patients received two units and nine single unit of umbilical cord blood. The diagnosis were: CML in CP1 (1), CML in blast crisis (2), HD relapsed within three months after autologous transplant (1), SAA (2), refractory CLL (1), ALL with multiple relapses (1), AML in CR3 (1), untreated secondary AML (2), primary refractory AML (1) and secondary AML in CR1 (1). Five patients received UCB units that were 1 antigen mismatch, 4 patients 2 antigen mismatches and 4 patients 3 antigen mismatches. GVHD prophylaxis in all cases consisted of cyclosporine A and methylprednisone. This is a group of mainly very high risk older patients. Not unexpectedly, early mortality rate was high. Death within 28 days of transplant occurred in 2 patients due to toxicity. Death within 100 days of transplant occurred in 8/13 (61.5%) patients. All the deaths occurred due to either infection or toxicity, except in one patient (age 67 years) who died due to a thrombotic stroke. Death due to disease relapse occurred in another patient 5 months after transplant for CML in blast crisis. Engraftment was documented in 9 patients. Despite the high antigen mismatches and the age of the patients, Grade I – II GVHD occurred in 7 patients and Grade III – IV in only 2 patients. With a maximum follow-up of 49 months, 4/13 (30%) patients are alive disease-free: 49+ months (age 45 years, one DRB1 mismatch), 22+ months (25 years, two antigen mismatches), 15+ months (48 years, three antigen mismatches) and 4+ months (54 years, three antigen mismatches). These results, in a group of very high risk unselected older patients in a community setting, are extremely encouraging and are comparable to those reported on younger groups of patients. Conclusions: Adult mismatched UBCT is feasible in a small program in a community setting; Patients >45 years may benefit from UBCT, even in the setting of multiple antigen mismatches; Patient selection should reduce early death and improve survival; Insurance companies should not deny patients to have transplant in their local program based on the size of the program.

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.

Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus?

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 399-410 ◽  
Author(s):  
Mariella Della Chiesa ◽  
Michela Falco ◽  
Marina Podestà ◽  
Franco Locatelli ◽  
Lorenzo Moretta ◽  
...  
Keyword(s):  
Cord Blood ◽  
Nk Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Nk Cell ◽  
Cord Blood Transplantation ◽  
Cell Subset ◽  
Hematologic Malignancies ◽  
Cell Development ◽  
Hematopoietic Stem

Abstract Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood. However, different patterns of NK-cell development could be identified. Indeed, in a group of patients, a relevant fraction of NK cells expressed a mature phenotype characterized by the KIR+NKG2A− signature 3-6 months after transplantation. In other patients, most NK cells maintained an immature phenotype even after 12 months. A possible role for cytomegalovirus in the promotion of NK-cell development was suggested by the observation that a more rapid NK-cell maturation together with expansion of NKG2C+ NK cells was confined to patients experiencing cytomegalovirus reactivation. In a fraction of these patients, an aberrant and hyporesponsive CD56−CD16+p75/AIRM1− NK-cell subset (mostly KIR+NKG2A−) reminiscent of that described in patients with viremic HIV was detected. Our data support the concept that cytomegalovirus infection may drive NK-cell development after umbilical CB transplantation.

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.

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.

Comparison of Outcomes of Unrelated Bone Marrow and Umbilical Cord Blood Transplants in Children with Hematologic Malignancies: Single Center Study in Korea.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5164-5164
Author(s):  
Nak-Gyun Chung ◽  
Bin Cho ◽  
Young-Shil Park ◽  
Dae-Chul Jeong ◽  
Pil-Sang Jang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematologic Malignancies ◽  
Bone Marrow Transplants ◽  
Single Center ◽  
Hematopoietic Stem ◽  
Single Center Study ◽  
Center Study

Abstract In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBT) or bone marrow transplants, 102 children with hematologic malignancies transplanted with unrelated umbilical cord blood (n=35, M:F=21:14, median age 4 years) or unrelated bone marrow transplants (UBMT) (n= 67, M:F=49:18, median age 9 years) were analyzed in a retrospective single center study (between Aug. 1997 and Dec. 2003 in the Catholic Hematopoietic Stem Cell Transplantation Center of Korea). HLA mismatches were defined by serology for class I and molecular typing for DRB1. The donor was HLA mismatched in 94% of UCBTs (33 of 35 UCBT) and in 0 % of UBMT. Non-adjusted estimates of 2-year event-free survival rates were 46 % and 57 %, respectively (P > 0.2). Engraftment failures of donor cells occurred in 17 % (6 out of 35) of UCBT and in 6 % (4 out of 67) of UBMT. Grade >= III acute GVHDs developed in 3 out of 29 (10 %) engrafted patients who underwent UCBT and in 17 out of 63 (27 %) engrafted patients who underwent UBMT. Early TRM at day 100 was 31 % (11 out of 35) for UCBT and 22 % (12 out of 67) for UBMTs. Within post-transplant month 3, CMV infections occurred in 37 % of UCBT and 54 % of UBMT, but most of them did not progress to CMV disease due to early ganciclovir treatment. Chronic GVHD developed in 2 out of 22 (9 %) patients who underwent UCBT and in 15 out of 49 (31 %) patients underwent UBMT. In conclusion, the use of UCBT as a source of hematopoietic stem cells is a reasonable option for children with hematologic malignancies lacking an acceptable, matched unrelated marrow donor.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document