scholarly journals Use of alternative donors for allogeneic stem cell transplantation

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 220-224 ◽  
Author(s):  
Claudio Anasetti
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Human Leukocyte ◽  
Unrelated Donor ◽  
Factors Affecting ◽  
Blood Transplantation ◽  
Cell Sources

Abstract For patients without a human leukocyte antigen (HLA)-matched sibling or unrelated donor, options include transplantation from HLA-mismatched related donors, HLA-mismatched unrelated donors, or unrelated cord blood units. Graft failure remains a problem in 10%-20% of cord blood transplants that contain a limited number of hematopoietic cells. Many approaches are tested in clinical trials to offset the risk of graft failure after cord blood transplantation. GVHD remains a hurdle with any HLA mismatched graft. The use of post-transplant cyclophosphamide holds the promise to overcome the HLA barrier and prevent GVHD despite donor mismatch for a full HLA haplotype. Priority should be given to enrolling patients onto transplant protocols addressing the fundamental problems of engraftment, GVHD, relapse or treatment-related mortality tested with one or more of the alternative stem cell sources. Principles for prioritization of alternative stem cell sources are discussed separately for children and adults who cannot be enrolled on clinical trials. It is difficult ranking currently available sources in the face of multiple factors affecting outcomes, rapidly changing transplant technology and without results from comparative trials.

scholarly journals INFECTIOUS COMPLICATIONS AFTER UMBILICAL CORD-BLOOD TRANSPLANTATION FROM UNRELATED DONORS

2016 ◽  
Vol 8 ◽  
pp. 2016051 ◽  
Author(s):  
Juan Montoro ◽  
Jaime Sanz
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Cord Blood Transplantation ◽  
Infectious Complications ◽  
Unrelated Donor ◽  
Alternative Source ◽  
Hematopoietic Stem ◽  
Blood Transplantation

Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT.

Reduced Intensity Umbilical Cord Blood Transplantation(RI-UCBT) in Adult Patients with Graft Failure or Relapse after First Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5121-5121
Author(s):  
Kazuhiro Masuoka ◽  
Koichiro Yuji ◽  
Yuji Miura ◽  
Tomohiro Myojo ◽  
Daisuke Kato ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Blood Transplantation ◽  
Reduced Intensity ◽  
Neutrophil Engraftment

Abstract Background: Graft failure, graft rejection, or disease relapse post allogeneic hematopoietic stem cell transplantation(HSCT) is life-threatening and serious complication that necessitate consideration for a second transplantation. Graft failure has been more frequently reported in patients with aplastic anemia with T-cell depletion of the graft, in cord blood transplants, or when unrelated or HLA-mismatched related donors were used. In second allogeneic stem cell transplant setting, current questions include suitable stem cell source, additional conditioning, immunosuppression, and the use of a different donor, still remain unknown. We performed a feasibility study of reduced intensity umbilical cord blood transplantation (RI-UCBT) in adult patients with graft failure or disease relapse after first allogeneic transplantation. Patients and Methods: Nine patients (median age, 53 years; range 17–68) with advanced hematological diseases [AML (n=4), ALL (n=2), MDS (n=2), ATL (n=1)] who showed relapse or graft failure after first allogeneic transplantation underwent RI-UCBT with single cord blood unit at Toranomon Hospital between May 2003 and February 2004. Eight cases were in non-CR at transplant. A median time from first to second transplant was 226 days (range 31–475). The median number of mononuclear cells transfused was 2.3 x 107 /kg (range 1.8–3.5). HLA disparities were as follows; 5/6 in two cases, 4/6 in seven cases. Conditioning regimen mainly consisted of fludarabine 25 mg/m2 on days -7 to −3, melphalan 40mg/m2 (n=8) or busulfan 4mg/kg(n=1) day −3 to −2, and 4 Gy total body irradiation on day −1. Graft-versus-host disease (GVHD) prophylaxis was composed of ciclosporin alone (n=6) and tacrolimus alone (n=3). Results: All of them achieved primary neutrophil engraftment (>500/μL) after a median of 22 days (range, 15–32) and achievement of donor T-cell chimerism was confirmed. Four cases developed grade II-IV GVHD, and one case developed limited chronic GVHD. Of all the nine cases received RI-UCBT, seven died from relapse (n=4), sepsis (n=2), and TMA (n=1). Two survived without relapse for +232 and +81 days, respectively. Discussion: Although the number of patients is small and the follow-up period is short, our results corroborate that RI-UCBT for graft failure or relapse post first transplant is tolerated and may be worth considering for further evaluation. Neutrophil engraftment was achieved, however, disease relapse rate and treatment-related mortality is high. The management of disease status and development of ideal conditioning regimen will be the focus of future investigation.

scholarly journals Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4318-4327 ◽  
Author(s):  
Joanne Kurtzberg ◽  
Vinod K. Prasad ◽  
Shelly L. Carter ◽  
John E. Wagner ◽  
Lee Ann Baxter-Lowe ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cumulative Incidence ◽  
Hematologic Malignancy ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Multicenter Trial ◽  
Unrelated Donor ◽  
Blood Transplantation

Abstract Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 × 107 TNC/kg (range, 1.5-23.7) with 3.9 × 107 TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm3 and platelets 50 000/μL) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% (95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www.clinicaltrials.gov as #NCT00000603.

Outcome Of Unrelated Umbilical Cord Blood Transplantation For Children With Osteopetrosis: An Eurocord and Inborn Errors Working Party (IEWP)-EBMT Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2100-2100 ◽  
Author(s):  
Robert Chiesa ◽  
Annalisa Ruggeri ◽  
Marco Zecca ◽  
Franco Locatelli ◽  
Marta Gonzalez-Vincent ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Cell Dose ◽  
Blood Transplantation

Abstract Osteopetrosis (OP) is a genetic disease characterized by increased bone density due to osteoclast dysfunction, leading to life-threatening multi-systemic complications in early childhood. Haematopoietic stem cell transplantation (HSCT) is the only curative approach for most children with OP and can effectively prevent serious complications such as blindness, bone fractures, hydrocephalus and cranial nerve compression. Since timing of transplant is critical in OP, umbilical cord blood is an attractive stem cell source, due to its prompt availability. We analysed the outcomes of unrelated umbilical cord blood transplantation (UCBT) in 45 children with osteopetrosis transplanted in EBMT centers between 1996 and 2012, using data reported to Eurocord. Median age at UCBT was 6 months (1.1 month - 7.4 years). Donor-recipient pairs were matched at HLA-A and -B (antigen level) and DRB1 (allelic level) in 14 or HLA mismatched at 1 (n= 23) or 2 (n= 7) loci. Information on conditioning regimen was available for 42 patients; it was myeloablative (mostly busulfan-based) in 40 children and reduced intensity in 2 patients. GvHD prophylaxis consisted mainly of cyclosporine combined with either prednisolone (n= 20), or methotrexate (n=6), or mycophenolate mofetil (n=3). Anti thymocyte globulin (ATG) or alemtuzumab was given to 37/40 patients. Median number of infused total nucleated cell (TNC) and CD34+ was 13x107/kg and 3.4x105/kg, respectively. Median follow-up for survivors was 44 (range 4-144) months. Neutrophil recovery with donor chimerism was documented in 27/45 patients; 19/25 evaluable patients presented full donor engraftment, while 6 children presented mixed donor chimerism. Median time to neutrophil recovery was 20 (range 10-60) days. Eighteen patients experienced graft failure and 3/18 are alive at last follow up. Information on treatment post-graft failure was available 7/18 children: 6 patients underwent a second HSCT and 3 of them survived. Stem cell dose was associated with a trend for a better probability of donor engraftment: the cumulative incidence of donor engraftment was 46% in patients who received a CD34+ cell dose<2 x 105/kg, versus 71% in children receiving a CD34+ cell dose ≥2x105/kg (p = 0.09). Eleven patients developed grade II-IV acute graft-versus-host disease (aGvHD: n=6 grade II, n=4 grade III, n=1 grade IV) and 5 patients chronic GVHD (cGvHD: n=3 limited, n=2 extensive). Overall survival (OS) at 3 years was 45+8%. Twenty-four patients died after UCBT due to: infections (n=13), acute respiratory distress syndrome (n=2), veno occlusive disease (VOD), (n=2) hemorrhage (n=2), or other causes (n=5). VOD was observed in 7/26 evaluable patients. Stem cell dose and HLA disparity were the only predictors of superior outcome in univariate analysis. The 3-year probability of OS was 50% in patients who received grafts with a CD34+ cell dose >2x105/kg versus 0% in children receiving grafts with a CD34+ cell dose < 2x105/kg (p=0.001). According to HLA disparities, 3-year probability OS was 54% versus 58% versus 0% in patients receiving a 6/6, 5/6 and 4/6 HLA-mismatched graft, respectively (p=0.01). Interestingly, 4/4 children receiving a treosulfan-based myeloablative regimen achieved donor engraftment and 3 children are alive at last follow up. These data suggest that transplantation of unrelated UCB is a valid alternative for children with OP without a matched sibling or a suitable matched unrelated adult donor. The use of CB units mismatched at >1 HLA locus should be avoided due to worse survival. The incidence of primary graft failure was high and therefore the optimization of the conditioning regimen and/or the use of CB units containing a high TNC and CD34+ cell dose must be considered in this setting. The use of treosulfan-based conditioning regimens is worth further investigation, as well as the use of defibrotide prophylaxis to reduce the risk of VOD in this population of high risk patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Optimizing cord blood selection

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 522-531 ◽  
Author(s):  
Annalisa Ruggeri
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Hla Typing ◽  
Unrelated Donor ◽  
Dose Requirement ◽  
Related Factors ◽  
Blood Transplantation ◽  
Donor Choice

Abstract Nowadays a donor can be found for virtually all patients in need of an allogeneic stem cell transplantation, and the decision whether to use a matched or mismatched unrelated donor, an unrelated donor for umbilical cord blood transplantation (UCBT), or a haploidentical donor depends not only on the availability of the donor but also on patient-, disease-, and center-related factors. This paper summarizes the recent criteria in the selection of cord blood unit, including the cell dose requirement and the HLA typing for the optimal donor choice. The main strategies to optimize the results of UCBT, the conditioning regimens, and the use of antithymocyte globulin and the other platforms of graft-versus-host disease prophylaxis are discussed. The paper describes the results of UCBT in children and adults with malignant and nonmalignant diseases and the comparative analysis with other donor type and stem cell sources. Emerging strategies, focusing on the different platforms of ex vivo expansion and the new applications using cord blood stem cell, are also examined.

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