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Claudio G. Brunstein - One of the best experts on this subject based on the ideXlab platform.

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    cGvHD after UCBT was less severe, and had more CR to therapy than MSD Transplant. NRM was similar in patients with cGvHD after UCBT and MSD Transplant. FFS was similar in patients with cGvHD after UCBT and MSD Transplant. We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • outcomes of chronic graft versus host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010-2017) with cGvHD after MSD (n = 104) and UCBT (n = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p = 0.01). Severe cGvHD (32% vs. 15%, p = 0.01) and de-novo onset (45% vs. 15%, p < 0.01) were more frequent following MSD. Liver was more frequently involved in MSD recipients (38% vs. 6%); and GI in UCBT (33% vs. 63%), both p < 0.01. Overall response (CR + PR) was similar between both cohorts. 2-year CR was higher in UCBT (14% vs 33%, p = 0.02). Karnofsky score (KPS) ≥ 90 at cGvHD diagnosis was associated with higher odds of response (95%CI: 1.42-10, p < 0.01). The cumulative incidence of durable discontinuation of immune-suppressive therapy, failure-free survival (FFS) and NRM at 2-years were similar between cohorts. KPS < 90 (95%CI: 3.1-24.9, p < 0.01) and platelets <100 × 10e9/L (95%CI: 1.25-10, p = 0.01) were associated with higher risk of NRM. UCBT patients were more likely to have a prior acute GvHD, less severe cGvHD and more likely to attain CR. Despite differences, both cohorts had similar NRM and FFS. High-risk groups, including those with platelets <100 × 10e9/L and KPS < 90, need careful monitoring and intensified therapy.

  • optimal donor for african americans with hematologic malignancy hla haploidentical relative or umbilical Cord Blood Transplant
    Biology of Blood and Marrow Transplantation, 2020
    Co-Authors: Scott R Solomon, Meijie Zhang, Claudio G. Brunstein, Karen K Ballen, Andrew St Martin, Asad Bashey, Minoo Battiwalla, Lee Ann Baxterlowe, Saurabh Chhabra
    Abstract:

    ABSTRACT Although hematopoietic cell Transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical Cord Blood Transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical Cord Blood (n = 118) Transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical Cord Blood Transplantation compared with HLA-haploidentical relative Transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P

  • unrelated umbilical Cord Blood Transplant for adult acute lymphoblastic leukemia in first and second complete remission a comparison with allografts from adult unrelated donors
    Haematologica, 2014
    Co-Authors: David I Marks, Claudio G. Brunstein, Juliet N. Barker, Partow Kebriaei, Frederick R Appelbaum, Kwang Ahn Woo, Xiaobo Zhong, Veronika Bachanova, John Gibson, Hillard M Lazarus
    Abstract:

    Allogeneic hematopoietic cell Transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated Cord Blood grafts in Transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double Cord Blood Transplants, 546 peripheral Blood progenitor cell Transplants and 140 bone marrow Transplants. The characteristics of the recipients and their diseases were similar except Cord Blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white Blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor Transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and –DRB1. In contrast, most Cord Blood Transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor Transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of Cord Blood (44%), matched adult donor (44%) and mismatched adult donor (43%) Transplants. Cord Blood Transplants engrafted slower and were associated with less grade 2–4 acute but similar chronic graft-versus-host disease, relapse, and Transplant-related mortality. The survival of Cord Blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so Cord Blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.

John E. Wagner - One of the best experts on this subject based on the ideXlab platform.

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    cGvHD after UCBT was less severe, and had more CR to therapy than MSD Transplant. NRM was similar in patients with cGvHD after UCBT and MSD Transplant. FFS was similar in patients with cGvHD after UCBT and MSD Transplant. We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • outcomes of chronic graft versus host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010-2017) with cGvHD after MSD (n = 104) and UCBT (n = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p = 0.01). Severe cGvHD (32% vs. 15%, p = 0.01) and de-novo onset (45% vs. 15%, p < 0.01) were more frequent following MSD. Liver was more frequently involved in MSD recipients (38% vs. 6%); and GI in UCBT (33% vs. 63%), both p < 0.01. Overall response (CR + PR) was similar between both cohorts. 2-year CR was higher in UCBT (14% vs 33%, p = 0.02). Karnofsky score (KPS) ≥ 90 at cGvHD diagnosis was associated with higher odds of response (95%CI: 1.42-10, p < 0.01). The cumulative incidence of durable discontinuation of immune-suppressive therapy, failure-free survival (FFS) and NRM at 2-years were similar between cohorts. KPS < 90 (95%CI: 3.1-24.9, p < 0.01) and platelets <100 × 10e9/L (95%CI: 1.25-10, p = 0.01) were associated with higher risk of NRM. UCBT patients were more likely to have a prior acute GvHD, less severe cGvHD and more likely to attain CR. Despite differences, both cohorts had similar NRM and FFS. High-risk groups, including those with platelets <100 × 10e9/L and KPS < 90, need careful monitoring and intensified therapy.

  • higher csa levels after umbilical Cord Blood Transplant for acute leukemia result in improved survival
    Blood, 2013
    Co-Authors: Michael J Burke, John E. Wagner, Daniel J. Weisdorf, Qing Cao, Angela R Smith, Margaret L Macmillan, Erica D Warlick, Michael R. Verneris
    Abstract:

    Background Cyclosporine A (CSA) is commonly used after bone marrow Transplantation for graft versus host disease (GVHD) prophylaxis. There have been conflicting reports regarding dosing of CSA and its effects on relapse and GVHD. Higher doses of CSA after bone marrow Transplantation have been associated with greater leukemia relapse. Because it was unknown whether umbilical Cord Blood Transplantation (UCBT) has a similar risk, we studied the impact of CSA levels on UCBT outcomes in patients with acute leukemia. Patients and Methods We reviewed the reCords of 242 consecutive patients with acute leukemia who received UCBT and CSA for GVHD prophylaxis at our institution from 2004-2011. Eighty (33%) patients had acute lymphoblastic leukemia and 162 (67%) had acute myelogenous leukemia. Fifty-seven patients (24%) had a single UCBT; one hundred fifty-four patients (64%) underwent myeloablative conditioning. The median age at Transplant was 30 (1-71) years and median follow-up 4.95 (0.56-10.29) years. Serum CSA levels were collected at least once a week around day -1 and continuing through ∼day 180. We hypothesized that early CSA levels would have the greatest impact on both graft vs. host disease (GVHD) and graft vs. leukemia (GVL) reactions. For the purpose of this study, we examined CSA levels during the first 6 weeks of administration and determined the median CSA level both early (day -3-20) and late (day 21-42). A median of 13 (range was 4-28) CSA levels were drawn during this time period. The median CSA level determined from day-3-20 was 273.5 and the median CSA from days 21-42 was 249.5. Based on the medians in each three week period, patients were divided into four different groups based CSA level and whether it was above or below the median (low-low; low-high; high-low and high-high). Results In multivariate analysis for patients with ALL, disease free survival (DFS) at one year and three years was significantly improved in patients that maintained high levels of CSA from days 21-42 (p=0.02 for low-high and p=0.01 for high-high). Overall survival (OS) was improved at one year for patients with high CSA levels late (p=<0.01 for low-high and high-high) but at three years was improved in only patients that had maintained high CSA levels throughout the entire 6 weeks (p=0.03 for high-high). Patients with high levels of CSA from days 21-42 were also associated with less Transplant related mortality (TRM) (p=0.04 for low-high and p=0.01 for high-high). There was no association of CSA levels and relapse or acute GVHD grades II-IV for ALL patients. In multivariate analysis of AML patients, we found that DFS at one year was significantly improved in patients that maintained high CSA levels at any time during the six weeks (p=0.01 for high-low, low-high and high-high) whereas at 3 years, patients that maintained high CSA levels early had a better chance of DFS (p=0.02 for high-low and high-high). OS at three years was also significantly greater in patients with high levels of CSA early (p=0.05 for high-low and high-high). TRM was decreased in patients that had high levels of CSA early (p=0.02 for high-low and high-high). Interestingly, in multivariate analysis, relapse was improved in patients that maintained initially low levels and then high levels of CSA (p=0.05). Acute GVHD grades II-IV was significantly improved in AML patients with high CSA levels for the entire 6 weeks (p=0.04 for high-high). Conclusions Taken together, these data suggest that high median CSA levels in the first six weeks is critical to ensure improved DFS and OS in patients with acute leukemia undergoing UCBT. Interestingly, in ALL patients, the improvement was seen in patients that maintained high CSA levels late, whereas in AML patients, it was seen in those that maintained high CSA levels early. This implies that the interaction between CSA dose and GVL may be different between myelogenous and lymphoid leukemia following UCBT. Disclosures: Wagner: Novartis: Research Funding.

  • the impact of bone marrow hematogones on umbilical Cord Blood Transplant outcomes in acute myeloid leukemia patients
    Blood, 2011
    Co-Authors: Theodore Honebrink, Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Jeffrey S. Miller, Vanessa J Dayton, Karen Larsen, Qing Cao, Michael R. Verneris
    Abstract:

    Abstract 4148 Hematogones are B-lymphocyte precursors which reside in the marrow and undergo an orderly maturation sequence to give rise to mature B cells. (McKenna, Blood 2001) Recently, the percentage of hematogones detected in the bone marrow (BM) after induction therapy for acute myeloid leukemia (AML) has been associated with improved leukemia-free survival and overall survival. (Chantepie, Blood 2011) Early after umbilical Cord Blood Transplant (UCBT), patients show marked differences in BM hematogone percentages. Little is known about whether such differences are clinically relevant, which may explain why hematogones are not routinely reported in BM differential counts and are, instead, combined with other lymphocytes. We hypothesized that increased hematogones would be associated with superior Transplant outcomes. Two independent reviewers assessed hematogone percentages in BM aspirates performed on day 21 and 100 post-UCBT (i.e. D21 & D100) from 88 patients with AML undergoing myeloablative UCBT at the University of Minnesota between 02/1999 and 07/2008. Patients with evidence of relapse at the time of the marrow analysis were excluded. Because of the morphological similarity between hematogones and leukemic lymphoblasts, only patients with AML were included in this analysis. The reviewers were blinded to clinical outcomes. Correlation coefficients for the morphologic assessment of hematogones at D21 and D100 were each >0.8, confirming good interobserver reproducibility (p Prospective outcome data for patients in the lowest marrow hematogone quartile (0% at D21 after UCBT and ≤0.9% at D100 after UCBT) were compared with those of patients in the upper three quartiles using a multivariate analysis (MVA) model. This model incorporated donor number (single vs. double), recipient age ( At D21 after UCBT, the percentage of marrow hematogones varied from 0 to 10.8% (N = 85). In MVA, a high percentage of hematogones at D21 was associated less aGVHD grade 3–4 (RR=0.3 [0.15–0.59], p=0.01). At D100 after UCBT the percentage of marrow hematogones varied from 0 to 29.8% (N = 69). In MVA, a high percentage of BM hematogones at D100 was associated with improved overall survival (p=0.02) and this was due to a lower treatment related mortality (p= This study shows that BM hematogone percentage may be a useful prognostic indicator in AML patients following UCBT. We propose that hematogones be routinely reported in BM differential counts. Disclosures: No relevant conflicts of interest to declare.

E Gluckman - One of the best experts on this subject based on the ideXlab platform.

  • Umbilical Cord Blood Transplantation for Patients With Acquired and Inherited Bone Marrow Failure Syndromes on Behalf of EuroCord
    Congenital and Acquired Bone Marrow Failure, 2017
    Co-Authors: E Gluckman, Annalisa Ruggeri, R Peffault De Latour
    Abstract:

    The number of umbilical Cord Blood Transplant (UCBT) for patients with acquired or hereditary bone marrow failure syndrome is relatively small compared to the use of other sources of hematopoietic stem cells. Results of related UCBT are comparable to other sources of stem cells with more than 95% survival but the small probability of getting a sibling HLA-identical Cord Blood unit limits its general use. Unrelated Cord Blood Transplant is limited by the availability of a unit with a high number of cells and not more than 0–1 HLA mismatches. Results in retrospective setting show that less than 40% of patients will survive because of a high rate of rejection and Transplant-related mortality. Progress is expected from the use of higher number of cells compared with malignant diseases as well as better selection of patients (children and negative recipient cytomegalovirus serology) and new methods of graft facilitation.

  • History of Cord Blood Transplantation
    Bone Marrow Transplantation, 2009
    Co-Authors: E Gluckman
    Abstract:

    Since the first human Cord Blood Transplant, performed 20 years ago, Cord Blood banks have been established worldwide for the collection and cryopreservation of Cord Blood for allogeneic hematopoietic stem cell Transplant. A global network of Cord Blood banks and Transplant centers has been established for a common inventory and study of clinical outcomes. Results of unrelated allogeneic Cord Blood Transplants in malignant and nonmalignant diseases, in adults and children, show that, compared with HLA-matched unrelated BM Transplant, Cord Blood has several advantages, including prompt availability of the Transplant, decrease of GVHD and better long-term immune recovery resulting in a similar long-term survival. Several studies have shown that the number of cells is the most important factor for engraftment, although some degree of HLA mismatches is acceptable. Developments are expected to facilitate engraftment, including ex vivo expansion of stem cells, intrabone injection of Cord Blood cells and double Cord Blood Transplants. In addition to hematopoietic stem cells, Cord Blood and placenta contain a large number of nonhematopoietic stem cells. In the absence of ethical concern, the unlimited supply of cells explains the increasing interest of using Cord Blood for developing regenerative medicine.

  • donor recipient matching at the hla c locus and early outcomes after unrelated umbilical Cord Blood Transplant ucbt
    Blood, 2008
    Co-Authors: Mary Eapen, E Gluckman, John P Klein, Mary M Horowitz, Mary J Laughlin, Guillermo Sanz, Claudio Anasetti, Joan Garcia, Gesine Koegler, Gerard Michel
    Abstract:

    Previous studies indicate unrelated donor bone marrow Transplantation mismatched at HLA-C locus (antigen-level but not allele-level) result in higher acute graft-versus-host disease (GVHD) and mortality. Hematopoietic recovery is not affected by mismatching at this locus. The current selection of Cord Blood units is based on antigen-level HLA typing at HLA A and B and allele-level at DRB1. The relative importance of matching at HLA-C has not yet been described for unrelated UCBT. To address this question we analyzed hematopoietic recovery, acute GVHD and mortality in 619 UCBT recipients who received a single Cord Blood (CB) unit, a myeloablative preparative regimen and a calcinuerin inhibitor for GVHD prophylaxis. Eighty-three percent of patients received UCBT for leukemia or lymphoma and 17% for immunologic, metabolic or histiocytic diseases. Seventy percent of patients were ≤16 years of age at Transplantation. HLA typing (using molecular methods) was performed for 96% (n=593) of donor-recipient pairs. Method of typing is not available for the remaining 4% (n=26). For all analysis, donor-recipient HLA matching was evaluated at the antigen-level (first 2 of 4 digits) for HLA-A, B, C and allele-level (4 digits) for DRB1. The median infused cell dose was 4 × 10 7 /kg and median follow-up, 2 years. We first examined the effect of donor-recipient HLA matching and cell dose on hematopoietic recovery and mortality considering the current standard for selection of Cord Blood units. Fifteen percent (n=94) were matched at HLA A, B and DRB1, with 43% (n=265) mismatched at 1-locus and 42% (n=260) mismatched at 2-loci. As reported previously, compared to matched UCBT, neutrophil recovery at day-42 was lower after UCBT mismatched at 1-locus (RR 0.48, p=0.042) and 2-loci (RR 0.38, p=0.007). After adjusting for infused cell dose, year of Transplant and disease status, platelet recovery and 1-year mortality rates were not different after matched and mismatched UCBT. We then examined whether the addition of another mismatch at the C locus impacted outcomes. The Table below shows the probabilities of hematopoietic recovery, acute GVHD and survival considering matching at the C-locus in addition to the standard criteria used for CB unit selection. The comparison groups for each of the categories below are patients who received UCBT matched at the C locus for the respective category. In conclusion, the data shown suggest HLA-C does not affect hematopoietic recovery, acute GVHD and 1-year overall survival after UCBT. However, definitive conclusions can only be achieved in a larger series. In the mean time, Cord Blood unit selection need not consider matching at the C-locus.

  • results of unrelated Cord Blood Transplant in fanconi anemia patients risk factor analysis for engraftment and survival
    Biology of Blood and Marrow Transplantation, 2007
    Co-Authors: E Gluckman, Joanne Kurtzberg, Vanderson Rocha, John E. Wagner, Irina Ionescu, Marc Bierings, Richard E Harris, Martin A Champagne, Carmem Bonfim, Marco A Bittencourt
    Abstract:

    Abstract We retrospectively analyzed results of unrelated Cord Blood Transplantation (UCBT) in 93 Fanconi anemia (FA) patients. Median age at Transplantation was 8.6 years (1-45). The units Transplanted were HLA-A, -B, or -DRB1 identical in 12 cases, 1 HLA mismatch in 35 cases, and 2 or 3 HLA differences in 45 cases. The median number of nucleated cells (NC) and CD34+ cells infused of recipient weight was 4.9 × 107/kg and 1.9 × 105/kg, respectively. Participating centers selected the preparative regimen of their choice, in 57 patients (61%), it included Fludarabine. Graft-versus-host disease (GVHD) prophylaxis consisted mostly of cyclosporine with prednisone. Cumulative incidence (CI) of neutrophil recovery was 60 ± 5% at day +60. In multivariate analysis, Fludarabine containing regimen and NC infused ≥4.9 × 107/kg were associated with higher probability of recovery. CI of grade II-IV acute and of chronic GVHD (aGVHD, cGVHD) was 32% ± 5% and 16% ± 4%, respectively. Overall survival (OS) was 40% ± 5%. In multivariate analysis, factors associated with favorable outcome were use of Fludarabine in the conditioning regimen, number of NC infused ≥4.9 × 107/kg, and negative cytomegalovirus (CMV) serology in the recipient. In conclusion, factors easily modifiable such as donor selection and a Fludarabine-containing regimen can considerably improve survival in FA patients given a UCBT. These data are the basis for designing prospective protocols.

  • second Transplant with two unrelated Cord Blood units for early graft failure after haematopoietic stem cell Transplantation
    British Journal of Haematology, 2007
    Co-Authors: Juliana Fernandes, Vanderson Rocha, Marie Robin, Regis Peffault De Latour, R Traineau, A Devergie, Patricia Ribaud, Delphine Rea, Jerome Larghero, E Gluckman
    Abstract:

    Graft failure (GF) can be a fatal complication following haematopoietic stem cell Transplantation (HSCT). We report four patients who developed early GF after unrelated HSCT and who subsequently received a double unrelated Cord Blood Transplant (dUCBT) after reduced-intensity conditioning, at a median 15 d after the decision to perform a second Transplant. Neutrophil recovery was observed in all four patients between day +15 and +31 with full donor chimaerism of one unit. Acute GVHD grades II-IV was observed in three patients. Three are alive, between 12 and 25 months after dUCBT. In conclusion, dUCBT is a promising procedure to treat early GF.

Daniel J. Weisdorf - One of the best experts on this subject based on the ideXlab platform.

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    cGvHD after UCBT was less severe, and had more CR to therapy than MSD Transplant. NRM was similar in patients with cGvHD after UCBT and MSD Transplant. FFS was similar in patients with cGvHD after UCBT and MSD Transplant. We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • outcomes of chronic graft versus host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010-2017) with cGvHD after MSD (n = 104) and UCBT (n = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p = 0.01). Severe cGvHD (32% vs. 15%, p = 0.01) and de-novo onset (45% vs. 15%, p < 0.01) were more frequent following MSD. Liver was more frequently involved in MSD recipients (38% vs. 6%); and GI in UCBT (33% vs. 63%), both p < 0.01. Overall response (CR + PR) was similar between both cohorts. 2-year CR was higher in UCBT (14% vs 33%, p = 0.02). Karnofsky score (KPS) ≥ 90 at cGvHD diagnosis was associated with higher odds of response (95%CI: 1.42-10, p < 0.01). The cumulative incidence of durable discontinuation of immune-suppressive therapy, failure-free survival (FFS) and NRM at 2-years were similar between cohorts. KPS < 90 (95%CI: 3.1-24.9, p < 0.01) and platelets <100 × 10e9/L (95%CI: 1.25-10, p = 0.01) were associated with higher risk of NRM. UCBT patients were more likely to have a prior acute GvHD, less severe cGvHD and more likely to attain CR. Despite differences, both cohorts had similar NRM and FFS. High-risk groups, including those with platelets <100 × 10e9/L and KPS < 90, need careful monitoring and intensified therapy.

  • higher csa levels after umbilical Cord Blood Transplant for acute leukemia result in improved survival
    Blood, 2013
    Co-Authors: Michael J Burke, John E. Wagner, Daniel J. Weisdorf, Qing Cao, Angela R Smith, Margaret L Macmillan, Erica D Warlick, Michael R. Verneris
    Abstract:

    Background Cyclosporine A (CSA) is commonly used after bone marrow Transplantation for graft versus host disease (GVHD) prophylaxis. There have been conflicting reports regarding dosing of CSA and its effects on relapse and GVHD. Higher doses of CSA after bone marrow Transplantation have been associated with greater leukemia relapse. Because it was unknown whether umbilical Cord Blood Transplantation (UCBT) has a similar risk, we studied the impact of CSA levels on UCBT outcomes in patients with acute leukemia. Patients and Methods We reviewed the reCords of 242 consecutive patients with acute leukemia who received UCBT and CSA for GVHD prophylaxis at our institution from 2004-2011. Eighty (33%) patients had acute lymphoblastic leukemia and 162 (67%) had acute myelogenous leukemia. Fifty-seven patients (24%) had a single UCBT; one hundred fifty-four patients (64%) underwent myeloablative conditioning. The median age at Transplant was 30 (1-71) years and median follow-up 4.95 (0.56-10.29) years. Serum CSA levels were collected at least once a week around day -1 and continuing through ∼day 180. We hypothesized that early CSA levels would have the greatest impact on both graft vs. host disease (GVHD) and graft vs. leukemia (GVL) reactions. For the purpose of this study, we examined CSA levels during the first 6 weeks of administration and determined the median CSA level both early (day -3-20) and late (day 21-42). A median of 13 (range was 4-28) CSA levels were drawn during this time period. The median CSA level determined from day-3-20 was 273.5 and the median CSA from days 21-42 was 249.5. Based on the medians in each three week period, patients were divided into four different groups based CSA level and whether it was above or below the median (low-low; low-high; high-low and high-high). Results In multivariate analysis for patients with ALL, disease free survival (DFS) at one year and three years was significantly improved in patients that maintained high levels of CSA from days 21-42 (p=0.02 for low-high and p=0.01 for high-high). Overall survival (OS) was improved at one year for patients with high CSA levels late (p=<0.01 for low-high and high-high) but at three years was improved in only patients that had maintained high CSA levels throughout the entire 6 weeks (p=0.03 for high-high). Patients with high levels of CSA from days 21-42 were also associated with less Transplant related mortality (TRM) (p=0.04 for low-high and p=0.01 for high-high). There was no association of CSA levels and relapse or acute GVHD grades II-IV for ALL patients. In multivariate analysis of AML patients, we found that DFS at one year was significantly improved in patients that maintained high CSA levels at any time during the six weeks (p=0.01 for high-low, low-high and high-high) whereas at 3 years, patients that maintained high CSA levels early had a better chance of DFS (p=0.02 for high-low and high-high). OS at three years was also significantly greater in patients with high levels of CSA early (p=0.05 for high-low and high-high). TRM was decreased in patients that had high levels of CSA early (p=0.02 for high-low and high-high). Interestingly, in multivariate analysis, relapse was improved in patients that maintained initially low levels and then high levels of CSA (p=0.05). Acute GVHD grades II-IV was significantly improved in AML patients with high CSA levels for the entire 6 weeks (p=0.04 for high-high). Conclusions Taken together, these data suggest that high median CSA levels in the first six weeks is critical to ensure improved DFS and OS in patients with acute leukemia undergoing UCBT. Interestingly, in ALL patients, the improvement was seen in patients that maintained high CSA levels late, whereas in AML patients, it was seen in those that maintained high CSA levels early. This implies that the interaction between CSA dose and GVL may be different between myelogenous and lymphoid leukemia following UCBT. Disclosures: Wagner: Novartis: Research Funding.

  • the impact of bone marrow hematogones on umbilical Cord Blood Transplant outcomes in acute myeloid leukemia patients
    Blood, 2011
    Co-Authors: Theodore Honebrink, Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Jeffrey S. Miller, Vanessa J Dayton, Karen Larsen, Qing Cao, Michael R. Verneris
    Abstract:

    Abstract 4148 Hematogones are B-lymphocyte precursors which reside in the marrow and undergo an orderly maturation sequence to give rise to mature B cells. (McKenna, Blood 2001) Recently, the percentage of hematogones detected in the bone marrow (BM) after induction therapy for acute myeloid leukemia (AML) has been associated with improved leukemia-free survival and overall survival. (Chantepie, Blood 2011) Early after umbilical Cord Blood Transplant (UCBT), patients show marked differences in BM hematogone percentages. Little is known about whether such differences are clinically relevant, which may explain why hematogones are not routinely reported in BM differential counts and are, instead, combined with other lymphocytes. We hypothesized that increased hematogones would be associated with superior Transplant outcomes. Two independent reviewers assessed hematogone percentages in BM aspirates performed on day 21 and 100 post-UCBT (i.e. D21 & D100) from 88 patients with AML undergoing myeloablative UCBT at the University of Minnesota between 02/1999 and 07/2008. Patients with evidence of relapse at the time of the marrow analysis were excluded. Because of the morphological similarity between hematogones and leukemic lymphoblasts, only patients with AML were included in this analysis. The reviewers were blinded to clinical outcomes. Correlation coefficients for the morphologic assessment of hematogones at D21 and D100 were each >0.8, confirming good interobserver reproducibility (p Prospective outcome data for patients in the lowest marrow hematogone quartile (0% at D21 after UCBT and ≤0.9% at D100 after UCBT) were compared with those of patients in the upper three quartiles using a multivariate analysis (MVA) model. This model incorporated donor number (single vs. double), recipient age ( At D21 after UCBT, the percentage of marrow hematogones varied from 0 to 10.8% (N = 85). In MVA, a high percentage of hematogones at D21 was associated less aGVHD grade 3–4 (RR=0.3 [0.15–0.59], p=0.01). At D100 after UCBT the percentage of marrow hematogones varied from 0 to 29.8% (N = 69). In MVA, a high percentage of BM hematogones at D100 was associated with improved overall survival (p=0.02) and this was due to a lower treatment related mortality (p= This study shows that BM hematogone percentage may be a useful prognostic indicator in AML patients following UCBT. We propose that hematogones be routinely reported in BM differential counts. Disclosures: No relevant conflicts of interest to declare.

Todd E. Defor - One of the best experts on this subject based on the ideXlab platform.

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    cGvHD after UCBT was less severe, and had more CR to therapy than MSD Transplant. NRM was similar in patients with cGvHD after UCBT and MSD Transplant. FFS was similar in patients with cGvHD after UCBT and MSD Transplant. We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • Outcomes of chronic graft-versus-host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010–2017) with cGvHD after MSD ( n  = 104) and UCBT ( n  = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p  = 0.01). Severe cGvHD (32% vs. 15%, p  = 0.01) and de-novo onset (45% vs. 15%, p  

  • outcomes of chronic graft versus host disease following matched sibling donor versus umbilical Cord Blood Transplant
    Bone Marrow Transplantation, 2021
    Co-Authors: Grigori Okoev, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Margaret L Macmillan, Aleksandr Lazaryan, Najla El Jurdi, Shernan G. Holtan, Claudio G. Brunstein
    Abstract:

    We compared chronic graft-versus-host disease (cGvHD) following umbilical Cord Blood (UCBT) and matched sibling donor peripheral Blood Transplant (MSD). 145 patients (2010-2017) with cGvHD after MSD (n = 104) and UCBT (n = 41) were included. Prior acute GvHD was less frequent in MSD (55% vs. 85%; p = 0.01). Severe cGvHD (32% vs. 15%, p = 0.01) and de-novo onset (45% vs. 15%, p < 0.01) were more frequent following MSD. Liver was more frequently involved in MSD recipients (38% vs. 6%); and GI in UCBT (33% vs. 63%), both p < 0.01. Overall response (CR + PR) was similar between both cohorts. 2-year CR was higher in UCBT (14% vs 33%, p = 0.02). Karnofsky score (KPS) ≥ 90 at cGvHD diagnosis was associated with higher odds of response (95%CI: 1.42-10, p < 0.01). The cumulative incidence of durable discontinuation of immune-suppressive therapy, failure-free survival (FFS) and NRM at 2-years were similar between cohorts. KPS < 90 (95%CI: 3.1-24.9, p < 0.01) and platelets <100 × 10e9/L (95%CI: 1.25-10, p = 0.01) were associated with higher risk of NRM. UCBT patients were more likely to have a prior acute GvHD, less severe cGvHD and more likely to attain CR. Despite differences, both cohorts had similar NRM and FFS. High-risk groups, including those with platelets <100 × 10e9/L and KPS < 90, need careful monitoring and intensified therapy.

  • elevated absolute lymphocyte counts following acute graft vs host disease treatment is associated with therapeutic responses and lower non relapse mortality following umbilical Cord Blood Transplant
    Blood, 2011
    Co-Authors: Michael R. Verneris, Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Todd E. Defor, Bruce R. Blazar, Jeffrey S. Miller, Michael J Burke, Sanyukta K Janardan, Margaret L Macmillan
    Abstract:

    Abstract 4085 Acute graft vs. host diseases (aGVHD) is a life threatening complication of allogeneic hematopoietic cell Transplantation (allo-HCT). In a large series of patients undergoing allo-HCT (n=863) we recently demonstrated that following the initiation of corticosteroids, a clinical response at day 28 was associated with an increased likelihood of overall treatment response and a reduction in treatment related mortality (TRM) (MacMillan, Blood, 2010). We have also shown that patients who have rapid lymphocyte recovery following umbilical Cord Blood Transplantation (UCBT) have improved outcomes (Burke, BBMT, 2010). To date, no study has addressed the influence of absolute lymphocyte count (ALC) on aGVHD treatment responses. We hypothesized that high ALC might predict favorable responses to aGVHD therapy. To test this hypothesis we reviewed the ALC at the time of aGVHD diagnosis and weekly following the initiation of corticosteroid therapy (48 mg/m 2 × 14 days followed by a 10% taper over 8 weeks). ALCs were collected on patients who had clinical laboratory data available in the electronic medical reCord and who had available data on clinical response to corticosteroid therapy. There were 211 patients Transplanted at our center from 2001–2007 who fit the above criteria. Median age was 42 years (range 0.2–69 yrs). Thirty nine patients (19%) were 35 years old. The majority of patients underwent UCBT (n=134, 64%) and most others received a sibling PBSC Transplant (n=71, 34%). Myeloablative conditioning was used in 55% of patients. GVHD prophylaxis was mainly with CSA/MMF (n=142, 67%) or MTX/CSA (n=42, 22%). Median time to aGVHD onset was 37 days (11–92). Patterns of aGVHD included skin only (n=91, 43%), gut only (n=36, 17%) or multi-organ involvement (n=82, 39%). At the time of GVHD diagnosis, ALC was not predictive of response to therapy. Likewise, there was no association with the ALC at D7 (after the start of steroid treatment) and therapeutic response. The D14 post-treatment ALC showed an association with clinical response at D28 (a time point previously associated with long-term responses and NRM). Patients with an ALC of 0–0.14, 0.15–0.34 and >0.35 at D+14 after corticosteroid therapy had a 40%, 54% and 68% chance of a clinical response at D28 (p>0.01). This translated into a reduction in non-relapse mortality for patients with higher ALC (0–0.14 vs. >0.15; 33% [19–47%] vs 23% [17–29%], p=0.04). Subgroup analysis showed that these observations were mainly driven by the myeloablatve UCB group. Treating ALC as a continuous variable and using a repeated measures approach, we observed that for every unit increase in ALC between the day of diagnosis and D14, there was a 2.26 higher increased likelihood of having a complete clinical response at D28 (p>0.001). Similar results were seen for NRM (OR=0.89 [0.81–9.8], p=0.01). In multivariate analysis, repeated measures of ALC (from D0-14) remained significant for both D28 clinical response (p=0.001) and NRM (p=0.05). Patients with steroid refractory aGVHD (n=17) were treated with ATG. Because steroid refractory aGVHD has poor outcomes and because ATG can negatively impact ALC, we removed these patients from the analysis to determine the impact of ALC. In this subgroup analysis, ALC at D14 after aGVHD treatment remained associated with D28 clinical response in multivariate analysis (OR=3.01, 95%CI[1.24–7.35], p=0.02). Using repeated analysis, the change in ALC from aGVHD treatment day D0 to 14 was associated with D28 treatment response (OR=4.42 [1.88–10.37], p Disclosures: No relevant conflicts of interest to declare.

  • Negative effect of KIR alloreactivity in recipients of umbilical Cord Blood Transplant depends on Transplantation conditioning intensity.
    Blood, 2009
    Co-Authors: Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Sarah Cooley, Harriet Noreen, Juliet N. Barker, Todd E. Defor, Michael R. Verneris, Bruce R. Blazar, Jeffrey S. Miller
    Abstract:

    We examined the clinical impact of killer-immunoglobulin receptor-ligand (KIR-L) mismatch in 257 recipients of single (n = 91) or double (n = 166) unit umbilical Cord Blood (UCB) grafts after myeloablative (n = 155) or reduced intensity (n = 102) conditioning regimens. Analyses of double unit grafts considered the KIR-L match status of the dominant engrafting unit. After myeloablative conditioning, KIR-L mismatch had no effect on grade III-IV acute graft-versus-host disease (GVHD), Transplantation-related mortality (TRM), relapse, and survival. In contrast, after reduced intensity conditioning, KIR-L mismatch between the engrafted unit and the recipient resulted in significantly higher rates of grade III-IV acute GVHD (42% [CI, 27-59] vs 13% [CI, 5-21], P < .01) and TRM (27% [CI, 12%-42%] vs 12% [CI, 5%-19%], P = .03) with inferior survival (32% [CI, 15%-59%] vs 52% [CI, 47%-67%], P = .03). Multivariate analysis identified KIR-L mismatch as the only predictive factor associated with the development of grade III-IV acute GVHD (RR, 1.8 [CI, 1.1-2.9]; P = .02) and demonstrated a significant association between KIR-L mismatch and increased risk of death (RR, 1.8; 95% CI, 1.0-3.1; P = .05). Our results do not support the selection of UCB units based on KIR-L status and suggest that KIR-L mismatching should be avoided in reduced intensity UCB Transplantation.