scholarly journals Optimizing selection of double cord blood units for transplantation of adult patients with malignant diseases

2020 ◽  
Vol 4 (24) ◽  
pp. 6327-6335
Author(s):  
Giancarlo Fatobene ◽  
Fernanda Volt ◽  
Frederico Moreira ◽  
Lívia Mariano ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Cord Blood ◽  
Single Unit ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Abo Incompatibility ◽  
Grade Ii ◽  
Unrelated Cord Blood ◽  
Hla Mismatches

Abstract Double-unit unrelated cord blood transplantation (DUCBT) is an option in patients for whom a single unit is not sufficient to provide an adequate number of cells. As current guidelines on UCB unit selection are mainly based on single-unit UCB data, we performed a retrospective analysis of 1375 adult recipients of DUCBT for hematologic malignancies to determine optimal criteria for graft selection. Cryopreserved total nucleated cells (TNCs; ≤3.5 vs >3.5 × 107/kg: hazard ratio [HR], 1.53; 30% vs 45%; P = .01), number of HLA mismatches (≥2 vs 0-1: HR, 1.28; 42% vs 48%; P = .01), and ABO compatibility (minor/major ABO incompatibility vs compatibility: HR, 1.28; P = .04) were independent risk factors for OS. Cryopreserved CD34+ cell dose ≥0.7 × 105/kg in the winning UCB was associated with improved OS (HR, 1.34; P = .03). Low TNC (≤3.5 × 107/kg) and CD34+ (≤1.4 × 105/kg) cell doses were related to decreased neutrophil recovery (HR, 0.65 [P = .01] and HR, 0.81 [P = .01], respectively). DUCBT recipients with ≥2 HLA mismatches had a higher incidence of grade II-IV and III-IV acute graft-versus-host disease (HR, 1.26 [P = .03] and 1.59 [P = .02], respectively). Low TNC dose (HR, 1.57; P = .02) and receiving UCB with ≥2 HLA mismatches (HR, 1.35; P = .03) were associated with increased transplant-related mortality. Our data support selecting adequately HLA-matched UCB units with a double-unit cryopreserved TNC dose >3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.

scholarly journals Prognostic Impact of Pre-Transplant Serum C-Reactive Protein in Patients Receiving a Single-Unit Unrelated Cord Blood Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5853-5853
Author(s):  
Akiko Negoro ◽  
Heiwa Kanamori ◽  
Jun Aoki ◽  
Satoshi Koyama ◽  
Takayoshi Tachibana ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Single Unit ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Blood Transplantation ◽  
Unrelated Cord Blood ◽  
Serum Crp

Abstract Background: C-reactive protein (CRP) is an acute-phase protein and its serum level rises in response to inflammation. There have been some reports about the relationship between the serum CRP level before allogeneic hematopoietic stem cell transplantation (HSCT) and transplant outcomes. This study particularly evaluated the impact of pre-transplant CRP on the outcome in patients who received a single-unit unrelated cord blood transplantation (UCBT) for hematologic malignancies. Patients and methods: Adult patients receiving UCBT as first HSCT for hematologic malignancies between April 2009 and April 2016 at Kanagawa Cancer Center were retrospectively analyzed in this study. Serum CRP was measured by a latex agglutination assay (normal range 0.0-0.3 mg /dl). The time of measurement was within a few days before the conditioning procedure. Patients were divided into 2 groups according to the serum CRP levels (normal CRP group [≤0.03 mg/dl] and high CRP group [> 0.03 mg/dl)]). A total of 80 patients (pts) included 36 pts with acute myeloid leukemia (AML), 27 pts with acute lymphoid leukemia (ALL), 13 pts with myelodysplastic syndrome (MDS), and 4 pts with others. The median age was 59 years (range, 20-68 years). There were 45 males and 35 females. A disease risk at transplantation indicated a standard risk in 47 pts and a high risk in 33 pts. Myeloablative conditioning (MAC) was employed for 25 pts and reduced intensity conditioning (RIC) was for 55 pts. Data were analyzed with EZR statistical software. Results: The median level of serum CRP at pre-transplant was 0.17 mg/dl (range: 0.01-12.93). No. of patients in normal and high CRP levels was 56 pts and 24 pts, respectively. Disease high risk was significantly associated with a high level of serum CRP. Other pre-transplant factors such as age, gender, diagnosis, comorbidity index, and serum ferritin levels were not related with serum CRP levels. The high incidence of gradeⅡ-Ⅳacute GVHD was significantly associated with high CRP group compared to normal CRP group (55% vs. 19%, p = 0.001). After a median follow-up of 16 months (range: 1-86 months), 3-year overall survival (OS) was 62%. The cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 3 years was 26% and 14%, respectively. According to univariate analysis, factors associated with worse 3-year OS included disease high risk at transplantation (vs. low risk; 49% vs. 70%, p = 0.025) and high CRP levels (vs. normal CRP levels; 28% vs. 77%, p < 0.001). Higher 3-year CIR was significantly correlated with high CRP levels (vs. normal CRP levels; 46% vs. 18%, P = 0.009). Adverse factors for NRM was high scores (≥3) of HCT-CI (vs. low scores (≤2) of HCT-CI; 25% vs. 5%, p=0.029). Multivariate analysis showed that high CRP levels (hazard ratio [HR], 4.13; 95% confidence interval [CI], 1.76-9.63; p = 0.001) was an independent determinant of 3-year OS. Prognostic factors related with CIR and NRM was high CRP levels (HR, 2.63; 95%CI, 0.96-7.21; p = 0.059) and high scores of HCT-CI (HR, 4.25; 95%CI, 0.89-20.29; p = 0.069) respectively, but those difference did not reach statistical significance. Conclusions: Pre-transplant serum CRP might be a useful biomarker for predicting the transplant outcome and the development of acute GVHD following UCBT. Disclosures No relevant conflicts of interest to declare.

Kinetics of Chimerism and Unit Predominance After Double Umbilical Cord Blood Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 225-225 ◽  
Author(s):  
Pablo A. Ramirez ◽  
John E. Wagner ◽  
Todd Defor ◽  
Bruce R. Blazar ◽  
Michael Verneris ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Conflicts Of Interest ◽  
Cord Blood Transplantation ◽  
Hematologic Malignancies ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Reduced Intensity

Abstract Abstract 225 Double umbilical cord blood (dUCB) transplantation (dUCBT) is a strategy to overcome dose limitation in adult recipients. It is established that after dUCBT, one unit will predominate by day +100 after transplant in >95%. While in some studies order of infusion has been associated with unit predominance, this has not been reproduced in an analysis at our center. However, significant differences in UCB infusion between these two analysis were present. In particular, at our center, unit order of infusion is random and the second infusion is within minutes of the first, while this prior study separated infusion time by 6 hours. Between 2001 and 2009, 262 patients with hematologic malignancies underwent a dUCBT and engrafted. Of these, 233 were >18 years of age with 39% conditioned with cyclophosphamide (CY) 60 mg/kg, fludarabine (FLU) 75 mg/m2 and total body irradiation (TBI) 1320–1375 cGy and 61% with CY 50 mg/kg, FLU 200 mg/m2 and TBI 200 cGy with 1/3 also receiving antithymocyte globulin (ATG); 100% received cyclosporine and mycophenolate mofetil posttransplant immunosuppression. Median recipient weight was 78 kg and median follow-up was 2.7 years (0.5-7.2). The following factors were considered in the logistic regression model: total nucleated cell (TNC), CD34+ and CD3+ cell and colony forming units-granulocyte macrophage (CFU-GM) doses, HLA match, sex and ABO-match, CXCR4 expression on CD34+ cells, order of infusion and cell viability. Cell viability, infused TNC, CD34+ and CD3+ cell and CFU-GM doses were remarkably similar between the predominating and non-predominating unit. By day 21, the predominating unit (i.e., representing >70% of hematopoiesis) was achieved in 73 of 90 (81%) patients after MA conditioning and in 88 of 145 (61%) patients after reduced dose conditioning (p<0.01). Subsequently, predominant unit chimerism in the bone marrow between MA and NMA was similar by day 100 (95% vs. 97%, p=0.35), day 180 (97% vs. 100%, p=0.3), day 365 (97% vs. 98%, p=0.84) and day 730 (94% vs. 93%, p=0.81). Notably, CD3+ cell dose and HLA were strongly associated with unit predominance. In the MA setting, CD3+ cell dose was the most significant factor that predicted unit predominance [OR 4.4 (95% CI, 1.8–10.6, p<0.01)]; while CD3+ cell dose [OR 2.1 (95%CI, 1.0–4.2, p=0.05)] and HLA-match [OR 3.4 (95%CI 1.0–11.4, p=0.05)] were independent predictors in the reduced intensity setting. In summary, immunological graft-graft interactions are likely responsible for unit predominance. While the combined CD34 dose and CFU-GM dose from the two UCB units are critical for rate of neutrophil recovery (data previously reported), CD3 dose and HLA match after reduced intensity conditioning are important in determining which unit will ultimately predominate. These findings have potential implications in the algorithm of graft selection. Disclosures: No relevant conflicts of interest to declare.

Reduced Intensity Conditioning Regimen Prior to Unrelated Cord Blood Transplantation In Patients with Acute Myeloid leukemia : Preliminary Analysis of a Prospective Phase II Multicentric Trial on Behalf of Societe Française De Greffe De Moelle Osseuse Et Therapie Cellulaire (SFGM-TC) and Eurocord

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 911-911 ◽  
Author(s):  
Bernard Rio ◽  
Sylvie Chevret ◽  
Stephane Vigouroux ◽  
Patrice Chevallier ◽  
Sabine Furst ◽  
...  
Keyword(s):  
Cord Blood ◽  
De Novo ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Blood Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Prospective Phase ◽  
Grade Ii ◽  
Unrelated Cord Blood

Abstract Abstract 911 Unrelated cord blood transplantation (UCBT) after reduced intensity conditioning regimen (RIC) has extended the use of CB in elderly patients(pts) and those with co-morbidities without an HLA identical donor. To evaluate RIC-UCBT in pts with Acute Myeloid Leukemia (AML), we conducted a prospective phase II multicentric trial in France, whose primary objective was to show a reduction in non-relapse mortality (NRM) from 40% (based on registry data) to 20%. We calculated that at least 76 pts should be enrolled (for controlling type I and type II error rates both at 5%). Inclusion criteria were: 1) de novo and secondary AML, 2) lack of HLA identical unrelated donor (10/10 or 9/10), 3) cord blood units (CBU) with less than 3/6 HLA disparities, 4) a nucleated cell dose before freezing of more than 3×107/Kg within 1 or 2 CBU. The conditioning regimen consisted of cyclophosphamide (50mg/kg) +fludarabine (200mg/m2)+ TBI(2Gy), CsA +MMF as GVHD prophylaxis and GCSF from day +1. Supportive care and infections prophylaxis were given according to the EBMT recommendations. Patients were enrolled in 23 centers from Oct. 2007 to Sept. 2009. This preliminary results include 65 pts, 55% female, median age at diagnosis of 49.7 years (range, 13–65), mostly with de novo AML, extramedullary leukemic involvement of AML in 8%. Cytogenetics was normal in 33 pts (52%), of those 10/33 were FLT3 positive, and abnormal in 48%, including 36% with a complex karyotype and/or abnormality of chr 5, 7, 11 and inv 3. Nine (14%) pts had been previously transplanted. 57% of the pts were transplanted in 1st complete remission (CR1), 40% in CR2 and 3% in non-remission. Median time from diagnosis to transplant was 6.6 months (range, 3.7–24) in pts transplanted in CR1 and was 21 months (range, 5.1–93) for pts transplanted in CR2. Median age was 51 years (14-65), median weight was 65 kg (49-105), 51% were CMV-seropositive. The median follow-up for survivors was 20 months (range 9–30). 51% of the pts had no comorbidity. The Sorror score was 1 in 17%, 2 in 8 and 3 or more in 24%. 60% of the pts received 2 CBU. The median number of nucleated cells (NC) and CD34 infused after thawing were 3.4 x107/kg (0.5-6) and 1.1 x105/kg (0.10-3.1), respectively. Patients transplanted with a single CBU received a median of 2.92 NC x107/kg and of 0.92 CD34 x105/kg. Those transplanted with 2 CBU received 3.5 x107/kg and 1.1 x105/kg, respectively; 3% of the units were HLA matched, 23% 5/6 and 74% 4/6 (HLA defined as low resolution for HLA-A and B and high resolution for HLA-DRB1; the highest HLA disparity between CB and pts was taken into consideration in double CBT). ABO major incompatibility was observed in 40% of the pts (in double CB, the highest incompatibility was considered). Results: Median time to cell recovery was 15 days (95CI: 11–20) for neutrophils and 43 days for platelets. Cumulative incidence (Cum Inc) of neutrophil recovery at day 60 was 86% (95CI: 78–95%); 85% (95CI: 69–99) after 1 CBU and 87% (95CI: 76–98) after 2 CBU (p=ns). Twenty-three pts developed grade II-IV acute(a) GVHD (grade II: n=8; grade III n=14; grade IV n=1); Cum Inc of aGVHD (II-IV) at day 100 was 37% (95CI: 24–47%)(38% (95CI: 20–57) for 1 and 34% (95CI: 19–49) for 2 CBT (p=ns)). At 1 year post-transplant, Cum Inc of chronic GVHD was 13% (95CI: 3–23%) and Cum Inc of NRM was 18% (95CI: 8–28%), with variations according to patient status (20% for pts transplanted in CR1 and 13% for pts transplanted in CR2) or number of CBU (21% for 1 CBU and 16% for 2 CBU). At 1 year, Cum Inc of relapse was 30% (95CI : 19–42%); it was 37% for patients transplanted in CR1 and 19% for patients transplanted in CR2 (p=ns), 32% for those transplanted with one CBU and 29% for those transplanted with 2 CBU (p=ns). At 1 year, overall survival was 60% (95CI: 48–74%) and LFS was 52% (95CI: 41–66%). LFS was 43% (95CI: 29–63%) for pts transplanted in CR1, 68% (95CI: 52–89%) for those transplanted in CR2 (p=0.05). According to number of graft, LFS was 48% (95CI: 31–73%) for those transplanted with 1 CBU and 55% (95CI: 41–74%) for those transplanted with 2 CBU (p=ns). In conclusion, the preliminary results of this prospective trial show the interest of RIC-UCBT in patients with AML without a HLA identical donor. A decreased NRM was observed, based on data with a median follow-up of 20 months. We have observed better LFS in patients transplanted in CR2, probably related to the very high risk group of patients transplanted in CR1. These results will be confirmed in the whole enrolled cohort. Disclosures: No relevant conflicts of interest to declare.

scholarly journals HLA mismatch direction in cord blood transplantation: impact on outcome and implications for cord blood unit selection

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3969-3978 ◽  
Author(s):  
Cladd E. Stevens ◽  
Carmelita Carrier ◽  
Carol Carpenter ◽  
Dorothy Sung ◽  
Andromachi Scaradavou
Keyword(s):  
New York ◽  
Human Leukocyte Antigen ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Leukocyte Antigen ◽  
Blood Transplantation ◽  
Cord Blood Unit ◽  
Unrelated Cord Blood

AbstractDonor-recipient human leukocyte antigen mismatch level affects the outcome of unrelated cord blood (CB) transplantation. To identify possible “permissive” mismatches, we examined the relationship between direction of human leukocyte antigen mismatch (“vector”) and transplantation outcomes in 1202 recipients of single CB units from the New York Blood Center National Cord Blood Program treated in United States Centers from 1993-2006. Altogether, 98 donor/patient pairs had only unidirectional mismatches: 58 in the graft-versus-host (GVH) direction only (GVH-O) and 40 in the host-versus-graft or rejection direction only (R-O). Engraftment was faster in patients with GVH-O mismatches compared with those with 1 bidirectional mismatch (hazard ratio [HR] = 1.6, P = .003). In addition, patients with hematologic malignancies given GVH-O grafts had lower transplantation-related mortality (HR = 0.5, P = .062), overall mortality (HR = 0.5, P = .019), and treatment failure (HR = 0.5, P = .016), resulting in outcomes similar to those of matched CB grafts. In contrast, R-O mismatches had slower engraftment, higher graft failure, and higher relapse rates (HR = 2.4, P = .010). Based on our findings, CB search algorithms should be modified to identify unidirectional mismatches. We recommend that transplant centers give priority to GVH-O-mismatched units over other mismatches and avoid selecting R-O mismatches, if possible.

scholarly journals Sequential Transplantation of Haploidentical Stem Cell and Unrelated Cord Blood With Using ATG/PTCY Increases Survival of Relapsed/Refractory Hematologic Malignancies

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Li ◽  
Xiaofan Li ◽  
Yiling Chen ◽  
Duihong Li ◽  
Xianling Chen ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hematologic Malignancies ◽  
Post Transplantation ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
Unrelated Cord Blood

Allogeneic haploidentical HSCT (haplo-HSCT) and unrelated umbilical cord blood transplantation(UCBT)are used in patients lacking HLA-identical sibling or unrelated donors. With myeloablative condition and GVHD prophylaxis of using low-dose ATG and post-transplantation cyclophosphamide (PTCY), we conducted a prospective clinical trial. Of eligible 122 patients from February 2015 to December 2019 in the study, 113 patients were involved. Forty-eight patients were in the group of sequential haplo-cord transplantation (haplo-cord HSCT), and 65 patients were in the group of single UCBT. The primary endpoint of 2-year disease-free survival (DFS) was no statistical difference between groups (64.1 vs. 56.5%), p&gt;0.05. The analysis of subgroup patients with relapsed/refractory showed haplo-cord HSCT was associated with better OS (HR 0.348, 95% CI, 0.175–0.691; p=0.0025), DFS (HR 0.402, 95% CI, 0.208–0.779; p=0.0069), and GRFS (HR 0.235, 95% CI, 0.120–0.457, p&lt;0.0001) compared to the single cord group. The 2-year’s probability in OS, DFS, and GRFS was 64.9 vs. 31.6%, 64.5 vs. 31.6%, and 60.8 vs. 15.0% in the haplo-cord group and single cord group, respectively. III-IV acute GVHD 8.3 vs. 6.2%, chronic GVHD 25.8 vs. 13.7%, and extensive chronic GVHD 5.3 vs. 1.8% were shown in corresponding group, p&gt;0.05. The patients engrafted persistently with UCB showed better survival outcomes. Our sequential Haplo-cord HSCT with ATG/PTCY improved the survival of patients and might be an alternative transplantation approach for patients with relapsed/refractory hematologic malignancies.

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