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.

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 &gt;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 &gt;3.5 × 107/kg and CD34+ cell dose of ≥0.7 × 105/kg per unit in DUCBT candidates.

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.

Unrelated Cord Blood Transplantation (UCBT) in Adults with MDS or Secondary Acute Myeloblastic Leukemia (sAML): a Survey On Behalf of Eurocord and CLWP of EBMT.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1198-1198
Author(s):  
Marie Robin ◽  
Guillermo Sanz ◽  
Irina Ionescu ◽  
Bernard Rio ◽  
Anne Sirvent ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Median Time ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Neutrophil Recovery ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract Abstract 1198 Poster Board I-220 Background: Unrelated cord blood transplantation is an alternative option to treat patients with high risk hematologic malignancies in the absence of an HLA identical donor. Results of UCBT in patients with MDS or secondary leukaemia (sAML) have been scarcely published. Method: We performed a survey to identify predictors of outcomes in a large cohort of 108 adults with MDS or sAML reported to Eurocord-Promise data bases (62 centres in 17 countries in Europe) and transplanted with an UCBT from 1998 to 2007. Sixty-seven patients were transplanted for sAML (secondary to MDS in 42 cases) and 41 for MDS. Worst status before UCBT for MDS was RA in 4, RAEB1 in 10, RAEB2 in 14, CMML or RAEBt in 9, unclassified in 4 patients. IPSS classification at transplantation was low, intermediate 1, intermediate 2, high or missing in 8, 12, 7, 6 and 8 patients, respectively. For patients with sAML, 48% were transplanted in CR1 at UCBT. Median age at UCBT was 43 years (from 18 to 72 years). Median time from diagnosis to UCBT was 10 months. Transplant characteristics: 77 patients received a single and 31 a double UCBT. UCB grafts had ≥ 2/6 HLA mismatched in 60 % of cases. Myeloablative conditioning regimen (MAC) was given to 57 patients whereas 51 patients received a reduced intensity conditioning regimen (RIC). GVHD prophylaxis consisted in CSA+MMF in 52, CSA+steroids in 43 and other combinations in 13 patients. Median number of collected nucleated cells was 3.4 for single and 4.6 × 107/kg for double UCBT. Median follow-up was 25 months. Results: cumulative incidence (CI) of neutrophil recovery at day 60 was 82±4% with a median time to achieve more than 500 ANC/mm3 of 23 days. Neutrophil recovery was independently associated with number of CD34+ cells/kg (> 1.1 × 105, Hazard Ratio (HR), 1.79; P= .02) and advanced disease status (intermediate 2 or high MDS and sAML not in CR; HR, 1.92; P= .007). CI of grade II-IV acute GVHD at day 100 and chronic GVHD at 2 years were 26±4% (II n=18, III n=6, IV n =6) and 42%±8, respectively. Two-year non-relapse mortality was significantly higher after MAC (62% vs. 34%, p=0.009). In counterpart, 2-year relapse rate was higher after RIC (14% vs 29%, p=0.02). Two-year DFS and OS were 30 and 34%, respectively. In univariate analysis, among patient-, disease- and transplant- factors studied only patients with high risk disease at maximal pre-transplant stage or transplanted > 18 months after diagnosis had significant poorer DFS (disease risk: 49% vs. 22%; time: 35% vs. 15%). However, in multivariate analysis, the only factor associated with decreased DFS was advanced disease (HR: 2.05; p= .01). Conclusion: These data indicate that UCBT is an acceptable alternative option to treat adults with high risk MDS or sAML without a HLA-matched related or unrelated bone marrow donor. Controlled disease at time of transplantation improves outcome. More investigations are needed to compare these results with outcomes after other stem cell sources from unrelated HSCT donor. Disclosures: No relevant conflicts of interest to declare.

Reduced-Intensity Unrelated Cord-Blood Transplantation (RI-UCBT) for Patients with High-Risk Myeloid Malignancies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2891-2891 ◽  
Author(s):  
Koichiro Yuji ◽  
Shigesaburo Miyakoshi ◽  
Shinsuke Takagi ◽  
Daisuke Kato ◽  
Yuji Miura ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Myeloid Malignancies ◽  
Blood Transplantation ◽  
Gvhd Prophylaxis ◽  
Preparative Regimen ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract &lt;Background&gt;Allogeneic stem cell transplantation (allo-SCT) is a curative treatment for advanced myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The therapeutic benefits are attributable to myeloablative radiochemotherapy and graft-versus-leukemia effect, whereas severe regimen-related toxicity (RRT) limits the efficacy of allo-HSCT to young patients without co-morbidities. Reduced-intensity stem-cell transplantation (RIST) using a non-myeloablative preparative regimen has been developed to decrease RRT, whilst preserving an adequate antitumor effect. RIST may be a curative treatment for heavily pretreated elderly patients with myeloid malignancies. Umbilical cord blood from unrelated donors has been used as an alternative stem cell source. We report the results of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in patients with advanced or high-risk myeloid malignancies. &lt;Patients and Methods&gt;Forty-eight patients (median age, 59 yr; range, 17–70) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2, melphalan 80 mg/m2, and 4 Gy of total body irradiation from 2002 to 2004. Twelve-seven patients were classified as AML not otherwise categorized, 16 as AML with multilineage dysplasia, 4 as RAEB and 1 as RA. The disease status at transplant was 2 CR1, 5 CR2 or CR3, 3 untreated and 38 refractory. The median infused total cell dose was 2.8 (range, 1.8–4.5) x 107/kg. HLA match was 6/6 in 1, 4/5 in 8, and 4/6 in 39 cases. GVHD prophylaxis was composed of cyclosporine (n=25) or tacrolimus alone (n=23). &lt;Results&gt; Fourty-three patients achieved primary neutrophil engraftment after a median of 20 days. Twelve patients developed grade II–IV acute GVHD and 7 developed chronic GVHD. Fifteen patients achieved CR. Eleven patients experienced relapse. Thirty-one patients died as a result of relapse (n=10), GVHD-associated complications (n=10), or infection (n=11). With a median follow-up of 489 days (range, 192–768), 17 of 48 patients are alive, resulting in a 2-year overall survival rate of 31% (95% CI, 16% to 45%). GVHD prophylaxis influenced outcomes (p&lt;0.05). &lt;Discussion&gt; These data suggest that RI-UCBT may be an effective option for patients with high-risk myeloid malignancies who lack an HLA-matched donor. RI-UCBT is associated with high TRM, providing a rationale for a larger clinical study, which should be modified to focus on enhancing any GVL effect, minimizing toxicities, and controlling infectious complications. Figure Figure Figure Figure

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