Momentum of neutrophil recovery using an exponential growth model predicts the prognosis of single cord blood transplantation

2021 ◽  
Author(s):  
Masamichi Isobe ◽  
Takaaki Konuma ◽  
Maki Monna‐Oiwa ◽  
Motohito Okabe ◽  
Seiko Kato ◽  
...  
Keyword(s):  
Cord Blood ◽  
Growth Model ◽  
Exponential Growth ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Exponential Growth Model

Cost-Effectiveness of Double-Unit Cord Blood Transplantation Versus Single-Unit Cord Blood Transplantation in Adult Patients with Acute Leukaemia in France- On Behalf of SFGM-TC, Eurocord, ALWP-EBMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3130-3130
Author(s):  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Namik Taright ◽  
Federico Garnier ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cord Blood ◽  
Median Time ◽  
Acute Leukaemia ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
The Cost ◽  
Mean Cost

Abstract Abstract 3130 Unrelated donor cord blood transplantation (UCBT) using a single (s) or double (d) CB unit has become a widely accepted treatment for hematologic diseases in the absence of an HLA identical stem cell donor. Retrospective studies have reported a reduced risk of relapse after dUCBT compared with sUCBT, however one limitation of using dUCBT is the cost of the 2 units, but comparison of the total cost of the 2 procedures has not yet been published. The aim of this study was to evaluate the outcome of adult patients transplanted for acute leukaemia in first remission and to access the cost-effectiveness of dUCBT compared to sUCBT). We analyzed clinical results and costs of 134 consecutive CBT performed in 31 transplant centers in France from 2001 to 2009. All hospital costs were estimated from donor search to 1 year after UCBT, according to the French public system. A Markov decision analysis model was used to calculate the QALY (quality-adjusted life years) and cost-effectiveness ratio (ICER). For cost-effectiveness analysis, reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) were studied separately. Forty patients were transplanted for ALL and 94 for AML in CR1. Median age was 42 years and median time from diagnosis to UCBT was 180 days. CMV serology for 49% of patients was negative. Sixty one patients received a sUCBT and 73 a dUCBT. Twenty eight percent of CB units were HLA identical to recipient or had 1 HLA disparity (antigen level for HLA-A and B allelic level for DRB1) and 72% had 2–3 HLA disparities. Median infused nucleated cell dose was 2.7×107/kg in sUCBT and 3.8×107/kg in dUCBT. Seventy nine patients received a RIC (97% TBI<4Gy based) and 55 a MAC (84% TBI ≥4Gy Based). The median follow-up was 31 months after sUCBT and 24 months after dUCBT. Neutrophil recovery was achieved in 115 patients (51 of 61 patients who received a sUCBT and 64 of 73 dUCBT), with a median time of 23 (6–53) days. No statistical difference was observed for neutrophil recovery after sUCBT or dUCBT. dUCBT was associated with a higher rate of acute GVHD grade II-IV: 56% versus 30% for sUCBT, p=0.003. At day +100, 53% of patients experienced CMV reactivation (37% after sUCBT and 71% after dUCBT, p=0.01), 45% had viral infection other than CMV and 49% had bacterial infection. Fifteen patients (11%) received a second transplant, 6 for graft failure (4 in sUCBT group and 2 in dUCBT group) and 9 for relapse (6 in sUCBT group and 3 in dUCBT group). The median interval between first and second transplant was 327 days. The estimated survival at 2 years was 40±6% vs 58±6% after sUCBT and dUCBT, respectively (p=0.04). Leukaemia-free survival at 2 years was 30±6% in sUCBT vs 49±6% in dUCBT, (p=0.09). Cumulative incidence of relapse at 2 years was lower after dUCBT: 29±4% vs to 42±4% after sUCBT, (p=0.04). No statistically significant difference was observed in terms of non-relapse mortality and incidence of chronic GVHD. The mean cost for donor identification and UCB acquisition was 28.164 € for sUCBT and 48.929 € for dUCBT. The estimated costs within 1 year after RIC-sUCBT was 133.790 € and it was 211.735 € after MAC-sUCBT. The estimated cost was 180.549 € after RIC-dUCBT and 205.375 €, after MAC-dUCBT. Table 1 summarizes details of costs by type of graft and conditioning. In the MAC group, dUCBT was associated with lower cost (minus 13.554€) and better effectiveness (plus 0, 53 QALY). The cost per QALY obtained after RIC-dUCBT compared with sUCBT was 91.199 €. In conclusion, In France, dUCBT is associated with higher incidence of acute GVHD, lower relapse and better survival in adults transplanted for acute leukaemia. With a MAC, dUCBT is the best option, and the cost per QALY obtained for dUCBT when using RIC is acceptable.Table.Estimated costs from donor search to 1 year after transplantation for single UCBT, double UCBT and type of conditioning regimen (MAC or RIC)sUCBTdUCBTCB unit search28 164 €48 929 €MACInitial hospitalisationMean duration (d)6665Mean cost137.757 €131.773 €Outpatient visitsNumber of days911Mean cost7.788 €9.223 €Further hospitalisationsMean duration (d)5023Mean cost38.026 €15.449 €Total mean cost within 1 year211.735 €205.374 €RICInitial hospitalisationMean duration (d)2948Mean cost58.621 €96.335 €Outpatient visitsNumber of days2123Mean cost17.870 €19.366 €Further hospitalisationsMean duration (d)4021Mean cost29.135 €15.918 €Total mean cost within 1 year133.790 €180.549 € Disclosures: No relevant conflicts of interest to declare.

Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT

Blood ◽  
2010 ◽  
Vol 116 (11) ◽  
pp. 1849-1856 ◽  
Author(s):  
Andrée-Laure Herr ◽  
Nabil Kabbara ◽  
Carmem M. S. Bonfim ◽  
Pierre Teira ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Cord Blood ◽  
Advanced Disease ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Human Leukocyte ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Factors Influencing ◽  
Gvhd Prophylaxis

AbstractWe analyzed risk factors influencing outcomes after related (R) human leukocyte antigen-identical cord blood transplantation (CBT) for 147 patients with malignancies reported to Eurocord–European Group for Blood and Marrow Transplantation. CBT has been performed since 1990; median follow-up was 6.7 years. Median patient age was 5 years. Acute leukemia was the most frequent diagnosis (74%). At CBT, 40 patients had early, 70 intermediate, and 37 advanced disease. CB grafts contained a median of 4.1 × 107/kg total nucleated cells (TNCs) after thawing. The cumulative incidence (CI) of neutrophil recovery was 90% at day +60. CIs of acute and chronic graft-versus-host disease (GVHD) were 12% and 10% at 2 years, respectively. At 5 years, CIs of nonrelapse mortality and relapse were 9% and 47%, respectively; the probability of disease-free survival (DFS) and overall survival were 44% and 55%, respectively. Among other factors, higher TNCs infused was associated with rapid neutrophil recovery and improved DFS. The use of methotrexate as GVHD prophylaxis decreased the CI of engraftment. Patients without advanced disease had improved DFS. These results support banking and use of CB units for RCBT. Cell dose, GVHD prophylaxis not including methotrexate, and disease status are important factors for outcomes after RCBT.

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.

In Vitro Assessment of Tolerance and Rejection Occurring After Co-Transplantation of Allogeneic Umbilical Cord Blood and Haploidentical CD34+ Cells as Treatment for Severe Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2352-2352
Author(s):  
Nicole J. Gormley ◽  
Aleah Smith ◽  
Maria Berg ◽  
Lisa Cook ◽  
Catalina Ramos ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Cd34 Cells ◽  
Cord Blood Cells

Abstract Abstract 2352 Introduction/Methods: The administration of highly purified haploidentical peripheral blood CD34+ cells combined with an unrelated cord blood transplant results in earlier neutrophil engraftment than is typically seen with a cord blood transplant alone. Chimerism data from pilot trials evaluating this strategy have reported 3 phases of engraftment: 1) early myeloid engraftment from transplanted haplo-CD34+ cells followed by 2) cord blood engraftment resulting in dual chimerism and 3) the subsequent disappearance of haploidentical donor cells with resultant full donor cord chimerism. The mechanism accounting for the disappearance of haploidentical cells has not been defined. Here the clinical results and an in vitro assessment of alloreactivity in three patients that underwent combined haploidentical CD34+ cell and cord blood transplantation for severe aplastic anemia (SAA) are described. The conditioning regimen consisted of cyclophosphamide (60mg/kg/day on days -7 and -6), fludarabine (25mg/m2/day on days -5 to -1), horse ATG (40mg/kg/day on days -5 to -2), and total body irradiation (200cGy on day -1). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. PCR of STRs was used to assess chimerism in T-cell and myeloid lineages and mixed lymphocyte reaction assays(MLR) were performed on peripheral blood samples collected at different time-points post-transplant to assess for alloreactivity against the recipient, the haploidentical donor, or the cord unit. Stimulator cord blood cells for the MLR were obtained from residual cord blood cells remaining in the infusion bag after patient administration and expanded in vitro using anti-CD28/CD3 Dynabeads. Results: Prior to transplantation, all three pts had transfusion dependent SAA associated with severe neutropenia that was refractory to conventional immunosuppressive therapy. Pt 1 had an early transient myeloid recovery (ANC 400 on day+11) from the haploidentical donor followed by engraftment of the cord unit (Cord ANC > 500) on day 21. The patient is currently 2 years post transplant and has 100% cord blood chimerism and is transfusion independent. An MLR assay performed when donor T-cell chimerism was 100% cord, showed evidence for rejection of the haploid cells by cord blood T-cells, with the MLR response to haploidentical donor cells being seven fold higher than the response to fully HLA-mismatched 3rd party cells. In pt 2, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing no evidence for cord engraftment in either myeloid or T-cell lineages at any point post-transplant. The patient is currently 15 months post transplant and is transfusion independent with normal blood counts and sustained “split” chimerism (T-cells recipient in origin with myeloid cells being 100% haploidentical donor). MLR assays showed that the recipient was tolerant to the haploid donor, with no statistically significant difference in the alloreactive response to the haploid donor compared to self. In pt 3, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing split chimerism (T-cell chimerism >90% cord and myeloid chimerism 88–100% haploid donor in origin). MLR assays again showed evidence of rejection of the haploid cells by cord blood T-cells, with a trend towards greater alloreactivity against the haploid donor compared to an HLA mismatched 3rd party on post-transplant day +63. Conclusions: Combined haploidentical CD34+ cell and unrelated cord blood transplantation following highly immunosuppressive conditioning represents a viable treatment option for patients with SAA who lack an HLA-matched donor. Using this approach, 2 of 3 pts had cord blood engraftment associated with early neutrophil recovery from the haploidentical donor. In one pt, the cord unit failed to engraft. Remarkably, sustained engraftment from the haploidentical donor in this pt resulted in transfusion independence. MLR appears to be a useful approach to assess the in vitro alloreactivity of this unique stem cell graft source. In the two pts who had cord engraftment, in vitro MLR assessments established that the disappearance of haploid cells occurred as a consequence of rejection of the haploidentical cells by engrafting cord blood T-cells, rather than from non-immunological haploidentical cell graft failure. Disclosures: No relevant conflicts of interest to declare.

Unrelated Cord Blood Transplantation after Reduced Intensity Conditioning (RIC) in Adults with Hematological Malignancy. An EBMT-Eurocord-Netcord, Société Française de Greffe de Moelle et de Thérapie Cellulaire and University of Minnesota Collaborative Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2027-2027
Author(s):  
Vanderson Rocha ◽  
Bernard Rio ◽  
Claudio Brunstein ◽  
Marc Renaud ◽  
Attilio Olivieri ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Disease Status ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Reduced Intensity

Abstract Single center studies have demonstrated promising results in recipients of unrelated umbilical cord blood transplantation (UCBT) treated with a reduced intensity conditioning (RIC). However, little is known about risk factors for outcomes with this strategy. We retrospectively evaluated outcomes after RIC-UCBT in 176 patients with hematological malignancies: 116 had acute leukemia (21 ALL, 77 AML, 18 secAML), 36 lymphoid/plasma-cell diseases (6 Hodgkin, 24 NHL, 4 CLL and 2 Myeloma) and 24 myelodysplastic/myeloproliferative diseases (14 MDS and 10 CML). Median follow-up was 12 months (3–80) and median age 45 years (16–76). At transplant, 51% of patients were in advanced phase of disease and 30% had a previous autologous transplants. The conditioning regimen varied according to disease and centre; however, 95% received Fludarabine (FLU)-containing regimen, 55% being FLU-CY-TBI(2Gy), and ATG/ALG was added in 23%. GVHD prophylaxis consisted most commonly (72%) of CsA+MMF. All received a single UCB unit graft that was HLA identical (6/6) (HLA A and B low resolution and DRB1 allelic typing) in 6%, 5/6 in 27%, 4/6 55% and 3/6 in 11%. The median total nucleated cell dose infused was 2.7 × 107/kg. Median time to neutrophil recovery was 20 days (5–56) and probability of neutrophil recovery was 78±3% at day-60. Chimerism analysis at 3 months was complete in 64%, mixed in 16% and absent (autologous reconstitution) in 19%. In multivariate analysis, cell dose (&lt; vs &gt;2.7 × 107/kg, HR=1.6, p=0.02), HLA compatibility (5–6/6 vs 3–4/6, HR=1.5, p=0.04) and use of FLU+CY+TBI versus other regimens (HR=1.7, p=0.01), were independently associated with neutrophil recovery. At day-100, probability of acute GVHD II–IV was 30% (18% grade II; 6% grade III, 6% grade IV), and no risk factor was associated with its incidence. At 1 year, probability of chronic GVHD was 30%. TRM was 38% at 1 year, being 19% for patients given low dose TBI (&lt;6Gy), vs 61% for those without TBI and 40% for those given a low cell dose (&lt;2.7 × 107/kg), vs 21% for the remainder. In multivariate analysis, both factors were associated with TRM. Probability of relapse at 1 year was 41% and it was associated with disease status and aGVHD (26% in those with and 47% in those without aGVHD, p=0.02). DFS at 1 year was 41% for patients with acute leukaemia, 31% for MDS/CML and 42% for lymphoid/plasma diseases. For those treated with FLU-CY-TBI, DFS was 51% as compared to 28% for those treated with other RICs (p=0.0002). In a multivariate analysis, advanced disease status (HR=1.6, p=0.03) and conditioning regimens other than FLU-CY-TBI (HR=1.9, p=0.004) were associated with decreased DFS. In conclusion, cell dose plays a critical role on engraftment and risk of TRM after UCBT in the RIC setting. Specific RIC regimen, namely FLU-CY-TBI, provides better engraftment, reduced TRM and better DFS. These results support the use of FLU-CY-TBI and UCBT as a strategy for broadening the application of transplant to patients previously excluded on the basis of age, co-morbidities and/or absence of a HLA-matched unrelated donor.

Pre-Transplant Conditioning Using Intravenous Busulfan Is a Feasible and Effective Option in Reduced-Intensity Cord Blood Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3273-3273
Author(s):  
Naoyuki Uchida ◽  
Hisashi Yamamoto ◽  
Naofumi Matsuno ◽  
Kazuya Ishiwata ◽  
Masanori Tsuji ◽  
...  
Keyword(s):  
Cord Blood ◽  
Performance Status ◽  
Cord Blood Transplantation ◽  
Disease Free Survival ◽  
Ecog Performance Status ◽  
Neutrophil Recovery ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Medium Range ◽  
Reduced Intensity

Abstract Although cord blood (CB) transplantation with reduced-intensity conditioning (RICBT) has been widely applied to those who lack available related or unrelated donors and are not eligible for conventional conditioning, the optimal pre-transplant conditioning has not been established yet. Intravenous busulfan (ivBu) has been incorporated in conditioning regimens before bone marrow or peripheral blood stem cell transplantation, but the feasibility in cord blood transplantation has been controversial. In order to address this issue, we retrospectively reviewed patients who underwent RICBT including ivBu. Twenty-one patients, who were at ECOG performance status of 2 or less and received RICBT at our institute from June 2007 to April 2008 consecutively, were included in this study. Median age was 56 years (range, 21–71). Seventeen were AML, 3 were ALL, and 1 was MDS RA. All but 2 (MDS RA and ALL in CR2) were not in remission, 5 had CNS involvement, and 9 had history of prior transplantation. Seventeen had HCT-specific comorbidity index score ≥1, including 8 ≥2, and 6 ≥3. Fludarabine phosphate 125–180mg/m2 and ivBu 6.4–12.8mg/kg were used in all patients. All but 2 received additional melphalan (Mel) or total body irradiation (TBI); Mel 80–140mg/m2 for 10, 2–8Gy of TBI for 8, and Mel 40mg/m2 plus 4Gy of TBI for 1. Graft-versus-host disease prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 11, tacrolimus alone in 8, and cyclosporine alone in 1. Single cord blood units, matched at 4/6 in 20 and 5/6 in 1, of 2 x 107/kg of recipient body weight at minimum were infused. Seventeen achieved neutrophil recovery ≥500/μl on day 19 post-transplant at medium (range, 12–30). Among 4 who failed to achieve neutrophil recovery, 2 experienced early disease progression, 1 showed rejection, and 1 died before engraftment due to interstitial pneumonia. All 17 patients who achieved neutrophil engraftment and 1 who died before engraftment showed complete donor-type chimerism on 13 days post-transplant at medium (range, 8–35). Median follow-up time of survivors was 398 days (range, 162–532) post-transplant. Cumulative incidence of non-relapse mortality at day 100 and day 365 post-transplant were both 19%. No VOD/SOS was observed. Disease-free survival and overall survival (OS) at 1 year post-transplant were 40±11% and 61±9%, respectively. Thus, ivBu can be safely administered, and have potential to achieve successful engraftment as well as sufficient disease control, indicating possible benefit of incorporating this drug in pre-transplant conditioning of RICBT. The optimal dosing schedule or combination with other therapeutic modalities needs further investigation in prospective clinical trials.

Pre-Engraftment Syndrome Following Umbilical Cord Blood Transplantation Is a Strong Predictor of Acute Graft-Versus-Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1267-1267
Author(s):  
Xingbing Wang ◽  
Zimin Sun ◽  
Huilan Liu ◽  
Liangquan Geng ◽  
Kaiyang Ding ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Research Funding ◽  
Cord Blood Transplantation ◽  
Umbilical Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Engraftment Syndrome

Abstract Abstract 1267 Pre-engraftment syndrome (PES) has been described in patients receiving umbilical cord blood transplantation (CBT). However, PES remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcome of PES in CBT recipients treated for hematological malignancies at our transplantation center. A total of 60 patients (median 20 years, range 3–48) received either myeloablative (n=52) or reduced-intensity (n=8) conditioning. 28 patients received double unit grafts to augment engraftment. Cyclosporine-A and mycophenolate mofetil were used as GVHD prophylaxis, and all patients received post-transplant granulocyte colony-stimulating factor. In this study, PES was defined as noninfectious fever (>38.3°C) and/or unexplained rash occurring before neutrophil engraftment. 38 patients (63.3%) fulfilled PES criteria: 33 with fever and 36 with rash. The median onset was 8 days (range 3–15) post-transplant (a median of 12 days before neutrophil recovery). 34 patients received IV methylprednisolone (MP) (0.5-2 mg/kg/d) with 27/34 (79.4%) having fever and/or rash resolution in <48 hours. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Use of TBI or ATG in conditioning regimen, the infused total nucleated cell dose, gender, weight, blood type mismatch, transplantation of UCB units and degree of donor-recipient HLA disparity were not significantly associated with the development of PES in our series. The cumulative incidence of sustained donor engraftment was 83.3%. Patients with PES had a higher incidence of developing grade II -IV acute GVHD, but PES was not associated with sustained donor engraftment, the day to neutrophil recovery and chronic GVHD. Overall survival did not significantly differ between patients with and without PES. We conclude that PES is common following CB transplant (CBT), predicts for aGVHD, and responds promptly to corticosteroids. Disclosures: Wang: Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Clinical Technology foundation of Anhui Provincial healthy department (2008A011): Research Funding; Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding; Anhui Provincial Outstanding Young Investigator Program (08040106810): Research Funding.

Outcomes of Unrelated Cord Blood Transplantation for Non-Malignant Diseases in Children Are Not Associated with KIR-Ligand Matching Between Donor and Recipient: a Study On Behalf of Eurocord.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2301-2301 ◽  
Author(s):  
Annalisa Ruggeri ◽  
Duncan Purtill ◽  
Michel Gerard ◽  
Pascale Loiseau ◽  
Marc B Bierings ◽  
...  
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Malignant Diseases ◽  
Neutrophil Recovery ◽  
Graft Versus Host ◽  
Unrelated Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Donor Choice ◽  
Unrelated Cord Blood ◽  
Reduced Intensity

Abstract Abstract 2301 Poster Board II-278 NK-cell alloreactivity in the setting of allogeneic transplantation is largely determined by the specificity of the killer immunoglobulin receptors (KIR) on donor NK cells for recipient HLA class I. We have recently shown that KIR ligand mismatch in the graft-versus-host (GvH) direction between donor and recipient is associated with improved outcomes after unrelated cord blood transplantation (UCBT) for patients with acute leukemia in complete remission. However, this finding was not confirmed in a series of reduced intensity conditioning and UCBT using 2 unrelated cord blood units. Therefore, those controversial results can raise some questions on the donor choice based on KIR ligand matching status. It is not known whether KIR ligand matching is associated with outcomes after UCBT for non-malignant disorders. To address this question we have analyzed patients with non-malignant disorders who had received a UCBT using a single cord blood unit and were reported to the Eurocord registry with sufficient HLA-A, -B, -C typing to assign KIR ligand groups. In agreement with previous studies in malignant diseases, KIR ligand mismatch (KIR+) in the GvH direction occurred when the donor expressed one or several of the following KIR ligands which were lacking in the recipient: HLA-Bw4, and HLA-C group 1 or 2. In addition patients and cord blood units were grouped according to HLA A-3/A-11 alleles, which are putative KIR ligands. One-hundred-thirty-seven eligible patients were selected, mostly children (n=124). UCBT was performed from January 2000 to December 2008 in 47 EBMT-centers. The frequency of KIR ligand mismatched (KIR+) pairs reported was 23% (n=31). Forty-three percent of patients had bone marrow failure syndromes (BMFS) (n=60), other diagnosis included metabolic disorders (n=41), SCID (n=32), hemoglobinopathies (n=2), autoimmune diseases (n=2). Median follow up was 24 months (4-101). Median recipient age was 3 years. UCB units were HLA matched at 6 of 6 (n=38), 5 of 6 (n=62), 4 of 6 (n=34) and 3 of 6 (n=3). Median cell dose infused was 5.6 ×10E7 TNC/Kg and 2.4 ×10E5 CD34 cells/Kg. Conditioning regimen was myeloablative in 48% of cases and reduced intensity in 52% and included ATG in 90% and fludarabine in 42%. Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine (CsA) and corticosteroids, CsA alone and CsA and MMF in 47%, 23% and 14% of patients, respectively. Cumulative incidence (CI) of the day-60-neutrophil recovery was 76±3% (median time: 22 days) and it was not associated with KIR mismatch [(74±4% for KIR- and 80±6% for KIR+ group (p=0.9)]. CI of aGvHD was 21±3%, only 3 patients out of 31 with KIR+ presented aGvHD (II-IV). The estimated probability of 2-year overall survival (OS) was 63±4%; it was 64±5% in the group of KIR- and 63±3% in the KIR+ (p=0.5). The main cause of death was graft failure associated with infections (n=16, 32%). There was no statistical difference in frequency of causes of death between the 2 KIR ligand groups. We have also looked the association of KIR ligand mismatch in the host versus graft (HvG) direction. The frequency of KIR mismatched pairs in the HvG direction was 22% and it was not associated with neutrophil recovery (76±4% for KIR ligand matched in HvG direction versus 73±6% for KIR ligand mismatched in HvG direction, p=0.9) or OS (64±5% for KIR ligand matched in HvG direction versus 58±7% for KIR ligand mismatched in HvG direction, p=0.6) In conclusion KIR ligand mismatching in the GvH or HvG direction is not associated with outcomes after UCBT for children with non malignant disease. Therefore it is not useful in the algorithm of donor choice in this setting. Disclosures: No relevant conflicts of interest to declare.

Outcomes After Double Unit Unrelated Cord Blood Transplantation (UCBT) Compared with Single UCBT In Adults with Acute Leukemia In Remission. An Eurocord and ALWP Collaboration Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 910-910 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Mohamad Mohty ◽  
Guillermo F Sanz ◽  
Bernard Rio ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Unrelated Cord Blood

Abstract Abstract 910 The Minnesota group has described that recipients of double unrelated cord blood transplantation (dUCBT) have a higher incidence of acute GVHD, lower relapse incidence (RI) but no difference in leukemia free survival (LFS) when compared to single unit UCBT (sUCBT) recipients. In order to confirm these results in a larger and more homogenous cohort of patients and to evaluate the effect of double UCBT in relapse and LFS, we have compared the outcomes after dUCBT (n=230) with sUCBT (n=377) in adult patients with acute myeloid or lymphoblastic leukemia in remission. There were some differences between the two groups: dUCBT recipients were heavier (median weight: 68kg vs 65kg, p<0.01), tended to be older (median age: 37 years vs 35 years, p=0.06), had lower frequency of poor cytogenetics (32% vs 36%, p=0.02), transplanted more recently (p<0.001), more frequently given RIC (53% vs 30%, p<0.001), and received less ATG/ALG (29% vs 70%, p<0.001) when compared to sUCBT recipients, respectively. No differences were observed in diagnosis (38% ALL and 62% AML), status of disease at transplant (CR1: 52%, CR2:40% and CR3:8%) and previous autograft (13%). As expected, dUCBT recipients received a graft containing a higher nucleated cell dose (median of 3.7×107/kg vs 2.6×107/kg; p<0.0001). Number of HLA disparities were not statistically different (5/6:32% and 4/6:58%) when compared to sUCB grafts. Two analyses for outcomes were performed: one in patients transplanted in CR1 and other in patients transplanted in CR2 or more. The differences between dUCBT and sUCBT remained the same in both analyses. Results: in patients transplanted in CR1, median follow-up was 17 months for dUCBT recipients (n=114) and 19 months for sUCBT recipients (n=203). Unadjusted univariate analysis showed that cumulative incidence (CI) of neutrophil recovery was 78% after dUCBT and 82% after sUCBT (p=0.11); acute GVHD was 45% and 27% (p<0.001), and chronic GVHD 21% and 27% (p=0.35), respectively. At 3 years, unadjusted CI of NRM and RI were 32% after dUCBT and 36% after sUCBT (p=0.89) and 15% and 25% (p=0.03), respectively. Estimated 3 years LFS was 53% after dUCBT and 39% after sUCBT (p=0.09). In multivariate analysis, adjusted for the differences between the 2 groups, dUCBT recipients have an increased risk of grade II-IV acute GVHD (HR 1.23, p=0.005) and decreased RI (HR:0.74, p=0.01) when compared to sUCBT recipients. In a multivariate analysis adjusted, neutrophil and platelets recovery, NRM and chronic GVHD were not statistically different after dUCBT or sUCBT. However, in a multivariate analysis, LFS was improved after dUCBT compared to sUCBT recipients (HR: 0.67, p=0.04). In patients transplanted in CR2 and CR3, median follow-up was 11 months for dUCBT recipients (n=116) and 22 mo for sUCBT recipients (n=174). Unadjusted univariate analysis showed that CI of neutrophil recovery was 85% after dUCBT and 83% after sUCBT (p=0.57); acute GVHD was 33% and 17% (p=0.003), and chronic GVHD 32% and 29% (p=0.64), respectively. At 3 years, unadjusted CI of NRM and RI were 34% after dUCBT and 36% after sUCBT (p=0.47) and 31% and 33% (p=0.68), respectively. Estimated 3 Y LFS was 35% after dUCBT and 31% after sUCBT (p=0.48). In multivariate analysis, adjusted for the differences between the 2 groups, outcomes after dUCBT recipients, namely neutrophil recovery, acute and chronic GVHD, NRM, RI and LFS were not statistically different between the two groups. In conclusion our study confirms the previous findings of higher incidence of acute GVHD, equivalent NRM and reduced relapse in adult recipients of dUCBT, mainly for those transplanted in CR1, showing a higher GVL effect with improved LFS. Outcomes after dUCBT in patients with CR2 and CR3 were not statistically different of sUCBT. Double UCBT has extended the use of UCBT for patients otherwise not eligible for single UCBT and importantly is associated with better outcomes in adults patients with AL transplanted in early phase of the disease. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document