Infliximab Versus Rabbit Anti-Thymocyte Globulin As a Salvage Treatment For Steroid-Refractory Acute Graft-Versus-Host Disease After Reduced-Intensity Cord Blood Transplantation In Adults

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4592-4592
Author(s):  
Kazuya Ishiwata ◽  
Hisashi Yamamoto ◽  
Kousei Kageyama ◽  
Daisuke Kaji ◽  
Sachie Wada ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Survival Rates ◽  
Salvage Treatment ◽  
Primary Therapy ◽  
Blood Transplantation ◽  
Reduced Intensity ◽  
Steroid Refractory

Introduction In reduced intensity cord blood transplantation (CBT) post transplant immune disorders, including early immune reactions (PIR) and acute GVHD, are potential complications following CBT in adult patients. Such reactions might increase the risk of organ dysfunction, leading to high rates of transplantation-related mortality, particularly in patients who do not respond to primary therapy, which usually consists of steroids. There is no consensus on the optimal salvage treatment of steroid-refractory acute GVHD. Patients and Methods We retrospectively reviewed 388 patients who underwent single-unit reduced intensity cord blood transplantation consecutively from June 2008 to October 2012 at Toranomon Hospital. Patients who were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. Patients in whom acute GVHD developed received methylpredonisolone 1-2 mg/kg per day. If no partial or complete resolution of symptoms occurred, they were considered steroid-refractory and proceeded to salvage treatment with infliximab or ATG. The dose of infliximab was 5 mg/kg/day once weekly for at least 1 course. ATG was given at 1mg/kg/day once weekly for at least 1 course. An observational study compared response and survival rates in all consecutive patients receiving 1 of these 2 treatments. Results 52 patients among this group developed steroid refractory acute GVHD. Infliximab group (n=31) had a higher proportion of patients with grade III-IV GVHD (69% VS 59%, p=0.18). ATG group (n=21) had a higher proportion of patients with stage 3-4 liver GVHD (28% VS 5%, p<0.01). Infliximab or ATG therapy was initiated after a median of 12 days (range, 2 to 85 days; 10 days for infliximab group VS 22 days for ATG group; p<0.01) of steroids for primary therapy for GVHD. Both overall response (PR+CR) were significantly higher in the infliximab group compared with the ATG group (54.8% VS 33.3%, p=0.015 ). In multivariate analysis, time from first-line therapy (days<10) was an independent predictor of response (HR, 3.91; 95%CI, 1.10-13.8; p=0.034), infliximab therapy was not significant, (HR, 1.30; 95%CI, 0.42-3.99; p=0.18). Median follow-up of surviving patients from the date of initiation of salvage treatment was 21.6 months (range, 5.5-57.9 months).Overall, median survival was 2 months after salvage treatment (95% CI, 1-3), with 25% of patients surviving at 12 months (95%CI, 11-20). Patients who achieved a CR have better survival rates. GVHD was the main cause of death (50%). When comparing survival according to salvage treatment, better OS with infliximab (33.9% VS 22.8, p=0.08) in univariate analysis was not confirmed in multivariate analysis. In multivariate analysis, grade IV GVHD at steroid refractory GVHD onset (HR,7.1; 95% CI, 1.29-38.7; P=0.021), and gut involvement with bleeding (HR, 7.65; 95% CI, 1.35-43.2; P=0.024) were significantly associated with worse survival. Conclusion We conclude that infliximab has more activity than ATG in the treatment of severe steroid-refractory GVHD, and earlier initiation of salvage therapy may give better response. But outcomes remain poor. New methods to prevent and treat GVHD are needed. Disclosures: No relevant conflicts of interest to declare.

Infliximab Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease After Reduced-Intensity Cord Blood Transplantation in Adults

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4553-4553
Author(s):  
Kazuya Ishiwata ◽  
Aya Nishida ◽  
Hikari Ota ◽  
Taichi Ikebe ◽  
Masanori Tsuji ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Infliximab Treatment ◽  
Graft Versus Host ◽  
Blood Transplantation ◽  
Reduced Intensity ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Abstract 4553 Introduction Acute graft versus host disease (GVHD) remains the most frequent complication after allogeneic hematopoietic stem cell transplantation (SCT). In reduced intensity cord blood transplantation (CBT) previous studies have reported a lower incidence of severe acute GVHD compared with conventional allo-SCT. However, in these studies the incidences of grade II-IV acute GVHD varied widely from 26% to 51% (H.Narimatsu Stem cell int. 2011: 607569). In particular, post transplant immune disorders, including early immune reactions (PIR) and acute GVHD, are potential complications following CBT in adult patients. Such reactions might increase the risk of organ dysfunction, leading to high rates of transplantation-related mortality, particularly in patients who do not respond to primary therapy, which usually consists of steroids. Infliximab, a chimeric monoclonal antibody against tumor necrosis factor alpha, has shown activity against steroid refractory acute GVHD. Patients and Methods We retrospectively reviewed 275 patients who underwent single-unit reduced intensity cord blood transplantation consecutively from March 2007 to December 2011 at our institute. Patients in whom PIR or acute GVHD developed received methylprednisolone 1–2 mg/kg per day. If no partial or complete resolution of symptoms occurred, they were considered steroid-refractory and proceeded to infliximab treatment. The dose of infliximab was 5 mg/kg/day once weekly for at least 1 course. An antifungal drug, itraconazole or micafungin or voriconazole was used until all immunosuppressive drus were withdrawn. Results In this study we retrospectively evaluated 54 patients who had steroid refractory acute GVHD. Of these, 21 who received infliximab were analyzed. GVHD prophylaxis was with only tacrolimus(n=15) and mycophenolate mofetil+tacrolimus(n=6). All of them developed grade III to IV GVHD. Median follow-up time of survivors was 548 days (range, 222–1152). The overall response rate was 62% (n=13), and 9 patients (43%) experienced complete response (CR). 5 patients (24%) did not respond and 3 (14%) had progressive GVHD. The Kaplan-Meier estimate of overall survival was 31%, with no signs of chronic GVHD (n=2). Four patients who responded subsequently died, one of exacerbation of GVHD, three of infections. All the 8 unresponsive patients died of GVHD or infections. Five patients (21%) had non-Candida invasive fungal infections. Sixteen patients(79%) had bacterial infections. Conclusion Infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD even following reduced intensity cord blood transplantation. However, it is associated with a high rate of infections. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of steroid refractory acute GVHD are warranted. Disclosures: No relevant conflicts of interest to declare.

Invasive Fungal Infections in Reduced Intensity Cord Blood Transplantation (RICBT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3226-3226
Author(s):  
Shigesaburo Miyakoshi ◽  
Koichiro Yuji ◽  
Eiji Kusumi ◽  
Daisuke Kato ◽  
Shinsuke Takagi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Fungal Infections ◽  
Cord Blood Transplantation ◽  
Invasive Fungal Infections ◽  
Steroid Use ◽  
Blood Transplantation ◽  
Reduced Intensity

Abstract &lt;Background&gt; Invasive fungal infection is one of the most fatal complications after stem cell transplantation (SCT). EBMT group reported the risk factors of invasive fungal infections were delayed neutrophile engraftment and steroid use for acute graft versus host disease (GVHD) in cord blood transplantation with myeloablative regimens. However it has not been clear about invasive fungal infections after RICBT. &lt;Objective&gt; The 1st purpose of this report was to investigate the incidence and pathogens of invasive fungal infections and the 2nd was to identify the risk factors for fungal infections after RICBT. &lt;Patients and Methods&gt; We reviewed medical records of 103 patients with hematological diseases who had received RICBT between March 2002 and May 2005 at Toranomon Hospital, Tokyo, Japan. Median age was 57 years (17–79). Primary diseases were advanced (n=81) or standard (n=22). Median follow-up was 14 months (0.5–27). Conditioning regimen was fludarabine 125 mg/m2, melphalan 80 mg/m2 and TBI 4 Gy. GVHD prophylaxis was cyclosporine (n=67) or tacrolimus (n=43). Median total nucleated cells (TNC): 2.8 x 10^7 cells (1.7–5.2); Median CD34+: 0.78 x 10^5 cells (0.01–3.28); HLA match: 6/6 (n=2), 5/6 (n=16), 4/6 (n=88), 3/6 (n=1). Fluconazole 200mg/day was used as prophylaxis of fungal infections. Diagnosis of invasive fungal infection was made with the following EORTC/MSG criteria. The following factors were considered potential predictors of outcomes about 2nd purpose: patient’s age, infused TNC dose, disease status at transplantation, speed of netrophile engraftment, pre-engraftment reactions (PER) which we reported (Clin Cancer Res.10:3586–92, 2004), and acute GVHD. &lt;Results&gt; Neutrophile (&gt;500/μL) and platelet recovery (&gt;20,000/μL) were observed in 83% at day 60 (median; 22 day), 55% at day 100 (43day), respectively. Cumulative incidence of acute GVHD (II-IV) was 33%. OS were 39% (95% CI: 29–50) in all cases, 67% (95% CI: 47–87) in standard, and 32% (95% CI: 20–43) in advanced (p&lt;0.05), respectively. Incidence of invasive fungal infections was 12% (95% CI: 6–20) and median onset day was 23 days (1–84) after RICBT. Pathogens of invasive fungal infections comprised 9 cases of probable invasive pulmonary aspergillosis, and one case each of Candida pneumonia and Trichosporon sepsis. Incidence of invasive fungal infections in patients with PER+/steroids + (n=22) was 28% (95% CI: 9–43), in patients without PER (n=80) was 7% (95% CI: 1–14). In multivariate analysis, the most important risk factor of invasive fungal infections was steroid use for PER (p&lt;0.05), while other factors did not influence. &lt;Discussion/Conclusion&gt; In our experience with reduced intensity cord blood transplantation, the only risk factor for invasive fungal infections was steroid use for PER within 30 days. Invasive fungal infections, especially invasive aspergillosis, remain an important complication after allogeneic stem cell transplantation, regardless of the type of conditioning regimens and the sources of stem cells. Figure Figure

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.

Risk Factors Analysis of Outcomes of Related Cord Blood Transplantation in Children with Hematological Malignancies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3014-3014
Author(s):  
Pierre Teira ◽  
Vanderson Rocha ◽  
Franco Locatelli ◽  
Ricardo Pasquini ◽  
Gerard Socie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Advanced Phase ◽  
Hla Incompatible ◽  
Hla Compatibility

Abstract Overall survival of HLA identical bone marrow are comparable to umbilical cord blood transplantation (RCBT) in children with malignant and non-malignant disorders, however there is no data analysing risk factors of outcomes in a large series of children with malignancies given a RCBT. Thus, we have studied 128 RCBT performed from 1990 to 2005 and reported to Eurocord. The median age was 5 years (1–20 y); weight 19kg (8–56); and the median follow up was 55 months (2–162). Most of the children had leukemia [ALL (n=73), AML or MDS (n=33) CML (n=13)] and 9 children had other malignancies (4 non-Hodgkin lymphoma, 4 solid tumors,1 histiocytosis). Previous autologous transplant was given to 11%. At transplant, 22 children (17%) were transplanted in early stage of the disease; 58 (45%) in intermediate and 47 (37%) in more advanced phase. Median time from diagnosis to transplantation was 19 months (4–105). The donor was HLA identical in 104 cases (81%) and HLA incompatible in 24 cases (1 antigen=3, 2 ag=10, 3 ag=11). TBI based regimen was used in 52% and as GVHD prophylaxis CSA alone in 59%. The median number of nucleated cells at collection was 4.8x107/kg (1–19x107) and at infusion was 4x107/kg (0.6–18). Most of cord blood units were banked at the local institution where the transplantation took place. Results: median days of neutrophils and platelets recovery were 23 (8–49) and 38 (12–165) days, respectively. Estimate probability of neutrophils recovery at day 60 was 89±3% and 180-day platelet recovery was 81%. In multivariate analysis for neutrophil recovery, HLA identity was the most important factor associated with increased probability of recovery (93%vs 72%, adjusted p=0.004). There was a trend of better recovery for patients receiving a higher cell dose (90%vs 85%, adjusted p=0.06). Acute GVHD (II-IV) was observed in 24 patients (II=23, III=5, IV=2). HLA compatibility and higher cell dose were associated with decreased incidence of acute GVHD. In fact children receiving an HLA incompatible graft had an incidence of 46% compared to 17% of the remainders (p<0.001). Chronic GVHD was observed in 12% of patients at risk. At 5 years relapse incidence was 44% for patients transplanted in early phase of the disease, 54% in intermediate and 65% for those in advanced phase (p=0.04). At 5 year transplantation related mortality was 21%, overall survival was 48% and disease-free survival (DFS) was 40%. In a multivariate analysis for DFS, HLA compatibility (p<0.001), female gender (p=0.03), younger children (<5 years)(p=0.05) and children transplanted in remission (p=0.02) were factors associated with increased DFS. In fact, 5 y-DFS of children transplanted with an HLA compatible donor was 46% compared to 13% in those transplanted with an incompatible relative. In conclusion, with these promising results, banking of a related HLA identical unit should be encouraged when possible. HLA compatibility plays an important role for neutrophils recovery, GVHD and DFS after RCBT.

Impact of HLA Haplotype Matching On Engraftment in Reduced Intensity Cord Blood Transplantation.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3043-3043
Author(s):  
Kazuya Ishiwata ◽  
Hikari Ota ◽  
Aya Nishida ◽  
Masanori Tsuji ◽  
Hisashi Yamamoto ◽  
...  
Keyword(s):  
High Resolution ◽  
Cord Blood ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Post Transplant ◽  
Matched Group ◽  
Blood Transplantation ◽  
The Impact ◽  
Reduced Intensity

Abstract Abstract 3043 Introduction HLA-mismatched unrelated cord blood transplantation (UCBT) is feasible and, in retrospective comparative analyses, allows survival rates similar to conventional unrelated HLA-matched adult-derived grafts. Although it is clear that the degree of UCB HLA mismatch in patients has a negative effect on outcomes, the biologic implications of HLA haplotype itself have not been explored for UCBT. In unrelated bone marrow transplantation, an effect of HLA haplotype matching on GVHD has been clarified. (S.Morishima. et al. Blood 2010). This study was conducted to determine the impact of HLA haplotype matching in reduced intensity UCBT. Patients and Methods To determine the impact of HLA haplotype matching with outcomes after UCBT, We retrospectively reviewed patients with hematologic malignancies who underwent reduced intensity CBT at Toranomon Hospital from August 2006 and December 2010 consecutively. Patients who had prior history of transplantation, were in poor performance status (ECOG PS >3), had active bacterial or fungal infections at the time of conditioning were excluded. Then, the remaining 164 consecutive patients were reviewed. The most frequently used conditioning regimens were fludarabine, alkylating agent (melphalan or busulfan) with total body irradination (TBI), tacrolimus plus mycophenolate mofetil for GVHD prophylaxis. DNAs of 164 pairs were analysed for HLA-A, -B, and -DRB1 based on High Resolution typing, and we have determined the HLA haplotype based on Japanese common HLA haplotypes referred from the previous reports. Results For A, B, DR based on high resolution typing the following mismatch occurred: no mismatch 3(2%), one mismatch 12(7%), two mismatch 58(35%), three mismatch 60(37%), four mismatch 28(17%), five mismatch 3(2%) in the GvH direction, and: no mismatch 2(1%), one mismatch 16(10%), two mismatch 55(34%), three mismatch 56(34%), four mismatch 32(20), five mismatch 3(2%) in the HvG direction. Then 37 among 164 pairs were defined as the HLA haplotype matched group. The number of total nucleated cells and CD34+ cells were not significantly different between HLA haplotype matched group and non-matched group. The cumulative incidence of neutrophil recovery was higher in HLA haplotype matched group than in non-matched group.( 94.6% vs. 80.3% up to day 60, p=0.0027). Lower incidence of pre-engraftment immune reaction(PIR) and acute GVHD were observed in haplotype matched group (37.8 % vs. 47.9 % up to day 60 post-transplant, P = 0.32), III to IV acute GVHD( 18.9% vs. 27.7% up to day 100 post-transplant, p=0.29). The cumulative incidences of relapse tended to be lower in haplotype matched group than in non-matched group (21.5% vs. 31.5%, P=0.28).Overall survival (OS) was estimated as 36.0 % at 3 years post-transplant. There were no significant differences between mathed and non-matched group in the cumulative incidence of OS (36.8 % vs. 34.3% at 3 years post-transplant, P = 0.84). Conclusion HLA haplotype matching in UCBT was found to have a significant impact on engraftment in this analysis. Disclosures: No relevant conflicts of interest to declare.

Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning

Blood ◽  
2003 ◽  
Vol 102 (5) ◽  
pp. 1915-1919 ◽  
Author(s):  
Juliet N. Barker ◽  
Daniel J. Weisdorf ◽  
Todd E. DeFor ◽  
Bruce R. Blazar ◽  
Jeffrey S. Miller ◽  
...  
Keyword(s):  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hla Antigen ◽  
Blood Transplantation ◽  
Reduced Intensity

AbstractReduced-intensity conditioning may reduce transplantation-related mortality in high-risk adults undergoing hematopoietic transplantation. We investigated unrelated donor umbilical cord blood (UCB) transplantation after such conditioning in 43 patients (median age, 49.5 years; range, 22-65 years) with a primary end point of donor engraftment. The first 21 patients received busulfan 8 mg/kg, fludarabine 200 mg/m2, and 200 cGy of total body irradiation (Bu/Flu/TBI). Subsequent patients (n = 22) received cyclophosphamide 50 mg/kg, fludarabine 200 mg/m2, and 200 cGy TBI (Cy/Flu/TBI). UCB grafts (93%) were 1-2 HLA antigen–mismatched with the recipient and contained a median cryopreserved cell dose of 3.7 × 107 (range, 1.6 × 107-6.0 × 107) nucleated cells per kilogram of recipient body weight (NC/kg). Graft versus host disease (GVHD) prophylaxis was cyclosporin A to day 180 plus mycophenolate mofetil to day 30. The cumulative incidence of sustained donor engraftment was 76% (95% confidence interval [CI], 56%-96%) for Bu/Flu/TBI recipients and 94% (95% CI, 84%-100%) for Cy/Flu/TBI recipients. The median day of neutrophil recovery (at least 0.5 × 109/L) for engrafting Bu/Flu/TBI recipients was 26 days (range, 12-30 days) and for Cy/Flu/TBI recipients was 9.5 days (range, 5-28 days). Incidence of grades III-IV acute GVHD was 9% (95% CI, 1%-17%), and survival at 1 year was 39% (95% CI, 23%-56%). These data demonstrate that 0-2 antigen mismatched UCB is sufficient to engraft most adults after reduced-intensity conditioning and is associated with a low incidence of severe acute GVHD.

Impact of ABO Imcompatibility On Acute GvHD and Thrombotic Microangiopathy After Reduced-Intensity Cord Blood Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2298-2298
Author(s):  
Masanori Tsuji ◽  
Atsushi Wake ◽  
Naoyuki Uchida ◽  
Kazuya Ishiwata ◽  
Nobuaki Nakano ◽  
...  
Keyword(s):  
Cord Blood ◽  
Thrombotic Microangiopathy ◽  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Reduced Intensity Conditioning ◽  
Blood Transplantation ◽  
Abo Incompatibility ◽  
One Year ◽  
Reduced Intensity ◽  
Neutrophil Engraftment

Abstract Abstract 2298 Poster Board II-275 Introduction: Althouth ABO blood type is one of two antigen system for transplantation, the effect of ABO incompatibility on transplantation outcome still remains controversy. Furthermore, there is little data about ABO incompatibility on the outcome of unrelated cord blood transplantation following reduced-intensity conditioning (RI-CBT). Design and Methods: We retrospectively analyzed data of 155 patients who underwent RI-CBT performed at Toranomon Hospital from January 2005 to December 2008. The patients include 45 ABO-identical, 47 minor, 43 major, and 20 bidirectional ABO mismatched. All patients were performed using fludarabine-based reduced-intensity conditioning, and 114 patients (74%) were performed using TBI-containing regimen. Median age were 57 years-old and 94 patients (61%) were over 55 years-old. We evaluated the association between ABO incompatibility and neutrophil engraftment, one-year overall survival (OS) ; one-year non-relapsed mortality (NRM) ; and one-year relapse rate. We also analyzed the incidence of pre-engraftment immune reaction (PIR), acute graft-versus-host disease (GvHD) including severity, and thrombotic microangiopathy (TMA). Results: There were no significant differences in neutrophil-engraftment time, reticulocyte-engraftment time, and the incidence of PIR. The incidence of acute GvHD and grade 2-4 acute GvHD were significantly higher in major/bidirectional ABO-incompatible group than ABO-identical/minor ABO-incompatible group (respectively P=0.0008 and P=0.0116). The incidence of TMA tended to be higher in minor/bidirectional ABO-incompatible group than ABO-identical/major ABO-incompatible group (P=0.0637). There were no significant differences in one-year OS, NRM, and relapse rate. In multivariate analysis, risk factors of acute GvHD were age over 55, TBI-containing regimen, CD34-positive cells>0.7×10e5/kg, and major/bi-directional ABO incompatibility, and those of TMA were grade 3-4 acute GvHD and minor/bi-directional ABO incompatibility. Discussion: This study showed major-directional ABO incompatibility setting increased the incidence of acute GvHD. Sex incompatibility and HLA incompatibility were not significantly influenced the incidence of acute GvHD. The use of steroid for severe GvHD and the expression of ABO antigen on the surface of vascular endothelial cell may influence pathogenesis of TMA. Further studies including larger patients numbers are required to elucidate the impact of ABO incompatibility on the clinical outcome of RI-CBT. 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.

Outcomes After Double Cord Blood Transplantation Compared to Single Cord Blood Transplantation in Adults with Acute Leukemia Given a Reduced Intensity Conditioning Regimen

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 232-232 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Didier Blaise ◽  
Bernard Rio ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Conditioning Regimen ◽  
Reduced Intensity Conditioning ◽  
Neutrophil Recovery ◽  
Blood Transplantation ◽  
Reduced Intensity Conditioning Regimen ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Abstract 232 Unrelated cord blood (UCB) is an alternative source of allogeneic hematopoietic stem cell transplantation (HSCT) for adults with acute leukemia lacking a HLA matched donor. Double cord blood unit (dUCBT) has been increasingly used over single CB unit (sUCBT) after reduced intensity conditioning regimen (RIC). Since there is an increased relapse incidence (RI) using RIC-HSCT compared to myeloablative conditioning regimen, we have driven the hypothesis that RI may be decreased and leukemia-free survival (LFS) rate increased after dUCBT compared to sUCBT, due to probably increased graft-versus leukemia (GVL) effect. With this aim, we analyzed 360 adults (>18 years) with ALL (n= 77) or AML (n=238) in CR1 (n=212) and in CR2 (n=148) transplanted with a sUCBT (n=131) or a dUCBT (n=229) after a RIC. Only patients transplanted with a single unit containing more than 2.5×107/kg total nucleated cells (TNC) were included. Patients were transplanted from 2005–2011 in EBMT centers. Comparing the two groups of patients receiving a sUCBT or a dUCBT in CR1, there were no statistical differences according to age, diagnosis (AML or ALL), weight, CMV serostatus, cytogenetics risk, number of HLA incompatibilities. However, dUCBT were performed more recently (2009 vs 2008), the time from CR1 to transplantation was longer (142 days vs 121 days), more frequently transplanted with CY+FLU+TBI2Gy (87% vs 68%), lower frequency of ATG use (21% vs 35%) and finally, dUCBT recipients received higher number of TNC collected (5×107/kg vs 3.9×107/kg) or infused (4×107/kg vs 3.1×107/kg). Median follow-up was 23 months in both groups. Cumulative incidence (CI) of 60 days neutrophil recovery was 82±3% after dUCBT and 76±2% after sUCBT (p=0.86) and frequency of full donor chimerism at day 100, was not statistically different between dUCBT (81%) and sUCBT (86%). At day 100, CI of acute GVHD (grade II-IV) was 35% in both groups, however there was a trend of increased incidence of grade III-IV after sUCBT (19%) compared to dUCBT (10%, p=0.06) but increased incidence of grade II aGVHD after dUCBT (28%) compared to 17% after sUCBT (p=0.05). CI of chronic GvHD at 2 years was 21±4% after dUCBT and it was 12±5% after sUCBT (p=0.15). At 2 years, CI of non relapse mortality (NRM) after dUCBT was 28±4% and it was 30±6% after sUCBT (p=0.87). However, CI of 2y relapse was 21±4% after dUCBT whereas it was 38±2% after sUCBT (p=0.03). In a multivariate analysis adjusting for the differences between the 2 groups, dUCBT was associated with lower incidence of relapse compared to sUCBT (HR=0.74, p=0.01). Therefore, there was an improved 2-y LFS after dUCBT (51±5%) compared to sUCBT (32±3%; p=0.03). This was confirmed in a multivariate analysis (HR=0.64, p=0.04). Concerning patients transplanted in CR2 (n=148), there were no statistically differences of outcomes after dUCBT (n=93) or sUCBT (n=55). At 2y, LFS was 40±6% after dUCBT and 48±3% after sUCBT (p=0.32). In a subgroup analysis of dUCBT (n=118) and sUCBT (n=51) recipients using the same conditioning regimen (CY+FLU+TBI2Gy), 2 y LFS were 54±5% and 33±7% respectively (p=0.05). Conclusion: In this retrospective comparative based registry analysis, in AL patients transplanted in CR1, neutrophil recovery, GVHD and NRM were not statistically different after RIC-dUCBT or RIC-sUCBT, however, dUCBT recipients had decreased relapse incidence and improved LFS. For AL patients transplanted in CR2, there was no benefit of using dUCBT when compared to sUCBT recipients. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document