Candida colonization is associated with severe acute GVHD in adult patients undergoing single‐unit cord blood transplantation

2019 ◽  
Vol 104 (1) ◽  
pp. 74-76 ◽  
Author(s):  
Takaaki Konuma ◽  
Mai Mizusawa ◽  
Masato Suzuki ◽  
Yuta Kaito ◽  
Masamichi Isobe ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 223-223 ◽  
Author(s):  
Vanderson Rocha ◽  
Myriam Labopin ◽  
Annalisa Ruggeri ◽  
Marina Podestà ◽  
Dolores Caballero ◽  
...  

Abstract Abstract 223 The use of single cord blood unit for transplantation in adult patients is limited due to the high risk of graft failure and delayed neutrophil and platelet recoveries. The limited hematopoietic progenitors in UCB grafts and their homing after IV injection, have prompted investigators to study the design of delivering CB grafts directly into the bone marrow (BM) space (IBCBT) or to use double cord blood transplantation (dUCBT) to improve engraftment. To evaluate the impact of IBCBT, we made a retrospective based registry comparison with dUCBT performed in the same time period (2006-2010) and reported to Eurocord-EBMT. We included 87 and 149 patients who received either IBCBT or dUCBT, respectively, after a myeloablative conditioning regimen for malignant disorders. IBCBT was performed in 8 EBMT centers whereas dUCBT was performed in 56 EBMT centers. Majority of patients in both groups had acute leukemia. IBCBT patients were older (p<0.001), more frequently received an autologous graft (p<0.001) and had positive CMV serology (p<0.001), and importantly had more advanced disease at transplantation (p=0.04). Median number of infused (after thawing) nucleated cells injected intrabone was 2.5×107/kg and it was 3.9×107/kg in dUCBT (p<0.001). In 72% of both groups, CB grafts were HLA 4/6 (the highest HLA disparity was taken into consideration in dUCBT). Other differences were regarding GVHD prophylaxis that was based on CSA+MMF in 100% of IBCBT and in 62% of dUCBT cases; ATG was used in all IBCBT and 40% of dUCBT. Median follow-up time was 18 months in IBCBT and 17 months in dUCBT. At day 30, cumulative incidence (CI) of neutrophil recovery (ANC >500) was 83% after IBCBT and 63% after dUCBT, and at day 60, it was 90% in both groups; the median time to reach ANC>500 was 23 and 28 days after IBCBT and after dUCBT (p=0.001) respectively. At Day-180 CI of platelets recovery was 81% after IBCBT and 65% after dUCBT (p<0.001) with a median time of 36 days and 49 respectively (p=0.002). At day 100, CI of acute GVHD (II-IV) was 19% and 47% (p<0.001) and chronic GVHD 34% and 37% respectively (p=NS) respectively. Unadjusted 2 years-CI of NRM and RI were 31% and 23% after IBCBT and 35% and 28% after dUCBT, respectively (p=NS). Unadjusted 2 y-DFS estimation was 47% after IBCBT and 37% after dUCBT (p=NS). In multivariate analysis adjusting for statistical differences between 2 groups (such as status of the disease at transplant, age, CMV, previous transplants, GVHD prophylaxis), recipients of IBCBT had improved DFS (HR: 1.64, p=0.035), faster platelet recovery (HR:2.13, p<0.001) and decreased acute GVHD (HR:0.31; p<0.001) compared to dUCBT recipients. We did not find a cut-off value of number of nucleated cells after IBCBT or dUCBT that could be associated with outcomes after both approaches. In conclusion, both strategies have extended the use of CB transplants to adults in need of cord blood transplantation. Therefore, IBCBT is an option to transplant adult patients with single CB units after myeloablative conditioning regimen and may impact the total costs of cord blood transplantation. Based on these results, intra-bone technique may disclose new transplant potentialities also with other HSC sources. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 23 (11) ◽  
pp. 1932-1938 ◽  
Author(s):  
Takaaki Konuma ◽  
Chisato Kohara ◽  
Eri Watanabe ◽  
Motoko Mizukami ◽  
Etsuko Nagai ◽  
...  

2016 ◽  
Vol 58 (1) ◽  
pp. 118-126 ◽  
Author(s):  
Hiroto Ishii ◽  
Takaaki Konuma ◽  
Seiko Kato ◽  
Maki Oiwa-Monna ◽  
Arinobu Tojo ◽  
...  

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3414-3414
Author(s):  
Mark Vander Lugt ◽  
Beth Carella ◽  
Heather Stanczak ◽  
Xiaohua Chen ◽  
Paul Szabolcs

Abstract Introduction: Success of umbilical cord blood transplantation (UCBT) is limited by an increased risk of graft rejection, mixed chimerism, infection, and delayed immune reconstitution. Additionally, strategies such as donor lymphocyte infusion (DLI) to improve declining donor chimerism or augment immune reconstitution are extremely limited in UCBT. We hypothesized that removing and storing a portion of the thawed cord blood graft for future use as a cord DLI (cDLI) could be used to improve mixed chimerism or augment immunity without adverse impact on engraftment or graft versus host disease (GVHD). Methods: Patients with inborn errors of metabolism, immunity, or hematopoiesis underwent a single unit UCBT following a reduced-intensity conditioning regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa (ClinicalTrials.gov: NCT00744692) with a thaw and dilute (no wash) methodology. Up to 5% of the cord blood graft was removed from the thawed graft and re-cryopreserved for potential cDLI. The cDLI was infused at the discretion of the treating physician in discussion with the study PI (P.S.) in cases of mixed or declining donor chimerism, viral infection, or delayed immune reconstitution. Results: A total of 33 patients had cells cryopreserved prior to UCBT for potential cDLI. The characteristics of these patients are shown in Table 1. A total of 18 patients received cDLI at a median of 65 days (range 14-124) post-UCBT. The median cell dose of the cDLI was 8.46e+05 CD3/kg and 1.53e+04 CD34/kg. The indication for cDLI was mixed whole blood or CD3 chimerism (n=9), viral infection (n=9), and delayed immune reconstitution (n=5); 5 patients had more than one indication for cDLI, most commonly infection with delayed immune reconstitution (n=4). All patients engrafted with neutrophils at a median of 15 days post-transplant (range: 10-31 days); however, one patient experienced secondary graft failure at day 38 post-transplant despite cDLI at day 28 post-transplant. Improvement in chimerism was seen in 5 of 9 patients, viral load and/or clinical symptoms of viral infection in 5 of 9 patients (including gastroenteritis due to rotavirus (n=1) or adenovirus (n=1)), and absolute CD3 count in 5 of 5 patients (Figure). A total of 15 patients (45%) developed acute grade I-III GVHD at a median of 69 days (range: 13-95 days) post-UCBT. In the group of patients who received cDLI, 8 developed grade I-II skin GVHD at a median of 19 days (range 4-81 days) post-cDLI. In addition, 2 patients with a history of GVHD received subsequent cDLI without GVHD flare post-cDLI and were analyzed for progression post-cDLI. No patients who received cDLI developed grade III or IV acute GVHD or extensive chronic GVHD, while 4 patients who did not receive cDLI developed grade III GVHD affecting skin and/or the gastrointestinal tract. There was no difference in the cumulative incidence of acute GVHD between those who received cDLI and those who did not (44% and 33%, respectively; p=0.81; Figure). The 3-year overall and event-free survival of the entire group was 94% and 91% respectively (Figure), with treatment-related mortality of 6% at 1 year post-transplant. Conclusions: The use of cDLI is safe in patients undergoing single-unit UCBT. Despite the removal of a small portion of the cord blood graft for cDLI, all patients engrafted with neutrophils and no increased morbidity was seen. In addition, although the sample size is small, over half of the patients who received cDLI had improvement in the primary indication (chimerism, viral infection, or immune reconstitution) for cDLI, with the most benefit seen in patients receiving cDLI for delayed immune reconstitution, as evidenced by both clinical improvement in infectious symptoms and increases in absolute CD3 count. This suggests that cDLI may be an effective way to address mixed chimerism, infection, and particularly, delayed immune reconstitution and should be explored in a larger clinical trial. Disclosures No relevant conflicts of interest to declare.


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