Acute Graft Versus Host Disease (GVHD) Is Increased in Patients Receiving Cyclosporine/Cellcept as Frontline Prophylaxis Against GVHD in Pediatric Patients Undergoing Allogeneic Stem Cell Transplantation.

Abstract Traditionally, pediatric patients are prophylaxed against GvHD with cyclosporine (CSA) plus either methotrexate (Mtx) or methylprednisolone (Pred). Mtx worsens the severity of mucositis and renal insufficiency while pred causes muscle wasting, hypertension, hyperglycemia and increased infections. Cellcept (myophenolic acid) is a better tolerated, less toxic agent with synergistic immunosuppressive effects when combined with cyclosporine or tacrolimus. We explored its use in combination with cyclosporine in 63 pediatric patients (49% male, 74% Caucasian, 36% CMV+) undergoing allogeneic transplantation. Patients with both malignant (n=24) and non-malignant (n=39) conditions ranging in age from 2 weeks to 26 years were transplanted after myeloablative preparative regimens with either related bone marrow or cord blood (n=11) or unrelated cord blood (n=52), using cellcept and cyclosporine for GVHD prophylaxis. Cellcept and CSA were administered intravenously through the first 40–60 days post transplant using cellcept at a dose of 15mg/kg/dose IV q8H beginning on day -2 or -3 and CSA in traditional fashion targeting trough levels of 200–450 (infusion) and 150–350 with intermittent dosing. The patient then transitioned to oral therapy at the same dose and schedule until day 100–180 for cellcept and day 270 for cyclosporine and then tapered if no active GVHD was present. There were no acute toxicities attributable to cellcept observed in patients on IV or oral therapy. Despite the lack of steroids in the GVHD prophylactic regimen, all patients required treatment with antihypertensive therapy. Grossly, infection rates did not vary from those previously observed in conventionally treated patients at our center. The cumulative incidence (CINC) of neutrophil engraftment by day 42 was 79.4% (95% CI 64.7–91.2) which is comparable to previous reports. Two patients engrafted after a second unrelated cord blood transplant. Of the six patients who did not engraft, 3 died of infectious complications, two died of VOD and multi-system organ failure and one died of congenital pulmonary hypertension. Of the 59 patients evaluable for GVHD, follow-up ranged between 52 and 994 days (median 224 days). The CINC of acute GVHD grades II–IV by day 100 was 64.1% (95% CI 47.8–82.1) and the CINC of acute GVHD grades III– IV by day 100 was 6.3% (95% CI 0–17.0). Follow-up is too short to comment on the incidence of chronic GvHD, but to date, 5 of 14 patients followed for >100 days have developed mild chronic GvHD. The incidence of grade II acute GVHD was higher than that previously reported in pediatric patients receiving CSA/Pred while the incidence of grade III–IV GVHD was comparable. While this data is early, it appears that the incidence of acute Grade II GVHD is increased compared to previous series in patients treated with cellcept instead of Mtx (related bone marrow transplantation) or pred (unrelated cord blood transplantation). Engraftment in UCBT recipients was not compromised with the use of IV cellcept administered in the peritransplant period. Overall, despite the use of steroids to treat aGVHD, there was overall steroid sparing with this regimen. Additional patients will need to be tested with this regimen and longer follow-up is necessary to fully define the risks or benefits of this therapy.

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Complementary Transplantation with Haploidentical Stem Cells and Unrelated Cord Blood for Leukemia and Thalassemia

Blood ◽

10.1182/blood.v128.22.1235.1235 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1235-1235

Author(s):

Chunfu Li ◽

Yuelin He ◽

Xuedong Wu ◽

Xiaoqin Feng ◽

Jianyun Liao ◽

...

Keyword(s):

Stem Cells ◽

Cord Blood ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Mixed Chimerism ◽

Gvhd Prophylaxis ◽

Grade Ii ◽

Unrelated Cord Blood ◽

Kinetics Of

Abstract Background Unrelated Cord Blood (UCB) Transplantation is a potentially curative therapy for leukemia and thalassemia; however, engraftment failure and slow immune reconstitution remain key clinical issues. We hypothesized that complementary transplantation (CT) of UCB with haploidentical stem cell graft (hap-SC) tolerized with post-transplant cyclophosphamide would result in rapid engraftment and low relapse rate without additional risk of graft-versus-host disease (GVHD). Therefore, we developed a novel complementary transplant approach. Patients and Method Sixty-six patients received CT between December 2012 and June 2016. Of them, 30 patients had malignance diseases (MD), including 11 lymphoid and 19 myeloid diseases, and 36 had thalassemia major (TM). Median age was 12 (range; 2-13) and 8 (3-17) years in the MD and TM group, respectively. Median follow-up time was 13 (7-32) and 19 (2-25) months, respectively. Conditioning (Regimen CT-13) included Cyclophosphamide on day-8 to -7, Busulfan on day-6 to -4, Fludarabine on day-6 to -2 and Thiotepa on day-3. Hap-SC was infused on day 0. GVHD prophylaxis consisted of Cyclophosphamide on day+3 to +4. UCB was infused on Day+6. Mycophenolate mofetil and Tacrolimuswas started on day+6 for GVHD prophylaxis. For 26 TM patients transplanted since 2014, they received identical regimen except with the additional Thymoglobulin on day -11 to -9 (Regimen CT-14). Results The chimerism status at last follow-up was Hap-SC, UCB, mixed stem cells (MSC) and rejection in 20, 9, 1 and 0 patient in the MD group; and 16, 14, 3 and 3 patients in the TM group. Interesting, the initial chimerism on day+28 in the TM group was Hap-SC, UCB and MSC engrafted in 15, 7 and 12 patients, respectively. Thus, the MSC was not stable in TM patients; UCB typically became dominant overtime instead of the initial majority from hap-SC (Fig. 1). In the MD group, the time to neutrophil >= 0.5x109/L, platelet >=20 x109/L and hemoglobin >=80 g/L was day+18 (14-36), +10.0 (6-51) and +7 (1-20) in the final hap-SC engrafted group; and+30 (22-35), +25 (1-64) and +7 (3-28) in the final UCB engrafted group. Overall survive (OS), disease-free survive (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were 75.6%, 64.3%, 24.7£¥ and 13.7%, respectively, in all 30 MD patients; and 79.3%,73.8%,15.5% and 12.3% (Fig.2), respectively, in the 25 cases with complete remission (CR) at the time of transplantation. The corresponding data were 89% vs. 88.9%£¬65.0% vs. 77.8%£¬31.1 % vs.12.5% and 10.3% vs.11.1%£¨p>0.05 in all pairs), respectively, in hap-SC and UCB engrafted groups. Donor carrying KIR centromeric B motif was associated with reduced RI (10 % vs. 33.9%). In TM group, OS, thalassemia free survive (TFS), rejection and transplant-related mortality were 91.2%, 85.7%, 5.6% and 8.8%, respectively in all 36 patients. Impressively, all of the 26 patients who received the newer CT-14 protocol were alive without TM (Fig. 2). 7/10 UCB carrying KIR centromeric B motif engrafted. In the MD group, 23.3% had grade II-IV and10.0% had III-IV acute GVHD. Grade II, III and IV acute GVHD occurred in 3 patients, respectively, in TM group. One MD patient had severe chronic GVHD (lung) after DLI for relapse. No moderate chronic GVHD occurred in TM groups. Summary The CT-13 regimen resulted in high OS and DFS, especially in CR patients in the MD group. The CT-14 leaded to 100% TFS in thalassemia patients. Acute and chronic GVHD were acceptable. Donor carrying centromeric B motif promoted engraftment and reduced RI. A multicenter study should be developed in the future based on our favorable results. Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 1. Kinetics of mixed chimerism in thalassemia patients Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 2. Results of malignance diseases in CR status at the time of transplant Figure 3. Thalassemia-free survive resulted from regimen CT-14 Figure 3. Thalassemia-free survive resulted from regimen CT-14 Disclosures No relevant conflicts of interest to declare.

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Unrelated Cord Blood Does Not Increase An Overall Risk Of Invasive Fungal Infections Compared To Unrelated Bone Marrow: A Single Center Retrospective Analysis For 749 Recipients

Blood ◽

10.1182/blood.v122.21.4541.4541 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4541-4541 ◽

Cited By ~ 1

Author(s):

Yuki Asano-Mori ◽

Hideki Araoka ◽

Muneyoshi Kimura ◽

Daisuke Kaji ◽

Hikari Ota ◽

...

Keyword(s):

Bone Marrow ◽

Cord Blood ◽

Cumulative Incidence ◽

Fungal Infections ◽

Chronic Gvhd ◽

Antifungal Prophylaxis ◽

Invasive Fungal Infections ◽

Systemic Corticosteroids ◽

Grade Ii ◽

Unrelated Cord Blood

Background Invasive fungal infections (IFIs) are of great concern after allogeneic hematopoietic stem cell transplantation (HSCT), the risk of which is considered to be particularly prominent among cord blood transplantation (CBT) recipients. Patients and Methods We retrospectively analysed the records of 749 adult patients who underwent CBT or unrelated bone marrow transplantation (uBMT) for the first time at the Toranomon Hospital between 2002 and 2012, and who had neither prior history nor suspicious findings of IFIs. As prophylaxis for IFIs, fluconazole (FLCZ) or itraconazole (ITCZ) capsules were conventionally used until around 2006, which were then changed to newer mold-active agents including ITCZ oral solution, voriconazole or micafungin after their approval in Japan, the choice of which was subjected to physician's discretion. Results Engraftment achieved in 418 CBT patients and 198 uBMT patients with a significantly longer neutropenic period in CBT patients (median 20 days vs 18 days, P<0.001), whereas 37 patients underwent re-transplantation and 96 died before engraftment. The incidences of grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were significantly less frequent after CBT compared to uBMT (40% vs 54% and 17% vs 46%, both P<0.001). Systemic corticosteroids at ≥0.5mg/kg/day was given in fewer CBT patients compared to uBMT patients (59% vs 66%, P=0.07). The median durations of immunosuppressants and antifungal prophylaxis were significantly shorter in CBT patients compared to uBMT patients (118 days vs 302 days and 315 days vs 491 days, both P<0.001). As prophylaxis for IFIs, 194 CBT patients and 91 uBMT patients received FLCZ/ITCZ capsules, while 341 CBT patients and 123 uBMT patients received newer mold-active agents. Seventy-nine patients (57 in CBT and 22 in uBMT) developed IFIs with a cumulative incidence of 12.2%, at a median of 27 (1-1646) days after HSCT. About 60% of the patients developed IFIs by day 50 and the percentage reached more than 90% until 1 year. The median onset was significantly earlier in CBT patients compared to uBMT patients (day 19 vs day 61, P=0.007). The cumulative incidence of IFIs was significantly higher in CBT patients compared to uBMT patients during 50 days after HSCT (7.9% vs 3.8%, P=0.04), but became significantly lower thereafter until 1 year (2.7% vs 6.9%, P=0.02), and an overall incidence was almost similar between the 2 groups (12.6% vs 11.6%, P=0.58) (Figure 1). Four patients had 2 infectious episodes caused by different fungal species, and a total of 83 infectious episodes were documented. Eighty-one cases were breakthrough infection during antifungal prophylaxis (FLCZ/ITCZ capsules in 28, and newer mold-active agents in 53). Invasive aspergillosis (IA) was the most common, accounting for 67.9% (proven in 11, probable in 46), followed by invasive candidiasis (IC), (19.3%; candidemia in 15, encephalitis in 1). Although the incidences of IA and IC were comparable between CBT and uBMT patients, relatively rare type of IFIs caused by Trichosporon (4 cases), Mucor (2 cases) and Rodotorula (1 case) exclusively occurred in CBT patients, except one case of Fusarium infection in a patient who relapsed after uBMT. Grade II-IV acute GVHD, extensive chronic GVHD and systemic corticosteroids at ≥0.5mg/kg/day were identified as significant risk factors of IFIs for both groups (HR 1.89, P=0.01, HR 4.16, P=0.006, and HR 1.83, P=0.02). However, the impact of all these were not apparent in CBT patients (HR 1.59, P=0.16, HR 2.18, P=0.29 and HR 1.48, P=0.22), in contrast with the powerful impact in uBMT patients (HR 2.51, P=0.049, HR 10.23, P=0.03 and HR 2.87, P=0.03). Although the cessation of antifungal prophylaxis significantly increased the risk of IFIs in uBMT patients (HR 5.95, P=0.01), it showed no impact in CBT patients (HR 0.87, P=0.89). IFIs were main causes of death in 21 patients, which significantly affected non-relapse mortality in both CBT and uBMT patients (HR 3.93 and HR 6.08, both P<0.001). Conclusion Unrelated cord blood did not increase an overall incidence of IFIs, because higher risk in the early post-transplant period was counterbalanced by the dramatically decreased risk due to lower frequencies of GVHD and its treatment in the later period. Particular attention might be required to the early-onset IFIs due to fungi other than Aspergillus or Candida species, in order to further decrease the risk of IFIs after CBT. Disclosures: No relevant conflicts of interest to declare.

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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 ◽

10.1182/blood.v116.21.910.910 ◽

2010 ◽

Vol 116 (21) ◽

pp. 910-910 ◽

Cited By ~ 3

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.

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Comparable Outcomes between Unrelated Donor (8/8 or 7/8 matched) and Haploidentical Donor for Allogeneic Stem Cell Transplantation in Adult Patients with Severe Aplastic Anemia

Blood ◽

10.1182/blood-2019-130419 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4619-4619

Author(s):

Jee Yon Shin ◽

Sung-Soo Park ◽

Gi June Min ◽

Silvia Park ◽

Sung-Eun Lee ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Advisory Committees ◽

Sibling Donor ◽

Alternative Donor ◽

Matched Sibling ◽

Grade Ii

Background Either allogeneic hematopoietic stem cell transplantation (SCT) from HLA-matched sibling donor or immunosuppressive therapy (IST) has been recommended as one of the standard treatments for severe aplastic anemia (SAA). Regarding only 30% of chance finding HLA‐matched sibling donor, SCT from an alternative donor including unrelated (URD) or haplo-identical related donor (HAPLO) is considered to be a treatment option after failure to IST in patients who lack of a HLA-matched sibling donor. The aim of this study was to compare the outcomes of URD SCT and HAPLO SCT for SAA patients. Method Consecutive 152 adult patients with SAA who received first SCT between March 2002 and May 2018 were included: 73 of HLA-well-matched (8/8) URD (WM-URD), 34 of HLA-mismatched URD (MM-URD), and 45 of HAPLO. With the intention to have a follow-up period at least 1 year, data were analyzed at May 2019. A conditioning regimen with total body irradiation (TBI) and cyclophosphamide was used for URD-SCT, whereas that with TBI and fludarabine was administered for HAPLO-SCT (Lee et al, BBMT 2011;17:101, Park et al, BBMT 2017;23:1498, Lee et al, Am J Hematol 2018;93:1368). The combination of tacrolimus and methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Results The median follow-up was 53.4 (range, 0.2-174.1) months. The median age of URD and HAPLO cohort was 30 (range 18-59) and 34 (range 18-59) years, respectively. Except for one and three patients who failed respective a neutrophil and platelet engraftment, other patients achieved neutrophil and platelet engraftments with median 11 and 15 days for WM-URD, 13 and 16.5 days for MM-URD, and 12 and 14 days for HAPLO, respectively. The five-years overall survival (OS), failure-free survival (FFS), and cumulative incidences (CIs) of graft-failure and transplant-related mortality were similar among three groups: 88.3%, 85.5%, 2.7%, and 11.7% for WM-URD; 81.7%, 81.7%, 0%, and 18.3% for MM-URD, and 86.3%, 84.1%, 6.7%, and 9.2% for HAPLO. The 180-days CI of grade II-IV acute GVHD in WM-URD, MM-URD and HAPLO were 35.6%, 52.9%, and 28.9%, respectively; and moderate to severe chronic GVHD were 28.7%, 38.7% and 11.8% in respective cohort. The CI of grade II-IV acute GVHD and moderate to severe chronic GVHD were significantly higher in MM-URD than those in HAPLO (both, p=0.026). ATG is the only factor affecting both grade II-IV acute GVHD (Hazard ratio 0.511, p=0.01) and moderate to severe chronic GVHD (Hazard ratio 0.378, p=0.003) in multivariate analysis. Other complications including CMV DNAemia, hemorrhagic cystitis, invasive fungal disease, secondary malignancy, and sinusoidal obstruction syndrome were similar among three groups. Survival outcomes of a subgroup of ≥ 2 allele MM-URD (n=16) extracted form MM-URD were inferior that of other donor types (n=136): 75.0% vs. 86.9% (p=0.163) for 5-year OS and 75.0% vs. 84.7% (p=0.272) for 5-year FFS. Conclusion This study shows that there were no significant differences between alternative donor sources in the absence of suitable matched sibling donor. Host/donor features and urgency of transplant should drive physician towards the best choice among alternative donor sources for SAA patients treated with SCT. However, selection of ≥ 2 allele MM-URD should not be recommended due to high incidence of GVHD and inferior outcomes. Figure Disclosures Kim: Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; Otsuka: Honoraria. Lee:Alexion: Consultancy, Honoraria, Research Funding; Achillion: Research Funding.

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Outcomes of 40 Adult Patients after Double Cord Blood Transplantation Using a Reduced Intensity Chemotherapy Conditioning Regimen.

Blood ◽

10.1182/blood.v108.11.605.605 ◽

2006 ◽

Vol 108 (11) ◽

pp. 605-605

Author(s):

Karen K. Ballen ◽

Corey Cutler ◽

Thomas R. Spitzer ◽

Beow Yeap ◽

Steve McAfee ◽

...

Keyword(s):

Cord Blood ◽

Total Dose ◽

Aplastic Anemia ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Cord Blood Unit ◽

Reduced Intensity ◽

Related Mortality

Abstract Umbilical cord blood is an alternative stem cell source for patients without matched related or unrelated donors. However, single cord blood unit transplantation in adults is associated with high transplant related mortality, mostly due to infection. In this study, we used a reduced intensity conditioning regimen followed by infusion of two partially matched cord blood units. The conditioning regimen was fludarabine 30mg/m2/day Days -8,-7,-6,-5,-4,-3 (total dose 180mg/m2), melphalan 100mg/m2/day Day -2, and rabbit antithymocyte globulin (thymoglobulin) 1.5 mg/kg/day Days -7,-5,-3,-1 (total dose 6.0 mg/kg). Cord blood units were a 4/6 or better HLA A, B, DR match with each other and with the patient, and contained a minimum combined pre-freeze cell dose of 3.7 x 107NC/kg. GVHD prophylaxis was cyclosporine and mycophenolate mofetil, for the first 21 patients, and tacrolimus and sirolimus for the second cohort of 19 patients. Forty patients, 22 males (55%) and 18 females (45%) with a median age of 48 years (range 19–64 years) were treated. The diagnoses were AML (n=14), ALL (n=1), NHL (n=10), CLL (n=2), MDS (n=5), Hodgkins Disease (n=5), aplastic anemia (n=2), and chronic myelogeneous leukemia (n=1). Thirty-five patients have greater than 100 days of follow-up and are included in this analysis. The cell doses infused were a median of 4.0 x 10 7NC/kg (range 3.0–6.7 x 107) and 1.9 x 10 5 CD34+ cells/kg (range 0.5–10.0 x 105). Two patients (both with MDS complicating aplastic anemia) experienced primary graft failure, and received second cord blood transplants using a different conditioning regimen. Among the remaining patients, the median time to an absolute neutrophil count >500 was 21 days (range 14–70 days). There were two late graft failures. The median time to a platelet count >20,000 unsupported was 43 days (range 21–125 days). The incidence of acute GVHD Grades II–IV was 40% for the patients receiving cyclosporine/MMF and 29% for patients receiving tacrolimus and sirolimus. There were no deaths from acute GVHD in the cyclosporine/MMF group and one death from acute GVHD in the tacrolimus/sirolimus group. Seven patients (20%) developed chronic GVHD. The 100-day transplant related mortality was 14%. Two deaths were related to Epstein Barr virus related lymphoproliferative disorder, and the other deaths were due to a CNS bleed, staphylococcal sepsis, and respiratory failure due to aspergillus infection. Two patients have relapsed and one has progressive disease. With a median follow up of 14 months (range 3–31 months) the overall survival is 74% and the disease-free survival is 67%. Chimerism analysis showed predominance of one cord by Day +100. In 71% of patients, the first cord blood unit infused predominated. In conclusion, engraftment of adult patients appears to be acceptable using double cord blood products and reduced intensity, non TBI conditioning regimen; the risk of serious acute and chronic GVHD is low, survival is excellent in a selected group of patients and relapse rate is low, suggesting preservation of graft versus leukemia effect despite the low T cell dose.

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Unrelated Cord Blood Cell Transplantation for Acquired Severe Aplastic Anemia: The Report from the Japan Cord Blood Bank Network.

Blood ◽

10.1182/blood.v110.11.2020.2020 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2020-2020

Author(s):

Seiji Kojima ◽

Ayami Yoshimi ◽

Shuichi Taniguchi ◽

Junichi Hara ◽

Toshimitsu Matsui ◽

...

Keyword(s):

Bone Marrow ◽

Cord Blood ◽

Aplastic Anemia ◽

Cumulative Incidence ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

Severe Aplastic Anemia ◽

Bone Marrow Donor ◽

Grade Ii ◽

Unrelated Cord Blood

Abstract Treatment approaches for patients with severe aplastic anemia (SAA), who failed immunosuppressive therapy and lack a bone marrow donor remains a great challenge. Unrelated cord blood transplantation (UCBT) has not been recommended for SAA because of historical poor outcome with high rate of engraftment failure. To evaluate the current feasibility of UCBT in SAA, we retrospectively analyzed the outcomes of 31 patients (median age 28 years old; ranged 0.9–72.3 years old) with SAA, who received UCBT as the first graft between 1998 and 2006 in Japan. Median disease duration before UCBT was 337 day (31–5063 days). By serology, HLA loci were matched in 4 recipient-donor pairs and mismatched (1–2 loci) in 27 patients. A minimum cell count of 2 × 107 nucleated cells/kg body weight was infused in all patients. Engraftment was observed in 17 of 24 evaluable patients. The median times to achieve a neutrophil count ≥ 0.5 × 109/l and a platelet count ≥ 50 × 109/l were 19 days (range 12–35 days) and 59 days (range 39–145 days), respectively. The results of chimerism analysis were available in 9 of them and all of them showed complete donor chimerism (>99%) except one with autologous recovery. Late rejection was seen in one patient. Acute GVHD (≥ grade II) was observed in 5 of 18 evaluable patients (grade II; n=4, grade III; n=1) (cumulative incidence =17.1%) and chronic GVHD was observed in 4 of 14 evaluable patients (extensive: n=1, limited: n=3) (cumulative incidence =19.7%). Currently, 13 patients are alive, having survived for median 22.5 months (ranged 3 to 77 months) after UCBT (overall survival at 2 years=40%). Causes of death of 18 patients were following: graft failure (n=7), bacterial/fungal infections (n=3), hepatic veno-occlusive disease (n=3), and others (n=5). The conditioning regimen appeared to be the most important factor for the outcome and low dose total body irradiation (2–4 Gy) + fludarabine (90–250/ mg/m2) and cyclophosphamide (50–100 mg/kg or 2250/mg/m2) (n=5) gave the best outcome with 80% of survival. The GVHD prophylaxis with single agent (cyclosporine or tacrolimus) related with a better engraftment rate than 2 or more agents (84.4% vs 47.3%, p=0.02). These results suggest that UCBT can be a salvage treatment for patients without a bone marrow donor and warrant further evaluation in prospective studies. Optimization of conditioning regimen will improve the engraftment and outcome of UCBT.

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Unrelated Cord Blood Transplants in Children/Adolescents in Multi-Racial Singapore.

Blood ◽

10.1182/blood.v110.11.5089.5089 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5089-5089

Author(s):

Poh-Lin Tan ◽

Ah-Moy Tan ◽

Mei-Yoke Chan ◽

Mariflor Villegas ◽

Allen Yeoh ◽

...

Keyword(s):

Cord Blood ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Chronic Gvhd ◽

Severe Combined Immunodeficiency ◽

Hla Antigen ◽

Cell Dose ◽

Malignant Group ◽

Unrelated Cord Blood

Abstract Alternative donor choices are limited in multi-racial, multi-ethnic societies with small families such as Singapore. Unrelated cord blood transplant (UCBT) provides a feasible alternative to patients lacking adult stem cell donors. We reviewed the Singapore experience in UCBT for 29 children/adolescents with malignant (N = 19) and non-malignant diseases (N = 10) from 1998 – 2006. A significant 25% of patients were of varied South-East Asian (SEA) descent with majority being SEA-Chinese. The median age at UCBT was 6.7 (0.5 – 17.7) years with younger patients in the non-malignant compared to the malignant group (4.7 versus 8.8 years). Malignant indications for UCBT included acute lymphoblastic leukemia (ALL, N = 12), acute myeloid leukemia (N = 4), chronic myeloid leukemia (N = 2) and hemophagolymphohistiocytosis (N = 1); and non-malignant indications severe combined immunodeficiency disease (N = 3), CD40 ligand deficiency (N = 2), chronic granulomatous disease (N = 1), leukocyte adhesion disease (N = 1), thalassaemia (N = 2) and Fanconi anemia (N = 1). Seventeen patients received myeloablative conditioning (MAC), 12 received reduced intensity conditioning (RIC). Of the 12 RIC patients, 8 received dual UCBT with a median total nucleated cell dose (TNC) of 7.2 (3.4 – 12.2) x 10(7)/kg, CD34 cell dose of 1.7 (0.7 – 3.7) x 10(5)/kg compared to a median 6.2 (2.4 – 21.8) x 10(7)/kg, CD34 of 3.1 (0.2 – 297.6) x 10(5)/kg in MAC patients who received single UCBT.All except 3 patients received 1 – 2 HLA antigen mismatched cords. Sixteen of 19 and 6 of 10 patients in the malignant and non-maligant groups engrafted at a median of 19.5 (2 – 21) days and 20 (14 – 41) days, respectively. Nine and 2 of 17 malignant patients and none of non-malignant patients developed grade 1- III aGVHD and chronic GVHD, respectively. Thirteen of 19 patients and 8 of 10 patients in the malignant and non-malignant groups are alive at a median follow-up of 23 (9 – 48) months and 31 (14 – 73) months, respectively. The main cause of death was disease relapse in the malignant group (5 of 6 patients). In the malignant group, a select group of ALL patients (ALL-RIC, N = 6) was given dual UCBT after RIC with the aim to reduce transplant-related morbidity/mortality while preserving chances of engraftment, graft-versus-leukemia effects and long-term neuro-endocrine outcome. These patients received a median total nucleated cells (TNC) dose of 7.2 (3.4 – 12.2) x 10(7)/kg and CD34 cell dose of 2.0 (0.8 – 3.7) x 10(5)/kg recipient BW and were discharged at a median of 17 (12 – 16) days. Compared to another 6 ALL patients who received single UCBT after MAC (ALL-MAC), these received a median TNC of 5.4 (2.6 – 8.1) x 10(7)/kg and CD34 of 2.8 (0.6 – 297.6) x 10(5)/kg recipient BW and were discharged at a median of 59 (31 – 118) days. ALL-RIC and ALL-MAC patients engrafted at a median of 6 (2 – 28) days and 21 (14 – 37) days, respectively, with one primary graft failure in the ALL-MAC group. There were 4 relapses, 2 in each group at a median follow-up of 23 (12 – 30) months and 16 (3.5 – 48) months, respectively. More patients in ALL-RIC group developed acute GVHD compared to the ALL-MAC (83% versus 33%). All patients except 1 from each group are alive as of last follow-up, with death occurring from a road-traffic accident while in complete remission and one from relapse in the ALL-RIC and ALL-MAC groups, respectively. UCBT successes in children/adolescent is high in multi-racial Singapore using conventional and novel approaches.

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

Blood ◽

10.1182/blood.v116.21.911.911 ◽

2010 ◽

Vol 116 (21) ◽

pp. 911-911 ◽

Cited By ~ 1

Author(s):

Bernard Rio ◽

Sylvie Chevret ◽

Stephane Vigouroux ◽

Patrice Chevallier ◽

Sabine Furst ◽

...

Keyword(s):

Cord Blood ◽

De Novo ◽

Cord Blood Transplantation ◽

Conditioning Regimen ◽

Blood Transplantation ◽

Reduced Intensity Conditioning Regimen ◽

Prospective Phase ◽

Grade Ii ◽

Unrelated Cord Blood

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

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Outcomes after Double Umbilical Cord Blood Transplantation in Children: A Survey on Behalf of Eurocord and PDWP-EBMT

Blood ◽

10.1182/blood.v124.21.2570.2570 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2570-2570

Author(s):

Federica Giannotti ◽

Annalisa Ruggeri ◽

Gerard Michel ◽

Jean-Hugues Dalle ◽

Tracey O'Brien ◽

...

Keyword(s):

Single Unit ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Univariate Analysis ◽

Median Number ◽

Cell Dose ◽

Gvhd Prophylaxis ◽

Grade Ii ◽

Grade Iii

Abstract Double UCBT (dUCBT) has been used in adults to reach an acceptable cell dose. For most children a single unit with a total nucleated cell (TNC) dose >3x107/Kg can be easily identified, but that is not always the case for heavier patients (pts). Use of dUCBT might decrease relapse and increase graft-versus-host-disease (GvHD). Data on dUCBT in children are scarce in the literature. A recent randomized study in children has described similar outcomes after double compared to single UCBT. Our study provides an overview of the use of dUCBT in the pediatric population reported to Eurocord. We retrospectively analyzed the outcomes of unrelated dUCBT in 177 children transplanted between 2002 and 2012 in 61 EBMT centres. Analysis was performed separately for pts with malignant (n=139) and non-malignant (NM, n=38) diseases. Among pts with malignancies, 76 had ALL, 40 AML, 6 MDS, 2 CML, 11 NHL, 3 Hodgkin Lymphoma and 1 Multiple Myeloma. Median age at dUCBT was 15 years (1.3-17.9) and median weight was 55 kg (13-97). Disease status at dUCBT was 1st complete remission (CR) (36%), ≥2nd CR (34%) or advanced (25%), and missing in 5% of the pts. In this group, 117pts received a myeloablative conditioning (MAC) and 22 a reduced intensity regimen (RIC). Cyclophosphamide+fludarabine+TBI was administered to 41% of the pts; 55% received ATG in the conditioning. Median number of collected TNC was 5.7x107/kg (3,6-12,8). Considering the unit with the higher number of HLA incompatibilities with the recipient, 56% had 2 mismatches. GvHD prophylaxis was cyclosporine-A (CSA) based in 93% of the pts (58% received CSA + mycofenolate mofetil). Median follow-up was 31 months. Cumulative incidence (CI) of neutrophil (PMN) and platelet (PLT) engraftment was 88% at 60 days and 64% at 180 days after dUCBT, and it was achieved with a median time of 24 and 45 days, respectively. Among the 122 pts with PMN engraftment, 85/94 with available data on chimerism were full donor and, of these, 20% had dual chimerism. CI of acute GvHD grade II-IV and grade III-IV at 100 days was 51% and 26%, respectively; it was significantly higher in pts who did not receive ATG (grade II-IV: 35% vs 67%, p=0.004; grade III-IV: 12% vs 37%, p=0.0075). Chronic GvHD was observed in 24/104 pts at risk (60% extensive; 2-year (yr) CI: 18%). The 2-yr CI of relapse was 31%. In univariate analysis, RIC, advanced stage at transplantation and a collected TNC dose lower than the median, were significantly associated with higher rates of relapse.The 2-yr CI of transplant related mortality (TRM) was 27%. Overall, 73 pts died: 35 of relapse, 15 of infections, 9 of GvHD and 14 of other causes. The 2-yr disease free survival (DFS) and overall survival (OS) were 42% and 45%, respectively. Among pts with NM disorders, 24 had bone marrow failure syndrome (BMFS) (10 Fanconi Anemia, 13 Acquired Aplastic Anemia and 1 other inherited BMFS), 2 hemoglobinopathies, 7 immune deficiencies and 5 metabolic disorders. Median age at dUCBT was 11 years (0.7-17.9) and the median weight was 40 kg (13-70). In this group, 27 pts received a RIC (40% TBI based), 10 a MAC (90% busulfan based), and 1 no conditioning regimen. ATG was administered to 82% of the pts and GvHD prophylaxis was CSA-based in 77%. The median number of collected TNC was 8.4x107/kg (1,2-11,2) and 60% of the grafts had ≥2 HLA mismatches with the recipient. Median follow-up was 39 months. Overall, 28 pts achieved PMN engraftment and 16 PLT engraftment, with a median time of 23 and 61 days, respectively. In univariate analysis, pts with BMFS compared to others had a significantly lower CI of PMN engraftment (58% vs 100%, p=0.002). Among the 10 pts who did not engraft, 3 had autologous reconstitution and 3 had a subsequent allogeneic HSCT. Forteen pts developed acute GvHD grade II-IV and 10/25 pts at risk had chronic GvHD (3 extensive). Overall 21 pts died (17 with BMFS): 9 of infections, 5 of GvHD and 7 of other causes. The 2-yr OS was 42% and it was significantly lower in pts with BMFS compared to those affected by other NM disorders (28% vs 70%, p=0.03). In pts with malignancies, despite a higher incidence of acute GvHD, DFS and OS seem to be comparable to those reported in the literature for single UCBT or HSCT from other alternative stem cell sources. In the NM disorders group, despite the high cell dose, dUCBT did not seem to improve results in pts with BMFS. This survey suggests that dUCBT is feasible in children and should be considered when a single unit with an adequate cell dose is not available. Disclosures No relevant conflicts of interest to declare.

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Impact of GvHD and Other Patient-, Disease-, Donor and Transplantation-Related Factors on 5 Year Relapse after Unrelated Cord Blood Transplantation for Children with Acute Lymphoblastic Leukemia in Remission

Blood ◽

10.1182/blood.v126.23.4384.4384 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4384-4384

Author(s):

Kristin M Page ◽

Myriam Labopin ◽

Annalisa Ruggeri ◽

Gerard Michel ◽

Cristina Diaz de Heredia ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Cord Blood ◽

B Cell ◽

Acute Gvhd ◽

Lymphoblastic Leukemia ◽

Poor Risk ◽

Younger Age ◽

Unrelated Cord Blood ◽

The Impact

Abstract Relapse remains a major barrier to the long-term overall survival (OS) of pediatric patients with acute lymphoblastic leukemia (ALL). Allogeneic HSCT is a potentially curative option for these patients and its mechanism relies on graft-versus-leukemia (GvL) and delivery of high-dose chemotherapy. However, the mechanism and degree of GvL in curing ALL is not fully understood. Unrelated cord blood (CB) is an attractive donor option for these patients due to rapid procurement and lenient HLA matching without increased graft-versus-host disease (GvHD). Despite less GvHD, relapse is not increased when compared to other donor sources. Therefore, through collaboration between Eurocord, PDWP-EBMT and Duke University, we performed a retrospective analysis to identify risk factors associated with relapse, and the role of GvHD (as time dependent co-variate) in preventing relapse after unrelated CB transplantation (CBT) for children with ALL. We analyzed 640 children (<18 years (y)) with ALL in complete remission (CR) who received a single-unit CBT in either first (n=257, 40%) or second (n=383, 60%) CR from 2000-2012. Most patients were diagnosed with B-cell (79%) or T-cell (18%) lineage ALL and had no CNS involvement (92%). Cytogenetic data was available for 411 patients (CR1=171, CR2=240), and 37% were considered intermediate risk and 36% poor risk. Pre-transplant, 49% of patients were CMV seropositive. All patients received myeloablative regimens and most received anti-thymocyte globulin (88%). Regimens included total body irradiation (TBI; 69%) with either cyclophosphamide (Cy)+Fludarabine (Flu; 10%) or other agents (59%), Busulfan (Bu)+ Cy (16%), or Thiotepa+Bu+Flu (8%). Most patients received HLA mismatched CBs at 1 (50%) or 2+ (34%) loci. GvHD prophylaxis included cyclosporine with either steroids (72%) or mycophenolate mofetil (21%), or other agents (6%). Considering CR1 patients only, the median age at CBT was 5.3 y. Most were diagnosed with B-cell ALL (75%) and approximately half of those with known cytogenetics were considered poor risk. The median duration from diagnosis to CBT was 6.7 months and median follow up was 47 months. Estimated OS and LFS at 5 y for CR1 patients was 59% and 52%, respectively. Improved OS and LFS were associated with TBI-containing regimens and younger age at time of CBT (Table 1). The CI of relapse at 5 y was 23% for CR1 patients. In a multivariate analysis (MVA) the presence of acute GvHD (grade II-IV) and TBI-containing regimens were both protective of relapse (Table 1). No impact of GvHD was observed on OS, LFS or NRM. In CR2 patients, the median age at CBT was 6.9 y. Disease was primarily B-lineage ALL (82%) with intermediate or poor risk cytogenetics in 40% and 28% of patients, respectively. Median time from diagnosis to CBT was 36 months and median follow up was 54 months. Estimated OS and LFS in CR2 patients were 46% and 44%, respectively. In MVA, younger age and longer duration from diagnosis to CBT (>30 months) was associated with improved OS and LFS (Table 2). Conversely, the use of ATG was associated with lower OS. In CR2 patients, the CI of relapse was 28%. In MVA, longer duration from diagnosis to CBT (>30 months) and receiving TBI were both associated with less relapse. Importantly, receiving a fully matched HLA CB graft was a strong risk factor for increased relapse compared to mismatched CB recipients. Acute GvHD (II-IV) in this cohort was associated with higher mortality but not with relapse. In this large retrospective collaborative study, we investigated the impact of GvHD as a marker of GvL in pediatric ALL patients after CBT. In CR1 patients, acute GvHD and use of TBI were protective of relapse. However in CR2 patients, use of TBI, longer duration from diagnosis to CBT and HLA mismatched grafts were associated with decreased incidence of relapse but not with the presence of GvHD. These results showed that the impact of GvHD as a GvL marker is more evident in CR1 patients than CR2. Whereas, the impact of HLA mismatch CB on relapse is more important in CR2 patients. Decreasing immunosuppression more rapidly for CR1 patients or avoiding HLA identical CB for CR2 patients should be further investigated. In both cohorts, TBI has shown to be an important protective factor for relapse. Disclosures Bader: Riemser: Other: Institutional grants; Neovii: Other: Institutional grants; Medac: Other: Institutional grants; Amgen: Consultancy; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy.

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