Cord Blood Transplantation Group Research Articles

Updated comparable efficacy of cord blood transplantation for chronic myelomonocytic leukaemia: a nationwide study.

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.

Haploidentical Transplantation with Post-Transplant Cyclophosphamide Versus Single Cord Blood Transplantation for Adults with Relapsed/Refractory Malignant Lymphoma

Introduction Although the treatment of malignant lymphoma has diversified with the advent of chimeric antigen receptor T-cell therapy and other novel agents, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative treatment for some patients with relapsed/refractory malignant lymphoma (R/R ML). R/R ML eligible for allo-HSCT often requires urgent transplantation, making human leukocyte antigen (HLA)-haploidentical transplantation with post-transplant cyclophosphamide (PTCY-haplo) or cord blood transplantation (CBT) a promising option when HLA-matched donors are unavailable. PTCY-haplo has recently been reported to achieve similar or better clinical outcomes than CBT for other hematological malignancies, though data regarding R/R ML are insufficient. Therefore, this study compares PTCY-haplo and CBT for patients with R/R ML using the Transplant Registry Unified Management Program 2 (TRUMP2) in Japan. Methods This study included adult patients with R/R ML registered with TRUMP2 who underwent PTCY-haplo and CBT for their first allo-HSCT between January 2013 and December 2021. In this study, R/R ML included mature B-, T-, and NK-cell neoplasms, as defined in the World Health Organization's 2017 classification. Patients undergoing allo-HSCT for Hodgkin's lymphoma, aggressive NK-cell leukemia, chronic active Epstein-Barr virus (EBV) infection, systemic EBV-positive T-cell lymphoma of childhood, or adult T-cell leukemia/lymphoma were excluded. The primary endpoint was 3-year overall survival (OS). A Cox proportional hazard regression model for OS was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) in the multivariate analysis. The following factors were included in the multivariate model: donor type, age, sex, performance status, Hematopoietic Cell Transplantation-specific Comorbidity Index score, disease status at allo-HSCT, conditioning regimen, cytomegalovirus seropositivity, and disease linage. The secondary endpoints were 3-year progression-free survival (PFS), 3-year graft versus host disease (GVHD)/relapse-free survival (GRFS), 3-year cumulative incidence of relapse and non-relapse mortality (NRM), 28-day cumulative incidence of neutrophil engraftment, 100-day cumulative incidence of platelet engraftment, 100-day cumulative incidence of grade II-IV and grade III-IV acute GVHD, and 3-year cumulative incidence of any and extensive chronic GVHD. Results A total of 1093 patients, including 223 who underwent PTCY-haplo and 870 who underwent CBT, were included in the study. The median age was 54 years (interquartile range, 44-61 years), and 616 (56%) patients had B-cell lymphoma. The PTCY-haplo group included older patients, more patients who were positive for cytomegalovirus antibodies in recipients or donors, and more patients who received a reduced-intensity conditioning regimen. The 3-year OS was 49% (95% CI: 41-56%) in the PTCY-haplo group and 42% (95% CI: 38-45%) in the CBT group (P=0.090). The adjusted HR was 0.88 (95% CI: 0.70-1.09, P=0.20). The PTCY-haplo group had comparable 3-year PFS, 3-year GRFS, 3-year relapse rates, and 3-year NRM as the CBT group. The PTCY-haplo group had higher neutrophil engraftment at 28 days (92.8% [95%CI: 88.5-95.6%] vs 81.6% [95%CI: 78.9-84.0%], P<0.001) and platelet engraftment at 100 days (77.6% [95%CI: 71.5-82.5%] vs 71.0% [95%CI: 67.9-73.9%], P<0.001); similar grade II-IV acute GVHD at 100 days and 3-year cumulative incidences of chronic GVHD and extensive chronic GVHD; and lower grade III-IV acute GVHD at 100 days (7.17% [95%CI: 4.27-11.1%] vs 13.6% [95%CI 11.5-16.0], P=0.01). Conclusion In this population, PTCY-haplo and CBT result in similar 3-year OS after allo-HSCT. Faster engraftment and less severe acute GVHD were noted in the PTCY-haplo group.

Efficacy of Cord Blood Transplantation for the Management of Chronic Myelomonocytic Leukemia: A Registry-Based Study in Japan

Introduction Chronic myelomonocytic leukemia (CMML) is a challenging malignancy that shares characteristics with myelodysplastic syndromes and myeloproliferative neoplasms. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for CMML. Numerous studies have examined transplant outcomes and prognostic factors; however, the focus has primarily been on bone marrow transplantation (BMT) and peripheral blood stem cell transplantation, while cord blood transplantation (CBT) is understudied. To address this knowledge gap, we conducted a nationwide retrospective study to comprehensively compare the outcomes of unrelated BMT and single-unit umbilical CBT in patients with CMML. Methods Data were collected from the Transplant Registry Unified Management Program 2 of the Japanese Data Center for Hematopoietic Cell Transplantation. The inclusion criteria were as follows: age of 16 years or higher, a diagnosis of CMML, and receipt of the first allo-HSCT between 2013 and 2019 through unrelated BMT from a human leukocyte antigen (HLA) 8/8-matched donor (UBMT group) or single-unit umbilical CBT (CBT group). The primary endpoint was overall survival (OS) after allo-HSCT, and the secondary endpoints included progression-free survival (PFS), cumulative incidences of relapse and non-relapse mortality (NRM), neutrophil engraftment, and graft-versus-host (GVHD)-free, relapse-free survival (GRFS). The impact of CBT versus unrelated BMT on outcomes was evaluated using inverse probability of treatment weighting (IPTW) analysis. In this analysis, the Cox proportional hazards regression model for OS, PFS, and GRFS and the Fine-Gray proportional hazards regression model for relapse, NRM, engraftment, and GVHD were used. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for all outcomes. The propensity score (PS) was calculated via logistic regression by using the following factors: age at allo-HSCT, sex, cytogenetic risk, disease status, days from diagnosis to allo-HSCT, and year of allo-HSCT. For the CBT group, the stabilized weights were calculated by dividing CBT prevalence by each individual's PS. Conversely, for the UBMT group, the weights were calculated by dividing the 1 minus prevalence of CBT by 1 minus each individual's PS. Results Between 2013 and 2021, 238 patients with CMML underwent their first allo-HSCT. Among them, 50 underwent HLA 8/8 allele-matched unrelated BMT (UBMT group) and 68 underwent single-unit umbilical CBT (CBT group). The median age at allo-HSCT was 58.5 (range: 26-75) years; the median follow-up period for survivors was 1,329.5 (range: 100-1,967) days. Intergroup differences in age at allo-HSCT, recipient sex, hematopoietic cell transplantation-specific comorbidity index, Eastern Cooperative Oncology Group performance status, cytogenetic risk, pre-transplant treatment, disease status at allo-HSCT, conditioning intensity, GVHD prophylaxis, and year of allo-HSCT were not significant. The transplantation outcomes are shown in Figure 1. There were no significant differences in the 3-year OS rate (UBMT: 51.0% [95% CI: 34.1-65.5%] vs CBT: 46.2% [95% CI: 33.2-58.1%]; P = 0.60; Figure 1A). IPTW analysis revealed no significant differences between the CBT and UBMT groups (HR: 1.21, 95% CI: 0.69-2.10, P = 0.51). PFS, relapse, NRM, and GRFS were not significantly different between the groups (Figure 1B-E). The neutrophil engraftment rate at 30 days was significantly higher in the UBMT group than in the CBT group (UBMT: 92.0% [95% CI: 78.9-97.1%] vs CBT: 79.4% [95% CI: 67.5-87.4%]; P < 0.01; Figure 1F). These observations associated with the secondary endpoints were concurrently corroborated by the IPTW analysis. Conclusion Our study suggests that CBT can serve as a viable treatment option, demonstrating efficacy comparable to that of unrelated BMT for patients with CMML. These findings underscore the improved outcomes over time after CBT in patients with CMML, which is a treatment previously perceived as inferior to other donor sources (Itonaga et al., Biol Blood Marrow Transplant. 2018;24:840-48). Further investigations are warranted to optimize transplantation strategies and improve outcomes in patients with CMML.

Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non-remission acute myeloid leukaemia: A nationwide retrospective study.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some patients with acute myeloid leukaemia (AML) who are refractory to chemotherapy. Cord blood transplantation (CBT) is a reasonable option in such cases because of its rapid availability. Recently, a growing number of human leucocyte antigen (HLA)-haploidentical related donor HSCTs (haplo-HSCTs) have been performed, although its effectiveness remains undetermined. Using the Japanese nationwide transplantation registry data, we identified 2438 patients aged ≥16 years who received CBT or haplo-HSCT as their first transplant for non-remission AML between January 2008 and December 2018. After 2:1 propensity score matching, 918 patients in the CBT group and 459 patients in the haplo-HSCT group were selected. In this matched cohort, no significant difference in overall survival (OS) was observed between the CBT and haplo-HSCT groups (hazard ratio [HR] of haplo-HSCT to CBT 1.02, 95% confidence interval [CI] 0.89-1.16). Similarly, no significant difference in the cumulative incidence of relapse (HR 1.09, 95% CI 0.93-1.28) or non-relapse mortality (HR 0.94, 95% CI 0.76-1.18). Subgroup analysis showed that CBT was significantly associated with preferable OS in patients receiving myeloablative conditioning. Our data showed comparable outcomes between haplo-HSCT and CBT recipients with non-remission AML.

Comparing cord blood transplantation and matched related donor transplantation in non-remission acute myeloid leukemia.

Cord blood transplantation (CBT) is an alternative donor transplantation method and has the advantages of rapid availability and the possibility of inducing a more potent graft-versus-leukemia effect, leading to a lower relapse rate for patients with non-remission relapse and refractory acute myeloid leukemia (R/R AML). This study aimed to investigate the impact of CBT, compared to human leukocyte antigen-matched related donor transplantation (MRDT). This study included 2451 adult patients with non-remission R/R AML who received CBT (1738 patients) or MRDT (713 patients) between January 2009 and December 2018. Five-year progression-free survival (PFS) and the prognostic impact of CBT were evaluated using a propensity score (PS) matching analysis. After PS matching, the patient characteristics were well balanced between the groups. The five-year PFS was 25.2% (95% confidence interval [CI]: 21.2-29.5%) in the CBT group and 18.1% (95% CI: 14.5-22.0%) in the MRDT group (P = 0.009). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69-1.00, P = 0.045); this was due to a more pronounced decrease in the relapse rate (HR: 0.78, 95% CI: 0.69-0.89, P < 0.001) than an increase in the NRM (1.42, 1.15-1.76, P = 0.001). In this population, CBT was associated with a better 5-year PFS than MRDT after allogeneic HSCT.

Comparing Single Cord Blood Transplantation and Matched Related Donor Transplantation in Non-Remission Acute Myeloid Leukemia

IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for refractory and relapsed acute myeloid leukemia (R/R AML) in non-remission status. Although human leukocyte antigen (HLA)-matched relatives are the preferred donors for R/R AML patients in non-remission status, their 2-year overall survival following HLA-matched related donor transplantation (MRDT) has only been reported to be 25% due to a high relapse rate of over 50%. Alternatively, cord blood transplantation (CBT) is a donor transplantation procedure that has similar advantages to MRDT in terms of rapid availability, making it possible for urgent HSCT. Moreover, CBT can induce a more potent graft-versus-leukemia (GVL) effect in AML patients under various conditions as compared to other donors. Therefore, this study aimed to investigate the impact of CBT as compared to MRDT using the Transplant Registry Unified Management Program 2 in Japan.MethodThis study included 2451 adult patients with non-remission AML who received CBT (1738 patients) or MRDT (713 patients), including bone marrow transplantation and peripheral blood transplantation, for their first HSCT between January 2009 and December 2018. The primary endpoint was set as 5-year progression-free survival (PFS), and secondary endpoints were set as 5-year overall survival (OS), 5-year cumulative incidence of relapse, 5-year cumulative incidence of non-relapse mortality (NRM), 100-day cumulative incidence of neutrophil engraftment, 1-year cumulative incidence of platelet engraftment, 1-year cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD), and 5-year cumulative incidence of extensive chronic GVHD. The impact of CBT compared to MRDT was then evaluated using propensity score (PS)-matching analysis. In PS calculation, covariates that may influence the selection of the donor and outcomes were selected clinically, and they included the following: age, sex, karyotype risk, disease status, presence of blasts in the peripheral blood, HCT-CI, intensity of conditioning regimen, acute graft versus host disease (GVHD) prophylaxis, and years of HSCT.ResultA total of 2451 patients, comprising 1738 who received CBT and 713 who received MRDT, were enrolled and analyzed. The median age was 55 years (interquartile range, 43-63 years), and 1484 patients (61%) were male. Differences in the clinical characteristics between the two groups were noted. Specifically, the CBT group had older patients, more patients with relapse, blasts in peripheral blood, a higher hematopoietic cell transplant comorbidity index, and had more patients who received reduced-intensity conditioning regimen, tacrolimus-based acute graft-versus-host disease prophylaxis, and transplanted recently. After PS matching, we selected 918 patients among the 2451 patients receiving CBT or MRD, and the patient characteristics were well balanced between the groups.Regarding the primary endpoint, the 5-year PFS was 25.2% (95% CI: 21.1%-25.5%) in the CBT group vs. 18.1% (95% CI: 14.5%-22.0%) in the MRDT group (P=0.009) in the PS-matched cohort (Figure 1). The adjusted hazard ratio (HR) was 0.83 (95% CI: 0.69-1.00, P=0.045).Regarding secondary endpoints, CBT group compared to MRDT group had similar 5-year OS (28.4% in CBT group vs 21.7% in MRDT group, P=0.152), lower 5-year cumulative incidence of relapse (49.3% s 62.8%, P<0.001), higher cumulative incidence of 5-year NRM (25.5% vs 19.1% P=0.0158), lower 100 days neutrophil engraftment (49.5% vs 93.5%, P<0.001), lower one-year platelet engraftment (62.6% vs 79.1%, P<0.001), similar one-year cumulative incidence of grade II-IV acute GVHD (35.5% vs 30.5%, P=0.092), and lower 5-year cumulative incidence of extensive chronic GVHD (8.6% vs 18.5%, P<0.001) in the PS-matched cohort.ConclusionIn this population, CBT was associated with a better 5-year PFS as compared to MRDT after allogeneic HSCT. [Display omitted] DisclosuresKondo: MSD Pharmaceutical: Honoraria; Asahi Kasei Pharmaceutical: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Chugai Pharma: Honoraria; Sumitomo Dainippon Pharma: Honoraria. Kanda: NextGeM Inc: Patents & Royalties; Ono Pharma Inc.: Honoraria; Novartis Pharma K.K.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sanofi K.K.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; SymBio Pharmaceuticals, Ltd.: Membership on an entity's Board of Directors or advisory committees; Takeda Pharmaceutical Company Limited: Honoraria, Membership on an entity's Board of Directors or advisory committees; Megakaryon Co: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Research Funding; DAIICHI SANKYO Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; CHUGAI PHARMACEUTICAL Co., Ltd.: Honoraria; Bristol-Myers Squibb Co: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Amgen Astellas BioPharma: Honoraria; TEIJIN PHARMA LIMITED.: Honoraria. Uchida: Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; Novartis Pharma Inc.: Honoraria. Atsuta: Astellas Pharma Inc.: Speakers Bureau; Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria.

Haploidentical Versus Cord Blood Stem Cell Transplantation As the Second Transplant for Relapsed Acute Myeloid Leukemia Patients after the First Stem Cell Transplantation

Haploidentical Versus Cord Blood Stem Cell Transplantation As the Second Transplant for Relapsed Acute Myeloid Leukemia Patients after the First Stem Cell Transplantation

Favorable Outcomes of Single-Unit Cord Blood Transplantation As Salvaged Treatment for Advanced Hematologic Malignancies

Treatments of advanced hematologic malignancies are limited, and the effects are very poor even after allogeneic hematopoietic stem cell transplantation. Recent study showed that cord blood transplantation was benefit for patients with pretransplantation minimal residual disease compared to both HLA-matched and HLA-mismatched unrelated donor transplantation. The relapse rate was lowest in cord blood transplantation group. But the effect of cord blood transplantation in advanced hematologic malignancies as salvaged treatment still remains unknown. We retrospectively analyzed 55 consecutive patients with advanced hematologic malignancies who received single-unit unrelated cord transplantation at our centre between December 2013 and December 2016. Among the patients, 42with acute leukemia, 8 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), 4 with CML-BC and 1 with plasma cell leukemia. All of them were in non-remission before transplantation. The median age was 10 years (range, 2-43 years), and the median weight was 31 kg (range, 9-82kg).All the patients received intensified conditioning regimen and a combination of CsA and MMF as GVHD prophylaxis. The infused total nucleated cell (TNC) dose was 4.99 (range 2.17-13.9) × 10⁷/kg and CD34⁺ cell dose was 2.53 (range 0.64-7.45) × 10⁵/kg. Neutrophil and platelet engraftment occurred in 49 (89.1%) and 42 (76.4%) patients, respectively. The median times to neutrophil recovery and platelet recovery were 16 days (range, 12-32 days) and 37.5 days (range, 18-83 days), respectively. Forty patients (72.7%) experienced pre-engraftment syndrome (PES). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 25.5% (95% CI, 14.8-37.6%) and 18.8% (95% CI, 8.6-32.1%), respectively. The median follow-up period for the surviving patients was 654 days (range, 208 to 720 days). The probability of 2- year OS and LFS were 53.9% and 46.8%, respectively, whereas the cumulative incidence of 2-year NRM and relapse rate were 34.5% (95% CI, 21.6-47.8%) and 20.7% (95% CI, 10.9-32.7%), respectively. To further define the importance of matching at the HLA C locus on our special patient cohort outcomes, we analyzed the effect of HLA C disparity on patient outcomes. Results showed that although OS, LFS and NRM were not significantly different between the two groups, the relapse rate was significantly higher after transplantations with matched at HLA C(n=12) than mismatched at HLA C(n=42)(58.5% VS 27.9%,P=0.0426).Since the favorable outcomes, our results showed that single-unit cord blood transplantation might be a feasible choice as salvaged treatment for advanced hematologic malignancies, even in patients with a high leukemia burden. Choosing the cord blood with mismatch at HLA C locus might reduce the relapse rate without increasing the NRM in our special patient cohort, but this metric still requires further evaluation with a larger cohort. DisclosuresNo relevant conflicts of interest to declare.

Outcome of Sibling's and Unrelated Umbilical Cord Blood Stem Cell Transplantation Combined PBSC in Thalassemia Major and Related Factors Analysis:76 Cases Reported in Single Center

Objectives: At present, allogeneic hematopoietic stem cell transplantation is still the only way to cure thalassemia major (TM) patients. But in fact, less than half of the patients can find matched sibling or unrelated donors.Umbilical cord blood stem cells(UCB) is a potential source of stem cells.This paper was to explore effectiveness and compare the outcomes of sibling's and unrelated cord blood stem cell transplantation combined with PBSC in TM. Methods: From Jan. 2008 to Oct. 2019, the clinical data of 76 children with TM who were first underwent cord blood stem cell transplantation was analyzed retrospectively. As of Dec.31, 2019, the median follow-up time was 53 months. The NF-08-TM protocol with CY + Bu + flu + TT in conditioning, was used for sibling cord blood transplantation(CBT) in which the graft including fresh cord blood and PBSC from newborns. Haploid peripheral blood stem cells combined unrelated cord blood transplantation was carried out with NF-14-TM protocol added CY in day +3, day+ 4 days ,followed infusion of unrelated cord blood in + 6 day.The average infusion of cord blood mononuclear cells was 8.50×10^7 (2.73-20.30×10^7), of which CD34+cells were 2.42×10^5 (0.26-8.06×10^5). Unrelated cord blood mononuclear cells were 5.90×10^7 (0.77-11.35×10^7), of which CD34+ cells were 1.78×10^5 (0.17-4.44×10^5). The number of haploid mononuclear cells was 27.70×10^8 (8.80-63.18×10^8). SPSS 20.0 software was used to analyze the subjects' clinical characteristics, long-term survival rate, factors affecting umbilical cord blood implantation and related complications Results:Total of 45 cases of sibling CBT and 31 cases of unrelated CBT combined with haploid PBSC were enrolled. Two of the 76 thalassemia children died, with an OS of 96.3±2.6%, TFS93.8±3.1%; TMR was 3.7%. The OS of the sibling CBT group and the unrelated CBT group were 97.8 ± 2.2% and 90.0±9.9%, P=0.586; Meanwhile TFS were 93.3 ± 3.7% and 92.9±6.9%, P=0.589. Liver iron concentration (MRI-T2) in the unrelated CBT group was significantly correlated with delayed implantation of stem cells and delayed reconstruction of platelets (P=0.013 and P=0.034).There was no significant difference in the rate of delayed implantation of stem cells and granulocyte reconstruction between the unrelated CBT group and the sibling CBT group, but the rate of delayed platelet reconstruction in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.002). The time of umbilical cord blood implantation in the unrelated CBT group was shorter than that in the sibling CBT group (24.32 days vs 37.67 days, P=0.058), but the platelet reconstruction in this group was slower than that in the sibling CBT group, with no statistically significant difference (P=0.061). In the ferritin level, the platelet reconstruction time in the unrelated CBT group was significantly higher than that in the sibling CBT group (P=0.031). Logistic regression analysis showed that ferrimin, umbilical cord blood sources, dose of umbilical cord blood mononuclear cells and acute GVHD were not risk factors for delayed implantation of stem cells (over 30 days).The incidence of acute and chronic GVHD in the unrelated CBT group was significantly higher than that in the sibling CBT group (P &amp;lt; 0.001 and P=0.034). The virus infection rate of the unrelated CBT group was significantly higher than that of the sibling CBT group (P=0.008). The infection of herpes simplex virus type I was common in sibling CBT, while cytomegalovirus was the main infectious virus in unrelated CBT. Conclusion:By increasing the dose of stem cells, the outcomes of TM after transplantation was favorable both in sibling and unrelated CBT group. Unrelated CBT combined with haploid PBSC can potentially reduce implantation time compared with sibling CBT. The strategies of prophylaxis and treatment of GVHD and cytomegalovirus infection should be strengthened. Iron overload may affect umbilical cord blood stem cell implantation and hematopoietic recovery. Figure 1 Disclosures No relevant conflicts of interest to declare.

Adult cord blood transplant results in comparable overall survival and improved GRFS vs matched related transplant

AbstractWe compared outcomes among adult matched related donor (MRD) patients undergoing peripheral blood stem cell transplantation and adult patients undergoing double unit cord blood transplantation (CBT) at our center between 2010 and 2017. A total of 190 CBT patients were compared with 123 MRD patients. Median follow-up was 896 days (range, 169-3350) among surviving CBT patients and 1262 days (range, 249-3327) among surviving MRD patients. Comparing all CBT with all MRD patients, overall survival (OS) was comparable (P = .61) and graft-versus-host disease (GVHD) relapse-free survival (GRFS) was significantly improved among CBT patients (P = .0056), primarily because of decreased moderate to severe chronic GVHD following CBT (P < .0001; hazard ratio [HR], 3.99; 95% confidence interval [CI], 2.26-7.04). Among patients undergoing our most commonly used MRD and umbilical cord blood (CB) myeloablative regimens, OS was comparable (P = .136) and GRFS was significantly improved among CBT patients (P = .006). Cumulative incidence of relapse trended toward decreased in the CBT group (P = .075; HR, 1.85; CI 0.94-3.67), whereas transplant-related mortality (TRM) was comparable (P = .55; HR, 0.75; CI, 0.29-1.95). Among patients undergoing our most commonly used nonmyeloablative regimens, OS and GRFS were comparable (P = .158 and P = .697). Cumulative incidence of both relapse and TRM were comparable (P = .32; HR, 1.35; CI, 0.75-2.5 for relapse and P = .14; HR, 0.482; CI, 0.18-1.23 for TRM). Our outcomes support the efficacy of CBT and suggest that among patients able to tolerate more intensive conditioning regimens at high risk for relapse, CB may be the preferred donor source.

Double vs. single cord blood transplantation in adolescent and adult hematological malignancies with heavier body weight (≥50 kg)

ABSTRACTBackground: Double-unit cord blood transplantation (CBT) can be used to overcome the limitation of single-unit CBT with low cell content for adults and larger adolescents. However, whether double-unit CBT is superior to single-unit CBT remains controversial.Methods: We reviewed the medical records of 228 consecutive hematological malignancies who received CBT between November 2005 and December 2013. Ninety-seven eligible patients met the criteria (age ≥14 years and body weight ≥50kg) and were enrolled in this study.Results: The incidence of myeloid engraftment in the double-unit CBT group was significantly lower that in the single-unit CBT group (89.2 vs. 96.7%) (p = 0.026), and the incidence of platelet engraftment in the double-unit CBT group was slightly lower (70.3 vs. 86.7%) (p = 0.057). The 5-year transplant-related mortality rate was significantly higher in the double-unit CBT group when compared with that of the single-unit CBT group [54.1 vs. 33.3%, p = 0.026]. The 5-year probabilities of overall survival, disease-free survival and graft-versus-host disease (GVHD) -free/relapse-free survival in the double-unit CBT group were significantly lower than that of the single-unit CBT group (37.8 vs. 56.7%, p = 0.037; 32.4 vs. 55.0%, p = 0.017; 24.3 vs. 50.0%, p = 0.006). The incidences of GVHD and relapse were similar.Conclusions: For adolescent and adult hematological malignancies with heavier body weight (≥50kg), double-unit CBT has an inferior clinical outcome when compared with single-unit CBT having a sufficient cell dose. Double-unit CBT should only reserve for patients who need an urgent transplant but lacking of a related or unrelated donor and without an adequately dosed single CB.

Prognostic Impact of Delayed Platelet Engraftment after Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancy

Introduction: Delayed platelet engraftment (DPE) is one of important complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies suggested that DPE was risk factor for higher non-relapse mortality (NRM) and worse overall survival (OS). However, prognostic impact of DPE after allo-HSCT remains unclear. Therefore we conducted retrospective analysis to examine the clinical impact of DPE on transplant outcomes. Methods: Clinical data were collected from the clinical records of Kanagawa Cancer Center.Patients with hematological malignancies aged 16 years or older who underwent first allo-HCT between January 2002 and December 2014 were evaluated for analysis. Patients who died before day 60 after allo-HSCT were excluded. DPE was defined as non-achievement of platelet engraftment (continuous platelet counts 50×109/L or higher without transfusion) before day 60. OS, relapse and NRM were compared between patients who achieved platelet engraftment before day 60 and DPE patients, using log-rank test and Gray’s test respectively. In a multivariate analysis, the Cox proportional hazard model and Fine-Gray methods were used for OS and cumulative incidence of relapse and NRM respectively, using the following variables: age, gender, donor source, disease, disease status at allo-HSCT, donor-recipient gender mismatch, ABO mismatch, hematopoietic cell transplant comorbidity index (HCT-CI) and preemptive cytomegalovirus (CMV) therapy. Results: Of 291 patients with hematological malignancies who received first allo-HSCT (AML n = 175, ALL n = 75, others n = 41), 222 patients (76.3%) achieved platelet engraftment before day 60, 69 patients (23.7%) did not. Patients with ALL and disease low risk at allo-HSCT patients achieved early platelet engraftment. Cord blood transplantation (CBT), higher comorbidity and preemptive CMV therapy were significant risk factors for DPE. The 5-year OS and NRM for the patients who achieved platelet engraftment before day 60 were favorable, compared with the DPE group (OS; 60.3% vs. 23.2%; P < 0.001, NRM; 14.6% vs. 40.3%; P < 0.001). The 5-year relapse were comparable between both groups (30.3% vs. 37.3%; P = 0.19). Subgroup analysis stratified by donor source showed that similar results were observed both in the CBT group and in the non-CBT group. Multivariate analysis indicated that DPE was significantly associated with poorer OS (HR 3.51; 95%CI 2.40 - 5.15; P < 0.001) and higher NRM (HR 3.07; 95%CI 1.78 - 5.29; P < 0.001) after adjusting covariates. DPE had no significant impact on relapse (HR 0.95; 95%CI 0.58 - 1.56; P = 0.84). The incidence of fatal infectious disease in the DPE group was significantly higher than that in the non-DPE group (15.9% vs. 5.0%, P = 0.007), while there was no significant difference for fatal bleeding, GVHD and organ failure. Conclusions: DPE is a common complication after allo-HSCT for hematological malignancies. DPE is a useful prognostic factor for poorer OS and increased NRM. We may have to pay more attention to severe infectious disease in patients with DPE. DisclosuresNo relevant conflicts of interest to declare.

Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia

The aim of this report was to present a clinical comparison of unrelated cord blood transplantation (CBT) and human leukocyte antigen (HLA)-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) in children with high-risk or advanced acute leukemia. A total of 115 consecutive pediatric patients received unrelated CBT (n = 90) or sibling allo-PBSCT/BMT (n = 25) between 2000 and 2012. Neutrophil and platelet recovery were significantly delayed after CBT compared to allo-PBSCT/BMT. There was no difference in the incidence of acute graft-versus-host disease (GVHD) or chronic GVHD between the two groups. The cumulative incidence of transplant-related mortality (TRM) was higher in the CBT group than in the allo-PBSCT/BMT group (32.5 vs 12.8 %) (p = 0.03). The cumulative incidence of relapse was 13.1 % after CBT, which was significantly lower than that of after allo-PBSCT/BMT (45.3 %) (p = 0.015). The overall survival (OS) and leukemia-free survival (LFS) in the CBT group were similar to those of the allo-PBSCT/BMT group; however, for acute myeloid leukemia (AML) patients, the 5-year LFS in the CBT group was slightly better than the allo-PBSCT/BMT group (55.7 % for CBT and 32.7 % for allo-PBSCT/BMT) (p = 0.08). Our comparisons suggest that for high-risk or advanced childhood acute leukemia, unrelated CBT has a higher TRM and similar long-term survival, but better antileukemia effect than HLA-matched sibling PBSCT/BMT. New strategies and better supportive care are required to decrease the TRM of CBT.

Comparison Of Umbilical Cord Blood and Haploidentical Donor Grafts In Adults With High Risk Hematologic Diseases After Fludarabine Cyclophosphamide and TBI 2 Gy Based Reduced-Intensity Conditioning Regimen Stem Cell Transplantation

IntroductionHuman leukocyte antigens (HLA)-matched sibling or unrelated donor are available for around only 50-60% of patients. However, for patients without a suitably matched related donor, Alternative donors such as mismatched unrelated, cord blood and mismatched family donors could be searched. The aim of this retrospective study was to compare the results of graft source on outcome of patients after haploidentical related donor (Haplo), and the unrelated umbilical cord blood (UCB) transplantation in the setting of Non myeloabalative conditioning regimen (NMA). Patients and methodsWe retrospectively analyzed outcomes in 150 adult patients with high risk hematologic diseases who received Allo-SCT from alternative donors from two centers (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy): These two centres have been applying common transplant approaches and procedures during the study period. 69 patients received Haplo and 81 patients received UCB. In the UCB group, the NMA regimen consisted of fludarabine (Flu), cyclophosphamide (Cy) and low dose TBI (2 Gy) combination in the two groups. The GVHD prophylaxis consisted of Cyclosporine A (CsA) and MMF in all patients in the two groups. In the Haplo group all patients received also 50 mg/kg Cy at day 3 and 4 post transplant. Of note, supportive care was the same during the whole study period. CMV infection management was also homogeneous. Patient characteristics are shown in Table 1.Table 1Patient and transplantation characteristics:Characteristic Total =150 patientsHaplo transplant (n = 69)CB transplant (n = 81)P valuePatients Age years (median) [range]44 (19-68)47 (18-66)Patients sexnsMale39 (57)46 (57)Female30 (43)35 (43)Disease typeAML3 (4)37 (46)<0.0001ALL1 (1)14 (17)<0.0001NHL24 (35)14 (17)nsHL30 (43)2 (2)<0.0001MM4 (6)2 (2)nsCLL5 (7)4 (5)nsCML01 (1)nsMDS/ MPS2 (3)7 (9)nsStatus of diseaseCR37 (54)56 (69)nsPR/SD24 (35)12 (15)0.04PD8 (11)13 (16)nsDonor typeSibiling32 (46)Parent18 (26)Child18 (26)cousin1 (2)Donor/recipient sex mis-match34 (49)56 (69)nsABO incompatibility24560.02Conditioning regimenFlu 5+Cy 1+ TBI075 (93)Flu 5+Cy 2+ TBI69 (100)6 (7)Stem cell sourcePeripheral Blood19 (28)Bone Marrow50 (72)Stem cell dose median [range] CD34+ x 106/kg3,96 (0,8-14)0,9 (0,08-1,28)GvHD prophylaxisCSA+MMF69 (100)81 (100)nsCy post transplant69 (100)0Days with ANC< 500 x 109/l20 (14-39)22 (6-67)nsDays with platelets<20 x 109/l29 (14-50)41 (18-80)ns ResultsWith a median follow-up of 59 months (8-101) and 18 months (3-51), in the UCB group versus the Haplo group, respectively. Nine patients (11%) in the UCB and 8 patients (12%) in the Haplo group had a spontaneous autologous reconstitution subsequent to primary graft failure. The median times to neutrophil and platelet recovery were 20 d (14–39) and 29 d (14–50) after Haplo and 22 d (6–67) and 41 d (18–80) after cord blood. All supportive care measures included red blood cell, and platelet transfusions were significantly increased in cord blood transplantation group. The cumulative incidence of transplant related mortality (TRM) at one year was 23% in the UCB group versus 17% in the Haplo group (P=0.39). Grade 2-4 acute graft-vs.-host disease (GVHD) and extensive chronic GVHD incidences were 52% versus 29% (P=0.05), and 12% versus 6% (P<0.0001), in the UCB group versus the Haplo group, respectively. The Kaplan-Meier estimate of overall survival at 2 years was 45% (95%CI, 34-56%) in the UCB group versus 69% (95%CI, 58-80%) in the Haplo group, (P=0.10). The estimate of progression-free survival at 2 years was 36% (95%CI, 25-47%) in the UCB group versus 65% (95% CI, 53-77%) in the Haplo group (P=0.01). Figure 1 ConclusionIn this study, relapse and PFS was lower in Haplo group than in UCB transplants. The main difference between the 2 groups was the significantly higher incidence of acute and chronic GVHD in the UCB group. Surprisingly, this did not translate into a decrease of the cumulative incidence of OS nor increase of the TRM, which may be explained by a slightly shorter follow-up in this group. Our results suggest that haploidentical transplants are a good and promising alternative option for patients with high risk hematological diseases who lack an HLA-matched donor (sibling or unrelated donor). This should be now investigated in prospective comparative studies. Disclosures:No relevant conflicts of interest to declare.

Comparison of Unrelated Cord Blood Transplantation and HLA-Matched Sibling Hematopoietic Stem Cell Transplantation for Patients with Chronic Myeloid Leukemia in Advanced Stage

This is the first report to present a clinical comparison of unrelated cord blood transplantation (CBT) and HLA-matched sibling allogeneic hematopoietic stem cell transplantation for patients with chronic myeloid leukemia (CML) in advanced stage (accelerated phase or blast crisis). A total of 32 consecutive patients with advanced CML received unrelated CBT (n = 16) or HLA-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) (n = 16) between 2002 and 2011. The median day to neutrophil engraftment and the median day to platelet engraftment were longer in the unrelated CBT group. The cumulative incidence of grades 1 to 2 acute graft-versus-host disease (aGVHD), grades 3 to 4 aGVHD, and chronic graft-versus-host disease did not differ significantly between the 2 cohorts. The cumulative incidence of transplantation-related mortality (TRM) at day +180 was higher in CBT group (37.5% versus 12.5%, P = .013). The risk of relapse was lower in CBT patients compared with that of allo-PBSCT/BMT patients (14.2% versus 42.7%, P = .03). The long-term survival in CBT group patients was slightly better than that of allo-PBSCT/BMT group, although the difference did not reach statistical significance: the 5-year overall survival for CBT patients and allo-PBSCT/BMT patients was 62.5% and 48.6%, respectively (P = .10), whereas the 5-year leukemia-free-survival rate was 50% and 40.5%, respectively (P = .12). Our comparisons suggest that patients with advanced CML receiving unrelated CBT had a lower relapse rate, a slightly better long-term survival, but a higher early TRM than those receiving HLA-matched related allo-PBSCT/BMT.

Comparison of stem cell sources in the severity of dry eye after allogeneic haematopoietic stem cell transplantation

AimsTo compare the incidence and severity of dry eye (DE) after allogeneic haematopoietic stem cell transplantation (HSCT) according to the stem cell source. The authors specifically focused on patients who...

CMV Infection after Transplant from Cord Blood Compared to Other Alternative Donors: The Importance of Donor-Negative CMV Serostatus

Cytomegalovirus (CMV) infection and disease are important complications after hematopoietic stem cell transplant, particularly after transplant from alternative donors. Allogeneic cord blood transplantation (CBT) is being increasingly used, but immune recovery may be delayed. The aim of this study was to compare CMV infection in CBT with transplants from unrelated or mismatched related donors, from now on defined as alternative donors. A total of 165 consecutive transplants were divided in 2 groups: (1) alternative donors transplants (n = 85) and (2) CBT recipients (n = 80). Donor and recipient (D/R) CMV serostatus were recorded. The incidence of CMV infection, its severity, timing, and outcome were compared. Median follow-up was 257 days (1-1328). CMV infection was monitored by CMV antigenemia and expressed as CMV Ag positive cell/2 × 10(5) polymorphonuclear blood cells. There was a trend toward a higher cumulative incidence of CMV infection among CBT than alternative donor transplant recipients (64% vs 51%, P = .12). The median time to CMV reactivation was 35 days, and was comparable in the 2 groups (P = .8). The maximum number of CMV-positive cells was similar in the 2 groups (11 versus 16, P = .2). The time interval between the first and the last positive CMV antigenemia was almost 4 times longer in CBT compared with alternative donor transplants (109 vs 29 days, respectively, P = .008). The incidence of late CMV infection was also higher in CBT (62% vs 24%, P < .001). The incidence of early and late CMV infection in CBT was similar to D-/R+ alternative transplants, and higher than in D+/R+ alternative transplants: early infection, 72% in CBT versus 69% in D-/R+ alternative versus 55% in D+/R+ alternative (P = .21); and late infection, 67% in CBT versus 60% in D-/R+ alternative versus 7% in D+/R+ alternative (P < .001). Transplant-related mortality and overall survival were similar between the groups: 34% versus 36% (P = .6) and 54% versus 46% (P = .3) for alternative transplant and CBT, respectively. Longer duration and higher incidence of late CMV infection was seen in CBT patients, when compared with alternative donor transplants, whereas no difference in mortality was observed. The duration and incidence of late CMV infection were similar when D-/R+ CBT were compared with D-/R+ alternative donor transplants.

Favorable Outcome of Unrelated Cord Blood Transplantation for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) is one of the highest-risk ALL groups. Whenever possible, patients with Ph(+)ALL should undergo allogeneic hematopoietic stem cell transplantation (HSCT) after induction of remission. Although unrelated cord blood transplantation (CBT) has become a common treatment in adult patients who lack a sibling donor, data on the efficacy of CBT for Ph(+)ALL are limited. We analyzed the clinical outcomes of 20 Ph(+)ALL patients who underwent CBT (n=8) or unrelated bone marrow transplantation (BMT) (n = 12). The median age was 41 years (range, 17-55 years). All but one of the patients were treated with an imatinib-based regimen before HSCT, and 19 patients were in first complete remission (CR) and 1 patient was in second CR at the time of HSCT. Seventeen patients received a myeloablative conditioning regimen containing 12 Gy of total-body irradiation, and 3 received a reduced-intensity conditioning regimen. After a median of 26 months of follow-up, estimated 3-year overall and leukemia-free survival rates were 100% and 85%, respectively, after CBT, and 49% and 38%, respectively, after unrelated BMT. The CBT group had significantly better overall survival than the BMT group (P = .02). Although BCR-ABL transcript was detected in 4 of 8 CBT patients at transplantation, 7 patients remained in molecular CR. Our findings suggest that CBT may be a viable option as postinduction therapy for Ph(+)ALL in patients lacking a sibling donor.

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; P<0.0001), with higher viral load (P<0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR)=5.4, P=0.02 and OR=3.5, P=0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.

Features of Herpesviruses (CMV, EBV, HHV6) Infections and Immune Reconstitution after Allogeneic Stem Cell Transplantation (allo-SCT) Using Alternative Donors: Comparison Between Matched Unrelated Donors (MUD) and Cord Blood (CB) as Stem Cell Source.

Features of herpesvirus infections (CMV, EBV, HHV6) and immune reconstitution after CB transplantation (CBT) has been little studied thus far. Here, we report a retrospective comparison between 15 consecutive adult CBT recipients (CBT group) and 40 patients who received allo-SCT using MUD (MUD group).The 2 groups had no significant differences in terms of gender, age, disease features, transplant characteristics (CB: meloablative conditioning 46% vs. MUD: 35%; P=NS). However, in vivo T-cell depletion was more frequently used in the MUD group (62.5% vs 6%, P=0.0002). As expected, median number of CD34+ stem cells infused was significantly lower in the CBT group (0.15 10*6/Kg vs 8.2 10*6/Kg, P<0.0001). Both groups were stringently monitored through CMV, EBV, and HHV6 DNA quantifications in the blood prior to allo-SCT, and then monthly up to 9 months after allo-SCT. An active infection was defined by the presence of at least one positive PCR during the follow-up period (detection limit at 2 Log/mL blood). Of note, both groups experienced similar incidences of acute grade 2–4 GVHD, chronic GVHD and disease relapses. Immune reconstitution (T4, T8, B and NK lymphocytes ) at 3, 6 and 9 months post transplant was investigated and compared between the two groups. In this cohort, 22, 29 and 29 patients experienced at least one positive PCR for CMV, EBV and HHV6 respectively, with the % of positive samples for CMV, EBV and HHV6 being 14%, 16% and 27% respectively. No correlation in term of incidence could be found between the 3 viruses. The incidence of CMV infection did not differ between the two groups, and the univariate analysis could not identify a significant risk factor for CMV infection. However, HHV6 positivity was significantly higher in the CBT group as compared to the MUD group (CBT: 80%; MUD: 42.5%; P <0.0001). HHV6 viral loads were also significantly higher in the CBT group (mean, 3.98±0.86 Log/mL, vs. 3.19±0.82 Log/ mL, P<0.0001). In multivariate analysis, the use of CB cells as stem cell source in combination with a myeloablative conditioning regimen appeared to be independent parameters associated with an increased risk of HHV6 infection (OR=5.4, 95%CI, 1.2- 23.0; P=0.02 and OR=3.5, 95%CI, 1.03–12.05, P= 0.04, respectively). Interestingly, the occurrence of HHV6 infection translated towards delayed engraftment (median time to neutrophils and platelets recovery: 37 vs 16 d.; P=0.03; and 98 vs. 12 d.; P=0.0001). In sharp contrast with HHV6, EBV infections were less frequent in the CBT group as compared to the MUD group (27% vs. 62%; P<0.0001). In multivariate analysis, the use of a MUD for allo-SCT, was the strongest risk factor associated with an increased EBV infection (OR=0.31, 95%CI, 0.07–1.37; P=0.04). At 3, 6 and 9 months post transplant, median B lymphocytes count in the CBT group was significantly higher (P=0.03; P=0.003; P=0.01) whereas median T8 lymphocytes count was significantly lower (P=0.05; P=0.01; P=0.09). We also noticed that median NK lymphocytes count in the CBT group was significantly higher at 3 months (P=0.0006) but this was not linked to HHV6 infections. Overall, these results show that after allo-SCT, the pattern of HHV6 and EBV infections is dependant on the source of stem cells. A specific relationship is suggested between HHV6 PCR positivity and the use of CB cells. In addition to a potential delayed engraftment, the clinical implications of the latter finding need to be refined and prospective screening and antiviral prophylaxis approaches are warranted in the context of CBT.