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Background and Objectives: In Japan, cord blood is used for more than half of all unrelated stem cell transplantations. The public cord blood banks (CBBs) have been collecting information on cord blood transplantation‐related adverse events from physicians on a voluntary basis, without common definitions of the adverse reactions. The aims of this study were to compare two classification systems to improve the reporting system and to clarify the actual risk from cord blood infusion, which can then provide the impetus to take appropriate measures to reduce adverse events. Materials and Methods: We classified the reports according to existing criteria; one is the Proposed Standard Definitions for Surveillance of Non‐Infectious Adverse Transfusion Reactions by the International Society of Blood Transfusion (ISBT) Working Party on Haemovigilance, and the other is the Common Terminology Criteria for Adverse Events (CTCAE). There were 140 cases with adverse events reported from April 2014 through March 2019. Results: Twelve cases, such as donor‐derived leukaemia/myelodysplastic syndromes (MDS) and chromosomal aberrations reported after engraftment, were excluded from this analysis. Of the 128 cases with adverse events at cord blood infusion, the CTCAE and ISBT criteria could not classify 6 cases and 68 cases, respectively. Classifying by the CTCAE, the most common side effect was hypertension in 35 cases, followed by anaphylaxis, allergic reactions, nausea, urticaria, etc. Serious adverse events (grades 4 and 5) were mainly anaphylaxis, with a frequency of 0.23%. Conclusion: It is necessary not only to provide information on adverse events but also to standardize the reporting of adverse events to support measures to reduce them. [ABSTRACT FROM AUTHOR]

Background: Adrenoleukodystrophy (ALD) is an X‐linked recessive disorder and 30–40% of patients develop progressive cerebral neurodegeneration. For symptomatic ALD patients, allogeneic stem cell transplantation (SCT) is considered the standard treatment modality to stabilize or prevent the progression of neurological symptoms. Methods: We retrospectively analyzed the transplant outcomes of 99 pediatric patients with cerebral ALD in Japan. The conditioning regimens included Regimen A: fludarabine/melphalan/low‐dose total body irradiation (TBI) with brain sparing (n = 39), Regimen B; busulfan/cyclophosphamide ± others (n = 23), Regimen C: melphalan/total lymphoid irradiation/thoracoabdominal irradiation ± anti‐T lymphocyte globulin ± fludarabine (n = 27), and Regimen D: others (n = 10). Results: The 5‐year overall survival (OS) and event‐free survival (EFS) of all patients were 90.0% and 72.9%, respectively. The 5‐year OS was 100.0% for Regimen A, 91.1% for Regimen B, 84.4% for Regimen C, and 67.5% for Regimen D (p = 0.028). The 5‐year EFS was 78.3% for Regimen A, 78.0% for Regimen B, 70.4% for Regimen C, and 48.0% for Regimen D (p = 0.304). The OS marginally improved after 2007 compared with before 2006 (95.3% vs. 85.2%, p = 0.066), due to the improvement of cord blood transplantation (CBT) outcomes after 2007 compared with before 2006 (96.6% vs. 68.4%, p = 0.005). On magnetic resonance imaging of the brain, a reduced Loes score after SCT was only observed in one of the 15 bone marrow transplantation (BMT) patients, but in 5 of the 15 CBT patients (p = 0.173). Conclusions: Our study revealed that a reduced conditioning regimen with fludarabine/melphalan/low‐dose TBI provides better outcomes, and the results of CBT significantly improved after 2007. [ABSTRACT FROM AUTHOR]

Allogeneic bone marrow and peripheral blood stem cell transplantations are curative treatment modalities for adult T cell leukemia/lymphoma (ATLL) because of the intrinsic graft-versus-ATLL effect. However, limited information is available regarding whether cord blood transplantation (CBT) induces a curative graft-versus-ATLL effect against aggressive ATLL. To evaluate the effect of CBT against ATLL, we retrospectively analyzed data from 175 patients with ATLL who initially underwent single-unit CBT. The 2-year overall survival (OS) rate was 20.6% (95% confidence interval [CI], 13.8% to 27.4%). A multivariate analysis revealed that the development of graft-versus-host disease (GVHD) was a favorable prognostic factor for OS (hazard ratio, .10; 95% CI, .01 to .94; P = .044). Furthermore, the 2-year OS (42.7%; 95% CI, 28.1% to 56.6%) of patients with grade 1 to 2 acute GVHD was higher than that of patients without acute GVHD (24.2%; 95% CI, 11.2% to 39.8%; P = .048). However, the cumulative incidence of treatment-related mortality (TRM) was high (46.1%; 95% CI, 38.2% to 53.7%), and early death was particularly problematic. In conclusion, CBT cures patients with ATLL partly through a graft-versus-ATLL effect. However, novel interventions will be required, particularly in the early phase, to reduce TRM and optimize GVHD. [ABSTRACT FROM AUTHOR]

Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases. [ABSTRACT FROM AUTHOR]

Summary. Cryopreserved umbilical cord blood (CB) from unrelated donors can restore haematopoiesis after myeloablative therapy in patients with haematological malignancy. We investigated the clinical outcomes of CB transplantation (CBT) with special emphasis on graft-versus-host disease (GVHD) prophylaxis. Patients with haematological malignancies (n = 216) received intensive chemotherapy or immunosuppressive therapy, followed by transplantation of cryopreserved CB cells from unrelated donors. The clinical outcomes, i.e. haematological reconstitution, the incidence of acute or chronic GVHD, relapse and event-free survival (EFS), were evaluated. The estimated probability of neutrophil recovery was 88·2%. The median follow-up for the survivors was 557 d (range 21–1492 d). The overall and EFS rates were 32·6% and 25·5%, respectively, 3·5 years after transplantation. Multivariate analysis using Cox's proportional hazards model showed that high-risk disease status at CBT and single-drug GVHD prophylaxis were associated with worse 2-year EFS rates [P = 0·0013, relative risk (RR) 1·90, 95% confidence interval (CI) 1·28–2·81 and P = 0·0007, RR 1·91, 95% CI 1·31–2·79 respectively). Age at CBT had no significant influence on EFS. Cryopreserved CB from unrelated donors can restore haematopoiesis in patients with haematological malignancy. Although the incidence is low, the prophylaxis for acute GVHD is an important factor for survival of CBT from unrelated donors. A high rate of suitable donors was found, with a probability of 1 to every 18 CB units, when compared with human leucocyte antigen matching at other haematopoietic stem cell banks. [ABSTRACT FROM AUTHOR]

Although killer Ig-like receptor ligands (KIR-L) mismatch has been associated with alloreactive natural killer cell activity and potent graft-versus-leukemia (GVL) effect among adults with acute myeloid leukemia (AML), its role among children with AML receiving cord blood transplantation (CBT) has not been determined. We conducted a retrospective study using a nationwide registry of the Japanese Society for Transplantation and Cellular Therapy. Patients who were diagnosed with de novo non-M3 AML and who underwent their first CBT in remission between 2000 and 2021 at under 16 years old were included. A total of 299 patients were included; 238 patients were in the KIR-L match group, and 61 patients were in the KIR-L mismatch group. The cumulative incidence rates of neutrophil recovery, platelet engraftment, and acute/chronic graft-versus-host disease did not differ significantly between the groups. The 5-year event-free survival (EFS) rate was 69.8% in the KIR-L match group and 74.0% in the KIR-L mismatch group (p = 0.490). Stratification by CD34 + cell dose into four groups revealed a significant correlation between CD34 + cell dose and EFS in the KIR-L mismatch group (p = 0.006) but not in the KIR-L match group (p = 0.325). According to our multivariate analysis, KIR-L mismatch with a high CD34 + cell dose (≥ median dose) was identified as an independent favorable prognostic factor for EFS (hazard ratio = 0.19, p = 0.029) and for the cumulative incidence of relapse (hazard ratio = 0.09, p = 0.021). Our results suggested that higher CD34 + cell doses are crucial for achieving a potent GVL effect in the context of KIR-L-mismatched CBT. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma. [ABSTRACT FROM AUTHOR]

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. Methods: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. Results: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985–1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. Conclusions: We present the 1985–2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning. [ABSTRACT FROM AUTHOR]

Abstract: Allogeneic hematopoietic cell transplantation (HCT), but not autologous HCT, can provide long-term remission in some patients with adult T cell leukemia-lymphoma (ATL). We retrospectively analyzed the effects of acute graft-versus-host disease (GVHD) among the 616 patients with ATL who survived at least 30 days after allogeneic HCT with other than cord blood grafts. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated an association between grade I-II acute GVHD and favorable overall survival (OS) (hazard ratio [HR], 0.634; 95% confidence interval [CI], 0.477 to 0.843), whereas grade III-IV acute GVHD showed a trend toward unfavorable OS (HR, 1.380; 95% CI, 0.988 to 1.927) compared with nonacute GVHD. In subsequent multivariate analyses of patients who survived at least 100 days after HCT (n = 431), the presence of limited chronic GVHD showed a trend toward favorable OS (HR, 0.597; 95% CI, 0.354 to 1.007), and extensive chronic GVHD had a significant effect on OS (HR, 0.585; 95% CI, 0.389 to 0.880). There were no significant interactions between myeloablative conditioning or reduced-intensity conditioning with OS even when acute GVHD was absent or present at grade I-II or grade III-IV or when chronic GVHD was absent, limited, or extensive. This study demonstrates the actual existence of graft-versus-ATL effects in patients with ATL regardless of whether myeloablative conditioning or reduced-intensity conditioning is used. [Copyright &y& Elsevier]

Purpose: Hematopoietic cell transplantation (HCT) is a curative therapy for patients with severe combined immunodeficiency (SCID). Here, we conducted a nationwide study to assess the outcome of SCID patients after HCT in Japan. Methods: A cohort of 181 SCID patients undergoing their first allogeneic HCT in 1974–2016 was studied by using the Japanese national database (Transplant Registry Unified Management Program, TRUMP). Results: The 10-year overall survival (OS) of the patients who received HCT in 2006–2016 was 67%. Umbilical cord blood (UCB) transplantation was performed in 81 patients (45%). The outcomes of HCT from HLA-matched UCB (n = 21) and matched sibling donors (n = 22) were comparable, including 10-year OS (91% vs. 91%), neutrophil recovery (cumulative incidence at 30 days, 89% vs. 100%), and platelet recovery (cumulative incidence at 60 days, 89% vs. 100%). Multivariate analysis of the patients who received HCT in 2006–2016 demonstrated that the following factors were associated with poor OS: bacterial or fungal infection at HCT (hazard ratio (HR): 3.8, P = 0.006), cytomegalovirus infection prior to HCT (HR: 9.4, P = 0.03), ≥ 4 months of age at HCT (HR: 25.5, P = 0.009), and mismatched UCB (HR: 19.8, P = 0.01). Conclusion: We showed the potential of HLA-matched UCB as a donor source with higher priority for SCID patients. We also demonstrated that early age at HCT without active infection is critical for a better prognosis, highlighting the importance of newborn screening for SCID. [ABSTRACT FROM AUTHOR]

The combined effects of HLA-allele matching at six-loci (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and CD34+ cell dose on clinical outcomes were analyzed in 1,226 adult cases with single-unit unrelated cord blood transplantation. In the six-loci analysis, low HLA-allele matches did not significantly increase the overall mortality compared to higher matches, whereas in the five-loci analysis excluding HLA-DPB1, they caused a higher overall mortality (HR 1.42, p =.002), possibly due to the graft-versus-leukemia effect of HLA-DPB1 mismatches. A lower CD34+ cell dose (<.50 × 105/kg) resulted in higher mortality and lower engraftment; these inferior outcomes were offset by high HLA-allele matches (7-10/10 match), while the inferior outcomes of low HLA-allele matches were improved by increasing the CD34+ cell dose. Consideration of the combined effects of the CD34+ cell dose and HLA matching may expand the options for transplantable units when HLA matching or the CD34+ cell dose is inadequate. [ABSTRACT FROM AUTHOR]

Abstract: Incidence and characteristics of early bacterial infection within 100 days after unrelated cord blood transplantation (UCBT) were assessed for 664 pediatric and 1208 adult recipients in Japan. Cumulative incidence of early bacterial infection at day 100 post-UCBT was 11% (95% confidence interval [CI], 8%-13%) for children and 21% (CI, 19%-24%) for adults (P < .0001). Early bacterial infection in adults had a significant impact on mortality (hazard ratio [HR] = 2.1, CI, 1.7-2.6; P < .0001), although no significant risk factors were identified. Multivariate analysis identified older age group (6-10, and 11-15 years versus 0-5 years of age) at transplant (HR = 2.0 and 2.7, CI, 1.1-3.5 and 1.4-4.9; P = .020 and .002, respectively) as an independent risk factor of early bacterial infection for children. Early bacterial infection in children did not have a significant impact on mortality when adjusted. Of 315 bacteremia, 74% were caused by Gram-positive microorganisms. Pneumonia occurred in 39 patients including 13 cases of Stenotrophomonas maltophilia pneumonia. Early bacterial infection had a negative effect on survival for adults and the median day of development was 10 days after transplant, suggesting that the prevention of bacterial infection in the very early post-UCBT phase is important. [Copyright &y& Elsevier]

• HLA-A, -B, -C, and -DRB1 allele mismatch effects were examined in 4050 cases of cord blood transplants. • Overall survival (OS) deteriorated in HLA 5-allele and higher mismatch in adult cord blood transplantation (CBT). • OS deteriorated in HLA 4-allele and higher mismatch in pediatric CBT. • In adult cases, 8/8 match mitigated severe acute graft-versus-host disease (GVHD) but increased the relapse rate. • In pediatric cases, 8/8 match and 1-allele mismatch mitigated acute GVHD. The impact of allele-level HLA mismatch on outcomes of cord blood transplantation has not been well established. We retrospectively analyzed the effects of HLA allele matching at HLA-A, -B, -C, and -DRB1 in cord blood transplantation for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome. In multivariate analysis, overall survival (OS) significantly deteriorated in the 4-allele or higher mismatch in pediatric cases (hazard ratio, 1.8 for 4/8 match [reference, 6/8 match] and 2.85 for 3-1/8 match) and the 5-allele or higher mismatch in adult cases (hazard ratio, 1.23 for 3-0/8 match). Incidence of grade Ⅲ to Ⅳ acute graft-versus-host disease was low in the 8/8 match and 1-allele mismatch in pediatric cases (hazard ratio, 0.19 for 8/8 match and 0.41 for 7/8 match) and the 8/8 match in adult cases (hazard ratio, 0.41 for 8/8 match). On the other hand, a higher incidence of relapse was noted in the 8/8 match in adults (hazard ratio, 1.53). The incidence of neutrophil and platelet engraftment decreased in the 3-allele or higher mismatch in adults. In subgroup analysis of graft-versus-host disease prophylaxis in adult cases, a deteriorating effect on OS of HLA 5-allele or higher mismatch was more significant in cases with calcineurin inhibitor with methotrexate than with mycophenolate mofetil. These results suggest that allele-level HLA mismatch affects the outcomes of cord blood transplantation. Information on HLA allele matching at HLA-A, -B, -C, and -DRB1 may be useful for cord blood unit selection. [ABSTRACT FROM AUTHOR]

The article discusses the study which identifies whether CD34-positive cells or total nucleated cells is the important method for the selection of cord blood units for haematopoietic cell transplantation. It states that cell doses should be considered when selecting cord blood units for transplantation as well as human leucocyte antigen matching.

Cord blood transplantation (CBT) is a distinct risk factor for human herpesvirus-6 (HHV-6) reactivation and HHV-6 encephalitis. In a prospective multicenter trial we investigated the effects of prophylactic foscarnet (90 mg/kg i.v. infusion from days 7 to 27 after CBT) on the occurrence of HHV-6 reactivation, HHV-6 encephalitis, and acute graft-versus-host disease (aGVHD) in CBT recipients. Between 2014 and 2016, 57 patients were included in a foscarnet-prophylaxis group. Outcomes were compared with an historical control group who received CBT between 2010 and 2014 (standard-treatment group, n = 63). The cumulative incidence of high-level HHV-6 reactivation, defined as plasma HHV-6 DNA ≥ 10 4 copies/mL, at 60 days after CBT was significantly lower in the foscarnet-prophylaxis group than in the standard-treatment group (18.3% versus 57.3%, P  < .001). Multivariate analysis revealed that myeloablative preconditioning and standard treatment were significant risk factors for high-level HHV-6 reactivation. The cumulative incidence of HHV-6 encephalitis at 60 days after CBT was not different between the groups (foscarnet-prophylaxis group, 12.4%; standard-treatment group, 4.9%; P  = .14). The cumulative incidences of grades II to IV and grades III to IV aGVHD at 60 days after CBT were not different between the groups (grades II to IV aGVHD: foscarnet-prophylaxis group, 42.0%; standard-treatment group, 40.5%; P  = .96; grades III to IV aGVHD: foscarnet-prophylaxis group, 14.5%; standard-treatment group, 14.5%; P  = 1.00). In the setting of this study foscarnet significantly suppressed systemic HHV-6 reactivation in CBT recipients but failed to prevent the development of HHV-6 encephalitis. Suppression of HHV-6 reactivation by foscarnet did not show any effects against the incidence of aGVHD. [ABSTRACT FROM AUTHOR]

Graft failure (GF) is the most critical life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia, for which a second transplantation is the only effective treatment. Optimal procedures have not been established for the second transplantation in this setting, however. Here we retrospectively analyzed the outcomes of 22 patients with aplastic anemia, age ≥16 years, who underwent umbilical cord blood transplantation for GF after the first HSCT using the registry database of the Japan Society for Hematopoietic Cell Transplantation. The median age of patients was 36 years (range, 16 to 72 years), and the median time from the first to the second transplant was 77 days (range, 29 to 1061 days). The cumulative incidence of neutrophil engraftment at day 60 post-transplantation was 45.5% (95% confidence interval [CI], 23.6% to 65.0%). With a median follow-up of 50 months, the 4-year overall survival (OS) was 38.5% (95% CI, 18.4% to 58.5%). Mycofenolate mofetil–based graft-versus-host disease prophylaxis demonstrated greater neutrophil recovery than prophylaxis with calcineurin inhibitor alone or methotrexate-based prophylaxis (66.7% versus 37.5%; P  = .04). The use of such conditioning regimens as fludarabine + melphalan or cyclophosphamide + low-dose total body irradiation was associated with better engraftment (58.3% versus 30%; P  = .05) and better 4-year OS (55.6% versus 20%; P  = .05) than other regimens. Although further investigation is needed, umbilical cord blood could be an effective and promising option for stem cell source for urgent second transplantation in patients with aplastic anemia who develop GF after the first HSCT. [ABSTRACT FROM AUTHOR]

Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P  = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. [ABSTRACT FROM AUTHOR]

Granulocyte colony–stimulating factor (G-CSF) increases the susceptibility of dormant malignant or nonmalignant hematopoietic cells to cytarabine arabinoside (Ara-C) through the induction of cell cycle entry. Therefore, G-CSF–combined conditioning before allogeneic stem cell transplantation might positively contribute to decreased incidences of relapse and graft failure without having to increase the dose of cytotoxic drugs. We conducted a retrospective nationwide study of 336 adult patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (sAML) after single-unit cord blood transplantation (CBT) who underwent 4 different kinds of conditioning regimens: total body irradiation (TBI) ≥ 8 Gy + Ara-C/G-CSF + cyclophosphamide (CY) (n = 65), TBI ≥ 8 Gy + Ara-C + CY (n = 119), TBI ≥ 8 Gy + other (n = 104), or TBI < 8 Gy or non-TBI (n = 48). The TBI ≥ 8 Gy + Ara-C/G-CSF + CY regimen showed significantly higher incidence of neutrophil engraftment (hazard ratio, 1.52; 95% confidence interval [CI], 1.10 to 2.08; P = .009) and lower overall mortality (hazard ratio, .46; 95% CI, .26 to .82; P = .008) rates compared with those without a G-CSF regimen. This retrospective study shows that the G-CSF–combined conditioning regimen provides better engraftment and survival results in CBT for adults with MDS and sAML. [ABSTRACT FROM AUTHOR]

Cord blood has been investigated as an alternative source for hematopoietic stem cell transplantation, but information about its use for multiple myeloma is limited. The purpose of this study was to evaluate the feasibility of cord blood transplantation (CBT) for patients with multiple myeloma. Eighty-six patients with multiple myeloma who underwent a first CBT between 2001 and 2011 were included in this retrospective study. Sixty-two of them had received other types of stem cell transplantation before CBT. The cumulative incidences of neutrophil engraftment at day 50, grade II to IV acute graft-versus-host disease (GVHD), and chronic GVHD were 81.4%, 39.0%, and 19.5%, respectively. The incidence of nonrelapse mortality at 2 years was 39.0%, but it was only 6.2% in patients who underwent planned tandem autologous/reduced-intensity conditioning CBT (auto/RIC-CBT). Progression-free survival (PFS) and overall survival (OS) at 6 years were 13.0% and 15.2%, respectively. Less than a partial response before CBT and lack of prior transplantation were independent significant adverse factors for PFS, whereas the presence of prior transplantation and planned tandem transplantation were associated with better OS. OS at 6 years in patients who underwent auto/RIC-CBT was 45.9%. In addition, the development of chronic GVHD was associated with superior PFS. In conclusion, we demonstrated that cord blood is feasible as an alternative graft source for myeloma patients. Although CBT provided long-term survival for a fraction of patients, optimal use of this graft requires further clinical studies. [ABSTRACT FROM AUTHOR]

Abstract: An earlier report identified higher risks of acute and chronic graft-versus-host disease (GVHD) in White children compared with the Japanese after HLA-matched sibling transplantations. The current analysis explored whether racial differences are associated with GVHD risks after unrelated umbilical cord blood transplantation. Included are patients of Japanese descent (n = 257) and Whites (n = 260; 168 of 260 received antithymocyte globulin [ATG]). Transplants were performed in the United States or Japan between 2000 and 2009; patients were aged 16 years or younger, had acute leukemia, were in complete remission, and received a myeloablative conditioning regimen. The median ages of the Japanese and Whites who received ATG were younger at 5 years compared with 8 years for Whites who did not receive ATG. In all groups most transplants were mismatched at 1 or 2 HLA loci. Multivariate analysis found no differences in risks of acute GVHD between the Japanese and Whites. However, chronic GVHD was higher in Whites who did not receive ATG compared with the Japanese (hazard ratio, 2.16; P < .001), and treatment-related mortality was higher in Whites who received ATG compared with the Japanese (relative risk, 1.81; P = .01). Nevertheless, there were no significant differences in overall survival between the 3 groups. [Copyright &y& Elsevier]

Abstract: The impact of the direction of HLA mismatch (MM) on outcome in unrelated cord blood (UCB) transplantation has not yet been clarified. We conducted a retrospective study using national registry data on 2977 patients who underwent transplantation using a single UCB for leukemia or myelodysplastic syndrome. HLA matching was assessed by serologic data for HLA-A, -B, and -DR loci. The median age of the recipients at transplantation was 41 years (range, 0-82 years), and 2300 recipients (77%) were age ≥16 years. The 2-year overall survival rate was 0.46. The presence of MM only in the graft-versus-host direction or only in the host-versus-graft direction was not associated with overall mortality (hazard ratio [HR], 0.88; P = .317 and HR, 0.95; P = .670, respectively) compared with 1 bidirectional MM. This finding was consistent in both the child and adult cohorts. The presence of MM only in the graft-versus-host direction was associated with a lower incidence of nonrelapse mortality (HR, 0.65; P = .040), significant only in the child cohort. No MM category was associated with relapse. Our findings suggest that the direction of HLA MM does not have a significant impact on overall survival after UCB transplantation. [Copyright &y& Elsevier]

Summary [ABSTRACT FROM AUTHOR]

Abstract: Umbilical cord blood (UCB) transplantation is limited by the low number of hematopoietic stem cells in UCB units, which results in a low engraftment rate in transplant recipients. Here, we measured the total nucleated cell count and CD34+, CD3+, CD4+, CD8+, CD14+, and CD16+/56+ cell doses in each UCB unit and evaluated their influence on engraftment and other outcomes in 146 recipients. Multivariate analysis showed a significant association between a higher incidence of successful engraftment and a dose of CD34+ and CD8+ cells above the median (1.4 × 105 and 15.7 × 105 cells/kg, respectively). Engraftment occurred 4 days earlier in patients who received UCB with more than the median dose of CD34+ cells than those receiving UCB at or below the median. Stratification of the group according to CD34+ cell dose revealed a significant influence of the CD8+ cell dose on the time to achieve neutrophil engraftment in patients receiving a lower CD34+ cell dose, whereas there was no significant influence in the patients receiving a higher CD34+ cell dose. These results suggest that consideration of CD34+ and CD8+ cell doses in UCB units may improve the engraftment in recipients of UCB transplantation. [Copyright &y& Elsevier]