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Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4 + and CD8 + effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation., (© 2023. Springer Nature Limited.)

Background: Although rather favorable probabilities of return to work have been reported after allogeneic hematopoietic cell transplantation (allo-HCT), survivors often have difficulty continuing to work because of their immunocompromised status and diverse late effects after allo-HCT. We evaluated the incidence of and risk factors for recurrent sick leave in allo-HCT survivors after they initially returned to work., Methods: We targeted allo-HCT survivors who were employed at diagnosis, aged 20-64 at survey, and survived for ≥ 2 years without relapse. Of the 1904 survivors who were informed of the study, 1148 returned the questionnaire (60%), and 1048 eligible participants were included in the overall analysis. In the present study that considered recurrent sick leave after return to work, we targeted 896 participants who returned to work at least once after allo-HCT. Participants stated if they had recurrent sick leave after returning to work and its reasons, as well as associated patient-, HCT/HCT center-, and work-related factors and clinical events after allo-HCT. A logistic regression analysis was conducted to explore correlated factors for recurrent sick leave., Results: In survivors who returned to work, 30% required recurrent sick leave. The most frequent causes of recurrent leave were physical issues (72%), and analysis of free descriptions demonstrated that these were mainly associated with graft-versus-host disease, infection, or readmission. Other reasons included work-related issues such as gap between physical and working conditions. Multivariate analysis showed that cord blood transplantation, longer employment duration, and counseling from healthcare professionals were associated with a lower risk of recurrent leave. Readmission, immunosuppressant use, and symptoms involving the respiratory system, gut, and joints and muscles were associated with a higher risk., Conclusions: Our results drawn from a large cohort study should help healthcare professionals identify and assist at-risk patients. Multi-professional teams that provide continuous support and effective communication with the workplace are necessary to improve long-term outcomes after allo-HCT., Implications for Cancer Survivors: In order to continue working after the initial return to work, it is important to receive counseling from healthcare professionals and obtain reasonable accommodation from workplace., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

We retrospectively compared outcomes of unrelated donor bone marrow transplant (UBMT) and HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide (PTCy-haploPBSCT) using the Japanese registry data. Recipients of first HCT for acute leukemia and myelodysplastic syndromes between 2012 and 2015 were included. The analyzed subjects comprised UBMT recipients with 8/8 matched HLA alleles (n = 1470), 7/8 matched alleles (n = 859), 6/8 matched alleles (n = 186), and recipients of PTCy-haploPBSCT (n = 133). In multivariate analyses with 8/8 matched UBMT as the reference, PTCy-haploPBSCT showed similar overall mortality, decreased risk of non-relapse mortality (NRM), increased risk of relapse, and decreased risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD. Adjusted probabilities for 8/8 matched UBMT, PTCy-haploPBSCT, and 7/8 and 6/8 matched UBMT groups at 2 years post-transplant were 61%, 60%, 58%, and 52% for overall survival, 23%, 28%, 21%, and 19% for relapse, and 20%, 7%, 24%, and 33% for NRM. PTCy-haploPBSCT was associated with remarkably low NRM, contributing to survival outcomes that were comparable to 8/8 matched UBMT. The higher relapse rate in the PTCy-haploPBSCT group might be associated with the higher proportion of high-risk patients. PTCy-haploPBSCT may be a viable alternative when HLA-matched related donors are not available., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

HLA-haploidentical stem cell transplantation using post-transplant cyclophosphamide (PTCy-haplo) and umbilical cord blood transplantation (UCBT) are alternative to HLA-matched stem cell transplantation. We conducted a matched-pair analysis of PTCy-haplo and UCBT using the Japanese registry data. We identified 136 patients aged between 16 and 69 years who received PTCy-haplo as their first transplantation for acute leukemia or myelodysplastic syndromes. Control group included 408 UCBT recipients selected to match the PTCy-haplo group. Overall and relapse-free survival probabilities at 2 years were comparable between the PTCy-haplo and UCBT groups: 55% vs. 53% for overall survival (p = 0.46), and 47% vs. 48% for relapse-free survival (p = 0.79), respectively. The cumulative incidence of relapse was significantly higher (43% vs. 29%, respectively, p = 0.006), while the cumulative incidence of non-relapse mortality (NRM) was significantly lower (9% vs. 23%, respectively, p < 0.001) in the PTCy-haplo group. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was lower in the PTCy-haplo group compared to the UCBT group (29% vs. 41%, respectively, p = 0.016), while those of grade III-IV acute GVHD and chronic GVHD were not statistically different between the two groups. Our results suggest that both PTCy-haplo and UCBT are viable alternatives to HLA-matched stem cell transplantation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on systemic chronic active Epstein-Barr virus infection (sCAEBV) are yet to be analyzed in a large number of patients. Using the Japanese registry database, Transplant Registry Unification Management Program, we investigated the outcomes of 102 sCAEBV patients who underwent allo-HSCT. The median age at HSCT was 21 years, and the three-year overall survival (3-year OS) rate was 72.5%. Of the 90 patients whose viral load after allo-HSCT was evaluated, 56 (62.2%) achieved a virological complete response, defined by the complete resolution of disease activity with a significant decrease in EBV-DNA in peripheral blood. The multivariate Cox proportional hazard model indicated that advanced age, in adolescents and young adults (AYA) (age, 15-39) and adults (age, ≥40 years) was a risk factor of poor OS. The hazard ratios (HRs) of the AYA and adult groups were 10.87 (95% confidence interval [CI]: 1.98-59.56, p = .006) and 15.93 (95% CI: 2.45-103.8, p = .004), respectively. Disease activity (HR 5.74), elevated soluble IL-2 receptor (sIL-2R) (≥ median, 691 U/mL) at HSCT (HR 6.93), and conditioning without radiotherapy (HR 3.53) were also independently associated with poor survival. Notably, 79% of radiotherapy doses were less than 6 Gy. Regardless of the presence of hemophagocytic lymphohistiocytosis, the group with a high sIL-2R level (≥2000 U/mL) showed a poorer prognosis. Although allo-HSCT is the only curative therapy for sCAEBV, treatment strategies need to be improved for high-risk patients, especially those with high levels of sIL-2R., (© 2022 Wiley Periodicals LLC.)

Purpose: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually., Method: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT., Result: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009)., Conclusion: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pretransplant measurable residual disease (MRD) has been shown to be associated with relapse incidence following allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). However, it remains less clear whether pretransplant MRD status affects transplant outcomes in core binding factor AML (CBF-AML). We retrospectively evaluated the effect of pretransplant MRD, which was measured by a polymerase chain reaction of RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcripts, on transplant outcomes for a cohort of 959 adult patients with t(8;21) or inv(16) AML treated by allogeneic HCT during complete remission (CR), between 2000 and 2018. Multivariate analysis showed the absence of pretransplant MRD was significantly associated with lower relapse (hazard ratio [HR], 0.46; P < 0.001), treatment failure (HR, 0.66; P = 0.004), and overall mortality (HR, 0.72; P = 0.037) among patients with t(8;21). However, pretransplant MRD negativity was not associated with relapse (HR, 0.73; P = 0.420), treatment failure (HR, 0.64; P = 0.063), or overall mortality (HR, 0.69; P = 0.149) among patients with inv(16). In subgroup analysis, pretransplant MRD status significantly affected relapse and LFS only in patients with t(8;21) undergoing allogeneic HCT during CR2. In conclusion, our data demonstrate the different prognostic values of pretransplant MRD for CBF-AML, highlighting the need to develop effective therapeutic strategies for such MRD-positive patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1., (© 2021. The Author(s).)

Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) confers a dismal prognosis when treated with chemotherapy alone. Data on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes are limited. We retrospectively analyzed 4649 AML patients who received allo-HCT and were in complete remission. Outcomes of Ph+ AML (n = 30), intermediate-risk, and poor-risk AML patients were compared. The 3-year overall survival after allo-HCT was similar in intermediate-risk (62.7%; 95% CI: 61.0-64.3%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.42); however, it differed significantly between the poor-risk (49.7%; 95% CI: 45.9-53.4%) and Ph+ AML (73.3%; 95% CI: 51.5-86.4%) groups (P = 0.049). Disease-free survival in Ph+ AML patients was comparable to that in intermediate-risk patients but better than that in poor-risk patients. Relapse rates were significantly lower in Ph+ AML patients than in other groups. Non-relapse mortality (NRM) rates were similar among groups. Multivariate analysis showed that Ph+ AML was not a significant predictor of poor prognosis in terms of overall survival, disease-free survival, relapse, and NRM. Our data showed better post-transplant outcomes for Ph+ AML patients than for those with poor-risk AML. Hence, allo-HCT could be a feasible treatment option for Ph+ AML patients.

Reactivation of human herpesvirus (HHV)-6B is relatively common after allogeneic hematopoietic stem cell transplantation (HSCT) and HHV-6B diseases may consequently develop. Among them, HHV-6B encephalitis is a serious and often fatal complication. The aim of these clinical practice recommendations is to provide diagnostic and therapeutic guidance for HHV-6B encephalitis after allogeneic HSCT. In this evidence-based review, we critically evaluated data from the published literature. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assist in generating recommendations. We have summarized the findings that contribute to decision-making and we have provided our recommendations. In cases where rigorous clinical data are unavailable, recommendations have been developed in discussions with physicians who have relevant expertize.

This study aimed to investigate time-varying effects of graft type on outcomes for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant. For this purpose we analyzed 3952 patients, 720 of whom underwent matched related bone marrow transplantation (BMT), 1004 matched related peripheral blood stem cell transplantation (PBSCT), 856 matched unrelated BMT, and 1372 umbilical cord blood transplantation (UCBT) during complete remission. The 4-year relapse-free survival (RFS) rates were 59.1%, 52.8%, 59.5%, and 50.6%, respectively. Compared with related BMT, related PBSCT, unrelated BMT, and UCBT were associated with higher risk of nonrelapse mortality and unrelated BMT and UCBT with lower risk of relapse. As a result, both RFS and overall survival were comparable between related BMT and unrelated BMT but were worse for related PBSCT and UCBT than for related BMT. Adverse impact of UCBT was observed only during the early phase of transplant, whereas that of related PBSCT continued even after 2 years post-transplant. Our findings raise concerns about the increased risk of late nonrelapse mortality with the use of PBSC grafts and suggest that related BMT is preferable to related PBSCT; matched unrelated BMT is the next choice in the absence of a matched related donor., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Acute graft-versus-host disease (aGVHD) is 1 of the critical complications that often occurs following allogeneic hematopoietic stem cell transplantation (HSCT). Thus far, various types of prediction scores have been created using statistical calculations. The primary objective of this study was to establish and validate the machine learning-dependent index for predicting aGVHD. This was a retrospective cohort study that involved analyzing databases of adult HSCT patients in Japan. The alternating decision tree (ADTree) machine learning algorithm was applied to develop models using the training cohort (70%). The ADTree algorithm was confirmed using the hazard model on data from the validation cohort (30%). Data from 26 695 HSCT patients transplanted from allogeneic donors between 1992 and 2016 were included in this study. The cumulative incidence of aGVHD was 42.8%. Of >40 variables considered, 15 were adapted into a model for aGVHD prediction. The model was tested in the validation cohort, and the incidence of aGVHD was clearly stratified according to the categorized ADTree scores; the cumulative incidence of aGVHD was 29.0% for low risk and 58.7% for high risk (hazard ratio, 2.57). Predicting scores for aGVHD also demonstrated the link between the risk of development aGVHD and overall survival after HSCT. The machine learning algorithms produced clinically reasonable and robust risk stratification scores. The relatively high reproducibility and low impacts from the interactions among the variables indicate that the ADTree algorithm, along with the other data-mining approaches, may provide tools for establishing risk score., (© 2019 by The American Society of Hematology.)

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for high-risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient-based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ-statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision-making process in the diversified allo-HSCT field and be useful for preventing the relapse of leukemia., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The prognosis of patients with acute myeloid leukemia (AML) is dismal after experiencing multiple relapses. This study retrospectively analyzed outcomes of allogeneic hematopoietic cell transplantation (HCT) for 192 adults with AML in third or subsequent complete remission (CR3+), 300 in second relapse (REL2), and 50 in third or subsequent relapse (REL3+) who were enrolled in a Japanese nationwide transplantation registry. The study population included patients undergoing umbilical cord blood transplantation, but not those undergoing haploidentical HCT. Patients transplanted in CR3+ had better survival than those transplanted in REL2 and REL3+ (48%, 21%, and 12% at 4 years; P < 0.001), and this was due to a reduction in post-transplant relapse (23%, 57%, and 52%; P < 0.001). The corresponding cumulative incidence of non-relapse mortality was 33%, 26%, and 36% (P = 0.022). Multivariate analysis revealed significantly lower relapse and overall mortality for those in CR3+ and significantly lower non-relapse mortality for those in REL2. Hazard ratios (95% confidence intervals) for overall mortality were 2.02 (1.56-2.64) for REL2+ versus CR3+ (P < 0.001) and 2.12 (1.40-3.19) for REL3+ versus CR3+ (P < 0.001). Our analysis demonstrates the curative potential of allogeneic HCT for patients with a history of multiple AML relapses and suggests the potential benefits and risks of reinduction attempt before transplantation, highlighting the need for an individualized approach in determining whether to give reinduction therapy in this setting.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994-2006 and 2007-2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P < 0.001), and their survival was significantly better than that of those undergoing mismatched unrelated HCT (P = 0.022). These findings suggest that advances in HLA-typing technology have been vital for improvement in transplantation outcomes.

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification; we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.

Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Natural killer cells have been identified as a mediator of alloimmune reactions in allogeneic hematopoietic stem cell transplantation (HSCT). Killer immunoglobulin-like receptors (KIRs) are an important determinant of natural killer cell function. The relationship between KIR genotypes/haplotypes and clinical outcomes of allogeneic HSCT is complex and inconsistent among several reports. We assessed the clinical impact of KIR haplotype on T cell-replete allogeneic HSCTs performed in a single Japanese center for hematological malignancies (n = 106). A comparison of 2 groups, donor haplotypes A/A and B/x, revealed no significant differences in overall survival, relapse, and nonrelapse mortality. However, grade III to IV acute graft-versus-host disease (GVHD) occurred significantly more frequently in the KIR haplotype B/x group (A/A versus B/x: 4.9% versus 20.0%; P = .02). This was even more evident when HLA mismatch was present. The highest incidences of grade II to IV and grade III to IV acute GVHD were observed in patients who received allografts from HLA-mismatched donors with KIR haplotype B/x. These data highlight the importance of KIR genotyping in donor matching, especially when HLA mismatch allogeneic grafting is planned., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened. After rituximab treatment, CD8 T-cells emerged and became dominant in the peripheral blood, some of which were positive on an EBV-specific tetramer analysis. However, an open biopsy of the lymphadenopathy lesions revealed the CD8 T-cells to be infected with EBV, exhibiting proliferation with oligoclonality. The patient ultimately died of multiple organ failure on day 99 post-HSCT.

Pharmacological study is predictably effective in establishing an optimal monitoring strategy for the usage of cyclosporine A (CsA) to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation recipients. Pharmacokinetic profiling of 33 recipients administered CsA twice daily by 3-h intravenous infusion revealed that levels peaked 2-3 h after the start of infusion, and an exponential decline of CsA concentrations after the termination of infusion was observed. The correlation between the area under the curve (AUC(0-12)) and CsA concentration at various time points after infusion revealed that C (2) and C (3) correlated best with AUC(0-12) (r (2) = 0.725), while the trough concentration correlated poorly. Ex vivo T cell stimulation followed by intracellular cytokine detection with flow cytometry revealed that the capacity of T cells to produce cytokines upon stimulation was inversely proportional to the CsA concentration, and reached a minimum at about 700 ng/mL with a marginal decrease above this concentration. Extrapolation using the regression equations of this study and the data from our retrospective study leads to the assumption that the dose adjustment of CsA based on maintaining the C (3) concentration above 800 ng/mL may effectively prevent acute GVHD. To confirm this assumption, a prospective clinical study is required.

Objective: Cardiovascular complication is one of the serious complications in stem cell transplantation (SCT). We measured plasma brain natriuretic peptide (BNP) concentrations in patients who received SCT to evaluate possible cardiac toxicity of the regimens employed in SCT., Patients: Ten patients with allogeneic SCT and 5 patients with autologous SCT using myeloablative conditioning regimens were enrolled. The preparative chemotherapy for 8 patients with allogeneic SCT included cyclophosphamide (60 mg/kg i.v. for 2 days) and other drugs and that for autologous SCT included cyclophosphamide (50 mg/kg for 2 days) and other drugs. Total body irradiation (TBI) was employed only in the patients who received allogeneic SCT., Method: Plasma BNP was measured using a radioimmunoassay for human BNP before and after SCT., Results: In 13 of 15 patients, BNP levels were elevated after SCT. In patients who received a total body irradiation (TBI) of 13.2 Gy, BNP levels were higher than those without irradiation (p=0.01). The BNP level reached a peak within 6 months after SCT in most patients and fell thereafter. But 7 of the 15 patients (46.7%) had an abnormally high level of plasma BNP even after 6 months of SCT which suggests subclinical myocardial damage., Conclusion: A rise in plasma BNP was frequently observed after SCT, and may be considered to represent cardiac damage caused by the preparative chemotherapy and/or total body irradiation. Since a rise was noted 6 months after SCT, long-term evaluation of cardiac function is important.

Chromosomal abnormalities in the role of prognostic factor for transplant patients with myelofibrosis (MF) are not fully investigated. Regarding complex karyotype (CK), we retrospectively analyzed 241 patients with primary and secondary MF who received a first allogeneic hematopoietic cell transplantation (HCT). Based on an unfavorable karyotype in the Dynamic International Prognostic Scoring System, we compared the outcomes in 3 groups: favorable karyotype, unfavorable karyotype including CK (unfavorable‐CK(+)), and unfavorable karyotype not including CK (unfavorable‐CK(–)). Overall survival was significantly shorter in the unfavorable‐CK(+) group (hazard ratio (HR) 2.49, 95% CI: 1.46–4.24, P < 0.001), whereas there was no difference between the unfavorable‐CK(–) group and the favorable group (HR 0.57, 95% CI: 0.20–1.59, P = 0.28). In addition, a significantly higher proportion of patients in the unfavorable‐CK(+) group did not achieve complete remission after HCT (P = 0.007). The cumulative incidence of disease progression was significantly higher in the unfavorable‐CK(+) group (HR 2.5, 95% CI 1.6–3.92, P < 0.001), whereas that in the unfavorable‐CK(–) group was comparable to that in the favorable group (HR 0.49, 95% CI 0.12–1.94, P = 0.31). Further investigations will be needed to clarify the impact of CK on transplant outcomes in MF. [ABSTRACT FROM AUTHOR]

The availability of alternative donor sources could allow elderly patients to receive allogeneic hematopoietic cell transplantation (HCT). We retrospectively evaluated the outcomes of single-unit cord blood transplantation (CBT) in 1577 patients aged ≥60 years with acute myeloid leukemia (AML) in Japan between 2002 and 2017. In total, 990 (63%) patients were not in complete remission (CR) at the time of CBT. A myeloablative conditioning regimen (52%) and calcineurin inhibitor (CI) + mycophenolate mofetil (MMF)–based graft-versus-host disease (GVHD) prophylaxis (45%) were more commonly used. With a median follow-up for survivors of 31 months, the probability of overall survival and the cumulative incidence of leukemia-related mortality at 3 years was 31% and 29%, respectively. The cumulative incidence of non-relapse mortality (NRM) at 100 days and 3 years were 24% and 41%, respectively. The cumulative incidences of grade II–IV and grade III–IV acute GVHD at 100 days and extensive chronic GVHD at 2 years were 44%, 16%, and 14%, respectively. The cumulative incidence of neutrophil engraftment was 80% at 42 days. Results of multivariate analysis indicated that the following factors were significantly associated with higher overall mortality: performance status ≥1, hematopoietic cell transplantation-specific comorbidity index ≥3, adverse cytogenetics, extramedullary disease at diagnosis, and non-CR status at CBT. By contrast, female sex, HLA disparities ≥2, mycophenolate mofetil–based GVHD prophylaxis, and recent CBT were significantly associated with lower overall mortality. In conclusion, single CBT offers a curative option for AML patients aged ≥60 years with careful patient selection. [ABSTRACT FROM AUTHOR]

Introduction: Chromosome analysis is necessary for the risk classification of acute myeloid leukemia (AML). Marker chromosome (MC) is a fragmented chromosome whose origin cannot be identified from other chromosomes and originates from marked genomic instability. Although AML with MC (MC+) has a poor prognosis even after intensive chemotherapy, its influence on the outcome after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is unclear. Objective and Methods: We retrospectively analyzed 162 AML patients after allo‐HSCT. To evaluate the significance of MC, we compared it with other chromosomal abnormalities. Result: Marker chromosome was detected in 14 (8.6%, MC+) patients (vs MC−, n = 158). The 2‐year overall survival (OS) in MC+ vs MC− was 26.8% vs 62.2% (P =.0098). The 2‐year cumulative incidence of relapse (CIR) in MC+ vs MC− was 80.4% vs 35.5% (P =.0004). Among adverse‐risk AML (AD‐AML, n = 36), AD‐AML/MC+ (n = 11) demonstrated a poorer 2‐year OS (9.1%, vs AD‐AML/MC− n = 25, 58.3%, P =.0031) and higher 2‐year CIR (89.6%, vs AD‐AML/MC− 44.7%, P =.002). In multivariate analysis, MC (HR 3.08, 95% CI; 1.02‐9.29, P =.046) and HCT‐CI (HR 3.23, 95% CI; 1.00‐10.4, P =.049) were independent risk factors for CIR among AD‐AML. Conclusion: Our study suggests MC as a new independent factor for chromosome risk classification to further classify AD‐AML. [ABSTRACT FROM AUTHOR]