Soluble SLAMF7 is generated by alternative splicing in multiple myeloma cells.

Not available.

Association between human herpesvirus-6 encephalitis and antiviral prophylaxis after allogeneic hematopoietic stem cell transplantation in the letermovir era.

The impact of letermovir (LTV)-an anti-cytomegalovirus (CMV) drug-on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II-IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies.

Allogeneic transplantation of bone marrow versus peripheral blood stem cells from HLA-identical sibling donors for hematological malignancies in 6064 adults from 2003 to 2020: different impacts on survival according to time period.

BACKGROUND: Mobilized peripheral blood stem cells (PBSC) have been widely used instead of bone marrow (BM) as the graft source for allogeneic hematopoietic cell transplantation (HCT). Although early studies demonstrated no significant differences in survival between PBSC transplantation (PBSCT) and BM transplantation (BMT) from human leukocyte antigen (HLA)-identical sibling donors to adults with hematological malignancies, recent results have been unclear. OBJECTIVE: The objective of this retrospective study was to compare overall survival (OS), relapse, non-relapse mortality (NRM), hematopoietic recovery and graft-versus-host disease (GVHD) between PBSCT and BMT according to the time period of HCT (2003-2008, 2009-2014, or 2015-2020). STUDY DESIGN: We retrospectively compared the outcomes after PBSCT versus BMT in 6064 adults with hematological malignancies using a Japanese registry database between 2003 and 2020. RESULTS: The adjusted probability of OS was significantly higher in BMT recipients compared to PBSCT recipients during the early period of 2003-2008 (adjusted hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.70-0.91; P < 0.001) and the middle period of 2009-2014 (adjusted HR, 0.80; 95% CI, 0.70-0.91; P < 0.001). However, during the late period of 2015-2020, the adjusted probability of OS was comparable between BMT and PBSCT recipients (adjusted HR, 0.94; 95% CI, 0.79-1.13; P = 0.564), which were mainly due to the reduction of NRM. There was no significant difference in the relapse rate between the groups, irrespective of the time period. Compared to BMT, PBSCT led to faster neutrophil and platelet recovery and the cumulative incidences of grades II-IV and grades III-IV acute and overall and extensive chronic GVHD were significantly higher in PBSCT recipients, irrespective of the time period. CONCLUSIONS: PBSCT and BMT had similar survival outcomes and relapse rates in adult patients with hematological malignancies during the late time period of 2015-2020 despite the hematopoietic recovery and acute and chronic GVHD being higher in PBSCT recipients in all time periods.

[Evidence of GVHD/GVL in allogeneic hematopoietic stem cell transplantation from sex-mismatched donors].

Hematopoietic cell transplantation (HCT) is considered a curative treatment for hematological malignancies. However, HCT recipients often face complications such as graft-versus-host disease (GVHD) and disease relapse. Clinical factors like age and HLA disparity are recognized as risks for GVHD. Notably, sex-mismatched HCT, particularly with female donors and male recipients (F→M), is reported to increase the risk of chronic GVHD. This adverse effect of F→M HCT is thought to result from allogeneic immune response against minor histocompatibility antigens encoded on the Y-chromosome of a male recipient (HY-antigens). Indeed, antibodies against HY-antigens (HY-Abs) were detected three months after F→M HCT, and the cumulative number of HY-Abs was significantly associated with increased risks of chronic GVHD and non-relapse mortality. This review focuses on F→M HCT, shedding light on its impact in several clinical settings and presenting clinical evidence of its allogeneic response, encompassing GVHD and graft-versus-leukemia (GVL) effects. Additionally, potential clinical options to mitigate adverse effects in F→M HCT will be discussed. Further investigation is required to improve clinical outcomes and understand allogenic immunological reconstitution after F→M HCT.

Comparative Analysis of Allogeneic Bone Marrow Transplantation Outcomes Between Japanese and Non-Japanese Populations.

BACKGROUND: As the Japanese population may have less genetic diversity than other ethnic groups, treatment outcomes may be affected when allogeneic hematopoietic cell transplantation is performed in other races. However, evidence explaining the effect of racial differences is limited. METHODS: We used the Japanese National Database to examine the outcomes of first allogeneic bone marrow transplantations (BMTs) performed between Japanese and non-Japanese patients from 1996 to 2021. We performed propensity score matching using sex, age group, underlying disease group, HLA mismatch, conditioning regimen intensity, and BMT implementation age to select Japanese-to-Japanese BMT patients as the controls. RESULTS: The numbers of non-Japanese-to-Japanese and Japanese-to-non-Japanese BMT cases included in the analysis were 48 and 75, respectively, and the following outcomes were compared: overall survival, non-relapse mortality, acute graft-vs-host disease (GVHD) ≥ grade II, chronic GVHD, and engraftment of neutrophils and platelets. Most parameters did not differ when comparing BMTs according to ethnicity; only platelet engraftment was delayed in Japanese-to-non-Japanese BMT but not in non-Japanese-to-Japanese BMT. CONCLUSIONS: The results of this study suggested that BMT performed in Japanese and non-Japanese patients has little effect on treatment outcomes. The results of this study may be useful for donor selection in Japan, where internationalization has progressed in recent years.

Association of individual comorbidities with outcomes in allogeneic hematopoietic cell transplantation from unrelated adult donors versus unrelated cord blood: A study on behalf of the Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy.

We retrospectively evaluated the effect of 17 individual comorbidities, defined by the hematopoietic cell transplantation (HCT)-specific comorbidity index, on non-relapse mortality (NRM) and overall survival (OS) in 9531 patients aged between 16 and 70 years who underwent their first allogeneic HCT from 8/8 and 7/8 allele-matched unrelated donors (8/8 and 7/8 MUDs) or single-unit unrelated cord blood (UCB) between 2011 and 2020 using data from a Japanese registry database. In the multivariate analysis, infection (adjusted hazard ratio [HR], 1.62, 95% confidence interval [CI], 1.33-1.99 for 8/8 and 7/8 MUDs; adjusted HR, 1.33, 95%CI, 1.12-1.58 for UCB) and moderate/severe hepatic comorbidity (adjusted HR, 1.57, 95%CI, 1.04-2.38 for 8/8 and 7/8 MUDs; adjusted HR, 1.53, 95%CI, 1.09-2.15 for UCB) had a significant impact on NRM in both donor groups. Cardiac comorbidity (adjusted HR, 1.40, 95%CI, 1.08-1.80), mild hepatic comorbidity (adjusted HR, 1.22, 95%CI, 1.01-1.48), rheumatologic comorbidity (adjusted HR, 1.67, 95%CI, 1.11-2.51), renal comorbidity (adjusted HR, 2.44, 95%CI, 1.46-4.09), and severe pulmonary comorbidity (adjusted HR, 1.40, 95%CI, 1.11-1.77) were significantly associated with an increased risk of NRM but only in UCB recipients. Renal comorbidity had the strongest impact on poor OS in both donor groups (adjusted HR, 1.73, 95%CI, 1.10-2.72 for 8/8 and 7/8 MUDs; adjusted HR, 2.24, 95%CI, 1.54-3.24 for UCB). Therefore, unrelated donor selection should be taken into consideration along with the presence of specific comorbidities, such as cardiac, rheumatologic, renal, mild hepatic, and severe pulmonary comorbidities.

Development of an umbilical cord blood transplantation-specific nonrelapse mortality risk assessment score.

ABSTRACT: Higher rate of nonrelapse mortality (NRM) remains yet to be resolved in umbilical cord blood transplantation (UCBT). Considering that UCBT has some unique features compared with allogeneic hematopoietic cell transplantation from other graft sources, a UCBT-specific NRM risk assessment system is required. Thus, in this study, we sought to develop a UCBT-specific NRM Risk Assessment (CoBRA) score. Using a nationwide registry database, we retrospectively analyzed 4437 recipients who had received their first single-unit UCBT. Using the backward elimination method, we constructed the CoBRA score in a training cohort (n = 2687), which consisted of recipients age ≥55 years (score 2), hematopoietic cell transplantation-specific comorbidity index ≥3 (score 2), male recipient, graft-versus-host disease prophylaxis other than tacrolimus in combination with methotrexate, performance status (PS) 2 to 4, HLA allele mismatch ≥ 2, refined Disease Risk Index high risk, myeloablative conditioning, and CD34+ cell doses < 0.82 × 105/kg (score 1 in each). The recipients were categorized into 3 groups: low (0-4 points), intermediate (5-7 points), and high (8-11 points) groups according to the CoBRA score. In the validation cohort (n = 1750), the cumulative incidence of NRM at 2 years was 14.9%, 25.5%, and 47.1% (P < .001), and 2-year overall survival (OS) was 74.2%, 52.7%, and 26.3% (P < .001) in the low, intermediate, and high groups, respectively. In summary, the CoBRA score could predict the NRM risk as well as OS after UCBT. Further external validation will be needed to confirm the significance of the CoBRA score.

Comparison of Allogeneic Transplant Outcomes Between Matched Sibling Donors and Alternative Donors in Patients Over 50 Years of Age with Acute Myeloid Leukemia: 8/8 Allele-Matched Unrelated Donors and Unrelated Cord Blood Provide Better Leukemia-Free Survival Compared with Matched Sibling Donors During Nonremission Status.

Acute myeloid leukemia (AML) is the most common indication for allogeneic hematopoietic cell transplantation (HCT). The increased availability of alternative donor sources has broadened donor types for older patients without HLA-matched sibling donors (MSD). It is uncertain if an MSD should be the first option for allogeneic HCT in patients with AML over 50 years of age. The objective of this study was to compare survival and other post-transplant outcomes between MSDs, 8/8 allele-matched unrelated donors (MUDs), 7/8 allele-MUDs, unrelated cord blood (UCB), and haploidentical donors for patients with AML over 50 years of age. We conducted a retrospective study to compare outcomes in 5704 patients with AML over 50 years of age and receiving allogeneic HCT between 2013 and 2021, using either MSD, 8/8 allele-MUD, 7/8 allele-MUD, UCB, or haploidentical donors in Japan. Complete remission (CR) and nonremission at HCT were analyzed separately for all analyses. In total, 3041 patients were CR, and 2663 patients were nonremission at the time of HCT. In multivariate analysis, donor type did not determine overall survival, irrespective of disease status at HCT. Leukemia-free survival (LFS) was significantly better for 8/8 allele-MUD (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.64 to 0.93; P = .005) and UCB (HR, 0.76; 95% CI, 0.65 to 0.88; P < .001), but not for 7/8 allele-MUD (HR, 0.97; 95% CI, 0.79 to 1.19; P = .794), and haploidentical donor (HR, 0.86; 95% CI, 0.70 to 1.05; P = .146) compared to the MSD group in nonremission status. However, donor type did not determine LFS among CR status. Relapse rates were significantly lower for 8/8 allele-MUD and UCB, whereas nonrelapse mortality was higher for UCB compared to the MSD group among both CR and nonremission status. Our registry-based study demonstrated that MSDs do not lead to superior survival compared to alternative donors for patients with AML over 50 years of age. Furthermore, 8/8 allele-MUDs and UCB provide better LFS compared with MSDs during nonremission status. Therefore, MSD is not necessarily the best donor option for allogeneic HCT in this population.

Outcomes of allogeneic hematopoietic cell transplantation under letermovir prophylaxis for cytomegalovirus infection.

Cytomegalovirus (CMV) infection is a major infectious complication following allogeneic hematopoietic cell transplantation (allo-HCT). Although letermovir (LMV) prophylaxis dramatically reduces the incidence of early clinically significant CMV (csCMV) infection, it remains unclear whether it has a beneficial effect on nonrelapse mortality (NRM) and overall survival (OS). Herein, we evaluated the impact of LMV prophylaxis on posttransplant outcomes using the registry database of the Japanese Society for Transplantation and Cellular Therapy. Adult patients who underwent allo-HCT between 2017 and 2019 were analyzed (n = 6004). LMV prophylaxis was administered to 1640 patients (LMV group) and it significantly reduced the incidence of csCMV infection compared with those not administered LMV prophylaxis (15.4% vs 54.1%; p < 0.01). However, it did not improve the 1-year NRM (hazard ratio [HR], 0.93; p = 0.40) and OS (HR, 0.96; p = 0.49). In the LMV group, 74 patients had breakthrough csCMV infection and showed inferior NRM (HR, 3.44; p < 0.01) and OS (HR, 1.93; p = 0.02) compared with those without infection. After completing LMV prophylaxis, 252 patients had late csCMV infection and showed inferior NRM (HR, 1.83; p < 0.01) and OS (HR, 1.58; p < 0.01). Our findings suggest that managing breakthrough and late csCMV infections is important for improving long-term outcomes.

Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy.

BACKGROUND AIMS: This study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes. METHODS: A retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0-70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020. RESULTS: Among 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0-24 years, indicating that both sources are viable choices for young patients. CONCLUSIONS: This real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection.

Analysis of risk factors for fatal renal complications after allogeneic hematopoietic cell transplantation.

Various complications can influence hematopoietic cell transplantation (HCT) outcomes. Renal complications can occur during the early to late phases of HCT along with various factors. However, studies focusing on fatal renal complications (FRCs) are scarce. Herein, we analyzed 36,596 first allogeneic HCT recipients retrospectively. Overall, 782 patients died of FRCs at a median of 108 (range, 0-3,440) days after HCT. The cumulative incidence of FRCs was 1.7% and 2.2% at one and five years, respectively. FRCs were associated with older age, male sex, non-complete remission (non-CR), lower performance status (PS), and HCT comorbidity index (HCT-CI) associated with renal comorbidity in multivariate analysis. The risk factors within 100 days included older age, multiple myeloma, PS, and HCT-CI comorbidities (psychiatric disturbance, hepatic disease, obesity, and renal disease). Older age and male sex were risk factors between 100 days and one year. After one year, HCT-CI was associated with the presence of diabetes and prior solid tumor; total body irradiation was identified as a risk factor. Non-CR was a common risk factor in all three phases. Furthermore, acute and chronic graft-versus-host disease, reactivation of cytomegalovirus, and relapse of underlying disease also affected FRCs. Systematic follow-up may be necessary based on the patients' risk factors and post-HCT events.

Outcomes in human T-cell leukemia virus type I carriers after hematopoietic stem cell transplantation for diseases other than adult T cell leukemia/lymphoma: a Japanese national survey.

Background: Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL. Methods: A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed. We investigated the overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) after HSCT in relation to HTLV-1 serologic status. Findings: Three hundred and forty-eight patients were HTLV-1 antibody carriers. The number of HTLV-1 carriers and noncarriers among adult patients who received allogeneic HSCT (allo-HSCT) or autologous HSCT (auto-HSCT) was 237/15,777 and 95/8920, respectively, and was 16/1424 among pediatric patients who received allo-HSCT. No pediatric HTLV-1 carrier recipients undergoing auto-HSCT were identified. There were no significant differences between HTLV-1 carriers and non-carriers regarding stem cell source, disease risk, or HCT-CI score prior to allo-HSCT. Multivariate analysis of OS (P = 0.020) and TRM (P = 0.017) in adult patients showed that HTLV-1 positive status was a significant prognostic factor. In children, TRM was significantly higher (P = 0.019), but OS was not significantly different. In adult patients who underwent auto-HSCT, HTLV-1 positive status was not a significant prognostic factor. In adult allo-HSCT patients, cytomegalovirus reactivation was significantly more common in HTLV-1 carriers (P = 0.001). Interpretation: HTLV-1 antibody positivity was shown to have a poor prognosis in OS and TRM after allo-HSCT in adult patients and in TRM after allo-HSCT in pediatric patients. Funding: This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under grant number 17ck0106342h0001.

Clinical Impact of Pretransplantation Physical Function on Transplantation after Allogeneic Hematopoietic Cell Transplantation in Older Adults.

Clinical research regarding the impact of pretransplantation physical function on transplantation outcomes in older adults remains limited. We retrospectively reviewed the charts of 150 consecutive patients age >55 years who underwent their first allogeneic hematopoietic cell transplantation (HCT) at our center between 2010 and 2021. We evaluated the clinical impact of pretransplantation physical function, including hand grip strength (HGS), knee extension strength (KES), and distance covered in a 6-minute walk test (6MWT), along with other clinical factors, on transplantation outcomes such as overall survival (OS), nonrelapse mortality (NRM), and cumulative incidence of disease relapse (CIR). There was no difference in OS, NRM, or CIR among the 3 age groups studied (56 to 60 years, 61 to 65 years, and 66 to 70 years). With regard to physical function tests, we divided the study patients into 2 groups based on the median HGS, KES, and 6MWT values: higher physical function and lower physical function groups. Because there were significant differences in HGS and KES between male and female patients, sex-specific threshold values were used. In a univariate analysis, OS tended to be better in the higher physical function group compared with the lower physical function group (4-year OS, 42.0% versus 32.0% in HGS, P = .14; 44.8% versus 37.8% in KES, P = .17; 46.7% versus 30.5% in 6MWT, P = .099). NRM was significantly lower in the higher physical function group (4-year NRM, 25.5% versus 39.9% in HGS, P = .045; 17.7% versus 38.0% in KES, P = .005; 22.5% versus 43.4% in 6MWT, P = .033). There was no significant difference in CIR between the higher and lower physical function groups (4-year CIR, 34.6% versus 28.7% in HGS, P = .38; 38.5% versus 25.8% in KES, P = .20; 33.0% versus 27.0% in 6MWT, P = .42). In multivariate analysis, the higher KES group (hazard ratio [HR], .54; 95% confidence interval [CI], .32 to .90) was significantly associated with better OS, as were female sex (HR, .48; 95% CI, .26 to .89) and low/intermediate Disease Risk Index (HR, 3.59; 95% CI, 2.04 to 6.31). Higher KES (HR, .37; 95% CI, .17 to .83) and female sex (HR .36; 95% CI, .13 to .998) were significantly associated with a reduced risk of NRM. Higher HGS and higher 6MWT tended to be associated with a reduced risk of NRM, but this trend was not statistically significant. Pretransplantation physical function, particularly the strength of the lower extremities, but not chronological age, is associated with NRM and OS after allogeneic HCT in adults age >55 years.

Treatment strategy at the decision for allogeneic transplantation in patients with myelodysplastic syndrome in the era of azacitidine: A KSGCT prospective study.

The optimal bridge strategy at the decision for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelodysplastic syndrome (MDS) is unclear. We performed a prospective observational study in which 110 patients with MDS who were decided to undergo HSCT were enrolled. Among these 110 patients, 77 patients were enrolled in this study within 1 month from the decision for HSCT. Among these 77 patients, 13 patients had a human leukocyte antigen (HLA)-matched sibling, 54 patients started an unrelated donor search, and the other 10 patients directly selected cord blood (CB) at the decision for HSCT, and 13 (100%), 38 (70.4%), and 9 (90%) patients actually underwent HSCT within 1 year, respectively. The overall survival (OS) at 1 year from their enrollment was 70.9%, and the selection of azacitidine use at the decision for HSCT was not associated with OS. Among 60 of the 77 patients who actually underwent HSCT within a year from their enrollment, a lower relapse rate after HSCT was observed in those who selected CB at the decision to undergo HSCT. However, this preferable effect of CB selection disappeared when patients who were enrolled in this study in > 1 month from the decision for HSCT were additionally included in the analyses. In conclusion, the selection of bridge strategy at the decision for HSCT did not affect outcomes in patients with MDS. The immediate performance of HSCT may be associated with better outcomes.

Plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1) level as a blood biomarker of neurological damage after allogeneic hematopoietic cell transplantation.

Several biofluid-based biomarkers for traumatic brain injury show promise for use in diagnosis and outcome prediction. In contrast, few studies have investigated biomarkers for non-traumatic brain injury. We focused on ubiquitin C-terminal hydrolase-L1 (UCH-L1), which has been proposed as a screening tool for traumatic brain injury, and investigated whether the plasma UCH-L1 level could also be a useful biomarker in patients with non-traumatic brain injury. We measured UCH-L1 in 25 patients who had experienced neurological complications after allogeneic hematopoietic cell transplantation (HCT) and 22 control patients without any complications or graft-versus-host disease. Although UCH-L1 levels before HCT did not differ significantly (P = 0.053), levels after HCT were higher in patients with neurological complications compared with the control group (P < 0.001). At a UCH-L1 cutoff value of 0.072 ng/ml, sensitivity was 68.0% and specificity was 100%. The statistical power of UCH-L1 for neurological complications seemed to be higher than that of CT and comparable to that of MRI. Thus, increased levels of UCH-L1 might reflect the presence of neurological damage even in patients with non-traumatic brain injury. Further large cohort investigations are warranted.

Substitution of calcineurin inhibitors with corticosteroids after allogeneic hematopoietic cell transplantation.

Combination of calcineurin inhibitors (CIs) with short-term methotrexate is a standard prophylactic regimen for graft-versus-host disease (GVHD). However, it is sometimes difficult to continue CIs due to adverse effects, such as renal impairment and fluid overload. In such cases, we replace CIs with corticosteroids, considering that full dose of CIs is equivalent to prednisolone (PSL) at 1 mg/kg. We retrospectively evaluated the clinical significance of replacement of CIs with corticosteroids after allogeneic hematopoietic cell transplantation (HCT). We evaluated 42 patients switched from CIs to corticosteroids within 90 days among the 479 patients who underwent allogeneic HCT at our center between 2007 and 2019. Renal impairment (n = 33), fluid overload (n = 13), and thrombotic microangiopathy (n = 3) were the main reasons for switching. Although creatinine and body weight returned to baseline at 4 weeks after switching, 100-day non-relapse mortality was high (57.1%). Grade II-IV acute GVHD was seen in 10 (24.4%) patients who did not have it before switching treatment (n = 41). In conclusion, CIs were switched to corticosteroids in patients with severe clinical conditions. The incidence of acute GVHD was acceptable. Although the short-term mortality rate was high, improvement of renal function or fluid overload was observed in a certain proportion of the patients.

Comparison and Development of Immunohistochemical Diagnostic Criteria for Blastic Plasmacytoid Dendritic Cell Neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy derived from the precursors of plasmacytoid dendritic cells. Diagnostic criteria for BPDCN have not been fully established. BPDCN is often diagnosed without other BPDCN markers than the 3 conventional markers (CD4, CD56, and CD123) in practice and case reports, although acute myeloid leukemia/myeloid sarcoma (AML/MS), which is always considered in the differential diagnosis of BPDCN, can express them. We reviewed published case reports on BPDCN and found that the diagnosis was made without any other BPDCN markers than the conventional markers in two-thirds of the cases. Next, 4 representative existing diagnostic criteria were applied to 284 cases of our cohort of BPDCN and mimics. The results differed in 20% (56/284) of the cases. The criterion based on the 3 conventional markers alone had a low concordance rate (80%-82%) with the other 3 criteria, which were almost concordant with each other. However, newly found minor limitations in these criteria prompted us to devise new diagnostic criterion for BPDCN composed of TCF4, CD123, TCL1, and lysozyme. We also revealed that CD123-positive AML/MS patients had a significantly poorer outcome than those with BPDCN and that 12% (24/205) of the cases were non-BPDCN even if all 3 conventional markers were positive, thus clarifying the risk of diagnosing BPDCN without more specific markers. In addition, histopathological features, such as the reticular pattern, which is not seen in BPDCN and suggests AML/MS, were also identified.

Unrelated female-to-male bone marrow transplantation would be preferred over cord blood transplantation in male patients.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation from female donors to male recipients (female-to-male allo-HCT) is a well-established risk factor for a greater incidence of non-relapse mortality (NRM) and chronic graft-versus-host disease (GVHD). In contrast, unrelated cord blood transplantation (UCBT) is associated with a lower incidence of chronic GVHD. In this study, survival outcomes were compared between the UCBT and unrelated female-to-male bone marrow transplantation (UFMBMT) groups. METHODS: We evaluated male allo-HCT recipients who underwent UCBT or UFMBMT between 2012 and 2020 in Japan. There were 2517 cases in the UCBT group, 456 cases in the HLA-matched UFMBMT group and 457 cases in the HLA-mismatched UFMBMT group. RESULTS: HLA-mismatched UFMBMT was significantly associated with a decreased risk of relapse (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.57-0.98], P = 0.033) and HLA-matched UFMBMT had the tendency of a decreased risk of relapse (HR 0.78; 95% CI 0.61-1.01, P = 0.059). HLA-matched UFMBMT was also associated with favorable OS (HR 0.82; 95% CI 0.69-0.97, P = 0.021). The relationship between the donor sources and relapse was similarly observed in the lymphoid malignancy cohort. CONCLUSIONS: The difference of graft-versus leukemia effect by H-Y immunity according to donor sources might contribute to the difference in clinical impact. It might be desirable for patients who could sufficiently wait for donor coordination to select BMT rather than UCBT, even if only unrelated female donors are available for male recipients.

Gene expression and TCR amino acid sequences selected by HLA-A02:01-restricted CTLs specific to HTLV-1 in ATL patients.

Adult T-cell leukaemia/lymphoma (ATL) is an aggressive malignancy of peripheral T cells caused by human T-cell lymphotropic virus type-1 (HTLV-1). Tax is the most important regulatory protein for HTLV-1. We aimed to reveal a unique amino acid sequence (AA) of complementarity-determining region 3 (CDR3) of the T-cell receptor (TCR)ß and TCRα chains of HLA-A*02:01-restricted Tax11-19 -specific cytotoxic T cells (Tax-CTLs). The gene expression profiles (GEP) of Tax-CTLs were assessed by the next-generation sequence (NGS) method with SMARTer technology. Tax-CTLs seemed to be oligoclonal, and their gene compositions were skewed. The unique motifs of 'DSWGK' in TCRα and 'LAG' in TCRß at CDR3 were observed in almost all patients. Tax-CTL clones harbouring the 'LAG' motif with BV28 had a higher binding score than those without either of them, besides a higher binding score associated with longer survival. Tax-CTLs established from a single cell showed killing activities against Tax-peptide-pulsed HLA-A2+ T2 cell lines. GEP of Tax-CTLs revealed that genes associated with immune response activity were well preserved in long-term survivors with stable status. These methods and results can help us better understand immunity against ATL, and should contribute to future studies on the clinical application of adoptive T-cell therapies.