Pneumocystis jirovecii pneumonia (PJP) after autologous stem cell transplantation (ASCT) remains insufficiently characterized. We retrospectively analyzed 304 ASCT recipients (2005-2024) at a single center (B-cell lymphoma n = 138; plasma cell tumor n = 126). Fourteen patients (4.6%) developed PJP at a median of 143 days (86-286) post-ASCT; none were on prophylaxis at diagnosis. The 1-year cumulative incidence was 5.2% overall, and varied by disease: 24% in follicular lymphoma (FL), 5.9% in other B-cell lymphomas, 1.9% in plasma cell tumor, and 0% in T-cell lymphomas. Prior rituximab exposure (HR 6.75; 95% CI 1.50-30.2) and FL diagnosis (HR 7.26; 95% CI 2.51-20.9) were associated with higher risk; age, purine analogs, lymphocyte count, globulin/IgG, and conditioning were not. No death was directly attributable to PJP. These data suggest, diagnosis-dependent risk after ASCT; prophylaxis may be considered for rituximab-treated patients, especially FL, while the optimal duration warrants further study.

This study evaluated cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation (allo-SCT) using both CMV-PCR and antigenemia assays in 109 adult recipients. CMV-PCR and antigenemia values had a moderate linear correlation. In total, 58 patients exhibited CMV-PCR positivity before starting antigenemia-based preemptive treatment. Excluding the two patients with persistent PCR positivity, the antigenemia value subsequently reached the threshold in 31 of 54 patients. On the other hand, 25 patients had spontaneous clearance of viremia without preemptive treatment. Spontaneous clearance was associated with letermovir use and the absence of graft-versus-host disease. The clinical course of CMV infection was simulated using various CMV-PCR thresholds (range 50–1000 IU/mL). In high-risk patients not treated with letermovir, a threshold of 50 IU/mL enables preemptive treatment initiation without increasing overtreatment risk in patients with spontaneous clearance. However, in high-risk patients treated with letermovir, thresholds > 150 IU/mL delayed the start of preemptive treatment. In low-risk patients, a threshold of 500–750 IU/mL balances avoiding spontaneous resolution and increasing delayed treatment. PCR thresholds of 50 and 150 IU/mL may be appropriate for initiating preemptive therapy in high-risk patients treated and not treated with letermovir, respectively, while 500–750 IU/mL may be optimal for low-risk patients.

R-GDP has been established as an effective salvage treatment for Rel/Ref DLBCL. We aimed to clarify the efficacy of R-GDP therapy. We included 41 consecutive patients with Rel/Ref DLBCL, who received R-GDP therapy as salvage chemotherapy at our hospital between January 2014 and August 2024. Thirty-three patients received R-GDP therapy as a 2nd-line regimen, whereas 8 received R-GDP as a 3rd or later-line regimen. The ORR was 70.7%. 23 out of 25 relapsed patients (92%) responded to R-GDP therapy, whereas only 6 out of 16 refractory patients responded (37.5%). With regard to the duration of response, the response rates in 19 patients with late relapse (at least 12 months) and 6 with early relapse (less than 12 months) were 94.7% and 83.3% (p = 0.43). Overall, the 2-year PFS and OS rates were 48.8% and 74.2%, respectively. 18 responders underwent ASCT with a 2-year PFS after ASCT of 61.2%. Although CAR-T is recommended in patients with Rel/Ref DLBCL, R-GDP is a realistic option given the limited availability of immediate CAR-T therapy. Further studies including genomic profiles are warranted to identify factors that can predict a response to R-GDP in Rel/Ref DLBCL.

This study evaluated the cost-effectiveness of blinatumomab for adult Philadelphia chromosome-negative (Ph-negative) patients with B-cell acute lymphoblastic leukaemia (B-ALL) who were in measurable residual disease (MRD)-negative first remission, according to the ECOG1910 trial. A Markov model was created to compare the cost-effectiveness of four cycles of blinatumomab alternating with chemotherapy versus standard-of-care chemotherapy (SOC), in both Japan and the United States. The analysis was conducted over a lifetime horizon. Incremental cost-effectiveness ratios (ICERs) were calculated, with willingness-to-pay (WTP) thresholds set at ¥7 500 000 in Japan and $150 000 in the United States. A discount rate was set at 3%. In Japan, blinatumomab led to incremental costs of ¥27 472 739 and yielded 3.82 quality-adjusted life years (QALYs), resulting in an ICER of ¥7 193 601 per QALY. In the United States, incremental costs were $463 539 with 3.45 QALYs, yielding an ICER of $134 298 per QALY. When the 3-year progression-free survival (PFS) with blinatumomab was assumed as 80%, it was cost-effective unless the 3-year PFS for SOC exceeded 64.9% in Japan and 65.6% in the United States. Blinatumomab was less cost-effective for patients older than 51.6 years in Japan and 55.6 years in the United States. Blinatumomab is cost-effective as consolidation therapy for MRD-negative Ph-negative B-ALL patients, with sensitivity to age and PFS gains.

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with resolved HBV infection undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Although HBV DNA-guided preemptive nucleos(t)ide analog therapy prevents HBV-related hepatitis, strategies to prevent HBV reactivation itself remain limited. Hepatitis B vaccination after allo-HCT has been suggested as a potential preventive strategy, but prospective randomized evidence is lacking. To evaluate whether hepatitis B (HepB) vaccination reduces HBV reactivation after allo-HCT and to examine the association between vaccination-induced anti-hepatitis B surface antibody (anti-HBs) response and protection against HBV reactivation. In this multicenter randomized controlled trial (UMIN000034113), adults who were hepatitis B surface antigen-negative and anti-hepatitis B core antigen-positive and underwent first allo-HCT were prospectively enrolled. At 140 days post-HCT, patients without HBV reactivation were randomized to receive HepB vaccination or no vaccination. HBV DNA levels and anti-HBs titers were centrally monitored for 2 years after transplantation. The primary endpoint was HBV reactivation, defined as HBV DNA ≥ 1.3 log IU/mL. Vaccine response was defined as anti-HBs response, requiring both an increase in anti-HBs from baseline and a post-vaccination anti-HBs ≥ 10 mIU/mL. Among 109 enrolled patients, 64 were randomized. With a median HBV DNA follow-up of 19.4 months, HBV reactivation occurred in 6 of 33 patients in the vaccination group, including 2 who experienced reactivation before receiving the first vaccine dose, and 9 of 31 patients in the control group. Probabilities of HBV reactivation were 19.8% and 37.9% in the HepB vaccination and control groups, respectively, at 18 months after randomization (P = .205). Baseline anti-HBs <10 mIU/mL was a significant risk factor for HBV reactivation. No HBV-related hepatitis was observed. Vaccine responses were achieved in 9 of 29 patients after the initial series and in 5 of 10 after the additional series. Importantly, HBV reactivation did not occur after patients achieved anti-HBs response, although several reactivation events occurred before vaccination or before anti-HBs response was achieved. No severe vaccine-related adverse events were observed. Although HepB vaccination did not significantly reduce HBV reactivation, it was feasible and induced anti-HBs response in a subset of patients. Achieving vaccine-induced anti-HBs response may provide protective immunity against HBV reactivation after allo-HCT.

This single-institution retrospective study evaluated a measurable residual disease (MRD)-guided induction intensification strategy in transplant-eligible patients with newly diagnosed multiple myeloma treated in the anti-CD38 antibody era. Sixty patients undergoing autologous stem cell transplantation (ASCT) between 2020 and 2025 were included. Most received bortezomib, lenalidomide, and dexamethasone as initial therapy. Patients with persistent MRD by multiparameter flow cytometry underwent treatment intensification, commonly with daratumumab, carfilzomib, and dexamethasone before ASCT. Among 52 evaluable patients, 35 (67.3%) achieved MRD negativity before ASCT, and 30 of 32 (93.8%) were MRD-negative after ASCT. Stem cell mobilization and engraftment were successful. After median follow-up of 28.5 months, 2-year progression-free and overall survival were 87.3% and 98.0%. R-ISS stage III and extramedullary disease were associated with inferior progression-free survival. High-risk cytogenetics showed poorer outcomes. This MRD-adapted strategy was feasible, achieved deep responses, and preserved mobilization, but high-risk disease remained prone to relapse, supporting post-transplant intensification.

[Background] We have been performing allogeneic hematopoietic stem cell transplantation from haploidentical related donor using anti-CD52 antibody, alemtuzumab, at a total dose of 1.2 mg/kg or 0.96 mg/kg (Am J Hematol 2013;88:294-300) and 0.5 mg/kg (Eur J Haematol 2019;102: 256-264) in pre-transplant regimens, combined with cyclosporine (CSA) at the target concentration of 500 ng/ml with rapid tapering and methotrexate (MTX) at a dose of 10-7-7-7 mg/m2 as graft-versus-host disease (GVHD) prophylaxis. However, high relapse rate (RR) in non-remission (non-CR) patients was observed, and the optimal strategy of haploidentical HSCT with low-dose alemtuzumab remained undermined. [Methods] Since 2015, haploidentical HSCT using low-dose alemtuzumab was performed with different GVHD prophylaxis according to the disease risk. High-risk disease included acute leukemia and blastic crisis of chronic myeloid leukemia (CML-BC) in non-CR at HSCT and any relapsed hematological malignancies after allogeneic HSCT. Others were classified as standard-risk disease. Total body irradiation (TBI) of 12 Gy and cyclophosphamide (CY) or fludarabine (FLU), intravenous busulfan (ivBU) and melphalan (MEL) were mainly used as myeloablative regimen, and FLU, MEL, and TBI of 4 Gy was the mainly used reduced-intensity regimen. Alemtuzumab was added to each regimen at a total dose of 0.48 or 0.5 mg/kg. In patients with high-risk disease, GVHD prophylaxis changed consisting of lower dose of MTX at 5-5-5-0 mg/m2 and CSA at the target concentration of 500 ng/ml followed by reducing to 300 ng/ml within 2 weeks after engraftment and rapid tapering thereafter if patients had not developed severe GVHD. In patients with standard-risk disease, GVHD prophylaxis did not change till 2020, and the same GVHD prophylaxis as high-risk disease was adopted afterwards. We retrospectively analyzed clinical courses of patients who underwent haploidentical HSCT using low-dose alemtuzumab between 2015 and 2024. This study was approved by the Institutional Review Board of Jichi Medical University Saitama Medical Center, and was carried out according to the principles of the Declaration of Helsinki. [Results] In total, 75 patients were included in this study. Their median age was 48 years (range 17 – 69 years). The underlying diseases were acute leukemia in 54, CML-BC in 4, other myeloproliferative neoplasm in 1, myelodysplastic syndrome in 7, and mature lymphoid malignancy in 9. Thirty-four patients were classified as having high-risk disease at HSCT, and 22 of 34 patients had relapsed disease after allogeneic HSCT. On the other hand, 34 patients were classified as having standard-risk disease at HSCT, including 2 patients after engraftment failure. With a median follow-up times for survivors of 905 days (range 75 – 3428 days), Overall survival (OS) rates, disease-free survival (DFS) rate, relapse rate (RR), and non-relapse mortality (NRM) at 1 year were 72.1% and 22.2%, 52.8% and 13.1%, 25.0% and 54.3%, and 15.5% and 32.4%, and those at 3 years were 50.9% and 7.4%, 48.4% and 7.1%, 28.3% and 54.3%, and 23.2% and 38.6%, in patients with standard- and high-risk disease, respectively. The superiority of OS (P < 0.001)and DFS (P < 0.001), and lower RR (P = 0.007) were observed in patients with standard-risk disease. In patients with standard-risk disease, 12 and 22 patients received HSCT till 2020 and since 2021, respectively. A median neutrophil engraftment day changed from at day 17 to 14. The cumulative incidences of Grade II – IV acute GVHD and chronic GVHD have a tendency to decrease from 50.0% to 18.2% (P = 0.077), and from 33.3% to 9.5% (P = 0.073), respectively, despite the MTX reduction. OS, DFS, RR, and NRM at 1 year were 58.3% and 80.4%, 41.7% and 70.2%, 33.3% and 20.1%, and 25.0% and 9.8%, and those at 3 years were 33.3% and 60.6%, 33.3% and 56.7%, 41.7% and 20.1%, and 25.0% and 23.3% in patients till 2020 and since 2021, respectively. OS was better in patients since 2021 with borderline significance (P = 0.080).[Conclusions] The efficacy of haploidentical HSCT using low-dose alemtuzumab for patients with high-risk disease is low, especially due to the high RR. On the other hand, outcomes of patients with standard-risk disease are promising, and combination with low-dose MTX may improve OS. Further studies are warranted to establish the optimal role of haploidentical HSCT using low-dose alemtuzumab, especially for patients with standard-risk patients.

The phase III ASC4FIRST study (NCT04971226) demonstrated superior efficacy and favorable safety and tolerability for asciminib against investigator-selected tyrosine kinase inhibitors (IS-TKI) in newly diagnosed chronic myeloid leukemia (CML). Results of a subgroup analysis in Japanese patients are presented here. Adult patients were randomized 1:1 to asciminib or IS-TKI following stratification by European Treatment and Outcome Study long-term survival risk score and prerandomization-selected TKI (imatinib and second-generation [2G] TKI strata). At week 48, major molecular response (MMR) rate in all patients and imatinib stratum (primary endpoints) were assessed along with MR4.0, MR4.5, and safety (cutoff: November 28, 2023). In Japanese patients (asciminib, n = 21; IS-TKI, n = 17 [imatinib/2G TKI, n = 8/9]), the MMR rate was higher with asciminib (81.0

Influenza virus infections (IVIs) are an important cause of complications and death in immunocompromised patients, but the incidence and risk factors for IVIs in hematological diseases including benign diseases are not fully understood. We retrospectively investigated IVIs in patients with hematological diseases who visited our hematology outpatient department between 2012 and 2019. In 4,864 outpatients, 81(1.67%) IVIs were identified. The incidence of IVIs was 4.82 (95% confidence interval [CI], 3.85-5.96) per 1,000 person-years, with significantly higher rates in post-allogeneic transplant patients (21.0, 95% CI, 12.8-32.5). Progression to lower respiratory tract infection (LRTI) was observed in 7 (8.6%) of 81 patients with IVIs. In a univariate logistic regression analysis, LTRI was associated with age ≥60 years and moderate to severe chronic GVHD. Patients after hematopoietic stem cell transplantation may be at a higher risk for IVIs. Advanced age exacerbated the effects of IVIs on hematological diseases.

This study explored the relationship between body temperature (BT) and heart rate (HR) data during acute myeloid leukemia (AML) treatment, using relative bradycardia (RB) as an index. RB trends were also assessed in confirmed infections and during intensive chemotherapy. Data from AML patients who received induction therapy (anthracycline and cytarabine) at Jichi Medical University Hospital between May 2015 and December 2023 were analyzed. A total of 1000 febrile events (axillary temperature ≥ 37.8 °C) in 97 patients were included. Multivariate analysis showed an HR increase of 6.57 bpm (95

Despite the increasing number of cancer survivors, the impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This multi-center retrospective study compared transplant outcomes in allo-HSCT recipients with and without a history of solid tumors. Of 5,850 adult patients who underwent first allo-HSCT, 303 (5.2%) had a prior solid tumor. After propensity score matching, overall survival (OS) and cumulative incidences of relapse, non-relapse mortality (NRM), and acute and chronic graft-versus-host diseases were almost comparable between the two groups. Progression or recurrence of solid tumors after allo-HSCT occurred in only eight cases (2.8%). Importantly, patients who received both chemotherapy and radiation therapy (Chemo + RT) for prior solid tumors had significantly worse OS (35.3% vs. 54.1% [P < 0.001] vs. 56.8% [P < 0.001] at 2 years) and higher NRM (36.2% vs. 18.7% [P = 0.002] vs. 19.3% [P = 0.001] at 2 years) compared to patients who received other treatment modalities for prior solid tumors or patients without prior solid tumors. These findings highlight the feasibility of allo-HSCT in selected patients with prior solid tumors, while demonstrating the negative impact of Chemo + RT on outcomes after allo-HSCT.

The study aimed to investigate the therapeutic effect of various initial treatments incorporating glucocorticoid (GC) in TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly). Cases of TAFRO syndrome up to November 2023 were retrospectively collected. Overall survival (OS) and resistance to GC therapy were assessed, with resistance analyzed based on the time to the next treatment or death (TTNTD). The study included 95 patients, including 5 diagnosed at our hospital. OS did not differ significantly between patients who received GC monotherapy and those who had a second-line therapy added within 2 weeks (100-day OS rate: 86.6

While chimeric antigen receptor (CAR-T) targeting CD19 as second-line therapy for diffuse large B cell lymphoma (DLBCL) is a promising strategy, the high costs and limited access to CAR-T pose significant challenges. When assessing the cost-effectiveness of CAR-T, we need to consider not only individual outcomes but also how to effectively integrate CAR-T into the overall treatment approach for relapsed DLBCL. We conducted a cost-effective analysis for patients with DLBCL in early relapse or primary refractory, to compare "immediate CAR-T," which proceeds directly to CAR-T, and "late CAR-T," which initially aims at ASCT and quickly switches to third-line CAR-T if non-responsive. The primary analysis used a patient age of 60 years, and it also examined variations from 40 to 70 years. The analysis was performed for both Japanese and US settings using a Markov model incorporating life expectancy in both countries, with extensive sensitivity analysis including factors such as age, the choice of CAR-T (lisocabtagene maraleucel or axicabtagene ciloleucel), and the opportunity to receive third-line CAR-T, to reflect real-world situations. The length of a Markov cycle was defined to be 1 month, and patients in the model were assumed to age 1 year every 12 Markov cycles. The analysis was made over a lifetime horizon, and the outcome was measured based on incremental cost-effectiveness ratio (ICER), with willingness-to-pay (WTP) thresholds of ¥7,500,000 and $150,000 per quality-adjusted life years (QALY) in Japan and the US, respectively, with an annual discount rate of 3%. Compared with "late CAR-T," the "immediate CAR-T" strategy gained QALYs of 0.97 and 0.89 with an incremental cost of ¥5,998,354 and $88,440 in Japan and the US, respectively. The ICERs were ¥6,170,058/QALY in Japan and $99,596/QALY in the US. In the probabilistic sensitivity analysis for patients aged 60, "immediate CAR-T" was cost-effective in 54.8% and 61.7% of the 10,000 Monte Carlo iterations in Japan and the US, respectively. Sensitivity analyses showed that "immediate CAR-T" was not cost-effective when patients were over 68.4 in Japan, when the standardized mortality ratio of CAR-T and ASCT survivors was close, and when utility during treatment-free remission was low. Incorporating various clinical factors, the analysis showed that "immediate CAR-T" is more cost-effective than "late CAR-T." However, this conclusion should be interpreted with caution, as the ICERs were very close to the WTP thresholds, and the results were highly sensitive to parameter changes.

[Introduction] Addition of daratumumab to induction, consolidation, and maintenance regimens confers significant benefit in progression-free survival (PFS) of transplantation-eligible patients with newly diagnosed multiple myeloma (MM). However, the relationship between daratumumab administration before autologous peripheral blood stem cell transplantation (ASCT) and ASCT-associated adverse events in patients with MM is not fully understood. In our institution, we add daratumumab-containing regimens before ASCT for patients with insufficient response to initial induction therapy to achieve deeper response. On the other hand, engraftment syndrome (ES), characterized by a continuum of peri-engraftment complications following ASCT, can include fever, diarrhea, rash, pulmonary infiltrates, and liver dysfunction. The present study aimed to determine risk factors for ES after ASCT in patients with MM, focusing daratumumab before ASCT. [Methods] This single-center retrospective study aimed to determine the impact of daratumumab before ASCT on disease prognosis and ES development after ASCT in patients with MM. [Results] The study cohort included 99 patients with MM who underwent 110 ASCTs, including 11 patients who underwent ASCT twice, with (N=37) or without (N=62) daratumumab administration before ASCT between May 2013 and December 2023. The median age was 61.2 (24.1-70.5) years, and 60.6% of the patients were male. The median follow-up duration was 877 (range, 185-2999) days, PFS at 36 months after diagnosis was 71.0% and 61.7% (P = 0.755), respectively, in patients with and without daratumumab treatment before ASCT. At the time of ASCT, the proportion of patients with very good partial response (VGPR) or better was higher in those with daratumumab treatment than in those without daratumumab treatment (86.5% vs. 71.0%, P = 0.537). The measurable residual disease (MRD) status could be evaluated in 20 of 37 patients treated with daratumumab before ASCT, and 12 patients (60.0%) did not have MRD (at 10−5 level). ES, determined using the Spitzer (3 major or 2 major + 1 minor) and Maiolino (major + 1 minor) criteria, was diagnosed upon fulfillment of at least one of the conditions. Fourteen cases of ES (12.8%) were recorded, with a median onset of 16 (9-23) days following ASCT. By multivariate analysis incorporating potentially confounding variables, age >65 years (odds ratio [OR] 3.820, 95% confidence interval [CI] 1.11-13.2, P = 0.034) and daratumumab treatment before ASCT (OR 6.23, 95% CI 1.55-25.0, P = 0.009) were significant independent risk factors for ES, whereas treatment response before ASCT ( We further investigated the incidence of CMV infection after ASCT as an ASCT-associated adverse event. In 33 patients who underwent post-ASCT CMV antigenemia testing, 11 patients tested positive for peripheral blood CMV antigenemia. The proportion of CMV antigenemia positivity tended to be higher in patients with daratumumab treatment than in those without daratumumab treatment (40% [10/25] vs. 12.5% [1/8], P = 0.218). [Summary/Conclusion] This is the first study reporting the association between pretransplant daratumumab treatment and the risk of ES after ASCT. These findings should be validated in larger cohorts evaluating immunological parameters.

BACKGROUND:Donor selection and harvest volume calculation typically use actual body weight (ABW). However, in obese donors, increased ABW mainly reflects adipose tissue rather than hematopoietic stem cell (HSC)-rich bone marrow. This study aimed to investigate whether ideal body weight (IBW) is a better indicator than ABW for estimating the required HSC yield. STUDY DESIGN AND METHODS:This study included 157 donors (106 men and 51 women) with a body mass index of ≥ 22. An analysis of the correlation between harvested HSCs and harvested volume per ABW and IBW was performed. Another analysis of the correlation between the decrease in hemoglobin levels and the harvested volume per ABW or IBW was performed. RESULTS:No significant differences were observed in the correlations between total nucleated cell counts and the harvested volume per ABW or IBW, between CD34+ HSCs and the harvested volume per ABW or IBW, and between the decrease in hemoglobin levels and the harvested volume per ABW or IBW in all donors and obese donors. CONCLUSIONS:These results showed no significant differences between IBW and ABW as indicators for estimating the required HSC yield. Additionally, the results showed that harvesting per ABW was not excessive.

Introduction Cytomegalovirus (CMV) remains a crucial virus in complications after allogeneic stem cell transplant (SCT). A preemptive treatment has been used to prevent the progression to CMV disease; however, no consensus has been reached on the CMV-DNA viral load threshold that should trigger preemptive treatment. We monitored both CMV-DNA and antigenemia and started preemptive treatment based on antigenemia, that enabled us to evaluate the clinical course of patients with positive CMV-DNA without antiviral treatment. Methods Adult patients who received allogeneic SCT at our institutes from 2022 to 2023 were retrospectively reviewed. CMV antigenemia and quantitative CMV-DNA polymerase chain reaction (PCR) assays were simultaneously evaluated from 2022. The study included 109 patients with available PCR and antigenemia data. High risk of CMV infection was defined as in-vivo T cell depletion, cord blood transplantation, or prednisolone use. All patients received CMV antigenemia-guided preemptive treatment for CMV infection defined as 20 positive cells/2 slides for low-risk and 3 positive cells/2 slides for high-risk patients. Prophylactic letermovir was administered until 100 days after SCT in patients scored 4 points or more in our scoring system (+2 for D+R+, +3 for D-R+, +1 for lymphoma, and +1 for unrelated or haploidentical donor). Results This study simultaneously evaluated 2,508 samples. The median CMV-DNA load was 0 (range: 0-260,000) IU/mL and median CMV antigenemia level was 0 (range: 0-959) cells per 2 slides. CMV-DNA and antigenemia level revealed a moderate linear correlation (r=0.63). The antigenemia levels of 0, 1-2, 3-4, 5-9, 10-19, and ≥20 positive cells per 2 slides corresponded to median CMV-DNA loads of 0, 210, 340, 495, 1,400, and 8,000 IU/mL, respectively. The cumulative incidence for CMV infection based on CMV antigenemia and CMV disease at day 200 after transplant was 36.7% and 3.9%, respectively. CMV-PCR became positive at any level before CMV antigenemia reached the threshold in 59 patients. Of the 57 evaluated patients, CMV antigenemia subsequently reached the threshold value in 34 (60%) patients, whereas the other 23 (40%) patients experienced spontaneous clearance of CMV viremia without positive CMV antigenemia. Spontaneous CMV DNA clearance was significantly associated with the absence of steroid use for GVHD. Next, we simulated the clinical course of these patients according to the various CMV-PCR thresholds for preemptive treatment between 50 and 1,000 IU/ml. In high-risk patients without letermovir (n=34), increasing the threshold from 50 IU/ml to 150 IU/ml increased the proportion of patients who did not require antiviral agents only by 3% but delayed the start of preemptive treatment in 23%. In high-risk patients with letermovir (n=28), increasing the threshold from 50 IU/ml to 150 IU/ml increased the proportion of patients who did not require antiviral agents by 7% but further increase of the threshold resulted in more patients with negative PCR but positive antigenemia. In low-risk patients without letermovir (n=44), increasing the threshold from 50 IU/ml to 500 or 750 IU/ml increased the proportion of patients who did not require antiviral agents by 18% but further increasement of the threshold resulted in the delay of preemptive treatment in 5% of the patients. There were only 9 low-risk patients with letermovir, but a threshold similar to that for low-risk patients without letermovir seemed appropriate. Conclusion For high-risk patients with or without letermovir, a threshold of 50 IU/ml and 150 IU/ml, respectively, may be recommended, while a threshold of 500-750 IU/ml may be proposed for low-risk patients, to decrease the overuse of antiviral agents with minimal delay in preemptive treatment.

To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16-39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post- transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status >0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.

Background: The number of CD34(+) cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34(+) in bone marrow transplantation (BMT) remained unclear. Methods: We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021. Results: The median nucleated cell count (NCC) and CD34(+) cell dose were 2.17 x 10(8)/kg (range .56-8.52) and 1.75 x 10(6)/kg (.21-5.84), respectively. Compared with 104 patients in the low CD34(+) group (below the median), 103 patients in the high CD34(+) group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p = .001), reticulocyte (51.5% vs. 79.6%; p < .001), and platelet (39.4% vs. 72.8%; p < .001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft-versus-host disease, either. While a positive correlation was observed between NCC and the CD34(+) cell dose, a high CD34(+) cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median. Conclusion: Measurement of CD34(+) cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long-term outcome in BMT.

The tumor microenvironment's cells can promote or inhibit tumor formation, and there are no reports on the CD4/CD8 ratio's association with outcomes post allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the pre-transplant peripheral blood CD4/CD8 ratio in 168 patients who underwent their first allo-HSCT for hematological malignancies at our institution. When patients were divided into two groups according to the median CD4/CD8 ratio 1.35 (range, 0.09-19.89), the high CD4/CD8 ratio group had a higher incidence of relapse, equivalent non-relapse mortality and worse overall survival (OS) than the low CD4/CD8 ratio group. In a multivariate analysis, the CD4/CD8 ratio was significantly associated with an increased risk of relapse, although there was a marginally significant difference in OS. The pre-transplant peripheral blood CD4/CD8 ratio could be a novel biomarker for predicting the prognosis of allo-HSCT.