冨永 龍太郎

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 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.

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.

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.

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.

Immune thrombocytopenia (ITP) is an uncommon yet clinically significant cause of thrombocytopenia in multiple myeloma (MM). We report a case of an 80-year-old female with severe thrombocytopenia identified during routine follow-up after breast cancer surgery, leading to the simultaneous diagnosis of Smoldering multiple myeloma (sMM) and secondary ITP. Laboratory findings, including an elevated immature platelet fraction, increased platelet-associated immunoglobulin G (IgG), and preserved megakaryopoiesis, supported a diagnosis of immune-mediated platelet destruction. The patient demonstrated only a transient response to corticosteroids but achieved sustained remission with eltrombopag (EPAG), while maintaining stable M-protein levels and showing no myeloma-defining events (MDEs). This report highlights the importance of considering secondary ITP in the evaluation of patients with MM.

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% CI 4.44-8.70) per 1 °C rise in BT. RB, defined as BT ≥ 37.8 °C with HR < 90 bpm, was observed in 630 events (63.0%). RB was more likely with age ≥ 44 years, hemoglobin ≥ 6.5 g/dL, and reduced-intensity regimens. In contrast, BT ≥ 38.6 °C, diastolic BP ≥ 70 mmHg, oxygen therapy, CRP ≥ 7.13 mg/dL, and incomplete hematologic recovery decreased the likelihood of RB. In addition, RB was significantly associated with documented infection (OR = 2.32, 95% CI 1.17-4.61, p = 0.016). RB frequently occurred during AML induction therapy, and may serve as an indicator of infection.

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.

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% vs. 77.7%; p = 0.338). Moreover, 100-day OS did not differ between patients who received GC pulse therapy within 2 weeks and those who did not (77.5% vs. 93.1%, p = 0.129). In multivariate analyses, pretreatment severity score ≥ 8 (hazard ratio [HR], 2.99; 95% confidence interval [CI] 1.05-8.50) and platelets ≥ 6.9 × 10^4/µL (HR, 2.26; 95% CI 1.01-5.02) were significantly associated with shorter TTNTD. Additional second-line or GC pulse therapy provided no advantage in the hyperacute phase. Higher severity scores and platelet values may predict resistance to GC therapy.

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.

Rapidly progressing ALL, a potentially fatal disease, demands timely diagnosis and treatment. On the other hand, spontaneous remission/regression (SR) is reported in various cancers including aggressive tumors like ALL. Infection or trauma-mediated immune system activation is assumed to cause SR, with the duration in cases of ALL typically being short. Indolent T-lymphoblastic proliferation (i-TLP) exhibits the uniform proliferation of TdT-positive T-cells, despite being a non-neoplastic disease, underscoring the significance of distinguishing it from T-cell acute lymphoblastic leukemia (T-ALL). i-TLP is expected to gain wider recognition and further advancements in understanding its pathology. Here, we present the case of a 59-year-old woman with T-ALL characterized by cycles of progression and SR followed by a rapid blast proliferation. This is the first reported case of T-ALL with repeated SR for more than one year, making this case an extremely rare clinical presentation. This challenging case will enhance comprehension of T-cell tumor pathogenesis.

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.

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 × 108/kg (range .56-8.52) and 1.75 × 106/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.

BACKGROUND: The early recovery of lymphocyte and monocyte cells is associated with a favorable prognosis after allogeneic stem cell transplantation (allo-HSCT); however, it is not clear whether the balance of lymphocyte and monocyte recovery affects the post-transplant prognosis. METHODS: We examined whether the time-point at which the number of lymphocytes exceeded the number of monocytes, which we termed lymphocyte-to-monocyte ratio reversal (LMRR), affected the prognosis after allo-HSCT. We retrospectively evaluated 235 patients who underwent their first allo-HSCT at our institution. RESULTS: The median number of days from HSCT to LMRR was 46 (range, 0-214), and the patients were divided into two groups according to the occurrence of LMRR by day 45 (LMRR45). In a multivariate analysis, early LMRR contributed favorably to overall survival (hazard ratio [HR] .519; 95% confidence interval [CI] .332-.812; p = .004) with fewer post-transplant relapses (HR .462; 95% CI, .274-.777; p = .004). Differences in the timing of LMRR did not affect non-relapse mortality (HR 1.477; 95% CI .779-2.80; p = .23) or the incidence of grade II-IV acute GVHD (LMRR45(+): 25.0% vs. LMRR45(-) 35.2%. p = .111). In subgroup analyses, LMRR45(+) was found to be a favorable factor for survival with less relapse, regardless of the disease risk, stem cell source, or the recovery of either lymphocyte or monocyte counts. CONCLUSIONS: An early LMRR may be a novel factor that is associated with reduced relapse and improved survival after allo-HSCT.

This report presents the case of a 51-year-old woman on an immunosuppressant drug and steroids, who presented with general fatigue and was admitted to the intensive care unit. Her serum procalcitonin, lactate, aspartate aminotransferase, and alanine aminotransferase levels and white blood cell counts were elevated. Computed tomography revealed gas formation in her liver, and her culture results revealed Edwardsiella tarda and Escherichia coli infections. She underwent percutaneous transhepatic abscess drainage in addition to antimicrobial administration. She was discharged after 40 days. Cases of emphysematous liver abscess with Edwardsiella tarda infections are rarely reported in the literature and may present in patients with poorly controlled type 2 diabetes. The fatality rate associated with the condition is markedly high.