The patient was an 89-year-old man who had been doing farm work for several days. He had previously visited a doctor with complaints of fever and nausea. He was referred to our hospital after pancytopenia was confirmed. On the 7th day after onset, he was found to have consciousness disturbances, liver dysfunction, and worsening pancytopenia, which led to a diagnosis of hemophagocytic syndrome by bone marrow examination. Considering the patient's history of outdoor activities and the presence of crusts on the right lower leg, we suspected severe fever with thrombocytopenia syndrome (SFTS). Reverse transcription polymerase chain reaction of peripheral blood was positive for the SFTS virus, confirming the diagnosis. Epstein-Barr virus reactivation was also observed. Steroid pulse therapy and plasma exchange led to prompt clinical improvement and hematopoietic recovery. The patient recovered without sequelae and was discharged home. Few reports have described the use of plasma exchange and steroid therapy in severe cases of SFTS. This case illustrates that early detection and aggressive treatment for elderly patients contributes to early symptom improvement and survival.

Background: Mature T-cell and natural killer-cell lymphomas (MTNKLs) are often refractory to conventional treatment and associated with a poor prognosis. Between March 2014 and March 2024, nine novel agents were approved in Japan as single agents (SAs) for relapsed or refractory (R/R) MTNKL. However, the real-world treatment patterns and prognosis of patients with R/R MTNKL in this new treatment era remains unclear. This study aimed to elucidate the outcomes of 2nd-line therapy and treatment patterns in patients with R/R MTNKL, for whom nine SAs are available. Methods: This nationwide, retrospective observational study was conducted across 23 institutions in Japan (ClinicalTrials.gov, ID: NCT06422247). Key inclusion criteria included: age ≥ 18 years and initiation of 2nd-line therapy for R/R MTNKL between April 2018 and March 2023. Eligible diagnoses included peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), nodal lymphomas of T follicular helper cell origin (TFHL), including angioimmunoblastic T-cell lymphoma, ALK-positive anaplastic large cell lymphoma (ALK+ALCL), ALK-negative ALCL (ALK-ALCL), breast implant-associated ALCL (BIA-ALCL), extranodal NK/T-cell lymphoma (ENKTL), and mycosis fungoides (MF) with large cell transformation (LCT), according to the revised 4th World Health Organization classification. The primary endpoint was overall survival (OS) after 2nd-line therapy initiation (OS-2L), and the secondary endpoints included time to next treatment (TTNT) and treatment patterns. Results: A total of 256 patients were analyzed. The median age was 66 years (range, 55–77 years), and 66% were male. The histological subtypes included PTCL-NOS (40%), TFHL (38%), ENKTL (11%), ALK+ALCL (6%), ALK-ALCL (3%), MF with LCT (2%), and BIA-ALCL (0%). Among all patients, 54% exhibited extranodal involvement, 41% had high International Prognostic Index scores (3–5), and 40% had disease refractory to 1st-line therapy. The overall median OS-2L (in months [mo], 95% confidence interval [CI]) was 18.3 (14.8–27.9), and by histological subtype, it was 14.9 (11.6–27.9) for PTCL-NOS; 19.7 (12.9–49.1) for TFHL; not reached (NR) (14.8–not estimable [NE]) for ALK+ALCL; 28.1 (4.6–NE) for ALK-ALCL; 15.9 (3.7–31.8) for ENKTL; and 22.9 (13.7–NE) for MF with LCT. Fifty-four percent and 12% of patients aged ≥ 65 and < 65 years, respectively, received SAs as 2nd-line therapy. Thirteen percent of patients underwent autologous hematopoietic stem cell transplantation (HSCT), and 18% underwent allogeneic HSCT during 2nd- or later-line therapies. OS-2L was significantly longer in patients who received HSCT after 2nd- or later-line therapies than in patients who did not receive HSCT (median OS [mo, 95% CI]: NR [28.3-NE] vs. 13.1 [9.6-16.8]). No difference in OS-2L or TTNT after 2nd-line treatment initiation (TTNT-2L) was observed between patients who received SAs and those who received conventional multiagent-chemotherapies (CCs) (median OS-2L [mo, 95% CI]: SAs, 16.8 [13.1-38.9]; CCs, 18.3 [13.7-28.3]; p=.99; median TTNT-2L: SAs, 5.9 [4.0-9.9]; CCs, 3.9 [2.7-5.1]; p=.25). It was consistent in different subgroups except for patients with refractory disease to 1st-line therapy or with Eastern Cooperative Oncology Group performance status ≥2, where SAs showed longer TTNT than CCs. The median TTNT of each SA after 2nd- or later-line therapies (mo, 95% CI) was 10.7 (3.9–17.3) for brentuximab vedotin (BV; n = 53, 21%), 5.0 (2.7–7.1) for tucidinostat (n = 36, 14%), 3.9 (2.6–4.8) for romidepsin (n = 80, 31%), 2.1 (0.4–5.2) for darinaparsin (n = 7, 3%), 1.8 (1.3–2.5) for pralatrexate (n = 58, 23%), 1.5 (0.6–NE) for forodesine (n = 8, 3%), 1.1 (0.4–2.4) for mogamulizumab (n = 22, 9%), 0.7 (0.4–3.5) for denileukin diftitox (n = 5, 2%), and NR (NE–NE) for alectinib (n = 1, 0.4%). In patients with TFHL, romidepsin (44%) and tucidinostat (18%) yielded median TTNTs (mo, 95% CI) of 4.0 (2.6–8.7) and 5.5 (1.9–7.8), respectively. Among the SAs, BV showed the longest median TTNT following 2nd- or later-line therapies in both TFHL (10.7 mo; 95% CI, 3.2–24.0) and PTCL-NOS (4.4 mo; 95% CI, 1.0–NE).Conclusion: To the best of our knowledge, this study reports the most recent treatment patterns and prognoses for patients with R/R MTNKL. No standard of care has been established, as diverse treatment patterns have been observed. SAs resulted in similar survival outcomes to CCs in 2nd-line therapy, despite distinctive clinical background of the groups.

Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) was approved in Japan for the treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) in 2022, based on findings of the POLARIX study (NCT03274492). Reports on real-world usage of Pola-R-CHP are lacking. Here we report safety and response rates at end of treatment (EOT) for Pola-R-CHP in Japan from the real-world observational POLASTAR study (jRCT1071220082). Patients (≥ 18 years) with previously untreated DLBCL who were scheduled to receive Pola-R-CHP were enrolled. The primary endpoint was overall survival. As of December 20, 2023, the full analysis set (FAS) included 192 of the initial 199 patients enrolled. Median age was 71.0 years (range 30–91). In the FAS, 99 (51.6%) patients had Grade ≥ 3 adverse events (AEs), 29 (15.1%) had serious AEs, and 15 (7.8%) discontinued polatuzumab vedotin due to AEs. In the efficacy-evaluable population at EOT ( n = 141), the overall response rate was 95.0% [95% confidence interval (CI), 90.1–97.6], and the complete response rate was 87.9% (95% CI, 81.5–92.3). These results are consistent with published data from POLARIX. The POLASTAR study is ongoing; the recruitment target of 500 patients has been reached. Clinical trial registration: Japan Registry of Clinical Trials (jRCT1071220082).

Novel agents inducing deeper responses have improved the prognosis of patients with multiple myeloma (MM). To assess minimal residual disease (MRD) and stratify patients achieving complete response (CR), advanced technologies such as EuroFlow next-generation flow cytometry (NGF) and next-generation sequencing (NGS) are increasingly utilized. This prospective study evaluated responses in newly diagnosed MM patients undergoing autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy across multiple Japanese medical centers. Patients achieving CR or stringent CR within 100-365 days post-ASCT were included. MRD levels in the bone marrow were assessed using both NGF and NGS (cutoff: 1×10-5) at three time points: 100-365 days, 1 year, and 2 years post-ASCT. A total of 52 patients were analyzed. MRD levels determined by NGF and NGS showed a strong correlation (r=0.9722; P<0.0001). After a median follow-up of 3 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 76.5% (95% confidence interval [CI]: 62.3-85.9%) and 96.2% (95% CI: 85.5-99.0%), respectively. Patients with sustained MRD negativity for >6 months demonstrated superior 3-year PFS compared to those without sustained MRD negativity, as measured by both NGF (100% vs. 67.6%; hazard ratio [HR] =0.06; 95% CI: 0.0005-0.50; P<0.007) and NGS (90.5% vs. 72.2%; HR=0.23; 95% CI: 0.06-0.94; P=0.048). These findings highlighted a strong correlation in the MRD levels assessed by NGF and NGS and validated that sustained MRD negativity was significantly associated with prolonged PFS (clinical trial registered at UMIN 000022238).

ABSTRACTBackgroundDue to its rarity, there are very limited data available on the cause of death (COD) and its association with comorbidities in Japanese chronic lymphocytic leukemia (CLL) patients.MethodsTo investigate the prevalence of comorbidities and their impact on cause‐specific mortality, we retrospectively reviewed 121 Japanese patients with CLL.ResultsThe median age was 69 years, with 47.9% having at least one comorbidity listed in the Charlson Comorbidity Index (CCI), and 12.4% were multimorbid. With a median follow‐up of 74 months, the 5‐ and 10‐year overall survival rates were 80.6% and 60.1%, respectively. Among the 44 deaths observed, CLL progression was the leading COD (38.6%), which together with infections and other malignancies accounted for nearly 80%. Patients with higher CCI risk categories had significantly higher 5‐year all‐cause mortality (CCI 1–2: 22.9% and ≥ 3: 31.4%) and non‐CLL‐specific mortality (CCI 1–2: 18.8% and ≥ 3: 31.4%) compared to those without (CCI 0: 12.6%, p = 0.005; 3.5%, p < 0.001, respectively), whereas CLL‐specific mortality was not influenced. On multivariate analysis, age and CCI retained a significant prognostic impact on all‐cause mortality (hazard ratio [HR] 1.08, p < 0.001 and HR 1.88, p = 0.004, respectively) and non‐CLL‐specific mortality (HR 1.12, p < 0.001 and HR 3.81, p < 0.001, respectively).ConclusionsOur study showed that CLL itself was the leading COD, and comorbidity burden was associated with non‐CLL‐specific deaths. This highlights the importance of better disease control and effective management of comorbidities.

A 41-year-old man with high-grade B-cell lymphoma developed neurolymphomatosis (NL) after frontline chemotherapy. He received CD19 chimeric antigen receptor (CAR) T-cell therapy (lisocabtagene maraleucel) and subsequently developed tumor inflammation-associated neurotoxicity (TIAN) type 2, a localized neurological event distinct from immune effector cell-associated neurotoxicity syndrome. Conservative treatment resulted in a neurological recovery and complete remission. This case suggests that CD19 CAR T-cell therapy may be effective for NL, and it highlights the importance of recognizing TIAN in patients with central nervous system involvement. As CAR T-cell use has increased in Japan, awareness of such complications is crucial for performing safe and effective treatment.

Background: Based on the results of the POLARIX study (NCT03274492; Tilly et al. N Engl J Med 2022), polatuzumab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) was approved in 2022 for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) in Japan. Currently, there are no comprehensive reports on the real-world usage of this regimen in Japan. This analysis of the real-world POLASTAR study (jRCT1071220082) provides information on the patient characteristics and safety data of Japanese patients with previously untreated DLBCL treated with Pola-R-CHP in a clinical setting. Methods: POLASTAR is a multicenter, prospective observational study in Japan. The target sample size of this study was 500 patients; patients were included if they were ≥18 years, had previously untreated DLBCL, and received Pola-R-CHP per the latest Package Insert as part of their routine care (initial dose reduction was permitted). Patients excluded from POLARIX, such as those aged >80 years, were included in this study based on the physicians' decision. The primary endpoint of POLASTAR was overall survival. This preliminary analysis aimed to evaluate the safety and response rate at end of treatment (EOT) of the first 200 patients prospectively enrolled in the POLASTAR study. Here we report Grade ≥3 adverse events (AEs) and AEs leading to polatuzumab vedotin discontinuation, complete response rate (CRR) at EOT, and overall response rate (ORR) at EOT. Results: Between 9 February 2023 and 6 December 2023, a total of 502 patients were prospectively enrolled across 71 sites. At data cut-off (20 December 2023),of the initial 200 patients enrolled, 192 (96.0%) were identified and included in the full analysis set. Median age was 71 years (range 30-91); age >80 years, n=25/192 (13.0%); Eastern Cooperative Oncology Group Performance Status 0-2, n=179/188 (95.2%); International Prognostic Index 2-5, n=134/188 (71.3%); Ann Arbor Stage III-IV, n=116/192 (60.4%); and bulky disease (≥7.5 cm), n=28/192 (14.6%). Median time from initial diagnosis to treatment initiation was 26.5 days (range 4.0-327.0). At data cut-off, the majority of patients (n=163/185; 88.1%) had completed planned treatment with Pola-R-CHP; seven patients were still ongoing treatment. In total, 99 (51.6%) patients had Grade ≥3 AEs, and 29 (15.1%) had serious AEs. Most common Grade ≥3 AEs included neutrophil count decreased (n=54; 28.1%), white blood cell decreased (n=22; 11.5%), and febrile neutropenia (n=19; 9.9%). Among patients >80 years (n=25), the most common Grade ≥3 AEs included neutrophil count decreased (n=7; 28.0%) and febrile neutropenia (n=6; 24.0%). Grade ≥3 febrile neutropenia was numerically higher in patients >80 years compared with the overall population (24.0% [n=6] vs 9.9% [n=19]). A total of two deaths were reported (sepsis, n=1; pneumonitis, n=1). Fifteen (7.8%) patients discontinued polatuzumab vedotin due to AEs, and the most common AEs leading to treatment discontinuation included peripheral sensory neuropathy (n=3), lung infection (n=2), and COVID-19 infection (n=2). No new safety signals were observed. In the efficacy-evaluable population at EOT (n=141), ORR was 95.0% (95% confidence interval [CI]: 90.1-97.6), and CRR was 87.9% (95% CI: 81.5-92.3). Conclusions: At the time of this preliminary analysis of the initial 200 patients enrolled, efficacy and safety of Pola-R-CHP in Japanese patients were consistent with previously published results from POLARIX. The POLASTAR study is ongoing and the planned enrollment of 500 patients has completed. Patients are currently under observation and further evaluation of the study will be reported both at future congresses and in future publications.

Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that is approved for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan based on randomized clinical trial data. The aim of the real-world, retrospective Orbit study was to describe long-term clinical outcomes and management in adults (aged ≥ 20 years) with CLL/SLL treated with ibrutinib, either as first-line (1L) treatment or for relapsed or refractory (RR) disease, in routine clinical practice in Japan between July 2018 and December 2020. A total of 246 patients were registered, and the safety and per-protocol sets included 237 and 234 patients, respectively. After a median follow-up of 35.7 months, the 36-month progression-free survival rate was 80.9

Introduction: Autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic HSCT (allo-HSCT) are one of the therapeutic options for patients with malignant lymphoma (ML). Over the years, the role of HSCT for ML has been changing with the advent of new treatment strategies, such as chimeric antigen receptor T-cell (CAR-T), bispecific antibody, and molecular targeted agents. In this study, we investigated the changes in the HSCT landscape for ML in Japan over 16 years. Methods: We conducted a registry-based analysis of auto- and allo-HSCT activities using data from the Japanese Transplant Registry Unified Management Program between 2006 and 2021. Patients aged over 16 years, diagnosed with mature B-, T- and NK-cell neoplasms, and undergoing their first auto-HSCT or first allo-HSCT were included. Results: In total, 12,112 patients underwent their first auto-HSCT, and 4,773, including 1,399 after auto-HSCT, underwent their first allo-HSCT. The number of patients who received auto-HSCT increased from 5,538 in 2006-2013 (Period 1) to 6,574 in 2014-2021 (Period 2) (p < .001), while the number of patients who received allo-HSCT increased from 2,231 to 2,542 during the same periods (p < .001). Regarding auto-HSCT, patients who received auto-HSCT included those with diffuse large B-cell lymphoma (DLBCL) (58%), T/NK-cell lymphoma (T/NK) (14%), follicular lymphoma (FL) (9%), mantle cell lymphoma (MCL) (7%), Hodgkin lymphoma (HL) (9%) and others (3%). The number of patients who received auto-HSCT increased in DLBCL [3,164 (Period 1) vs. 3,818 (Period 2), p < .001], MCL [324 (Period 1) vs. 512 (Period 2), p < .001], and HL [491 (Period 1) vs. 599 (Period 2), p < .001]. Significant changes were observed in the median age at the time of auto-HSCT [56 (Period 1) vs. 59 (Period 2), p < .001] and in performance status (PS) at the time of auto-HSCT [ECOG PS 2-4; 7.7% (Period 1) vs. 6.2% (Period 2), p < .001]. The frequency of patients in first complete remission (CR) or partial remission (PR) , that is upfront auto-SCT setting, decreased from 51.0% (Period 1) to 43.4% (Period 2) (p < .001). With a median follow-up time for survivors of 4.2 years (range 0-16.5) for patients who received auto-HSCT, 4-year overall survival (OS) tended to improve from 67.6% (Period 1) to 69.4% (Period 2) (p = .06). As for allo-HSCT, patients who received allo-HSCT included those with DLBCL (29%), T/NK (38%), FL (16%), MCL (3%), HL (7%), and others (7%). The number of patients who received allo-HSCT increased in DLBCL [619 (Period 1) vs. 767 (Period 2), p < .001], T/NK [765 (Period 1) vs. 1,042 (Period 2), p < .001]; in contrast, the number of patients who received allo-HSCT decreased in FL [442 (Period 1) vs. 313 (Period 2), p < .001]. Significant changes included an increase in the median age at allo-HSCT [56 (Period 1) vs. 59 (Period 2), p < .001] and in PS at allo-HSCT [ECOG PS 2-4; 17.4% (Period 1) vs. 14.3% (Period 2), p = .006]. The number of patients who received allo-HSCT in first CR or PR increased from 17.1% (Period 1) to 21.2% (Period 2) (p < .001). Regarding donor/stem cell sources, bone marrow was most used until 2014, and cord blood in 2015. But, since 2016, the use of peripheral blood stem cell became the most common. The rate of patients used myeloablative conditioning protocols was not different between the 2 cohorts [35.5% (Period 1) vs. 35.4 (Period 2), p = .89]. With a median follow-up of 4.9 years (range 0-16.6), the 4-year OS of patients who received allo-HSCT in Period 2 was significantly improved compared to in Period 1 [41.8% (Period 1) vs. 44.6% (Period 2), p = .006]. The 4-year non-relapse mortality was not different between the 2 cohorts [30.4 % (Period 1) vs. 28.8 % (Period 2), p = .20]. There was no change in the number of patients with DLBCL who received auto-HSCT or allo-HSCT since the approval of CAR-T therapy for the treatment of relapsed/refractory DLBCL in Japan in 2019 (p = .13). Conclusions: The number of HSCT is increasing in most of lymphoma type and its outcome is improving over time in Japan. One reason for this can be the development of supportive care enabled us to perform HSCT even in elderly patients. On the other hand, the number of HSCT for FL is decreasing due to the changes in the therapeutic strategy. Our results can serve as real-world benchmark data of transplant for ML in Japan, and provide valuable insights for future treatment in ML.

Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.

Use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients. However, most MM patients eventually relapse and require salvage treatments. We report herein the result of a phase I/II study, performed from 2014 to 2017 to assess the feasibility and efficacy of a maximum tolerated dose (MTD) of lenalidomide (Len) combined with a fixed dose of once weekly subcutaneous (sc) 1.3 mg/m2 of bortezomib plus 20 mg of dexamethasone (scVRd regimen) in relapsed/refractory MM patients in the Japanese population. In the phase I part, dose-limiting toxicities were observed in three of six patients treated with 20 mg of Len; the MTD was accordingly defined as 15 mg in our cohort. In the phase II part, the recommended dose of the scVRD regimen showed a 71.4% best overall response rate, with a median overall survival of 14.8 months and a median progression-free survival of 8 months. Severe adverse events (≥ grade 3) were observed in ~ 15% of the patients, indicating the tolerability and efficacy of the regimen. Less prior treatment was associated with higher probability of durable response. This scVRd regimen may thus be a better fit for MM patients in early-stage relapse.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)-related disease that manifests as a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused by uncontrolled activation of the complement system. We report the case of a 61-year-old woman with acute type A aortic dissection that subsequently developed into aHUS. The hematologic disorders underlying aHUS improved after treatment with the complement inhibitor eculizumab. It is important to consider aHUS when a patient clinically develops a triad of microangiopathic hemolytic anemia, thrombocytopenia, and an increasing creatinine level following cardiovascular surgery.

To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABLIns35bp , accounting for 0.8% of the total IS BCR-ABL, corresponding to actual BCR-ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR-ABL but not BCR-ABLIns35bp , leading to the initial increase in the proportion of BCR-ABLIns35bp . Thereafter, both native BCR-ABL and BCR-ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI-resistant BCR-ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR-ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function-dead BCR-ABLIns35bp , suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis-splicing BCR-ABLIns35bp , occurring at the particular pseudo-splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR-ABL extracting BCR-ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.

Outcomes for patients with multiple myeloma (MM) have improved through use of novel treatments, especially lenalidomide combined with autologous stem cell transplantation. However, because of their increased life expectancy, an increased risk of secondary primary malignancies (SPMs) has been observed in MM patients, particularly after lenalidomide maintenance in both transplant-eligible (TE) and transplant-ineligible (TI) patients. To evaluate the incidence and risk factors of developing SPMs, we identified 17 TE-MM and 12 TI-MM patients with SPMs among 211 TE-MM and 280 TI-MM patients, including seven TE-MM and four TI-MM patients with hematological malignancies and ten TE-MM and eight TI-MM patients with non-hematological cancers, respectively. The median follow-up time from diagnosis was > 4 years. Multivariate analysis identified a history of high-dose cyclophosphamide use for peripheral blood stem cell harvest in TE-MM patients and > 65 years of age at diagnosis, or a history of adriamycin, lenalidomide, or thalidomide use in TI-MM patients as independent risk factors for SPMs (P < 0.001). Patients with a history of lenalidomide use had a lower risk of death among both TE-MM (P = 0.0326) and TI-MM (P < 0.001) patients. The survival benefit of receiving lenalidomide outweighed the increased risk of SPMs in both TE-and TI-MM patients.