Clinical Significance of Cytomegalovirus Reactivation in Patients With Plasma Cell Dyscrasia Who Were Treated With Anti-CD38 Monoclonal Antibody: A Retrospective Analysis in a Single Institution.

INTRODUCTION: Anti-CD38 monoclonal antibodies (mAbs) have improved the prognosis of patients with plasma cell dyscrasia (PCD), but are also associated with increased infectious adverse events. Cytomegalovirus (CMV) is a common latent pathogen that is reactivated in immunocompromised individuals. Although CMV reactivation has mostly been reported after high-dose chemotherapy followed by stem cell transplantation in patients with PCD, cases of reactivation during anti-CD38 mAb therapy have been reported recently. Due to limited studies, we aimed to determine the frequency and impact of CMV reactivation during anti-CD38 mAb therapy. PATIENTS AND METHODS: This retrospective analysis included 154 consecutive patients with PCD who were treated with anti-CD38 mAbs at a single institution. RESULTS: Seventy-six patients were evaluated for CMV reactivation by CMV pp65 antigen testing, and 29 (38%) patients, including nine with newly diagnosed PCD, showed positive results. Patients who tested positive for the CMV pp65 antigen had substantially lower serum albumin levels than those who tested negative. However, the two groups showed no marked difference in the concurrent anti-PCD medications or baseline absolute lymphocyte count. Although most patients showing positive results in the CMV pp65 antigen test had mild or no symptoms, with fever being the most common symptom, some patients developed CMV end-organ disease. In addition, CMV reactivation interfered with the course of anti-PCD treatment in most patients, necessitating dose reductions, delays, and discontinuation of chemotherapy. CONCLUSION: This study provides an overview of the clinical impact of CMV reactivation in patients with PCD treated with anti-CD38 mAb-containing regimens.

Effects of sensory afferent input on motor cortex excitability of agonist and antagonist muscles.

In this study, we aimed to analyze control mechanisms of short-latency afferent inhibition (SAI) during motor output exertion from an agonist or antagonist muscle. The motor task involved index finger abduction (agonist) and adduction (antagonist). In Experiment 1, motor-evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) muscle with and without SAI at three output force levels. In Experiment 2, MEPs were recorded with and without SAI at various time points immediately before the muscle output. Experiment 1 showed that inhibition decreased with an increase in muscle output in the agonist muscle but increased in the antagonist muscle. Experiment 2 showed a decreasing trend of inhibition in the agonist muscle immediately before contraction but showed no significant change in the antagonist muscle. MEPs without electrical stimulation during the reaction time increased in both directions of movement as compared to those in the resting state. These results suggest that SAI modulation strongly influences smooth motor output. Analyzing the inhibitory or enhanced mechanisms during the performance of motor output by SAI in patients with motor impairment and comparing them with the mechanisms seen in healthy participants will improve our understanding of the neurophysiological mechanisms relevant to various situations (e.g., rehabilitation and sports).

Nomogram for predicting survival of patients with diffuse large B-cell lymphoma.

The international prognostic index (IPI) system has been widely used to predict prognosis in diffuse large B-cell lymphoma (DLBCL). However, this system categorizes DLBCL patients into four risk groups, and cannot optimize individualized prognosis. In addition, other clinicopathological factors, such as molecular aberrations, are not incorporated into the system. To partly overcome these weak points, we developed nomograms to predict individual patient survival. We also incorporated MYD88L265P and CD79BY196 mutations into the nomograms since these mutations are associated with a worse prognosis and their signaling pathways have been highlighted as a therapeutic target. We analyzed 302 DLBCL cases for which multivariate analysis by Cox proportional hazard regression was performed. Nomograms for progression-free survival (PFS) and overall survival (OS) were constructed and assessed by a concordance index (C-index). The nomograms were also evaluated using an open external dataset (n = 187). The MYD88L265P and/or CD79BY196 (MYD88/CD79B) mutation was detected in 62/302 patients. The nomograms incorporating IPI factors exhibited a C-index of 0.738 for PFS and a C-index of 0.765 for OS. The nomograms incorporating IPI factors and the MYD88/CD79B mutation showed a C-index of 0.745 for PFS and a C-index of 0.769 for OS. The nomograms we created were evaluated using an external dataset and were well validated. The present nomograms incorporating IPI factors and the MYD88/CD79B mutation have sufficient discrimination ability, and may effectively predict prognosis in DLBCL patients. The prognostic models we have presented here may help clinicians personalize prognostic assessments and clinical decisions.

Low-dose fluconazole as a useful and safe prophylactic option in patients receiving allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day). METHODS: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant. RESULTS: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group. CONCLUSION: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation.

Corticospinal excitability changes during muscle relaxation and contraction in motor imagery.

To enhance smooth muscle contraction and relaxation during rehabilitation and sports activities, a comprehensive understanding of the motor control mechanisms within the central nervous system is necessary. However, current knowledge on these aspects is insufficient. Therefore, this study aimed to deepen our understanding of motor controls, by investigating the alterations in corticospinal excitability within cortical motor areas related to muscle contraction and relaxation using motor imagery with a reaction time task paradigm. Transcranial magnetic stimulation was used to measure the motor-evoked potentials in the first dorsal interosseous muscle of the right hand after the 'go' signal. Static weak muscle contraction (Experiment 1: 18 healthy participants) and resting state (Experiment 2: 16 healthy participants) were applied as background factors, and a trial without motor imagery was performed as a control. Muscle contraction was maintained in the background in the contraction motor imagery. A decrease in excitability in the relaxation motor imagery task occurred compared with the control. When the muscles were at rest, an increase in excitability in the contraction motor imagery and a transient increase in excitability in the relaxation motor imagery occurred compared with the control condition. Hence, the excitability of contraction and relaxation motor imagery is characterized by a continuous increase in excitability, transient increase and subsequent decrease in excitability, respectively. These results suggest that muscle contraction sensory information in the background condition may be necessary for muscle relaxation. Matching the background conditions may be crucial when utilizing motor imagery for rehabilitation or sports training.

Laryngeal edema as a symptom of local cytokine release syndrome after BCMA-targeting CAR-T therapy for relapsed and refractory multiple myeloma.

Cytokine release syndrome (CRS) can be a major side effect of chimeric antigen receptor T-cell (CAR-T) therapy, and may occasionally become life-threatening in patients with factors such as high tumor burden or poor performance status. Among the many CRS events observed in B-cell maturation antigen (BCMA)-targeting CAR-T therapy, local symptoms (also called local CRS) are poorly understood due to their low frequency. Here, we present the case of a 54-year-old woman with refractory multiple myeloma exhibiting laryngeal edema as a local CRS. Before CAR-T therapy, she was diagnosed with progressive disease indicated by a left thyroid mass. After local irradiation, she received the BCMA-targeting CAR-T agent idecabtagene vicleucel (ide-cel). On day 2, the patient developed CRS, which resolved on treatment with tocilizumab. However, on day 4, laryngeal edema worsened, and was judged to be a local CRS. Intravenous dexamethasone rapidly reduced this edema. In conclusion, laryngeal edema rarely occurs as a local CRS, and to the best of our knowledge, has never been reported after ide-cel infusion. Dexamethasone was effective for reducing the local reaction that persisted after treatment of systemic symptoms with tocilizumab.

Humoral and cellular immune response to second and third severe acute respiratory syndrome coronavirus 2 mRNA vaccine in patients with plasma cell dyscrasia.

BACKGROUND: The recently developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). METHODS: We retrospectively measured serum SARS-CoV-2 antibodies against the spike protein (S-IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S-IgG titers ≥300 antibody units/mL). RESULTS: Although active anti-myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B-cell maturation antigen-targeted therapy. Dose 3 (booster vaccination) led to significantly higher S-IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine-induced cellular immune response in patients using T-spot Discovery SARS-CoV-2 kit, revealed an enhanced cellular immune response after Dose 3. CONCLUSIONS: This study highlighted the significance of booster SARS-CoV-2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine-induced humoral immune response.

The effect of initiation prediction and non-prediction on muscle relaxation control.

[Purpose] This study aimed to examine the difference in the excitability of the primary motor cortex between initiation-predictive and non-predictive tasks, where the onset of muscle relaxation is predicted and not predicted, respectively. [Participants and Methods] Seventeen participants were asked to perform rapid muscle relaxation either through an initiation-predictive or non-predictive task. The baseline was set at 20 percent of the maximum voluntary contraction. Motor-evoked potentials and H-reflexes elicited by transcranial magnetic stimulation and median nerve electrical stimulation, respectively, were measured. The mean stimulation time from the onset of relaxation was calculated, and the motor-evoked potentials and Hoffmann's reflexes elicited during the first (immediately before relaxation) and second half (long before relaxation) were compared. [Results] The amplitude of the motor-evoked potential significantly increased in both initiation-predictive and non-predictive tasks when compared to the baseline, indicating increased excitability of the primary motor cortex. The motor-evoked potential from the initiation-non-predictive task, but not the initiation-predictive task, was associated with increased excitability of the primary motor cortex immediately before relaxation. [Conclusion] Variations in the predictability of motor movements are associated with changes in muscle relaxation control in the central nervous system.

Evaluating the immediate effect of the speed alteration task on walking stability using the Timed Up and Go test.

[Purpose] This study aimed to investigate how the speed alteration task, which gradually increases or conversely decreases walking speed, affected walking stability. [Participants and Methods] Thirteen healthy young adults performed two walking tasks as follows: the speed alteration task, in which the walking speed was gradually increased or decreased, and the speed constant task, in which the walking speed was maintained at a comfortable level. Before and after each task, the Timed Up and Go test was performed to analyze time, walking speed, and trajectory. The overall score of the Timed Up and Go test, as well as the scores of the three major segments (i.e., forward, turning around, and return), and nine subsegments, were calculated and analyzed. [Results] During the speed alteration task, parameters including time and walking speed of the Timed Up and Go test were significantly improved. Also, the same parameters increased significantly in the forward and return segments. These increases were also observed in the first subsegment of the forward segment and the second subsegment of the return segment. [Conclusion] The speed alteration task improved walking stability, so it could be used in gait training to improve walking stability.

Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features.

We report a 69-year-old female who was a human T-cell leukemia virus type 1 carrier and exhibited a unique clinical course of developing three hematological malignancies within a short period: diffuse large B-cell lymphoma (DLBCL), chronic myelomonocytic leukemia (CMMoL), and acute myeloid leukemia (AML). Although the blast cells in AML showed typical morphological and immunophenotypical features of acute promyelocytic leukemia (APL), it did not harbor RARα gene fusion and thus initially diagnosed as APL-like leukemia (APLL). The patient developed heart failure with a fulminant clinical course and died soon after the diagnosis of APLL. Retrospective analysis with whole-genome sequencing detected a chromosomal rearrangement between KMT2A and ACTN4 gene loci both in CMMoL and APLL samples, but not in the DLBCL sample. Therefore, CMMoL and APLL were considered to be derived from the same clone with KMT2A translocation associated with prior immunochemotherapy. However, KMT2A rearrangement is rarely found in CMMoL in general and ACTN4 is also a rare partner of KMT2A translocation. Thus, this case did not follow typical transformational process of CMMoL or KMT2A-rearranged leukemia. Importantly, additional genetic alterations, including NRAS G12 mutation, were found in APLL, but not in CMMoL samples, suggesting that they might contribute to leukemic transformation. This report highlights the diverse effects of KMT2A translocation and NRAS mutation on the transformation of hematological cells as well as the importance of upfront sequencing analysis to detect genetic backgrounds for a better understanding of therapy-related leukemia.

Two cases of transplant-acquired food allergy who developed resensitization after a negative oral food challenge.

BACKGROUND: Cases of food allergy after hematopoietic stem cell and solid organ transplantation in previously nonallergic transplant recipients were reported as transplant-acquired food allergy (TAFA), but information about its long-term outcome is still limited. A phenomenon where patients reacquire food allergy by resuming daily consumption after a negative oral food challenge has not yet been reported. CASE PRESENTATION: We report two cases of TAFA after liver transplantation and cord blood transplantation. In each case, the threshold of daily consumption to cause allergic symptoms decreased when a negative oral food challenge was obtained. CONCLUSIONS: Our cases show an importance of gastrointestinal tract as a route of food sensitization because thresholds that caused allergic reactions decreased during their resuming process. We need to be careful with possible resensitization once a negative substantial dose was confirmed.

A comprehensive evaluation of humoral immune response to second and third SARS-CoV-2 mRNA vaccination in patients with malignant lymphoma.

More information is needed regarding the efficacy of SARS-CoV-2 mRNA vaccines in immunocompromised populations, including patients with malignant lymphoma. This study aimed to evaluate humoral responses to the second and third mRNA vaccine doses in 165 lymphoma patients by retrospective analysis of serum SARS-CoV-2 spike protein antibody (S-IgG) titers. Patients with S-IgG titers ≥ 300, 10-300, and ≤ 10 binding antibody units (BAU)/mL were defined as adequate responders, low responders, and non-responders, respectively. S-IgG titers > 10 BAU/mL were considered to indicate seroconversion. After the second dose, 56%, 16%, and 28% of patients were adequate responders, low responders and non-responders, respectively. Multivariate analysis revealed that being an adequate responder after the second dose was associated with receiving the vaccine > 12 months after last chemotherapy, total peripheral lymphocyte count of ≥ 1000/µL, estimated glomerular filtration rate of ≥ 50 mL/min/1.73 m2, and vaccine type (mRNA-1273). After the third dose, patients had significantly higher S-IgG titers and a greater proportion achieved seroconversion. With this third dose, 26% of second-dose non-responders achieved seroconversion and 68% of second-dose low responders became adequate responders. Subsequent SARS-CoV-2 mRNA vaccinations may elicit an immune response in immunocompromised patients who do not initially respond to vaccination.

Aberrant tryptophan metabolism leads to unfavorable outcomes in lenalidomide-treated myeloma patients.

Indoleamine 2,3-dioxygenase 1 (IDO), an enzyme that metabolizes tryptophan (Trp) to kynurenine (Kyn), is an important microenvironmental factor suppressing antitumor immunity. Here, we investigated the clinical impact of aberrant Trp metabolism in patients with multiple myeloma (MM) treated with lenalidomide (Len) and evaluated its effects on T cell immunity ex vivo. Kyn and Trp concentrations were quantified in sera from 72 patients with relapsed or refractory MM prior to the initiation of therapy with Len plus dexamethasone (Ld). Associations of the Kyn/Trp ratio with progression-free survival (PFS) and overall survival (OS) were analyzed. The expressions of IDO in tumor and stromal cells were evaluated during co-culture, and the effects of culture medium containing low Trp and high Kyn concentrations on T cells in the presence of Len were investigated. Patients with high serum Kyn/Trp ratios (≥46.0, n = 22) had significantly shorter PFS and OS than those with low ratios (4.9 vs. 12.6 months, and 15.5 vs. 45.7 months, respectively). MM cells promoted IDO expression in stromal cells during co-culture in both a direct contact and an indirect manner. Incubation in medium with a high Kyn/Trp ratio significantly inhibited T cell cytokine production and upregulated the expression of inhibitory immune receptors. These effects were sustained even in the presence of Len. In conclusion, a high serum Kyn/Trp ratio is associated with poor prognosis in patients with MM. We propose that aberrant Trp metabolism reduces anti-tumor immunity and the efficacy of Len therapy.

Recurrent pain attacks during romiplostim treatment in a patient with ITP carrying a heterozygous MEFV mutation.

We report a case of recurrent pain attacks during romiplostim treatment in a woman with immune thrombocytopenia carrying a heterozygous MEFV mutation. Five months after starting treatment with romiplostim for immune thrombocytopenia, she was diagnosed with idiopathic pericarditis. She was switched to eltrombopag, but thrombocytopenia did not improve. Romiplostim was restarted 7 months later, although she then developed recurrent right hypochondrial pain. The pain typically occurred three days after the romiplostim injection and resolved two days later. She had never experienced such recurrent pain before starting romiplostim or after discontinuing it. Genetic analysis showed that she carried a heterozygous R202Q alteration in exon 2 of the MEFV gene. MEFV mutation is known to cause familial Mediterranean fever, which is characterized by symptoms such as recurrent fever, abdominal and chest pain, arthritis, and pericarditis. This case suggests that romiplostim has the potential to trigger recurrent pain/inflammation attacks in individuals with systemic inflammatory abnormalities.

Comparing movement-related cortical potential between real and simulated movement tasks from an ecological validity perspective.

Introduction: Concerns regarding the ecological validity of movement-related cortical potential (MRCP) experimental tasks that are related to motor learning have recently been growing. Therefore, we compared MRCP during real movement task (RMT) and simulated movement task (SMT) from an ecological validity perspective. Methods: The participants performed both RMT and SMT, and MRCP were measured using electroencephalogram (EEG). EEG was based on the 10-20 method, with electrodes placed in the motor cortex (C3 and C4) and supplementary motor cortex (FCz [between Fz and Cz] and Cz) areas. This experiment examined the MRCP using Bereitschaftspotential (BP) and negative slope (NS') onset times, and BP, NS', and motor potential (MP) amplitudes during the task. Results: The results revealed that the SMT exhibited later BP and NS' onset times and smaller BP, NS', and MP amplitudes than the RMT. Furthermore, in RMT, the onset time of MRCP was delayed, and the amplitude of MRCP was smaller in the second half of the 200 times task than in the first half, whereas in SMT, there was no change in onset time and amplitude. The SMT showed a different MRCP than the RMT, suggesting that the ecological validity of the task should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP. Conclusion: Ecological validity of the study should be fully considered when investigating the cortical activity associated with motor skill learning using MRCP. Moreover, it is important to understand the differences between the two methods when applied clinically.

Recent advances in the management of older adults with newly diagnosed multiple myeloma in Japan.

Multiple myeloma is a cancer of plasma cells; the incidence rate of multiple myeloma is high among older adults. Although significant advances have been made in the clinical management of multiple myeloma driven by the introduction of novel drugs, such as proteasome inhibitors, immuno- modulators and antibodies, multiple myeloma remains incurable. Hence, the current therapeutic goal for multiple myeloma is to achieve long-term survival while maintaining a good quality of life. In this context, personalized treatment to balance the efficacy and safety of therapies is important, especially for older adults as they display diverse physical, cognitive or organ functioning. Furthermore, old age is also often associated with frailty. Several tools for evaluating frailty in older adults with multiple myeloma are now available, and frail patients defined by these tools have shown a poor prognosis and more treatment-related toxicities. In addition, it is important to evaluate other factors, such as the International Staging System, high-risk chromosomal abnormalities and treatment response, to predict the clinical course of patients. Further investigations are required to determine how these factors can optimize the treatment for multiple myeloma. In this review, we present a detailed account on the developments and issues related to the current treatment approaches for older adults with newly diagnosed multiple myeloma. We also discuss the ongoing phase III clinical study conducted by the lymphoma study group of the Japan Clinical Oncology Group, which targeted older adults with newly diagnosed multiple myeloma.

Acute Promyelocytic Leukemia in a Patient With Chronic Continuous Type of Crohn's Disease.

Chronic inflammation can induce leukemogenic mutations in hematopoietic stem cells (HSCs). We report a case of acute promyelocytic leukemia (APL) in a patient with chronic continuous type of Crohn's disease. The patient had been diagnosed with Crohn's disease at the age of 28 years and had received conventional treatments with biologics, but not azathioprine. At the age of 51, he was diagnosed with APL with ider(17). Long-term exposure to chronic continuous inflammation from Crohn's disease might be a factor inducing genomic instability in HSCs, which lead to the subsequent development of APL. APL is a rare hematological manifestation that required attention in Crohn's disease patients.

Time course effect of corticospinal excitability for motor imagery.

This study examined the effect of temporal changes in corticospinal excitability in motor imagery (MI) and the effect of real-time guides for MI on excitability changes. The MI task involved wrist flexion and motor evoked potentials using transcranial magnetic stimulation were recorded and examined from the flexor carpi radialis. Ballistic (momentary MI) and tonic (continuous MI) conditions were used, and the duration of each MI was different. In Experiment 1, each MI task was performed using an acoustic trigger. In Experiment 2, a real-time guide was presented on a computer screen, which provided a visual indication of the onset and duration of the MI task through via moving dots on the screen. The results indicate that the corticospinal excitability changed differently, depending on the duration of MI. Additionally, with real-time guides, the change in corticospinal excitability became clearer. Thus, corticospinal excitability changes due to the temporal specificities of MI, as well as with actual motor output. Moreover, if MI is actively performed without a guide, it is likely to show an unintended change in corticospinal excitability. It is suggested that when MI is performed with visual guide, the excitatory changes of the corticospinal tract might be different from the actual motor output. Therefore, when using MI for mental practices, it is possible to improve the effect of a guide for MI, such as a visual indicator for motor output. Additionally, when examining neural activities in MI, it may be necessary to consider the characteristics of motion performed by MI.

Clinicopathological analysis of primary refractory diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone chemoimmunotherapy.

BACKGROUND: Approximately 15% of patients with diffuse large B-cell lymphoma (DLBCL) experience refractory or early relapsed disease after initial rituximab-containing chemoimmunotherapy is regarded as a primary refractory disease. Although the standard treatment for relapsed DLBCL is high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), the efficacy of this approach for primary refractory DLBCL is not well understood. We aimed to investigate the clinicopathological characteristics and outcomes of patients with primary refractory DLBCL. METHODS: Sixty-nine consecutive patients with primary refractory DLBCL who were treated at our institution were categorized as partial responders (partial response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone [R-CHOP] or relapse within 6 months of R-CHOP) (n = 41) or primary progressors (no response to R-CHOP) (n = 28). Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: At initial diagnosis, 70% of patients had Ann Arbor stage III/IV disease, 56% had non-germinal center B-cell-like type DLBCL, and 42% had double-expressor lymphoma (MYC and BCL2 expression). The 3-year overall survival rate was significantly poorer in the primary progressors group than in the partial responders' group (15% vs. 48%, p < 0.001). Four of 17 patients treated with HDC-ASCT were primary progressors; only one patient survived without relapse. Although double-expressor lymphoma status did not significantly impact overall survival among all patients (p = 0.794), it was identified as an independent poor prognostic factor in HDC-ASCT-treated patients (p = 0.002). CONCLUSIONS: We identified a subgroup of patients with primary refractory DLBCL who may not benefit from current treatment strategies. Further treatment development is needed to improve the outcomes of these patients.