Autopsy Case of Epstein-Barr Virus-associated T-cell Post-transplant Lymphoproliferative Disorder with Mono- and Polymorphic Lesions: Possibility of 'Polymorphic T-cell Post-transplant Lymphoproliferative Disorder'.

Background Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is predominantly of B cell origin. The concept of clonal evolution from poly- to monoclonal lymphoproliferation has been put forward, but T-cell PTLDs are rare with an unknown etiology. Case Presentation In a unique autopsy case of a 53-year-old man with EBV-associated T-cell PTLD, we observed polymorphic T-cell proliferation across several organs and monomorphic T-cell proliferation in the perforated ileum. Interestingly, both manifestations exhibited identical monoclonal peaks in the T-cell receptor rearrangement polymerase chain reaction (PCR) analyses. Conclusion These findings suggest the existence of clonal evolution in EBV-associated T-cell PTLD, leading to the proposal of the novel concept of polymorphic T-cell PTLD.

Neuroprotective effects of Si-based hydrogen-producing agent on 6-hydroxydopamine-induced neurotoxicity in juvenile mouse model.

Neurotoxins have been extensively investigated, particularly in the field of neuroscience. They induce toxic damage, oxidative stress, and inflammation on neurons, triggering neuronal dysfunction and neurodegenerative diseases. Here we demonstrate the neuroprotective effect of a silicon (Si)-based hydrogen-producing agent (Si-based agent) in a juvenile neurotoxic mouse model induced by 6-hydroxydopamine (6-OHDA). The Si-based agent produces hydrogen in bowels and functions as an antioxidant and anti-inflammatory agent. However, the effects of the Si-based agent on neural degeneration in areas other than the lesion and behavioral alterations caused by it are largely unknown. Moreover, the neuroprotective effects of Si-based agent in the context of lactation and use during infancy have not been explored in prior studies. In this study, we show the neuroprotective effect of the Si-based agent on 6-OHDA during lactation period and infancy using the mouse model. The Si-based agent safeguards against the degradation and neuronal cell death of dopaminergic neurons and loss of dopaminergic fibers in the striatum (STR) and ventral tegmental area (VTA) caused by 6-OHDA. Furthermore, the Si-based agent exhibits a neuroprotective effect on the length of axon initial segment (AIS) in the layer 2/3 (L2/3) neurons of the medial prefrontal cortex (mPFC). As a result, the Si-based agent mitigates hyperactive behavior in a juvenile neurotoxic mouse model induced by 6-OHDA. These results suggest that the Si-based agent serves as an effective neuroprotectant and antioxidant against neurotoxic effects in the brain, offering the possibility of the Si-based agent as a neuroprotectant for nervous system diseases.

Sarcopenia assessed using a questionnaire can predict in-hospital mortality in older patients with pulmonary tuberculosis.

BACKGROUND & AIMS: Pulmonary tuberculosis is a severe disease with a high mortality rate. However, whether sarcopenia is a risk factor for in-hospital mortality remains unclear. The SARC-F (five items: strength, assistance in walking, rising from a chair, climbing stairs, and falls) is a questionnaire developed to screen for sarcopenia. This study aimed to determine whether the high risk of sarcopenia, assessed using the SARC-F questionnaire, affects in-hospital mortality in older patients with pulmonary tuberculosis. METHODS: This was a retrospective, observational study. We included patients with active pulmonary tuberculosis aged ≥65 years who required inpatient treatment between 30 April 2021 and 30 November 2022. We assessed sarcopenia using SARC-F, and SARC-F ≥ 4 points at admission was defined as a high risk of sarcopenia. The primary outcome was all-cause mortality during hospitalisation. We extracted information on age, sex, body mass index, comorbidities, blood and biochemical tests, modified Glasgow Prognostic Score, calf circumference, geriatric nutritional risk index, physiotherapy, and length of hospital stay from medical records. RESULTS: We included 147 patients (mean age: 83.0 ± 7.8 years; males: 61.9%). Ninety-three (63.3%) patients had a high risk of developing sarcopenia. Patients with a high risk of sarcopenia were significantly older (mean: 85.0 ± 7.1 years), had a lower body mass index (median: 18.1 kg/m2, range: 16.1-20.5 kg/m2), had a higher modified Glasgow Prognostic Score (median: 2, range: 2-2), and had a lower calf circumference (mean: 26.8 ± 3.6 cm), had a lower geriatric nutritional risk index (mean: 72.2 ± 12.9) than those without high-risk sarcopenia. More patients with a high risk of sarcopenia underwent physiotherapy (93.5%) than those without high-risk sarcopenia (P < 0.01, all). Kaplan-Meier survival curves showed that patients with a high risk of sarcopenia had significantly lower overall survival than those without high-risk sarcopenia (log-rank test, P = 0.001). Logistic regression analysis for in-hospital mortality showed that a high risk of sarcopenia significantly affected in-hospital mortality (odds ratio [OR]: 6.425, 95% confidence interval [CI]: 1.399-47.299). In addition, logistic regression analysis for each item of SARC-F showed that assistance in walking (OR: 3.931, 95% CI: 1.816-9.617) and rising from a chair (OR: 2.458, 95% CI: 1.235-5.330) significantly affected in-hospital mortality. CONCLUSION: A high risk of sarcopenia, as assessed using SARC-F at admission, was a risk factor for in-hospital mortality in older patients with pulmonary tuberculosis. Among the SARC-F items, assistance in walking and rising from a chair were the risk factors for in-hospital mortality.

Updated comparable efficacy of cord blood transplantation for chronic myelomonocytic leukaemia: a nationwide study.

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.

Comparison of Melphalan Dose in Patients with Myelodysplastic Syndrome Undergoing Allogeneic Transplantation with Reduced-Intensity Conditioning.

The present study compared lower-dose melphalan (80 mg/m2, FM80) and higher-dose melphalan (140 mg/m2, FM140) when administering reduced-intensity conditioning with fludarabine in adult patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed nationwide registry data (2006 to 2019) and compared transplant outcomes between the 2 groups. Ninety-two patients (median age, 61 [interquartile range, 56 to 65] years) were assigned to the FM80 and FM140 groups by propensity score matching. The 3-year overall survival (OS) rate in the FM140 group (63.9%; 95% confidence interval [CI], 52.9% to 73.0%) was significantly higher than that in the FM80 group (54.2%; 95% CI, 37.1% to 52.1%) (P = .038). The FM140 group had a nonsignificantly (P = .095) lower 3-year cumulative incidence of relapse (15.5%; 95% CI, 8.9% to 23.8% versus 26.0%; 95% CI, 17.3% to 35.5%). The 3-year cumulative incidences of nonrelapse mortality were 22.3% (95% CI, 14.1% to 31.8%) and 23.7% (95% CI, 15.4% to 33.2%) in the FM80 and FM140 groups, respectively (P = .49). The beneficial effect of FM140 was more evident in patients with a poor cytogenetic risk. Our findings suggest the superiority of FM140 in patients with MDS undergoing allo-HSCT, especially in high-risk patients.

Si-based agent alleviated small bowel ischemia-reperfusion injury through antioxidant effects.

The progression of small bowel ischemia-reperfusion (IR) injury causes cells in the intestinal tract to undergo necrosis, necessitating surgical resection, which may result in loss of intestinal function. Therefore, developing therapeutic agents that can prevent IR injury at early stages and suppress its progression is imperative. As IR injury may be closely related to oxidative stress, antioxidants can be effective therapeutic agents. Our silicon (Si)-based agent, an antioxidant, generated a large amount of hydrogen in the intestinal tract for a prolonged period after oral administration. As it has been effective for ulcerative colitis, renal failure, and IR injury during skin flap transplantation, it could be effective for small intestinal IR injury. Herein, we investigated the efficacy of an Si-based agent in a mouse model of small intestinal IR injury. The Si-based agent suppressed the apoptosis of small intestinal epithelial cells by reducing the oxidative stress induced by IR injury. In addition, the thickness of the mucosal layer in the small intestine of the Si-based agent-administered group was significantly higher than that in the untreated group, revealing that Si-based agent is effective against small intestinal IR injuries. In the future, Si-based agents may improve the success rate of small intestine transplantation.

Modelling the system dynamics of household food, water, and energy nexus effects.

The food-energy-water nexus (F-E-W) serves as a crucial resource for the sustainability of households, while the efficiency of resource use largely depends on our understanding and management of the nexus including all three factors. Limited research has been conducted on this topic thus far because of the increasing complexity of home technologies and data availability. This study develops an evidence-based system dynamics model for assessing the synergy and trade-offs of the household F-E-W. By applying the system dynamics (SD) methodology, the FEW consumption and generation originating from home appliances were modelled and simulated. The model was applied to an eco-house in Tokyo, and its efficacy was validated with one-year hour-based observations of a home energy management system (HEMS). The findings revealed that water-related and food-related energy use accounted for approximately 55% of the total energy use. In addition, water-related energy use showed high uncertainty, suggesting a management potential of approximately 24% for reduction, and was significantly correlated with household carbon emissions. Moreover, this result verified that the effective management of household energy consumption requires the adept manipulation of the diverse array of energy sources employed for air and water heating, while HEMSs could play a key role in implementation.

Comparison of fludarabine-based conditioning regimens in adult cord blood transplantation for myeloid malignancy: A retrospective, registry-based study.

Fludarabine/busulfan and fludarabine/melphalan are viable options as conditioning regimens. However, the optimal fludarabine-based conditioning in cord blood transplantation (CBT) remains unclear. Therefore, this retrospective, registry-based study aimed to analyze the impact of five fludarabine-containing conditioning regimens on 1395 adult patients (median age, 61 years) with acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia who underwent their first CBT. Treatment outcomes of fludarabine combined with melphalan (100-140 mg/m2 ) and low-dose total body irradiation (TBI; FM140T); melphalan (80-99 mg/m2 ) and TBI (FM80T); busulfan (12.8 mg/kg) and melphalan (FB4M); busulfan (12.8 mg/kg) and TBI (FB4T); and busulfan (6.4 mg/kg) and TBI (FB2T) were compared. The 3-year survival rate was 67%, 53%, 44%, 36%, and 39%, respectively (p < .0001). The FM140T survival rate was the most favorable after adjusting for confounders, and the hazard ratios (vs. FM140T) for overall mortality were as follows: FM80T, 1.6 (95% confidence interval [CI], 1.2-2.2); FB4M, 2.1 (95% CI, 1.6-2.8); FB4T, 2.7 (95% CI, 2.0-3.7); and FB2T, 2.2 (95% CI, 1.6-3.1). The better survival observed with FM140T, regardless of the disease, disease risk, age, or transplant year, was attributed to the lower relapse rate and lower non-relapse mortality (NRM) associated with fewer infectious deaths. Conversely, FB4T was associated with a higher relapse rate and higher NRM. The findings indicate that the outcomes of CBT in myeloid malignancies were highly dependent on both the alkylating agent and its dose in combination with fludarabine. Therefore, compared with fludarabine/busulfan-based conditioning, FM140T may be the preferred regimen.

Successful Treatment of Epstein-Barr Virus Reactivation-associated Transverse Myelitis Following Herpes Zoster with Intravenous Rituximab in a Cord Blood Transplant Recipient.

The Epstein-Barr virus (EBV) is associated with many malignancies and autoimmune diseases, including multiple sclerosis. In addition, EBV rarely but occasionally causes central nervous system (CNS) complications. We herein report a case of transverse myelitis (TM) associated with systemic EBV reactivation after herpes zoster infection in a cord blood transplant recipient. Identification of EBV-infected peripheral blood cells revealed a predominance of B cells. Notably, intravenous rituximab ameliorated EBV reactivation and TM. Since the CNS infiltration rate of intravenous rituximab is markedly low, the clinical efficacy of rituximab against TM suggests that EBV reactivation may cause TM via immune-mediated mechanisms.

Outcomes of allogeneic hematopoietic stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a currative treatment modality for diffuse large B-cell lymphoma (DLBCL) because of the intrinsic graft-versus-lymphoma effect. However, limited information is available regarding which patients with relapsed or refractory DLBCL are likely to benefit from allo-HSCT. We retrospectively analyzed data from 1268 DLBCL patients who received allo-HSCT. The overall survival and progression-free survival (PFS) rates were 30.3% and 21.6% at 3 years, respectively. Multivariate analysis revealed that stable or progressive disease at transplantation, male patient, poorer performance status at transplantation, and shorter intervals from previous transplantation were associated independently with a lower PFS. Four prognostic factors were used to construct a prognostic index for PFS, predicting 3-year PFS of 55.4%, 43.7%, 20.4% and 6.6%, respectively. The prognostic model predicted relapse rates following allo-HSCT accordingly (P < 0.0001), whereas did not predict transplantation-related mortality (P = 0.249). The prognostic index can identify a subgroup of DLBCL patients who benefit from allo-HSCT and it is worthwhile to evaluate whether this model is also applicable to patients undergoing allo-HSCT in cases of relapse after chimeric antigen receptor engineered T-cell therapy, although the application of allo-HSCT has been declining with the increase of novel immunotherapies.

[Sustaining molecular response with very low dose ponatinib and further response after hemodialysis initiation in a patient with chronic myeloid leukemia].

A 46-year-old man was diagnosed with chronic myeloid leukemia (CML) in chronic phase. He was treated with imatinib, nilotinib, and dasatinib, but failed to achieve a complete cytogenetic response (CCyR). After tyrosine kinase inhibitor therapy, F317L BCR-ABL1 kinase domain mutation was detected. At age 66, the patient started ponatinib (PON) at 45 mg/day, and achieved CCyR within three months. Subsequently, PON was tapered to 15 mg once weekly due to arterial-occlusive events. PON was discontinued after a 3-year deep molecular response (≥ MR4.5). However, the patient lost MR4.0 within two months, and PON (15 mg once weekly) was restarted. He achieved MR4.0 again within one month, and then a deeper molecular response (MR5.0) after starting dialysis therapy at the same PON dose. The trough value of PON (15 mg once weekly) was 5.8 ng/ml, which suppressed F317L mutation in the CML clone. Currently, the patient is 77 years old and is sustaining MR5.0. Chronic renal failure may cause hyperabsorption and metabolic retardation in patients receiving PON. Initiation of hemodialysis may improve homeostasis resulting in enhanced anti-tumor immunity against CML.

[Estilo de vida, hábitos de higiene oral y autopercepción del estado anímico en estudiantes de Odontología de la Comunidad de Madrid durante la pandemia de la COVID-19: ¿pudo la pandemia tener algún efecto favorable?] / Lifestyle, oral hygiene habits and self-perception of mood in Dental students of the Community of Madrid during the COVID-19 pandemic: could the pandemic have any favorable effect?

OBJECTIVE: The COVID-19 pandemic and its control measures seem to have altered the vital dynamics of the population. It was justifiable, therefore, to try to specify the impact on lifestyle, oral hygiene and mood, in specific groups, such as dental university students in Madrid, who were accessible to us. METHODS: An anonymous and voluntary cross-sectional observational study was carried out in the first fortnight of December 2021, through an ad hoc online questionnaire, in dentistry students from the Autonomous Community of Madrid. Descriptive analysis of the variables was performed and the associations and significance were assessed using Chi-square and T-student. RESULTS: There were received seventy-two surveys. 82% were women and 18% men, with 23±3 years of mean age. 94% had good oral hygiene habits that improved with the pandemic. Their usual diet was varied and complete. Women consumed less meat (p=0.014) and more fruit (p=0.066), habits that they maintained, and men have improved with an increase in fruits (p<0.002), vegetables and legumes (p<0.003) in the pandemic. Tobacco (23,4%) and alcohol (54%) consumption decreased in confinement and increase in post-confinement. 36% increased their physical activity, initially low, especially in post-confinement. CONCLUSIONS: The students in the sample have good oral hygiene and eating habits, which they keep and even improve with the pandemic, including an increase in physical exercise in a significant fraction of the sample. The confinement affect the mood and social relationships, even altering the sleep of women, with an increase in night awakenings, especially in post-confinement.

OBJECTIVE: La pandemia de la COVID-19 y sus medidas de control parecen haber alterado la dinámica vital de la población. Fue justificable, por tanto, tratar de precisar el impacto sobre el estilo de vida, la higiene bucodental y el estado anímico, en grupos específicos, como estudiantes universitarios de Odontología de Madrid, que nos eran accesibles. METHODS: Se realizó un estudio observacional transversal anónimo y voluntario en la primera quincena de diciembre de 2021, mediante cuestionario online ad hoc, en estudiantes de Odontología de universidades de la Comunidad Autónoma de Madrid (CAM). Se realizó análisis descriptivo de las variables y se valoraron las asociaciones y significación con Chi-cuadrado y T-student. RESULTS: Se recibieron setenta y dos encuestas. El 82% eran mujeres y el 18% varones, con 23±3 años de media. El 94% tenía buenos hábitos de higiene oral, que mejoraron con la pandemia. Su dieta habitual era variada y completa. Las mujeres consumían menos carne (p=0,014) y más fruta (p=0,066), hábitos que mantenían, y mejoraron los varones con incremento en frutas (p<0,002), verduras y legumbres (p<0,003) en la pandemia. El consumo de tabaco (23,4%) y alcohol (54%) disminuyó en confinamiento y subió en postconfinamiento. Un 36% aumentó, especialmente en postconfinamiento, su actividad física, antes baja. CONCLUSIONS: Los estudiantes de la muestra tienen buenos hábitos de higiene oral y alimentación que mantienen e incluso mejoran con la pandemia, incluido un incremento del ejercicio físico en una fracción importante de la muestra. El confinamiento afecta al estado anímico y las relaciones sociales, llegando a alterar el sueño de las mujeres, con aumento de despertares nocturnos, sobre todo, en postconfinamiento.

Estilo de vida, hábitos de higiene oral y autopercepción del estado anímico en estudiantes de Odontología de la Comunidad de Madrid durante la pandemia de la COVID-19: ¿pudo la pandemia tener algún efecto favorable? / Lifestyle, oral hygiene habits and self-perception of mood in Dental students of the Community of Madrid during the COVID-19 pandemic: could the pandemic have any favorable effect?

Fundamentos: La pandemia de la COVID-19 y sus medidas de control parecen haber alterado la dinámica vital de la población. Fue justificable, por tanto, tratar de precisar el impacto sobre el estilo de vida, la higiene bucodental y el estado anímico, en grupos específicos, como estudiantes universitarios de Odontología de Madrid, que nos eran accesibles.Métodos: Se realizó un estudio observacional transversal anónimo y voluntario en la primera quincena de diciembre de 2021, mediante cuestionario online ad hoc, en estudiantes de Odontología de universidades de la Comunidad Autónoma de Madrid (CAM). Se realizó análisis descriptivo de las variables y se valoraron las asociaciones y significación con Chi-cuadrado y T-student. Resultados: Se recibieron setenta y dos encuestas. El 82% eran mujeres y el 18% varones, con 23±3 años de media. El 94% tenía buenos hábitos de higiene oral, que mejoraron con la pandemia. Su dieta habitual era variada y completa. Las mujeres consumían menos carne (p=0,014) y más fruta (p=0,066), hábitos que mantenían, y mejoraron los varones con incremento en frutas (p<0,002), verduras y legumbres (p<0,003) en la pandemia. El consumo de tabaco (23,4%) y alcohol (54%) disminuyó en confinamiento y subió en postconfinamiento. Un 36% aumentó, especialmente en postconfinamiento, su actividad física, antes baja. Conclusiones: Los estudiantes de la muestra tienen buenos hábitos de higiene oral y alimentación que mantienen e incluso mejoran con la pandemia, incluido un incremento del ejercicio físico en una fracción importante de la muestra. El confinamiento afecta al estado anímico y las relaciones sociales, llegando a alterar el sueño de las mujeres, con aumento de despertares nocturnos, sobre todo, en postconfinamiento.(AU)

Background: The COVID-19 pandemic and its control measures seem to have altered the vital dynamics of the population. It was justifiable, therefore, to try to specify the impact on lifestyle, oral hygiene and mood, in specific groups, such as dental university students in Madrid, who were accessible to us. Methods: An anonymous and voluntary cross-sectional observational study was carried out in the first fortnight of December 2021, through an ad hoc online questionnaire, in dentistry students from the Autonomous Community of Madrid. Descriptive analysis of the variables was performed and the associations and significance were assessed using Chi-square and T-student. Results: There were received seventy-two surveys. 82% were women and 18% men, with 23±3 years of mean age. 94% had good oral hygiene habits that improved with the pandemic. Their usual diet was varied and complete. Women consumed less meat (p=0.014) and more fruit (p=0.066), habits that they maintained, and men have improved with an increase in fruits (p<0.002), vegetables and legumes (p<0.003) in the pandemic. Tobacco (23,4%) and alcohol (54%) consumption decreased in confinement and increase in post-confinement. 36% increased their physical activity, initially low, especially in post-confinement. Conclusions: The students in the sample have good oral hygiene and eating habits, which they keep and even improve with the pandemic, including an increase in physical exercise in a significant fraction of the sample. The confinement affect the mood and social relationships, even altering the sleep of women, with an increase in night awakenings, especially in post-confinement.(AU)

A gene regulatory network combining Pax3/7, Sox10 and Mitf generates diverse pigment cell types in medaka and zebrafish.

Neural crest cells generate numerous derivatives, including pigment cells, and are a model for studying how fate specification from multipotent progenitors is controlled. In mammals, the core gene regulatory network for melanocytes (their only pigment cell type) contains three transcription factors, Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development. In teleosts, which have three to four pigment cell types (melanophores, iridophores and xanthophores, plus leucophores e.g. in medaka), gene regulatory networks governing fate specification are poorly understood, although Mitf function is considered conserved. Here, we show that the regulatory relationships between Sox10, Pax3 and Mitf are conserved in zebrafish, but the role for Mitf is more complex than previously emphasized, affecting xanthophore development too. Similarly, medaka Mitf is necessary for melanophore, xanthophore and leucophore formation. Furthermore, expression patterns and mutant phenotypes of pax3 and pax7 suggest that Pax3 and Pax7 act sequentially, activating mitf expression. Pax7 modulates Mitf function, driving co-expressing cells to differentiate as xanthophores and leucophores rather than melanophores. We propose that pigment cell fate specification should be considered to result from the combinatorial activity of Mitf with other transcription factors.

Disseminated Infection by Scedosporium/Lomentospora During Induction Therapy for Acute Myeloid Leukemia Complicated by Nontuberculous Mycobacteria.

Scedosporium/Lomentospora infections are rare and are associated with a high mortality rate in immunocompromised patients. A 69-year-old man with nontuberculous mycobacteria (NTM) died during induction chemotherapy for acute myeloid leukemia because of multiple organ failure due to pneumonia. During an autopsy, Lomentospora prolificans was detected using a fungal gene analysis of the blood, lungs, spleen, kidneys, and intestines, and Scedosporium aurantiacum was detected in the lungs. NTM disease may predispose patients to Scedosporium/Lomentospora infections. Physicians should consider Scedosporium/Lomentospora spp. as an invasive fungal infection that occurs during myelosuppression, particularly when NTM is a complication.

Impact of GVHD on lymphoma progression: Nationwide study from Japanese Society for Transplantation and Cellular Therapy.

The graft-versus-lymphoma (GVL) effect and its association with acute and chronic GVHD (aGVHD, cGVHD) has not been comprehensively elucidated. We retrospectively analysed 2204 Japanese patients with non-Hodgkin lymphomas (NHLs; indolent B-NHLs, n = 689; aggressive B-NHLs, n = 720; mature T/NK-NHLs, n = 795) receiving a first allo-HSCT in 2003-2017. Pre-transplant lymphoma control showed complete response (CR) in 759 and non-CR in 1445. We assessed the impact of aGVHD/cGVHD on lymphoma progression and other outcomes. Although aGVHD/cGVHD showed no statistical impact on lymphoma progression in the overall cohort, their impact was clear in certain groups: Grade I-II aGVHD in CR patients (HR, 0.63; 95% CI, 0.43-0.91), especially in mature T/NK-NHL (HR, 0.46; 95% CI, 0.26-0.83) and extensive cGVHD in patients with mature aggressive B-NHLs (HR, 0.55; 95% CI, 0.31-0.97). In total, limited cGVHD was associated with superior survivals (progression-free survival: HR, 0.71; 95% CI, 0.56-0.90), whereas severe GVHDs showed negative impacts on them. Our results support the presence of GVL effects differentially associated with GVHD in different lymphoma subtypes/controls. Meanwhile, it was also suggested that we should manage GVHDs within a limited activity, considering the negative impact of severe GVHDs. As pre-transplant lymphoma control remains a strong factor influencing transplant outcomes, improving its management is an important issue to be addressed.

Successful allogeneic hematopoietic stem cell transplantation in a patient with type I CD36 deficiency: a case study and literature review.

BACKGROUND: CD36-deficient individuals may produce anti-CD36 antibodies through antigenic exposure to CD36, in situations including blood transfusions. Therefore, allogeneic hematopoietic stem cell transplantation (HSCT) from CD36-positive donors to CD36-negative patients remains a challenge. CASE REPORT: A 64-year-old man with acute myeloid leukemia became refractory to platelet transfusions during chemotherapy. Anti-CD36 antibodies without anti-HLA antibodies were detected in serum, and the absence of CD36 expression on platelets and monocytes confirmed type I CD36 deficiency. The patient achieved complete remission, and received maintenance therapy with CD36-negative platelet transfusions. However, he relapsed soon afterward, and thus underwent peripheral blood stem cell transplantation (PBSCT) from a CD36-positive unrelated donor. The anti-CD36 antibody titer had decreased before the transplant, and the PBSCT-course was uneventful. The patient has been well without any complications associated with CD36 status mismatch. DISCUSSION: The few reports of allogeneic HSCT in patients with CD36 deficiency have suggested that anti-CD36 antibodies could be involved in several post-transplant complications, such as delayed platelet recovery, transfusion refractoriness, and transfusion-related acute lung injury. Our present case confirmed that stem cell transplantation from CD36-positive donors to negative patients is feasible, when it includes careful prior assessment of anti-CD36 antibody titers and interventions to attenuate them.

"Hydrogen-generating Si-based agent improves fat graft survival in rats".

BACKGROUND: Regulating excessive inflammation and oxidative stress in fat grafting may improve retention rates. Hydrogen effectively combats oxidative stress and inflammation and reportedly inhibits ischemia-reperfusion injury in various organs. Unfortunately, with conventional methods of hydrogen administration, incorporating hydrogen continuously into the body over a long period of time is difficult. We hypothesized that a Silicon (Si)-based agent we recently developed would aid in fat grafting as it can generate large amounts of hydrogen continuously in the body. METHODS: Fat grafting was performed on the backs of rats fed either a normal or 1.0 wt% Si-based agent-containing diet. To investigate synergistic effects with adipose-derived stromal cells (ASCs), which improve retention rates of fat grafting, fat grafting with ASCs (1.0×10 5/400 mg fat) was also performed in each rat. Postoperative retention rates of grafted fat over time, inflammatory indices, apoptosis and oxidative stress markers, histological findings, and expression levels of inflammation-related cytokines and growth factors were compared between the four groups. RESULTS: Intake of Si-based agent and addition of ASCs significantly reduced inflammatory indices, oxidative stress, and apoptosis of grafted fat, and improved long-term retention rates, histological parameters, and grafted fat quality. Under our experimental conditions, intake of the Si-based agent and addition of ASCs yielded comparable improvements in fat graft retention. Combining the two enhanced these effects even further. CONCLUSION: Oral administration of the hydrogen-generating Si-based agent may improve grafted fat retention by regulating the inflammatory response and oxidative stress in grafted fat. CLINICAL RELEVANCE STATEMENT: This study demonstrates improved grafted fat retention rates using a Si-based agent. This Si-based agent has the potential to expand the range of therapeutic indications of hydrogen-based therapy to conditions for which hydrogen has yet to be found effective, such as fat grafting.