The IL-6 signaling pathway contributes critically to the immunomodulatory mechanism of human decidua-derived mesenchymal stromal cells.

Human bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been proposed as a treatment for graft-versus-host disease (GVHD), which is a major complication following allogeneic hematopoietic cell transplantation. However, clinical trials have not yielded good results, and human decidua-derived mesenchymal stromal cells (DSCs) have been proposed as an alternative. In addition, the mechanism by which DSCs exert their immunomodulatory effects is still unknown. We found that knockdown of IL-6 in DSCs reduced the expression of PD-L1 and PD-L2, which are known as classical immune checkpoint inhibitors. Expression of PD-L1 and PD-L2 was restored by adding recombinant IL-6 to the DSCs. When DSCs and IL-6-knockdown DSCs were administered as treatment in a murine GVHD model, the group receiving IL-6-knockdown DSCs had significantly higher mortality and clinical scores compared to the group receiving DSCs. Taken together, these data suggest that the IL-6 signaling pathway is a crucial contributor to the immunosuppressive capacity of DSCs.

TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8+ T cell priming.

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist. In a mouse tumor model, combination therapy with TLR5 agonist and anti-PD-1 significantly inhibited tumor growth. The TLR5 agonist shifted the balance from M2-like to M1-like macrophages and upregulated the expression of co-stimulatory molecules in macrophages. Furthermore, TLR5 agonist promoted the activation and tumor infiltration of CD8+ T cells. As a result, the TLR5 agonist augmented the anti-tumor efficacy of anti-PD-1, suggesting its potential in modulating the tumor microenvironment to enhance the anti-tumor response. Our findings point toward the possibility of optimizing immune checkpoint inhibitor therapy using TLR5 agonists.

Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1.

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.

Dynamic changes in physical function during intensive chemotherapy affect transplant outcomes in older adults with AML.

Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.

Long-term Clinical Outcomes of Optimizing Combination Therapy for Primary Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma: A Retrospective Study.

INTRODUCTION: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma progresses with advancing disease stage. However, no standard treatment approach has been established. This single-center retrospective study evaluated clinical and radiological characteristics, treatment modalities, and long-term prognosis of pulmonary MALT lymphoma. METHODS: The study included 42 patients diagnosed with pulmonary MALT lymphoma between October 2004 and July 2019. Primary therapeutic modalities were determined using modified Ann Arbor staging. Therapeutic response was evaluated via computed tomography and laboratory analyses every 6 months for 5 years. Radiological findings were categorized based on the Lugano classification as complete response (CR), partial response, stable disease (SD), or progressive disease. RESULTS: Initial treatment included observation (n=2), surgical resection (n=6), or systemic chemotherapy (n=34). Patients treated surgically had localized disease and achieved initial and long-term CR. Of the 34 patients who underwent chemotherapy, 30 achieved CR, 2 achieved SD, and 2 died. Overall and progression-free survival (PFS) rates were 93.9% and 54.3%, respectively. Multivariate analysis indicated that PFS was lower in patients with modified Ann Arbor stage III-IV lymphoma and those who did not achieve CR. CONCLUSIONS: Optimized treatment based on anatomical location, pulmonary function, and disease stage can improve long-term survival in patients with pulmonary MALT lymphoma.

The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma.

To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

Prognostic Value of FDG PET/CT in Patients with Nodal Peripheral T-Cell Lymphoma.

This study evaluated the prognostic significance of FDG PET/CT in patients with nodal peripheral T-cell lymphoma (PTCL). We retrospectively reviewed patients with histologically confirmed nodal PTCL who underwent FDG PET/CT at baseline, after three cycles of first-line chemotherapy (interim), and at the end of therapy. Response was assessed visually using the Deauville 5-point scale (D5PS); scores of 1, 2, and 3 were considered PET-negative, and scores of 4 and 5 were considered PET-positive. The associations between FDG PET/CT findings and survival were assessed using Cox regression analysis. A total of 79 patients (44 males and 35 females; median age 56 years) were included in this study. In response assessment, 17 (22%) had an interim PET-positive result and 10 (13%) had an end-of-therapy PET-positive result. During a median follow-up of 50 months, 37 patients (47%) presented with disease progression and 30 patients (38%) died. The estimated 5-year progression-free survival (PFS) and overall survival (OS) were 57% and 64%, respectively. An interim PET-positive result was the only significant indicator of PFS. Higher International Prognostic Index and end-of-therapy PET-positive result were significant independent prognostic factors of OS. Interim and end-of-therapy FDG PET/CT responses based on D5PS are meaningful in predicting the outcomes of patients with nodal PTCL.

Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients.

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.

Effectiveness of pegfilgrastim prophylaxis in preventing febrile neutropenia during R-FC chemoimmunotherapy for chronic lymphocytic leukemia: A multicenter prospective phase II study.

Background: A chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic lymphocytic leukemia (CLL). Although R-FC regimen is a relatively dose-dense regimen and neutropenia incidence is more than 50%, primary prophylactic pegfilgrastim was not fully recommended in the clinical field. Therefore, the study evaluated the prophylactic effectiveness of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-FC of patients with CLL. Patients and methods: A single-arm, multicenter, prospective phase II study was designed to assess the efficacy of prophylactic pegfilgrastim. Thirty-four CLL patients were enrolled and analyzed for neutropenia and other related factors, and comparative analysis was performed with historical cohort. Results: Compared with our historical cohort, incidence of grade 3-4 neutropenia and febrile neutropenia was remarkably reduced during any cycle of chemotherapy (14.7% vs. 48.2% of study cohort vs. historical cohort during C1, 5.9% vs. 65.8% during C2, 12.9% vs. 80.6% during C3, 10% vs. 84.6% during C4, 3.4% vs. 83.6% during C5, and 10.7% vs. 85.7% during C6, p <0.001). Also, cumulative incidence of disrupted chemotherapy was noticeably reduced in study cohort on any cycles of R-FC regimen (8.8% vs. 22.2% of study cohort vs. historical cohort on C2, 9.7% vs. 25.2% on C3, 13.4% vs. 26.9% on C4, 13.8% vs. 45.2% on C5, 17.9% vs. 47.3% on C6, p=0.007). In addition, treatment-related mortality was 5.9%, which significantly reduced compared to 9.6% of our historical cohort (HR 0.64, 95% CI 0.42-0.79, P = 0.032). Conclusion: Primary prophylactic pegfilgrastim is effective in the prevention of neutropenia/febrile neutropenia, and infection-related mortality during R-FC regimen in patients with CLL.

Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score-matched cohort analysis.

Background: Blinatumomab showed a higher complete remission (CR) rate and a safe bridging to allogeneic hematopoietic cell transplantation (allo-HCT) in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Objectives: We tried to analyze the outcome of blinatumomab compared with the real-world historical data. We expected superior outcome of blinatumomab compared with historical conventional chemotherapy. Design: We conducted a retrospective study using real-world data in the Catholic Hematology Hospital. Methods: Total 197 consecutive cases of R/R BCP-ALL were treated with conventional chemotherapy (n = 113) or blinatumomab, which was available since late 2016 (n = 84). Patients who achieved CR underwent allo-HCT if donor was available. We conducted a propensity score-matched cohort analysis using 5 criteria of age, CR duration, cytogenetics, previous allo-HCT, and salvage lines between historical group and blinatumomab. Results: Each cohort consisted of 52 patients. In blinatumomab group, CR rate was higher (80.8% versus 53.8%, p = 0.006) and more patients proceeded to allo-HCT (80.8% versus 46.2%, p < 0.001). Among the CR patients with available minimal residual disease (MRD) results, 68.6% in blinatumomab group and 40.0% in conventional chemotherapy group were MRD-negative. Regimen-related mortality during the chemotherapy cycles was significantly higher in the conventional chemotherapy group (40.4% versus 1.9%, p < 0.001). Estimated 3-year overall survival (OS) was 33.2% (median, 26.3 months) after blinatumomab, and 15.4% (median, 8.2 months) after conventional chemotherapy (p < 0.001). Estimated 3-year non-relapse mortality were 30.3% and 51.9% (p = 0.004), respectively. In multivariate analysis, CR duration < 12 months showed more relapses and poor OS, and conventional chemotherapy showed higher non-relapse mortality and poor OS. Conclusions: Matched cohort analysis showed superior outcomes of blinatumomab compared with conventional chemotherapy. However, large numbers of relapses and non-relapse mortalities continue to occur even after blinatumomab followed by allo-HCT. Novel therapeutic strategies are still needed for R/R BCP-ALL.

Migratory Pneumonia in Prolonged SARS-CoV-2 Infection in Patients Treated With B-cell Depletion Therapies for B-cell Lymphoma.

OBJECTIVE: To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms. MATERIALS AND METHODS: From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37-71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features. RESULTS: All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, follow-up CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25. CONCLUSION: COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.

A Successful Bridge Therapy Combining Hypomethylating Agents with Venetoclax for Adult Patients with Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia.

Recently, the combination of VEN-HMA has been shown to achieve durable responses in patients with both newly diagnosed (ND) and R/R-AML. We retrospectively evaluated the post-allo-HCT outcomes of 50 patients who received VEN-HMA therapy. In total, 10 were ND and 40 were R/R and, at the time of HCT, the median age was 53 years. In the ND- and R/R-AML groups, the percentage of patients who achieved CR/CRi or MLFS was 90% and 92.5%, respectively. In all, after a median follow-up of 13.7 months, the probabilities of overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) at 1 year were 63.7%, 59.3%, 28.5%, and 12.2%, respectively. In addition, the cumulative incidences of grade II-IV acute graft-versus-host disease (GVHD) and moderate-severe chronic GVHD at 1 year were 28.4% and 37.4%, respectively. In multivariate analysis, the factors associated with a statistically significant impact on OS were VEN-HMA cycle (p = 0.021), ELN risk group (p = 0.041), and the response to VEN-HMA therapy before allo-HCT (p = 0.003). Although 80% of our patients had R/R-AML and 30% underwent a second allo-HCT, our data still suggest that allo-HCT following VEN-HMA therapy is a safe and effective treatment option.

Diagnosis, treatment, and prognosis of primary intraocular lymphoma: Single-center real-world clinical experience.

BACKGROUND: The diagnosis and management of primary intraocular lymphoma (PIOL) remain challenging. This study identified factors indicative of PIOL, described treatment outcomes, and determined modalities to prevent relapse. METHODS: We included 21 PIOL-diagnosed patients, seven via cytology, 12 via genetic evaluation, and two via interleukin (IL) level measurements, who underwent vitrectomy and received local intravitreal methotrexate (IV-MTX) injection. Clinical outcomes, including treatment response and relapse, were compared between patients receiving IV-MTX alone (n = 13) or IV-MTX with systemic high-dose methotrexate (HD-MTX) as prophylaxis (n = 8). RESULTS: Twelve ophthalmologic and eight central nervous system (CNS) relapse cases within a median of 20.3 and 11.6 months were shown, regardless of the treatment modalities, with a median progression-free survival of 21.3 (95% confidence interval, 9.5-36.7) months. There was no difference in demographic characteristics between the two groups, except with the poorer performance status in patients in the HD-MTX prophylaxis group. Furthermore, patients demonstrated rapid elevations in the vitreous fluid IL-10/IL-6 cytokine ratio before ophthalmologic and CNS relapse. Therefore, diagnosis should be based on clinical signs and assisted by vitrectomy, cytologic, molecular, and cytokine studies. CONCLUSION: For PIOL, aggressive systemic treatment equivalent to that of primary CNS lymphoma (PCNSL) is recommended because solely HD-MTX did not prevent or delay CNS relapse. To prevent PIOL relapse in the CNS efficiently, prospective trials with large numbers of patients and advanced therapeutic regimens are necessary. Furthermore, regular clinical follow-up is crucial, and the IL-10/IL-6 ratio can help evaluate relapse promptly.

Long-term clinical outcomes of gastric mucosa-associated lymphoid tissue lymphoma in real-world experience.

This long-term, retrospective, single-center study evaluated real-world clinical outcomes of gastric mucosa-associated lymphoid tissue (MALT) lymphoma using different therapeutic modalities and analyzed factors affecting survival outcomes and long-term prognosis. We enrolled 203 patients with pathologically confirmed low-grade gastric MALT lymphoma and examined their treatment responses. Helicobacter pylori eradication was performed in all patients with H. pylori infection (HPI) and localized stage gastric MALT lymphoma. All patients underwent pre-treatment and physical evaluations, with complete blood count, biochemistry panel, and staging workup. Among 144 HPI-positive patients with stage I or II1-2 disease who underwent H. pylori eradication, 112 (77.8%) achieved complete remission (CR). All HPI-negative patients who received first-line radiotherapy achieved CR (100%), but only 22 of 27 first-line chemotherapy-treated patients achieved CR (81.5%). Lesions in the proximal upper-third or in multiple locations and an invasion depth to the submucosa or deeper were associated with poor response to eradication, and HPI negativity was significantly correlated with poor progression-free survival. HPI eradication treatment should be the first-line treatment for patients with localized stage HPI-positive gastric MALT lymphoma. The "watch-and-wait" strategy should be adopted for delayed responders. We suggest radiotherapy for patients with a localized HPI-negative status or when eradication has failed.

Haploidentical versus Double-Cord Blood Stem Cells as a Second Transplantation for Relapsed Acute Myeloid Leukemia.

There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 adult AML patients who received SCT2 from haploidentical donors (HIT, N = 32) and double-cord blood (dCBT, N = 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow WT1 measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that WT1-MRD negativity may be warranted for better SCT2 outcomes.

Cytogenetic and molecular characteristics and outcomes of adult patients with early T-cell precursor acute lymphoblastic leukemia.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently identified high-risk subgroup of T-cell ALL in children. However, there have been conflicting reports and limited data have been reported in adult patients. We retrospectively analyzed the cytogenetic and molecular characteristics and long-term survival outcomes of adult patients with ETP-ALL versus non-ETP-ALL. We analyzed 58 patients (median age, 35 years [range, 18-76 years]) with newly diagnosed T-cell ALL who received a uniform remission induction and consolidation chemotherapy with suitable samples for genetic analyses. If a donor was available, all patients were recommended allogeneic hematopoietic cell transplantation (allo-HCT) for post-remission therapy. Out of 58 patients, 21 (36.2%) had ETP-ALL. Patients with ETP-ALL were older and had a higher proportion of complex karyotype than non-ETP-ALL. Additionally, more DNMT3A mutations were detected in ETP-ALL, whereas FBXW7 mutations and CDKN2A/CDKN2B deletions were found nearly exclusively in non-ETP-ALL. The overall complete remission (CR) rates were not different between ETP-ALL (95.2%) and non-ETP-ALL (81.1%) and subsequent allo-HCT proceeding rates in CR1 were 61.9% for ETP-ALL and 43.2% for non-ETP-ALL, respectively. The overall prognosis of patients with T-ALL was poor that estimated 5-year overall survival (OS) was 33.3% for ETP-ALL and 29.5% for non-ETP-ALL. In a subgroup analysis of patients treated with allo-HCT in CR1 (n = 29), 5-year OS was 53.8% for ETP-ALL and 55.4% for non-ETP-ALL. Our data showed molecular characteristics of ETP-ALL and non-ETP-ALL and revealed that intensive chemotherapy followed by allo-HCT for post-remission therapy can contribute to preserved survival outcome of adult patients with ETP-ALL.

A Case of Hemophagocytic Lymphohistiocytosis following Second Dose of COVID-19 Vaccination.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, severe hyperinflammatory disease characterized by overproduction of cytokines and hemophagocytosis of hematopoietic cells, resulting in multiorgan failure. Prompt treatment initiation is essential for patient survival. The coronavirus disease 2019 (COVID-19) pandemic has led to the rapid development of several vaccines, including BNT162b2 by Pfizer-BioNTech. Few cases of immune-mediated complications of COVID-19 and its vaccines have been reported, characterized by persistent stimulation of the immune system, resembling HLH. We report the case of a 21-year-old man with secondary HLH following a second dose of the BNT162b2 vaccine. The patient did not have primary HLH or other contributors to secondary HLH and met the HLH-2004 diagnostic criteria. He was safely treated with steroid pulse therapy alone, without etoposide, cyclosporin, or immunoglobulins, which are recommended for pediatric patients. Physicians need to be aware of such severe complications following a second dose of the COVID-19 vaccine.

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis.

Venetoclax (VEN) combined with azacitidine (AZA) or decitabine (DEC) has been approved for older adults with acute myeloid leukemia (AML) unfit for intensive chemotherapy based on the pivotal VIALE-A trial. However, this trial only compared AZA + VEN with AZA monotherapy. Therefore, we compared the outcomes of consecutive older adults (65 years or older) with newly diagnosed AML who received DEC (n = 230) or DEC + VEN (n = 74) after propensity score matching to construct a one-to-one matched cohort by the nearest neighbor algorithm. The median overall survival was longer in the DEC + VEN group than in the DEC group (13.4 months vs. 8.3 months, p = 0.01). The median event-free survivals were 8.6 and 5.8 months in the DEC + VEN and DEC groups, respectively (p = 0.02). The response rate (complete response, complete response with incomplete hematologic recovery, and morphologic leukemia-free state) was significantly higher in the DEC + VEN group than in the DEC group (70.3% vs. 24.3%, p < 0.01). The 30-day (2.7% vs. 9.5%, p = 0.17) and 60-day (9.5% vs. 18.9%, p = 0.16) mortality rates did not differ between the two groups, nor did the median hospitalization and transfusion rates (hospitalization: 23 days vs. 21 days, p = 0.20; red blood cells: 3.2 units/month vs. 3.5 units/month, p = 0.73; platelets: 2.7 units/month vs. 2.3 units/months, p = 0.48). Of those who received DEC + VEN and became leukemia-free, 29% underwent allogeneic stem cell transplantation and had excellent survival outcomes (one-year survival: 79.4%; one-year non-relapse mortality: 13.3%). This study is the first to provide real-world evidence that DEC + VEN has superior outcomes to DEC monotherapy.

Clinical Features, Gene Alterations, and Outcomes in Prefibrotic and Overt Primary and Secondary Myelofibrotic Patients.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are divided in three major groups: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 WHO classification incorporates also prefibrotic PMF (pre-PMF) and overt PMF. This study aimed to discriminate the clinical features, genetic alterations, and outcomes in patients with prefibrotic, overt PMF, and secondary MF (SMF). This study included 229 patients with diagnosed myelofibrosis (MF). Among 229 patients, 67 (29%), 122 (53%), and 40 (18%) were confirmed as SMF, overt PMF, and pre-PMF, respectively. The JAK2 V617F mutation was differentially distributed in SMF and PMF, contradictory to CALR and MPL mutations. Regarding nondriver mutations, the occurrence of ASXL1 mutations differed between PMF and SMF or pre-PMF. The three-year overall survival was 91.5%, 85.3%, and 94.8% in SMF, overt PMF, and pre-PMF groups. Various scoring systems could discriminate the overall survival in PMF but not in SMF and pre-PMF. Still, clinical features including anemia and thrombocytopenia were poor prognostic factors throughout the myelofibrosis, whereas mutations contributed differently. Molecular grouping by wild-type SF3B1 and SRSF2/RUNX1/U2AF1/ASXL1/TP53 mutations showed inferior progression-free survival (PFS) in PMF, SMF, and pre-PMF. We determined the clinical and genetic features related to poor prognosis in myelofibrosis.

Long-term treatment outcome of Castleman's disease: A real-world experience.

Background: Castleman disease (CD), classified as unicentric CD (UCD) or multicentric CD (MCD), is a rare non-neoplastic lymphoproliferative disorder of unknown origin. Owing to its rarity, the clinical characteristics, therapeutic modalities, treatment outcomes, and prognostic factors related to UCD or MCD are not well defined. Method: We retrospectively analyzed 88 patients with CD, including those with hyaline-vascular, plasma-cell, mixed type, hypervascular, and plasmablastic subtypes, for presenting symptoms, physical, laboratory, and radiologic findings, and treatment response in the Korean population. Results: The median patient age was 44 years (range: 18-84 years) with slight predominance of women (53.4%). UCD and MCD accounted for 38.6% (n=34) and 61.4% (n=54) of cases, respectively. Histopathologically, UCD patients were classified as 88.2% (n=30) hyaline-vascular and 11.8% (n=4) plasma cell types, whereas MCD patients were classified as 27.8% (n=15) hypervascular, 61.1% (n=33) plasma cell, 7.4% (n=4) mixed, and 3.7% (n=2) plasmablastic types. Twelve (13.6%) patients exhibited a poor performance status with an Eastern Cooperative Oncology Group score of 2. The most common presenting symptom was sustained fever, followed by fatigue, anorexia, peripheral edema, and weight loss. Furthermore, splenomegaly, pleural effusion, and ascites were observed to be associated with CD. Surgical resection and siltuximab were the preferred treatment modalities for UCD and MCD, respectively, with favorable symptomatic, laboratory, and radiologic outcomes and safety profiles. The overall survival was 90.2%, with no significant difference between the UCD and MCD groups (p=0.073), but progression-free survival was significantly poorer in the MCD group (p=0.001). Age ≥60 years and splenomegaly significantly affected the overall and progression-free survival rates. Conclusion: Patients with UCD had favorable outcomes with surgical resection of a solitary mass, whereas in patients with MCD, old age and splenomegaly were identified as independent prognostic factors. Further well-designed prospective studies under advancing knowledge of the pathophysiology of MCD are warranted to establish suitable guidelines for the discontinuation or prolonging infusion intervals of siltuximab and treatment modalities for HHV-8 positive MCD patients or patients with siltuximab failure.