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.

Cerebrovascular Malformation Mimicking Recurrent Lymphoma on Dual Time-Point 18F-FDOPA PET.

ABSTRACT: Although 18F-FDG is the dominant radiotracer for PET imaging of hematological malignancies, radiolabeled amino acids have also been investigated to improve image quality in areas of high 18F-FDG uptake such as the central nervous system. We present a case of a 57-year-old woman who underwent an 18F-FDOPA scan for primary CNS lymphoma, which demonstrated an unexpected false-positive uptake in the right frontal lobe, due to a developmental venous anomaly.

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.

Prospective Comparative Study of Etoposide plus G-CSF versus G-CSF Alone, Followed by Risk-Adapted Plerixafor for Peripheral Blood Stem Cell Mobilization in Patients with Newly Diagnosed Multiple Myeloma: CAtholic REsearch Network for Multiple Myeloma Study (CAREMM-2001).

To explore the optimal mobilization for multiple myeloma (MM) patients, we conducted a prospective trial comparing single-dose etoposide (375 mg/m2 for one day) plus G-CSF versus G-CSF alone, followed by risk-adapted plerixafor. After randomization, 27 patients in the etoposide group and 29 patients in the G-CSF alone group received mobilizations. Six (22.2%) patients in the etoposide group and 15 (51.7%) patients in the G-CSF alone group received plerixafor based on a peripheral blood CD34+ cell count of < 15/mm3 (p = 0.045). The median count of CD34+ cells collected was significantly higher in the etoposide group (9.5 × 106/kg vs. 7.9 × 106/kg; p = 0.018), but the optimal collection rate (CD34+ cells ≥ 6 × 106/kg) was not significantly different between the two groups (96.3% vs. 82.8%; p = 0.195). The rate of CD34+ cells collected of ≥ 8.0 × 106/kg was significantly higher in the etoposide group (77.8% vs. 44.8%; p = 0.025). Although the rates of grade II-IV thrombocytopenia (63.0% vs. 31.0%; p = 0.031) and grade I-IV nausea (14.8% vs. 0%; p = 0.048) were significantly higher in the etoposide group, the rates of adverse events were low in both groups, with no neutropenic fever or septic shock. Thus, both single-dose etoposide plus G-CSF and G-CSF alone with risk-adapted plerixafor were effective and safe, but the former may be the better option for patients who are expected to receive two or more transplantations.

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.

Real-world treatment outcomes of carfilzomib plus dexamethasone in patients with relapsed and/or refractory multiple myeloma, focusing on the impact of trial-fitness: CAtholic REsearch network for Multiple Myeloma study (CAREMM-2203).

INTRODUCTION: Carfilzomib plus dexamethasone (Kd) is widely used in patients with relapsed and/or refractory multiple myeloma (RRMM). However, the treatment outcomes of Kd, especially in trial-unfit patients, have not been extensively studied in the real-world setting. METHODS: We analyzed the outcomes of 152 RRMM patients who received Kd at our hospitals from April 2018 to March 2022. RESULTS: At the commencement of Kd, patients received a median of two (range 1-7) lines of prior anti-myeloma therapy. According to the ENDEAVOR study criteria, 93 (61.2%) and 59 (38.8%) patients were classified as the trial-fit and the trial-unfit group, respectively. The overall response (OR) rate for the entire cohort was 71.1% (95% CI 63.2-78.1%). Progression-free survival (PFS) and overall survival (OS) were 5.6 months (95% CI 3.9-6.9 months) and 24.0 months (95% CI 13.4-38.0 months), respectively. There was no significant difference in the OR rate between the trial-fit and the trial-unfit groups (76.3% vs. 62.7%; P = 0.105). However, the median PFS (3.6 months vs. 7.3 months; P < 0.001) and OS (15.0 vs. 36.8 months; P = 0.009) were significantly shorter in the trial-unfit group. On multivariate analysis, trial-fitness (unfit vs. fit) remained a significant covariate influencing the TRM (HR: 4.84, 95% CI 1.66-14.06; P = 0.004) and PFS (HR: 1.82, 95% CI 1.27-2.62; P = 0.001). CONCLUSION: Our data suggest that the treatment outcomes of Kd are acceptable in the real-world setting with significant differences between the trial-fit and the trial-unfit groups, although they are relatively inferior to those of a pivotal trial.

Comparisons of efficacy between frontline treatment with bortezomib-melphalan-prednisone and lenalidomide-dexamethasone for transplant-ineligible multiple myeloma: a multicenter real-world based registry report, CAREMM-2102 study.

BACKGROUND: Bortezomib-melphalan-prednisone (VMP) and lenalidomide-dexamethasone (Rd) remain the standard treatments for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). This study aimed to compare real-world benefits between the two regimens. We also were interested in exploring efficacy according to subsequent therapy following VMP or Rd. METHODS: A total of 559 NDMM patients treated with VMP (n = 443, 79.2%) or Rd (n = 116, 20.8%) was recruited retrospectively from a multicenter database. RESULTS: Rd provided more benefits than VMP-overall response rate: 92.2 vs. 81.8%, p = 0.018; median progression-free survival (PFS): 20.0 vs. 14.5 months, p <0.001; second PFS (PFS2): 43.9 vs. 36.9 months, p = 0.012; overall survival (OS): 100.1 vs. 85.0 months, p = 0.017. Multivariable analysis revealed significant benefits of Rd over VMP, with hazard ratios of 0.722, 0.627, and 0.586 for PFS, PFS2, and OS, respectively. In propensity score-matched cohorts with matched VMP (n = 201) and Rd (n = 67) arms to balance baseline characteristics, Rd still showed significantly better outcomes for PFS, PFS2, and OS than VMP. Following VMP failure, triplet therapy showed significant benefits for response and PFS2; after Rd failure, PFS2 with carfilzomib-dexamethasone was significantly better than bortezomib-based doublet treatment. CONCLUSION: These real-world findings may assist with better selection between VMP and Rd as well as subsequent therapy for NDMM.

Prognostic value of low muscle mass at the 12th thoracic vertebral level in multiple myeloma treated with transplantation: CAREMM-2101 study.

PURPOSE: Autologous hematopoietic stem cell transplantation (ASCT) has been introduced as a standard treatment for newly diagnosed multiple myeloma (NDMM) following novel agent-based induction chemotherapy. This study investigated whether pre-ASCT low muscle mass evaluated using the paraspinal muscle index (PMI) at the 12th thoracic vertebra (T12) level is a reliable prognostic marker in NDMM after chemotherapy. METHODS: A multi-center registry database was retrospectively analyzed. Between 2009 and 2020, 190 patients with chest computed tomography images underwent frontline ASCT following induction therapy. The PMI was defined as the value of the paraspinal muscle area at the T12 level divided by the square of the patient's height. The cut-off value indicating a low muscle mass was sex-specific, using the lowest quintiles. RESULTS: Of the 190 patients, 38 (20%) were in the low muscle mass group. The low muscle mass group had a lower 4-year overall survival (OS) rate than the non-low muscle mass group (68.5% vs. 81.2%; P = 0.074). The median progression-free survival (PFS) in the low muscle mass group was significantly shorter compared with the non-low muscle mass group (23.3 months vs. 29.2 months; P = 0.029). The cumulative incidence of transplant-related mortality (TRM) was significantly higher in the low muscle mass group than in the non-low muscle mass group (4-year probability of TRM incidence, 10.6% vs. 0.7%; P < 0.001). In contrast, no significant difference in the cumulative incidence of disease progression was found between the two groups. Multivariate analysis revealed that low muscle mass was associated with significant negative outcomes for OS [(hazard ratio (HR): 2.14; P = 0.047], PFS (HR: 1.78; P = 0.012), and TRM (HR: 12.05; P = 0.025). CONCLUSION: Paraspinal muscle mass may have a prognostic role in NDMM patients who undergo ASCT. Patients with low paraspinal muscle mass have lower survival outcomes compared to non-low muscle mass group.

ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma.

Optimal first-line treatment that enables deeper and longer remission is crucially important for newly diagnosed multiple myeloma (NDMM). In this study, we developed the machine learning (ML) models predicting overall survival (OS) or response of the transplant-ineligible NDMM patients when treated by one of the two regimens-bortezomib plus melphalan plus prednisone (VMP) or lenalidomide plus dexamethasone (RD). Demographic and clinical characteristics obtained during diagnosis were used to train the ML models, which enabled treatment-specific risk stratification. Survival was superior when the patients were treated with the regimen to which they were low risk. The largest difference in OS was observed in the VMP-low risk & RD-high risk group, who recorded a hazard ratio of 0.15 (95% CI: 0.04-0.55) when treated with VMP vs. RD regimen. Retrospective analysis showed that the use of the ML models might have helped to improve the survival and/or response of up to 202 (39%) patients among the entire cohort (N = 514). In this manner, we believe that the ML models trained on clinical data available at diagnosis can assist the individualized selection of optimal first-line treatment for transplant-ineligible NDMM patients.

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study.

Background: The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone; VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone; D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd. Methods: Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled. Results: After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P=0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups. Conclusion: Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.

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.

Response and Dynamics of Renal Function in Transplantation-Eligible Multiple Myeloma Patients Treated with a Novel Agent: The CAREMM-2201 Study.

Newly diagnosed multiple myeloma (NDMM) frequently results in renal impairment (RI), and its natural course has not been fully elucidated in the era of novel agents. We aimed to identify the dynamics of renal function after autologous stem cell transplantation (ASCT) following induction treatment using a novel agent in transplantation-eligible NDMM patients with RI (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m2) at diagnosis. The factors associated with achieving a renal response based on the term renal benefit regardless of baseline eGFR were investigated as well. In a multicenter registry database including 1795 patients with plasma cell disorder, 140 transplantation-eligible NDMM patients who developed RI at the time of initiation of treatment for NDMM were identified. They received protocol-based treatment (PBT) consisting of induction treatment using proteasome inhibitors and/or immunomodulatory drugs followed by ASCT. MM and renal responses were evaluated using the International Myeloma Working Group response criteria. To evaluate the standardized improvement of renal function irrespective of baseline eGFR, renal benefit was defined as a sustained (for at least 3 months) increase in eGFR >15 mL/min/1.73 m2. The mean patient age was 54.7 ± 7.4 years. With a mean baseline eGFR of 24.8 ± 13.9, the renal complete response (renalCR) and renal benefit rates were 49.3% and 67.9%, respectively. In a multivariable analysis, the 3 factors significantly associated with reduced likelihood of achieving both renalCR and renal benefit were age ≥55 years, light chain type NDMM, and failure to improve eGFR by 5 mL/min/1.73 m2 with supportive care when measured 3 days prior to induction therapy and at the initiation of chemotherapy. Hypertension and advanced eGFR also were associated with poor renalCR achievement. The mean eGFR improved until the time of ASCT and then decreased gradually over time. The mean eGFR improved significantly until 4 months post-PBT compared with each eGFR at previous time points, but this significant improvement disappeared by 5 months post-PBT. In a subgroup of patients who developed RI after undergoing ASCT (n = 55), the eGFR increased temporarily at 1 month post-ASCT; however, this improvement reverted to baseline at 2 months post-ASCT. Among another subgroup of 27 patients who were dialysis-dependent at the time of initial treatment, 18 (66.7%) were no longer dialysis-dependent after a median of 60 days. The best renal response was acquired early during the PBT period, and ASCT did not have a robust impact on the renal outcome. Patients who failed to achieve a renal benefit should be provided with the best supportive care for chronic kidney disease, and this simplified criterion for evaluating the renal response needs to be validated in larger studies before it can be recommended. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

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.

Treatment for relapsed acute promyelocytic leukemia: what is the best post-remission treatment?

Background: Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking. Methods: We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC). Results: The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P=0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since. Conclusion: Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

Depth of Response to Intensive Chemotherapy Has Significant Prognostic Value among Acute Myeloid Leukemia (AML) Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation with Intermediate or Adverse Risk at Diagnosis Compared to At-Risk Group According to European Leukemia Net 2017 Risk Stratification.

We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n = 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p < 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.

Long-Term Clinical Outcomes in Treatment-Naïve Patients With Orbital Adnexal Mucosa-Associated Lymphoid Tissue Lymphoma: A Single-Center Study.

Ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (OAML) is the most common type of ocular lymphoma with a higher prevalence in Asia than in Western countries. OAML represents 1%-2% of all non-Hodgkin's lymphoma, 5%-15% of extranodal lymphomas, and approximately 55% of orbital malignancies. "Watch and wait" after biopsy or surgical resection, radiation therapy, and systemic treatment, including antibiotics administration and chemotherapy with various combinations of regimens can be considered for OAML treatment. Radiotherapy is adapted for limited-stage disease with excellent clinical outcomes of 85-100% complete remission and relatively superior local control efficacy and treatment duration. In contrast, chemotherapy has rarely been tested as frontline therapy. Nonetheless, several studies have reported a favorable response and long duration of progression-free survival using chemotherapy adaptations. When the disease involves both eyes or spreads beyond the conjunctiva, the risk of recurrence increases and limited-stage OAML has a recurrence rate of approximately 25% following radiotherapy only. Therefore, although recent consensus in the literature is that patients with limited-stage OAML recommended treating with radiation, physicians may choose the treatment modality not only by its efficiency but also by its adverse events profile and patients' well-being. Herein, we present a large single-center study on OAML that included 292 patients who were followed up for up to 237 months. We collected and analyzed real-world data focusing on treatment outcomes and the role of radiotherapy as frontline therapy, and aimed to compare outcomes and complication profiles of chemotherapy, especially in limited-stage OAML, to identify an optimal treatment strategy.

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML).

Background: Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML. Methods: We compared AML patients who received IC (n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) (n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy. Results: The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) (p = 0.724), respectively. Conclusion: VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.