Evaluation of the cachexia index using a bioelectrical impedance analysis in elderly patients with non-Hodgkin's lymphoma: A single-center prospective study.

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78 years (60-93 years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion.

The prognostic value of the Fibrinogen-Albumin Ratio Index in patients with myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes treated with azacitidine.

Inflammation is a major hallmark of several cancers. The present study evaluated the prognostic value of the Fibrinogen-Albumin Ratio Index (FARI) at the diagnosis in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine (AZA). A retrospective study was conducted in a single cohort of 99 patients with de novo MDS and AML-MRC who were treated with AZA between May 2011 and June 2019 in our hospital. Plasma fibrinogen and serum albumin levels were measured before the start of AZA treatment. A total of 99 patients were included in the analysis. The optimal cut-off value of FARI for predicting the 1-year overall survival (OS) was determined by a receiver operating characteristic (ROC) analysis to be 0.079. A total of 59 (60%) and 40 (40%) patients had an FARI ≥0.079 (high-FARI group) and < 0.079 (low-FARI group), respectively. The high-FARI patients had a significantly shorter OS than low-FARI patients (1-year OS, 35.6% vs. 77.5%, p < 0.001). In a multivariate analysis, parameters with independent adverse significance for the OS were a high FARI (≥0.079) (hazard ratio (HR) 2.41, 95% confidence interval (CI), 1.36-4.29; p = 0.006), and Revised-International Prognostic Scoring System (IPSS-R) very high (HR 1.483, 95% CI, 1.12-1.963, p = 0.006). A high FARI was found to be associated with a poor outcome in MDS and AML-MRC patients treated with AZA, and FARI was an independent prognostic factor for the OS in these patients. Further internal and external validations are needed to clarify the prognostic role of the FARI for MDS and AML-MRC patients.

The prognostic value of positron emission tomography/computed tomography in rheumatoid arthritis patients with methotrexate-associated lymphoproliferative disorders.

Recently, methotrexate-associated lymphoproliferative disorders (MTX-LPDs) in rheumatoid arthritis (RA) have been found to commonly occur in association with iatrogenic immunodeficiency. Several factors have been reported to be related to the prognosis. We herein investigate the efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the prognosis of MTX-LPD. We performed a retrospective analysis of the clinical features, characteristics, and outcomes of 18 patients with MTX-LPDs who were treated from 2004 to 2015. All of the patients were diagnosed with MTX-LPD based on the histological examination of biopsy specimens. Spontaneous regression was detected after the cessation of MTX in 5 of 18 cases (28%). The maximum standardized uptake value (SUVmax) of the FDG uptake on PET/CT was significantly lower, and the maximum size of the LPD-associated tumor was significantly smaller among the patients who showed spontaneous regression (p = 0.01, p = 0.04, respectively). Both the SUVmax and the maximum tumor size were related to better overall survival (p = 0.02, p = 0.04, respectively). Thus, PET/CT can be used to predict spontaneous regression and the prognosis at the diagnosis of MTX/LPD. Cases that showed spontaneous regression never relapsed during the follow-up period, despite the usage of several anti-rheumatoid arthritis drugs, including biological agents. The early detection of LPDs and the early cessation of MTX are important for the management of RA patients. An evaluation by F-FDG-PET/CT can be useful for predicting spontaneous regression and the prognosis.

Clinical characteristics of methotrexate-associated lymphoproliferative disorders: relationship between absolute lymphocyte count recovery and spontaneous regression.

Several reports have shown that patients with rheumatoid arthritis (RA) are at increased risk of developing lymphoproliferative disorders (LPD). Methotrexate (MTX) has been recognized as a major cause of LPD. Sometimes spontaneous regression (SR) occurs after withdrawal of MTX. Recent studies suggest that the early recovery of the absolute lymphocyte count (ALC) after withdrawal of MTX is associated with the spontaneous regression of MTX-LPD. We retrospectively analyzed 26 patients with MTX-LPD to identify predictive factors for spontaneous regression. The spontaneous regression after withdrawal of MTX occurred in 13 of 26 (50%) cases. We assessed the ALC at the time of MTX cessation and 1 month after cessation in 23 evaluable cases. The spontaneous regression was observed in 3 of 11 in the ALC recovery group (27%) and in 8 of the 12 in the ALC non-recovery group (67%). Thus, we could not detect any relationship between the recovery of ALC after withdrawal of MTX and the spontaneous regression. The patients in the ALC recovery group had a poorer prognosis than those in the ALC non-recovery group (2-year overall survival: 65.6 vs. 100%, p = 0.05). According to these results, the recovery of the ALC might not be useful as a predictor of the spontaneous regression. Furthermore, the existence of extranodal sites and advanced-stage were associated with non-SR. It is suspected that MTX-LPD patients with high disease activity at the time of their diagnosis might have little hope of spontaneous regression. This result indicated the importance of the early detection of MTX-LPD.

Cytomegalovirus reactivation in patients with multiple myeloma.

The introduction of novel antimyeloma agents has improved the outcome of multiple myeloma (MM) dramatically. However, it has also led to an increasing incidence of Herpesviridae family virus infections, including a high incidence of post-transplant cytomegalovirus (CMV) reactivation after treatment with novel agents. We herein retrospectively assessed the CMV reactivation in all 120 newly diagnosed patients with MM consecutively seen and treated at our hospital. CMV antigenemia tests were ordered in 58 patients depending on the clinical context, and the incidence of CMV reactivation and proven/suspected CMV disease requiring antiviral therapy was 20% (24 of 120) and 11% (13 of 120) respectively, including those without stem cell transplantation (SCT). The clinical and laboratory characteristics of these patients were compared with those in 34 CMV antigenemia-negative (CMV-negative) patients. Patients with extramedullary disease or a low absolute lymphocyte count (ALC) had a higher risk of developing CMV reactivation. In addition, the median duration from the time of MM diagnosis to CMV reactivation was 5.0 months. These results suggest that, regardless of whether or not undergoing SCT, elderly patients with MM receiving novel agents should be monitored for CMV reactivation to allow for the timely diagnosis and treatment, especially for those with extramedullary disease.

Unprecedented Megakaryocytic Blast Phase Transformation in Chronic Myeloid Leukemia After 16 Years of Tyrosine Kinase Inhibitor Therapy.

We report the case of a 51-year-old Japanese man with chronic myeloid leukemia (CML) initially diagnosed in the chronic phase. For 16 years, the patient maintained chronic phase (CP) under treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib, and bosutinib, none of which resulted in ABL1 mutations. However, despite long-term disease stability, the patient experienced an abrupt progression to the megakaryocytic blast phase (MBP), a rare and aggressive form of CML. In response to this progression, ponatinib, a third-generation TKI, was introduced as a fourth-line therapy. Remarkably, within 7 months of initiating ponatinib, the patient achieved a deep molecular response (DMR), evidenced by a reduction in BCR::ABL1 transcript levels to undetectable levels (MR5.0). This molecular remission enabled the patient to proceed with an allogeneic bone marrow transplantation from a human leukocyte antigen (HLA) 8/8-allele-matched unrelated donor. Post-transplantation, the patient has maintained DMR for 14 months without recurrence, despite the challenges posed by graft-versus-host disease. This case illustrates the critical role of third-generation TKIs like ponatinib in managing advanced CML phases, especially when previous therapies fail. It also emphasizes the necessity of vigilant long-term monitoring during the chronic phase to detect and address any signs of disease progression promptly.

Pioneering cord blood transplantation in relapsed/refractory HIV-related lymphoma: a case study with concurrent intramuscular antiretroviral therapy.

A 44-year-old HIV-positive man diagnosed with diffuse large B-cell lymphoma in 2021 achieved complete remission with six cycles of R-CHOP therapy but had a relapse in November 2022. ESHAP therapy failed to induce remission, leading to complete remission with four cycles of Pola-BR therapy. Post-failure of autologous stem cell harvest, cord blood transplantation (CBT) was performed in June 2023. Notably, this case used recently approved intramuscular antiretroviral therapy (ART) with cabotegravir and rilpivirine, addressing gastrointestinal complications during CBT. This innovative use of intramuscular ART in the treatment of malignancy represents a first in the field, offering a pioneering approach to HIV-related lymphoma.

A predictive model for HIV-related lymphoma.

OBJECTIVES: To address the paucity of HIV-related lymphoma (HRL)-specific prognostic scores for the Japanese population by analyzing domestic cases of HRL and constructing a predictive model. DESIGN: A single-center retrospective study coupled with a review of case reports of HRL. METHODS: We reviewed all patients with HRL treated at our hospital between 2007 and 2023 and conducted a comprehensive search for case reports of HRL from Japan using public databases. A multivariate analysis for overall survival (OS) was performed using clinical parameters, leading to the formulation of the HIV-Japanese Prognostic Index (HIV-JPI). RESULTS: A total of 19 patients with HRL were identified in our institution, whereas the literature review yielded 44 cases. In the HIV-JPI, a weighted score of 1 was assigned to the following factors: age at least 45 years, HIV-RNA at least 8.0×10 4  copies/ml, Epstein-Barr virus-encoded small RNA positivity, and Ann Arbor classification stage IV. The overall score ranged from 0 to 4. We defined the low-risk group as scores ranging from 0 to 2 and the high-risk group as scores ranging from 3 to 4. The 3-year OS probability of the high-risk group [30.8%; 95% confidence interval (CI): 9.5-55.4%) was significantly poorer than that of the low-risk group (76.8%; 95% CI: 52.8-89.7%; P  < 0.01). CONCLUSION: This retrospective analysis established pivotal prognostic factors for HRL in Japanese patients. The HIV-JPI, derived exclusively from Japanese patients, highlights the potential for stratified treatments and emphasizes the need for broader studies to further refine this clinical prediction model.

Overcoming post-transplant graft failure and adenovirus infection in a patient with FLT3-TKD-mutated mixed-phenotype acute leukemia: A case report.

Mixed-phenotype acute leukemia (MPAL) with FLT3-TKD mutations is a rare and challenging subtype of leukemia. Effective management strategies are crucial for improving patient outcomes. A 31-year-old man with FLT3-TKD-mutated MPAL achieved hematological remission through the JALSG ALL202-O protocol and gilteritinib, followed by cord blood transplantation (CBT). Post-transplant complications included adenovirus-induced hemorrhagic cystitis, managed with bladder irrigation and ribavirin, and engraftment failure, necessitating a second CBT on Day 35. Subsequent adenoviral conjunctivitis resolved with vidarabine. The patient achieved neutrophil engraftment by Day 76 and was discharged on Day 173 without relapse. This case highlights the importance of vigilant supportive care and tailored therapy in managing MPAL with FLT3 mutations, especially in the context of post-transplant complications.