The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

BACKGROUND: The Children\'s Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy.
METHODS: ARST1431 was a randomised, open-label, phase 3 trial conducted across 210 institutions in Australia, Canada, New Zealand, and the USA. Eligible patients were those aged 40 years or younger with non-metastatic FOXO1-positive rhabdomyosarcoma or unresected FOXO1-negative rhabdomyosarcoma disease from unfavourable sites. Two other groups of patients were also eligible: those who had FOXO1-negative disease at a favourable site (excluding orbit) that was unresected; and those who were aged younger than 10 years with stage IV FOXO1-negative disease with distant metastases. Eligible patients had to have a Lansky performance status score of 50 or higher if 16 years or younger and a Karnofsky performance status score of 50 or higher if older than 16 years; all patients were previously untreated. Patients were randomised (1:1) in blocks of four and stratified by histology, stage, and group. Patients received intravenous VAC/VI chemotherapy with a cyclophosphamide dose of 1·2 g/m2 per dose per cycle with or without a reducing dose of intravenous weekly temsirolimus starting at 15 mg/m2 or 0·5 mg/kg per dose for those who weighed less than 10 kg. The total duration of therapy was 42 weeks followed by 6 months of maintenance therapy with oral cyclophosphamide plus intravenous vinorelbine for all patients. Temsirolimus was withheld during radiotherapy and for 2 weeks before any major surgical procedure. The primary endpoint was 3-year event-free survival. Data were analysed with a revised intention-to-treat approach. The study is registered with ClinicalTrials.gov (NCT02567435) and is complete.
RESULTS: Between May 23, 2016, and Jan 1, 2022, 325 patients were enrolled. In 297 evaluable patients (148 assigned to VAC/VI alone and 149 assigned to VAC/VI with temsirolimus), the median age was 6·3 years (IQR 3·0-11·3); 33 (11%) patients were aged 18 years or older; 179 (60%) of 297 were male. 113 (77%) of 148 patients were FOXO1 negative in the VAC/VI group, and 108 (73%) of 149 were FOXO1 negative in the VAC/VI with temsirolimus group. With a median follow-up of 3·6 years (IQR 2·8-4·5), 3-year event-free survival did not differ significantly between the two groups (64·8% [95% CI 55·5-74·1] in the VAC/VI group vs 66·8% [57·5-76·2] in the VAC/VI plus temsirolimus group (hazard ratio 0·86 [95% CI 0·58-1·26]; log-rank p=0·44). The most common grade 3-4 adverse events were anaemia (62 events in 60 [41%] of 148 patients in the VAC/VI group vs 89 events in 87 [58%] of 149 patients in the VAC/VI with temsirolimus group), lymphopenia (83 events in 65 [44%] vs 99 events in 71 [48%]), neutropenia (160 events in 99 [67%] vs 164 events in 105 [70%]), and leukopenia (121 events in 86 [58%] vs 132 events in 93 [62%]). There was one treatment-related death in the VAC/VI with temsirolimus group, categorised as not otherwise specified.
CONCLUSIONS: Addition of temsirolimus to VAC/VI did not improve event-free survival in patients with intermediate-risk rhabdomyosarcoma defined by their FOXO1 translocation status and clinical factors. Novel biology-based strategies are needed to improve outcomes in this population.
BACKGROUND: The Children\'s Oncology Group (supported by the US National Cancer Institute, US National Institutes of Health).

OBJECTIVE: To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
METHODS: A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed.
RESULTS: Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CR［(27.8%（5/18） vs 50.0%（9/18）; P >0.05］ and PR ［44.4%（8/18） vs 50.0%（9/18）; P >0.05］ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORR［72.2%（13/18） vs 100.0%（18/18）; P =0.045］ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001).
CONCLUSIONS: For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.
UNASSIGNED: 利妥昔单抗联合DHAX方案与CHOP方案一线治疗老年初诊弥漫大B细胞淋巴瘤的回顾性研究.
UNASSIGNED: 探讨R±DHAX方案与R-CHOP方案一线治疗老年初诊弥漫大B细胞淋巴瘤（DLBCL）患者的临床疗效及预后。.
UNASSIGNED: 回顾性分析江苏大学附属医院血液科2011年8月—2021年8月收治并至少完成3疗程的36例老年DLBCL患者，根据治疗方案分为利妥昔单抗±DHAX（R±DHAX）方案组（18例）和利妥昔单抗联合CHOP（R-CHOP）方案组（18例），观察患者的临床特征、疗效及生存。.
UNASSIGNED: 与R-CHOP组比较，R±DHAX组患者更高龄、体能状态更差及IPI评分更高，在年龄、ECOG评分、IPI评分上两组间差异有统计学意义(P =0.005，P =0.018，P =0.035)，而在性别、有无B症状、LDH是否升高、有无结外累及、细胞来源、有无骨髓浸润、是否联合使用利妥昔单抗上两组间差异均无统计学意义(P =0.738，P =1，P =0.315，P =0.305，P =0.413，P =0.177，P =0.711，P =0.229)。36例患者均可评价疗效，其中CR 14例（38.9%）、PR 17例（47.2%）、PD 5例（13.9%），ORR为86.1%（31/36）。R±DHAX组和R-CHOP组CR［(27.8%（5/18）对50.0%（9/18）］、PR［44.4%（8/18）对50.0%（9/18）］差异无统计学意义，但ORR［72.2%（13/18）对100.0%（18/18）］差异有统计学意义(P =0.045)。R±DHAX组和R-CHOP组1年OS率分别为（38.9±11.5）%和（94.4±7.4）%，2年OS率分别为（16.7±8.8）%和（72.2±10.6）%，组间比较差异有统计学意义（P =0.001，P =0.002）。R±DHAX组中位生存时间11个月（95%CI ：8.9-13.1），R-CHOP组中位生存时间未达到，组间存在统计学差异(P <0.001)。.
UNASSIGNED: 对于老年DLBCL患者，在OS方面R±DHAX方案可能不优于R-CHOP方案，且ECOG评分、IPI评分、年龄可能影响老年DLBCL患者生存。但R±DHAX方案安全、可耐受且具有一定疗效，可作为临床上老年DLBCL治疗选择之一。.

OBJECTIVE: To investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin\'s lymphoma (NHL).
METHODS: Fifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters.
RESULTS: After three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001).
CONCLUSIONS: CEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.

BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT.
METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258.
RESULTS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238).
CONCLUSIONS: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined.
BACKGROUND: Janssen and Leukemia & Lymphoma Society.

OBJECTIVE: Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%.
METHODS: A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention.
RESULTS: The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy.
CONCLUSIONS: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

Few data are known regarding the use of interim positron emission tomography (iPET) after the first two cycles (iPET2) of chemotherapy in treatment-naïve classical Hodgkin lymphoma (cHL) in routine clinical practice, and about the real-life adoption of intensification strategies for iPET positive patients. We conducted a multicenter retrospective study on cHL to investigate the use of iPET in the real-life setting, its prognostic role and outcomes of patients early shifted to intensification. Six hundreds and forty-one patients were enrolled (62% had advanced stage). iPET2 was positive in 89 patients (14%) including 8.7% and 17% early and advanced stage patients, respectively (p = 0.003). Among iPET 2 positive cases treatment was immediately modified in 19 cases; in 14 cases treatment was modified after an additional positive iPET4. Overall 56 iPET2 positive patients never received intensified therapies. Most frequently used intensified therapy was autologous stem cell transplantation followed by BEACOPP. After a median follow-up of 72 months, the 5-year progression-free survival (PFS) was 82% with iPET2 positive patients showing a worse PFS compared with iPET2 negative cases: 31% versus 85%. Focusing on advanced stage patients with a positive iPET2, the 5-year PFS was 59% for patients shifted to intensified therapy at any time point versus 61% for patients who never received intensified therapy. Our study confirmed the higher curability of naïve cHL patients in a real-world setting, and the prognostic role of iPET2 in this setting. A poor adherence to response-adapted strategy which however did not translate into a difference in patient outcomes.

The frontline immuno-chemotherapy regimen for HIV-associated non-Hodgkin Lymphoma is dose-adjusted EPOCH ± R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). Chemotherapy-induced peripheral neuropathy (CIPN), caused by vincristine, is a common adverse effect of EPOCH ± R, negatively impacting long-term patient outcomes. The primary objective of this study was to determine the incidence of CIPN, stratified by HIV status, in patients treated with EPOCH ± R. A retrospective cohort study at a tertiary referral comprehensive cancer center evaluated patients treated with EPOCH ± R from 2011 to 2018. The final sample included 27 patients with HIV compared to 279 without HIV (total n = 306). Overall, the incidence of CIPN was 29.4% (n = 90), including 5 with HIV (18.5%) and 85 without HIV (30.5%). Propensity scores were used to match patients by HIV status. Although no relationship was found between HIV status and neuropathy, CIPN affects too many undergoing treatments for lymphoma, supporting future investigations to minimize toxicities.