bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review determining the characteristics of primary bone lymphoma.
Authors: Benkhadra Raed , Auster Michael , Nayfeh Tarek , Abbas Alzhraa S. , Alsibai Reem , Benkhadra Khalid , Datta Paromita , Kaur Supreet 
Published: June 2023

e19543 Background: Primary Bone Lymphoma (PBL) is defined as a lymphoma originating in an osseous site with no systemic disease. It is rare, constituting around 1% of all lymphomas. Due to its rarity, ascertaining natural history and standard of care treatments are based primarily on small case series but there have been no systematic reviews, randomized control trials or meta-analysis to establish optimal treatment strategies. Methods: We searched MEDLINE, Embase, Scopus and other sources, from each database's inception to September 2022. Outcomes of interest included mortality and progression at different time points, as well as complete response and partial response. Meta-analysis was conducted using the random-effects model. Results: The number of studies matching our inquiry was 51 ranging from 1955 to 2019. Total patients studied were 5,847 of which 3,055 were male and the dominant histology was diffuse large B cell lymphoma with 3,816. Treatment primarily consisted of radiation therapy, chemotherapy, or a combination of the two. Overall mortality at 2, 5 and 10 years was 17%, 29% and 39% respectively. Complete response to initial treatment was noted in 73% of patients. Disease progression at 2 and 5 years was 26% and 29% respectively. Patients aged older than 60 years and multiple sites of disease in the skeleton (such as axial and spine etc.) had worse outcomes with RR 1.76 (P value 0.0027) and 1.133 (P value 0.0167) respectively. Additionally, patients who underwent chemotherapy with radiation vs radiation alone had improved outcomes with a relative risk of 0.38 (P value of 0.0001). Patients who underwent radiation treatment in addition to chemotherapy tended to have improved outcomes with a relative risk of 0.60 but this was not statistically significant with a P value of 0.068. Conclusions: We performed a systematic review to determine the characteristics and current treatment of PBL. The analysis demonstrates the rarity and heterogenicity of the disease. The current standard of care is for chemoradiation, but this is based primarily on old case studies. Our study confirms the utility of multimodal treatment with a tendency for improved outcomes. However, further prospective trials are needed to determine the necessity of multimodal treatment given this hypothesis generating study. [Table: see text]
Serum IL-6 levels following siltuximab administration in castleman disease.
Authors: Mango Natalie , Shyamsundar Saishravan , Sarmiento Bustamante Mateo , Lavery Criswell , Pierson Sheila K. , van Rhee Frits , Fajgenbaum David 
Published: June 2023

e19545 Background: Idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder. Though etiology is unknown, interleukin-6 (IL-6) is a driver in a portion of cases. Siltuximab is a monoclonal antibody that targets IL-6 and has been approved by the Food and Drug Administration to treat iMCD. Treatment guidelines for iMCD note that IL-6 directed therapy can result in spurious elevation of serum IL-6, based on anecdotal reports. This could lead physicians to erroneously infer treatment failure. Herein we investigate an international natural history registry of CD to evaluate whether IL-6 levels are increased following siltuximab. Methods: Data on peak IL-6 levels measured in patients before and after receiving siltuximab was available for 40 patients. C-reactive protein (CRP) levels measured near peak IL-6 values before and after siltuximab were also collected where available (n=32). Peak IL-6 values were standardized by the upper end of the reference range. Median values and interquartile ranges were calculated for pre- and post-siltuximab CRP and peak IL-6 values. Wilcoxon signed-rank tests were used for statistical comparison. Results: Our cohort consisted of 40 patients who had lymph node histopathology consistent with Castleman disease. An expert panel confirmed 16 iMCD, 5 POEMS-MCD, 1 regional CD, 3 unicentric CD, 11 other diagnoses, and 4 remain to be determined. Breakdown by gender was 50% male (n=20) and 50% female (n=20) with a mean age of 40.76 years. We analyzed peak standardized IL-6 levels before and after treatment with siltuximab. Prior to treatment with siltuximab, the median IL-6 level was 3.18, whereas after treatment with siltuximab, the median IL-6 level was elevated to 557 (p = 1.8 x 10-12). Given that CRP is a well-established biomarker of IL-6 activity, we investigated whether the increased IL-6 was a reflection of increased disease activity in these patients. Here, we found that median CRP before treatment was 59.7 mg/L, whereas after treatment, median CRP decreased to 4.95 mg/L (p = 0.0005) suggesting that IL-6 levels were rising despite reduced disease activity. IL-6 levels rose almost 200-fold while CRP reduced over 10-fold. Conclusions: Our results indicate that IL-6 levels significantly increase after patients receive siltuximab. Given that CRP is a biomarker of IL-6 activity, we infer that IL-6 is artificially elevated but not having a functional impact in the patient. Therefore, IL-6 levels should not be measured after siltuximab is given and they should not be used to guide treatment decisions. [Table: see text]
Outcomes of intravenous and subcutaneous cladribine administration in patients with hairy cell leukemia: A systematic review and meta-analysis.
Authors: Basit Jawad , Zaheer Zaofashan , Khan Muhammad Hammad , Fatima Maurish , Taj Sobaan , Akbar Usman Ali , Rehman Mohammad Ebad Ur , Saeed Sajeel , Vikash Sindhu , Ramesh Nithya , Shahab Asna , Shahid Muhammad , Komel Aqsa , Irshad Umer , Tabassum Shehroze , Naeem Aroma 
Published: June 2023

e19546 Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Cladribine (2CdA) monotherapy is used as a first line treatment for HCL. 2CdA can be administered intravenously (IV) or subcutaneously (SC). The aim of our study is to compare the safety and efficacy of these two routes of administration of 2CdA as a first line treatment of HCL. Methods: We conducted a systematic literature search across multiple databases and Google up to February 2023. We included studies that reported outcomes for either intravenous (IV) or subcutaneous (SC) cladribine (2CdA) therapy, as well as those that directly compared the two routes. Our primary efficacy outcomes were overall response rate (ORR) and complete response rate (CRR), and our primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random effects model and conducted subgroup analysis for HCL type (classical vs classic and variant both). We calculated odds ratios (ORs) for studies involving a head-to-head comparison between the two routes and used the Higgins I2 statistic to assess heterogeneity. Results: We identified a total of 25 studies (15 trials, 10 cohorts) with a patient population of 2669. The median age of the patients was 53.5 years. The pooled ORR and CRR for IV and SC 2CdA therapy were 96%, 82%, 88% and 67% respectively. The incidence of neutropenia (82% vs 61%) and infections (13% vs 16%) was greater for SC 2CdA than IV 2CdA. Five studies provided a direct comparison between SC and IV routes but three were excluded from the analysis due to unavailability of desired outcomes. Studies involving a direct comparison between the 2 routes of administration showed that the odds of achieving CRR were 86.6% greater with IV than SC 2CdA but these results were not significant. The proportion of adverse events was comparable for IV and SC routes. Subgroup analysis for HCL type did not resolve heterogeneity for ORR and CRR. It did, however, result in greater ORR for classic (92%) and mixed (92%) HCL treated with SC 2CdA. Conclusions: Compared to SC 2CdA, IV 2CdA is safer and more effective as a first-line treatment of HCL. However, future high-power randomized control trials that directly compare IV and SC routes are needed to confirm this evidence. [Table: see text]
Evaluating the effectiveness and tolerability of chemotherapy in hairy cell leukemia: A comprehensive systematic review and meta-analysis.
Authors: Basit Jawad , Zaheer Zaofashan , Ahmed Aleena , Fatima Maurish , Akbar Usman Ali , Ramesh Nithya , Shahab Asna , Rehman Mohammad Ebad Ur , Shah Zunairah , Saeed Sajeel , Ahmad Mahboob , Aisha Azka 
Published: June 2023

e19547 Background: Hairy cell leukaemia (HCL) is a rare, chronic B cell cancer that involves the bone marrow, peripheral blood, and spleen. Many treatment options are available for HCL. Our study aims to elucidate the safety and efficacy of each intervention through the pooled proportion of response to treatment and adverse events. Methods: We conducted a literature search across PubMed, Embase, Cochrane, and Google Scholar from inception till February 2023. We included clinical trials and cohorts of patients with HCL receiving modern anticancer drugs (cladribine, rituximab, cladribine plus rituximab, BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib). The primary efficacy outcomes were Objective Response Rate (ORR) and Complete Response Rate (CRR) and the primary safety outcome was adverse effects (AEs). We used OpenMetaAnalyst to pool data using the Hedges-Olkin Random Effects Model, with subgroup analysis for HCL type and study design. Results: Our meta-analysis included 44 studies (28 trials and 16 cohorts) with 3976 patients with HCL. The median age was 56.7 years. The highest efficacy was seen in patients receiving combination therapy of cladribine and rituximab, with an ORR of 97% and CRR of 92%. Cladribine monotherapy showed an ORR of 95% and CRR of 79%, while rituximab monotherapy had an ORR of 62% and CRR of 31%. BRAF inhibitors, anti-CD22 monoclonal antibodies, and ibrutinib showed less efficacy, with ORRs of 92%,78% and 51% and CRRs of 41%, 49%, and 17% respectively. Subgroup analysis for study design and HCL type did not resolve heterogeneity. The ORR and CRR with 95% Confidence Intervals and AEs for each regimen are given in the table. Conclusions: Cladribine with rituximab is the most effective treatment for untreated and relapsed HCL patients, with neutropenia as the most common AE. Since we pooled the proportions for treatment-naïve and relapsed cases together due to inavailability of segregated data, the results should be used cautiously in clinical decision making and limit the derivation of consensus for treatment of newly diagnosed or relapsed HCL. [Table: see text]
Clinical characteristics, survival outcomes, and prognostic factors in subcutaneous panniculitis like T-cell lymphoma: National Cancer Database analysis (2004-2018).
Authors: Baidoun Firas , Sluzevich Jason , Tun Han W. , Alhaj Moustafa Muhamad 
Published: June 2023

e19548 Background: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare lymphoma accounting for less than 1% of mature T-cell lymphomas. Its natural history is not understood due to lack of large studies with long-term followup and an optimal therapeutic approach is not well-defined. Methods: The National Cancer Database was queried for patients aged 18 years and older diagnosed with SPTCL between 2004 and 2018. We excluded patients who lost to follow-up. Kaplan-Meier and multivariate Cox regression were used in the analyses. Results: 353 patients with SPTCL were included. 63% were females, 62% Caucasian, and 26% African American, 50% had early stage (I and II) and 32% had advanced stage (III and IV). 58.4% received chemotherapy, 38.2% did not receive chemotherapy and 3.4% had unknown chemotherapy status. The median age at diagnosis was 49 years (range 18-90). The median overall survival (mOS) for the whole cohort was not reached In early-stage (N = 178), 49.5% had chemotherapy with 39% receiving single-agent chemotherapy and 60% receiving multi-agent chemotherapy. 18.5% received radiation. In advanced-stage (N = 112), 75.9% received chemotherapy with 19% receiving single-agent chemotherapy and 81% receiving multi-agent chemotherapy. 9.8% received radiation There was no significant difference in the mOS between advanced-stage and early-stage (161.5 months vs not reached, P = 0.051) In early stage, there was no significant difference in the OS between chemotherapy and no chemotherapy (mOS was not reached in both groups, P = 0.324). The same trend was seen in the advanced stage (mOS was not reached in both groups, P = 0.851) Compared to Caucasian, African American patients were younger (median age 47 vs 54 years), but there was no significant difference in disease stage, receiving chemotherapy or radiation or other disease related characteristics (IPI score, B-symptoms, and HIV infection). African American patients had better OS (mOS was not reached, P = 0.003). This significant difference was seen in early stage (mOS was not reached, P = 0.003), but not in advanced stage (mOS 162 vs 122 months, P = 0.113) On multivariate analysis, age and Charlson-Deyo score ≥3 were associated with worse OS (HR 1.028 95% CI 1.005-1.052; P = 0.018 and HR 14.711 95% CI 2.316-93.449; P = 0.004, respectively), whereas disease stage and chemotherapy status did not affect the OS (HR 0.938 95% CI 0.545-1.617; P = 0.819, HR 1.271 95% CI 0.175-9.255; P = 0.813, and HR 0.922 95% CI 0.489-1.738; P = 0.802, respectively). Conclusions: Our study indicates that SPTCL is predominantly an indolent lymphoma associated with long-term survival irrespective of stage and chemotherapy. A conservative therapeutic approach appears to be more appropriate than intensive therapeutic approach in most patients. A risk stratification algorithm is needed to determine the therapeutic intensity.
Racial bias in multiple myeloma clinical trials: Racial minorities continue to miss out on treatment advances.
Authors: Jasaraj Ranjit , Gaire Suman , Proskuriakova Ekaterina , Jasaraj Ranjana , Keruakous Amany R. 
Published: June 2023

e20009 Background: Adequate representation of participants based on race and ethnicity in a clinical trial helps ensure the results' generalizability. There is a disparity in the participation of minorities in oncology clinical trials despite higher incidence and disease burden in them. The incidence of Multiple Myeloma (MM) in AA (African American) is twice as compared to White, and they are twice as likely to die from MM compared to White. Methods: We queried ClinicalTrials.gov in February 2023 for all completed interventional trials with the published results for Multiple Myeloma in the US. Demographic data were collected from all the studies. If not available, the primary manuscript was searched using the trial number. We excluded the studies involving other malignancies and conducted outside of the USA. Trials on prevention, diagnostics, supportive care, and antibiotics were also excluded. Incidence data of Multiple myeloma was obtained from the SEER database for each ethnicity and race. Results: Out of 194 trials included in our study, 133 (68.56%) reported at least either race or ethnicity. Of these trials, 83 (42.78) reported race, 124 (63.91) reported ethnicity, and 77 (39.69) reported both race and ethnicity. 5.67% of the trial participants were reported as Hispanic race. White, AA, and Asian represented 79.82%, 11.36%, and 3.10% of the trial participants, respectively. The number of trials reporting race or ethnicity has increased when comparing the trials conducted between 2001-2011 and 2012-2022 (58.3% vs. 90.3%); OR 6.4; 95% CI 2.77-17.98; p<0.001. Participation of Asians increased (2% vs. 5.5%; p<0.0005), while there were slight changes among AA (11.7% vs. 10.6%, p=0.1475), Hispanic (5.4% vs. 6%; p=0.3863), and White (80.8% vs. 77.8%, p=0.208) between 2001-2011 and 2012-2022. Conclusions: Despite ongoing efforts to improve the diversity of minorities in oncology trials, they are still under-enrolled in multiple myeloma. More studies and interventions are needed to address this disparity. [Table: see text]
Efficacy and safety of elranatamab in patients with high-risk relapsed/refractory multiple myeloma (RRMM): A subgroup analysis from MagnetisMM-3.
Authors: Larson Sarah Marie , Bahlis Nizar J. , Maisel Christopher , Karlin Lionel , Varshavsky Yanovsky Asya , Leip Eric , Sullivan Sharon T. , Viqueira Andrea , Touzeau Cyrille 
Published: June 2023

e20017 Background: Data from the ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of elranatamab in patients (pts) with RRMM and no prior BCMA-directed therapy (Cohort A). Results in high-risk subgroups are reported. Methods: Eligibility criteria, dosing and administration were previously reported (Bahlis, ASH 2022). Subgroups analyzed were R-ISS stage (I/II/III ), cytogenetic abnormalities (standard/high risk [high-risk defined by the presence of t(4;14), t(14;16) or del(17p)]), extramedullary disease (EMD) at baseline (Y/N), bone marrow plasma cell involvement (BMPC) at baseline (<50%/≥50%), and penta-refractory disease (Y/N). Results include data up through ~12 months after last pt initial dose. Results: Median treatment durations and the proportions of pts receiving treatment at the data cut-off are reported in the Table. The most frequent cause of discontinuation was progressive disease which was higher for all high-risk subgroups than the corresponding lower risk subgroups. A clinical benefit, assessed by the objective response rate (ORR), was observed across subgroups (Table). A multivariable logistic regression analysis for ORR including baseline age, ECOG, sex, region, cytogenetic risk, presence of EMD, BMPC involvement, prior stem cell transplant, R-ISS stage, number of prior lines, type of myeloma, and penta-refractory disease showed presence of EMD at baseline and non-IgG myeloma (vs IgG) as predictive of lower ORR. Light chain-only myeloma (vs IgG) was predictive of higher ORR. Median duration of response (DOR) was not reached in subgroups by 12 months, DOR rate at 12 months is reported in the Table. Any grade TEAEs were reported in 100% of pts in the study. The incidence of grade 3/4 TEAEs was overall similar across subgroups (Table). Conclusions: Elranatamab is efficacious and has a manageable safety profile in pts with high-risk RRMM and no prior BCMA-directed therapy. Clinical trial information: NCT04649359 . [Table: see text]
Role of PETCT in multiple myeloma: A 3 year data analysis of tertiary care center.
Authors: Gupta Neha , Pendharkar Dinesh 
Published: June 2023

e20030 Background: Bone involvement is one of the most common presentations of multiple myeloma, seen in about two-thirds of patients at the time of diagnosis. Therefore, imaging is an integral part of diagnosis for detection of lytic bone lesions and extra medullary disease. Evaluation of disease burden in both multiple myeloma and plasmacytoma as measured by PET/CT scan and response evaluation to induction therapy using PET based SUV changes is an important research topic. Methods: Single center prospective study done from 1st January,2020 to 30th June,2021 in Sarvodaya hospital and research center, Faridabad. All patients with multiple myeloma and solitary plasmacytoma coming to Sarvodaya hospital were eligible for the study. Total of 42 patients were enrolled into the study. PET-CT was done at baseline and post treatment as planned. Results: Out of 42 patients, 2 patients were diagnosed as solitary plasmacytoma and 40 patients were diagnosed as multiple myeloma. The median age of presentation was 64 years with male predominance (64.29%). PET-CT was done pre-treatment, On the basis of PET-CT findings it was seen that < 3 focal lesions were seen in 24(57.14%) patients and > 3 focal lesions were seen in 18(42.86%) of patients, based on SUV max, lesions with < 4.2 SUV max value were seen in 23(54.77%) patients and lesions with > 4.2 SUV max values were seen in 19(45.23%) patients. Presence of extra medullary disease was seen in 17(40.48%) of patients. 39(92.86%) patients were available for response analysis post treatment.3(7.14%) patients were expired during the study due to treatment complications and comorbidities. On the basis of PET-CT findings post treatment there was statistically significant response seen with p value of < 0.05 in the number of focal lesions, lesions with SUV max and burden of extra medullary disease. Evaluation of response when assessed radio logically by PET-CT scan, it was seen that Complete response was found in 22(56.40%) patients, VGPR was seen in 4(10.25%) patients, PR was found in 12(30.77%) patients and PD was seen in 1(2.58%) patient. But the results of co-relation of PET-CT findings with survival outcomes were not significant. Conclusions: PET-CT plays a significant role in diagnosis and response assessment. But there is still no uniform criteria for quantification and visualization of FDG avid lesions for patients with multiple myeloma.
Comparison of daratumumab-based regimens as second-line therapy in relapsed/refractory multiple myeloma.
Authors: Charalampous Charalampos , Goel Utkarsh , Kapoor Prashant , Binder Moritz , Buadi Francis , Dingli David , Dispenzieri Angela , Fonder Amie L. , Gertz Morie A. , Gonsalves Wilson I. , Hayman Suzanne R. , Hobbs Miriam A. , Hwa Yi Lisa , Kourelis Taxiarchis , Lacy Martha , Leung Nelson , Lin Yi , Warsame Rahma M. , Rajkumar S. Vincent , Kumar Shaji 
Published: June 2023

e20032 Background: The introduction of anti-CD38 antibodies (daratumumab) in the treatment landscape of multiple myeloma (MM) has increased the progression-free survival (PFS) in recent years. Still, the ideal combination (Dara-IMiD vs. Dara-PI) of these drugs in patients with relapsed MM is unclear. Methods: We reviewed MM patients treated with daratumumab as second-line therapy at our institution from 2016 to 2022 to assess the outcomes with the different combination therapies. We used the Kaplan-Meier method to estimate PFS from the first relapse. Results: We identified 329 patients with a median age of 63.6 years (range: 27.1 – 90.4). Most of the patients received triplet induction therapy (95%) and upfront transplant (67%) as primary therapy. At the time of Dara initiation, 41% were refractory to IMiDs, 22% to PIs, 18% to both, and 18% to neither drug. Patients treated with Dara-IMiD had significantly better PFS than Dara-PI (28.7 months vs. 18.5 months, p < 0.01, respectively). In a subgroup analysis based on the FISH results, high-risk patients had similar PFS outcomes (24.3 vs. 10.2 months, p = NS, respectively), while standard-risk patients benefited significantly from the Dara-IMiD regimen (48.3 vs. 19.2 months, p < 0.01, respectively). Among patients treated with Dara-IMiD, those already refractory to IMiDs from the first line had significantly shorter PFS than those without IMiD resistance (14.9 vs. 43.3 months, p < 0.01, respectively). In addition, the lenalidomide-based combination resulted in significantly better PFS compared to pomalidomide in our cohort (40.5 vs. 19.2 months, p < 0.01, respectively). However, no difference was found in the IMiD refractory population (12.3 vs. 15.1 months, respectively). Finally, no significant differences were seen between Dara-IMiD and Dara-PI in patients only refractory to IMiDs (16.1 vs. 12.8 months, p = NS, respectively). Conclusions: While further studies are required to adjudicate the best combination, we conclude that Dara-IMiD might be more effective in patients with relapsed MM, especially for patients not refractory to IMiD at first line. [Table: see text]