Hasil untuk "Diseases of the blood and blood-forming organs"

Zhiting Tang, Linjun Zha, Ruqiang Liang et al.

Abstract Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape of lung cancer over the past decade, markedly improving antitumor responses, overall survival, and quality of life. However, durable clinical benefit is achieved in only a subset of patients, and resistance to ICIs remains a major clinical challenge. Mechanistically, resistance arises from multiple, often overlapping processes, including inadequate tumor antigen presentation, dysfunctional T-cell priming and expansion, and the presence of physical and immunosuppressive barriers within the tumor microenvironment that limit immune cell infiltration and effector function. Cancer vaccines have re-emerged as a rational immunotherapeutic strategy to overcome these obstacles by inducing de novo or amplifying pre-existing tumor-specific immune responses, thereby enhancing long-term immunological memory while maintaining a favorable safety profile. Advances in antigen discovery, neoantigen prediction, and vaccine platforms have accelerated the development of both personalized and off-the-shelf neoantigen vaccines. Although personalized neoantigen vaccines have gained considerable attention following the success of mRNA-based COVID-19 vaccines, off-the-shelf approaches offer advantages in scalability, cost, and manufacturing timelines, facilitating broader clinical implementation. Accumulating preclinical and clinical evidence suggests that cancer vaccines are more effective in the adjuvant setting than in the metastatic setting, where high tumor burden and an immunosuppressive tumor microenvironment constrain vaccine-induced immune responses. Consistent with their limited efficacy as monotherapy, contemporary clinical trials increasingly evaluate cancer vaccines in combination with ICIs or other immunotherapeutic agents to enhance T-cell activation, reverse immune suppression, and restore antitumor immunity. This review synthesizes current mechanistic insights, highlights ongoing clinical efforts, and discusses future directions for rational cancer vaccine development in lung cancer, with an emphasis on overcoming resistance to ICI.

P. Scala, M. Gorrese, B. Serio et al.

Background. Clonal evolution is mainly defined based on appearance or expansion of clones harboring certain somatic mutations and/or cytogenetic abnormalities, while few studies have also investigated flow cytometry immunophenotyping variations associated with disease progression. In this study, flow cytometry immunophenotyping of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) with increased blast-2, and leukemic cells were characterized to identify the presence of subclones based on marker expression below the cut-off. Once identified, these clones were monitored by flow cytometry during follow-up, and these clone frequencies were correlated with variant allele frequency (VAF) of somatic mutations found by NGS at the same time point. Methods. Bone marrow (BM) specimens were collected in ethylenediaminetetraacetic acid tubes for immunophenotyping obtained from patients followed at the Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, after informed consent obtained in accordance with the Declaration of Helsinki and protocols approved by our local Ethic Committee. Next-generation sequencing (NGS) will be performed using SOPHIA Genetics Myeloid Solution panel (Sophia Genetics, Saint Sulpice, Switzerland), covering 30 genes, following manufacturer’s instructions, and analysis will be carried out as previously described. For immunophenotyping, 50 μL of fresh heparinized whole peripheral blood or bone marrow specimen will be stained with specific antibodies for characterization, as previously described. Results and Conclusions. A total of 38 consecutive patients diagnosed with AML or MDS with increased blast-2 followed at the Hematology and Transplant Center of Salerno from January 2024 to December 2024 were included. For 19 of them, flow cytometry was also available at disease re-evaluation and/or relapse. We showed that the immunophenotype of leukemic cells might greatly vary at disease relapse and certain phenotypic signatures might suggest a more aggressive disease.

Piotr F. Czempik, Małgorzata Pięta, Tomasz Jaworski et al.

C. Liberatore, A. Piciocchi, F. Accardi et al.

Quadruplet induction with D-VTd followed by single ASCT is the current standard treatment for NDMM in European Countries. However, in the latest EHA guidelines tandem ASCT is still recommended as an option for high-risk (HR) patients (pts), based on previous studies suggesting a survival benefit in this setting. On behalf of the GIMEMA Multiple Myeloma Working Party, we conducted a retrospective, multicenter, nationwide survey across 65 Italian centers on the use of tandem ASCT in NDMM pts from January 1st, 2022 to June 30th, 2024 (Table 1). The analysis of patients who actually received treatment are herein reported. During the study period, 2759 NDMM pts received D-VTd induction. Of these, 1106 (40.1%) pts had <60 years at diagnosis, 747 (27.1%) carried at least one HR FISH abnormality, including del17(p13), t(4;14), t(14;16), and gain/amp(1q21), and 686 (24.9%) pts had ISS 3 or R-ISS 3 disease stage. After D-VTd induction, 971 (35.2%) pts obtained ≥ CR. At data cut-off (January 9th, 2025), 1779 pts had received a single ASCT: of these, 647 (68.1%) in 2022, 744 (64.5%) in 2023, and 388 (59.1%) pts in the first six months of 2024. Over the same period, tandem ASCT was preplanned in 980 pts (35.6%) and was actually received in 741 of them: 257 (27.1%) pts in 2022, 346 (30%) in 2023, and 138 (21%) pts in the first six months of 2024. Across participating centers, the choice of tandem ASCT was based on multiple criteria, the most common being the presence at baseline of HR FISH abnormalities (86%), extramedullary disease or circulating plasma cells (66%), and advanced disease stage (37%). A suboptimal response (<VGPR) after first ASCT was a choice criterion of tandem ASCT in 34% of pts. Overall, 239 pts failed to receive a pre-planned tandem ASCT, 84 of them (35%) because of inadequate stem-cell collection and the remaining 155 pts for other reason, including treatment-related toxicities, patients’ refusal, and disease progression. At data-cut off, 1074 pts had completed D-VTd consolidation, and 2106 pts received post-ASCT maintenance therapy with lenalidomide. In the era of antiCD38-based quadruplet induction, tandem ASCT was considered an appropriate treatment option in approximately one third of NDMM Italian pts, above all with HR features, and its use was stable during the years. Poor stem-cell collection after D-VTd was the main limitation to this procedure. Lenalidomide maintenance therapy was offered to the majority of pts.  

Konul Baghirova

Introduction: Acute Lymphoblastic Leukemia (ALL) remains the most common malignant disease of childhood, accounting for approximately 26% of pediatric oncology diagnoses. Modern treatment approaches, particularly multi-agent chemotherapy regimens such as the BFM protocol, have significantly improved 5-year survival rates, reaching up to 96%. However, the toxicity of chemotherapy regimens, particularly late effects, negatively impacts long-term quality of life and clinical outcomes. These adverse effects include cardiotoxicity, secondary malignancies, endocrine dysfunction, and neurological damage. Given the limitations of conventional treatment protocols, exploring less toxic and more effective therapeutic strategies is of critical importance. Objective: • To identify the late effects of chemotherapy in pediatric patients treated for ALL.• To propose effective strategies for the early detection and management of these effects.• To compare the BFM protocol applied in Azerbaijan with international experiences. Materials and methods: This study includes 120 pediatric patients diagnosed with ALL and treated at the National Hematology Center of Azerbaijan between 2020 and 2023. A retrospective analysis of patient records was conducted. The evaluation of late chemotherapy effects was performed using internationally standardized methodologies:• Cardiotoxicity: Echocardiography and pro-BNP biomarker measurements.• Neurotoxicity: Clinical neurological assessment and electrophysiological testing.• Endocrine dysfunction: Thyroid function tests, insulin resistance evaluation, and growth hormone monitoring.• Secondary malignancies: Long-term follow-up and biomolecular analyses. Results: Among the analyzed patients, 38% exhibited various late-onset adverse effects. The incidence rates of key toxicity types were as follows: Conclusion: This study demonstrates the significant late effects of chemotherapy in pediatric patients treated with the BFM protocol in Azerbaijan. The findings emphasize the importance of implementing routine monitoring mechanisms, particularly for cardiotoxicity and endocrine dysfunction. International literature suggests that incorporating novel therapeutic agents, such as CAR-T cell therapy and targeted therapies like blinatumomab, into treatment regimens may improve clinical outcomes.

David A. Gell

Rinaldi I, Mauludi R, Jusman SW et al.

Ikhwan Rinaldi,1,2 Radinal Mauludi,2 Sri Widia Jusman,3 Robert Sinto,4 Kuntjoro Harimurti5,6 1Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 2Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 3Department of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 4Division of Tropical and Infectious Diseases, Department of Internal Medicine, Cipto Mangunkusumo National General hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 5Clinical Epidemiology Unit, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia; 6Division of Geriatrics, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaCorrespondence: Ikhwan Rinaldi, Email ikhwanrinaldi@gmail.comIntroduction: Currently, Imatinib (IM) which is a Tyrosine Kinase Inhibitor (TKI), is the main treatment for patients with chronic myeloid leukemia (CML). Major molecular response (MMR) is used as therapeutic response. Resistance to IM may be caused by hypoxia which is regulated by hypoxia inducible factor (HIF) 2-α. The role of HIF2-α is currently not researched extensively. This study aimed to analyse the differences in HIF-2α expression between chronic phase CML patients that achieved MMR and those that did not achieve MMR.Methods: This study used a cross-sectional method which analysed secondary data from whole blood samples in chronic phase CML patients aged 18– 60 years that received hydroxyurea (HU) before IM, aged 18– 60 years, received IM therapy for more than 12 months, and were willing to participate in the study. The exclusion criteria for this study were patients who were receiving IM at a dose of more than 400 mg/day. HIF-2α protein expression was examined using the enzyme-linked immunosorbent assay (ELISA) method. Differences between HIF-2α protein expression in groups that achieved MMR versus not achieving MMR was analysed using the Mann–Whitney test.Results: A total of 79 subjects were obtained. The median HIF-2α was 90.56 pg/mg protein (3.01– 4628.74). There was no statistically significant difference in expression of HIF-2α in the group that reached MMR and did not reach MMR, namely 123.45 pg/mg protein and 89.25 pg/mg protein respectively (p 0.718).Conclusion: This study found no statistically significant difference between HIF-2α expression level and MMR achievement of chronic phase CML patients who received HU before IM therapy.Keywords: CML, leukemia, imatinib, resistance, chronic myeloid leukemia, IM

J Rech, N Caetano, CA Kreisig et al.

Objetivos: Conforme Portaria de Consolidação nº5 de 28 de setembro de 2017, o doador de repetição é aquele que realiza duas ou mais doações no período de doze meses. Por ser doador de repetição, sabe os cuidados que deve ter, sendo muito menor o índice de sorologia reagente deste grupo de doadores, garantindo também a manutenção dos estoques de hemocomponentes dos serviços, pois realiza várias doações dentro do período observado. O objetivo deste estudo foi analisar o impacto do índice de doadores de repetição e o descarte de hemocomponentes por sorologia reagente no Hemovita Caxias. Material e métodos: A coleta de dados foi realizada através do sistema informatizado, abrangendo o número total de doações realizadas, o total de doadores sem repetição de doação, o total de doadores com repetição e o total de doadores com sorologia reagente ou inconclusiva no período de janeiro de 2022 à julho de 2023. Resultados: Foram avaliadas 14.794 doações que ocorreram no período mencionado, destas, 4.787 (32,36%) foram doações de repetição e 10.007 (67,64%) foram doações esporádicas ou de primeira vez. Dos doadores de repetição, 3.151 (66%) eram do sexo masculino e 1.636 (34%) do sexo feminino. No período foram descartadas 139 doações (0,93%) por sorologia reagente, sendo 133 doações de primeira vez (95%) e 6 doações esporádicas, ou seja, doador repete a doação após um intervalo superior a doze meses da última doação. Discussão: Embora o índice de doadores de repetição do Hemovita de 32,36%, seja menor quando comparado aos dados do 9ºboletim de produção hemoterápica, o Hemoprod, que é de 45,82% em serviços privados do sul do Brasil, o Hemovita mantém o índice de sorologia reagente abaixo do que aponta o mesmo relatório, sendo 0,93% das doações descartadas por sorologia reagente. Conclusão: Doações de repetição agregam segurança ao ato transfusional, visto que os doadores tem conhecimento dos fatores de impedimento e de risco, e, por esse motivo, tem hábitos de vida mais saudáveis e seguros, contribuindo para a manutenção dos estoques dos serviços de hemoterapia, realizando doações seguidas dentro do período permitido.

M. Bektaş, A. E. Eşkazan, T. O. Tiryaki et al.

Zachary S. Pallister, Jayer Chung

While rare, abdominal aortic infections remain one of the most technically and emotionally challenging cases that a vascular surgeon may face. Secondary infections of either endovascular, or open aortic reconstructions range from 0.2% to 8%. Primary aortic infections are much more rare. Diagnosis can be elusive, depending upon the virulence of the causative microbes, and extent of the infection. Patients are often brittle, with immunocompromise and malnutrition prevalent in this patient population. The gold standard diagnostic test remains a computed tomographic angiogram. The mainstay of management requires vascular control, and wide debridement of all infected materials and revascularization. Multiple methods exist to reconstruct the vascular supply. The neo-aortoiliac system (NAIS) is attractive as it utilizes the patient’s own femoral veins to reconstruct the vascular supply after the infection has been extirpated. The procedure is demanding upon the patient and surgeons alike. Also, the rarity of aortic infections limit experiences the literature to centers of excellence. However, the NAIS resists infection well, leaving the patient without any remaining foreign bodies. No further costs for conduit are incurred. Moreover, multiple experiences show excellent durability. While comparative effectiveness literature remains sparse, we believe the NAIS to be the optimal method of revascularization for select patients. In this article, we will review the use of NAIS for primary and secondary aortic infections. In particular, we will emphasize procedural details to help enable the reader to apply this procedure most effectively to their own patients.

Muruvvet Seda AYDIN, Funda CERAN, Simten DAGDAS et al.

Objective: Next-generation sequencing (NGS)-based technologies are  novel methodologies for the diagnosis, prognostic assessment and decision of individualized treatment strategy in hematological neoplasia. NGS led to a more comprehensive understanding of the mutational landscape, especially in the myeloid neoplasms. Herein, we present the results of the patients who underwent NGS with the suspicion of myeloid neoplasia. Methodology: Retrospective data from a total of 13 patients were analyzed who were diagnosed between 01.10.2018 and 01.06.2021. There were four myeloid panels in the NGS. Panel 1 consists of ASXL1, CALR, CBL, CEBPA, CSF3R, and DNMT3A mutations. Panel 2 consists of EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, and MPL mutations. Panel 3 consists of NPM1, NRAS, RUNX1, SETBP1, and SF3B1 mutations. Panel 4 consists of SH2B3/LNK, SRSF2, TET2, TP53, U2AF1, ZRSR2 mutations. Results: Median age was 48. Diagnoses were AML (n=7), AA (n=1), MDS (n=2), DLBCL (n=1), MM (n=1), and Evans syndrome (n=1). Seven cases with malignant diagnoses were eligible for intensive therapy. There were no mutations detected by NGS in MM, AA, DLBCL, and Evans syndrome cases. Biallelic CEBPA mutation accompanied FLT3 mutation in 1 case. IDH1 and NPM mutation were detected in 1 APL case. MPL, SRSF2, ASXL1, CBL, U2AF1, SF2B1, and TET2 were mutations detected in cases with dysplasia. Conclusion: In our cohort, NGS did not add any significant information in the lymphoid malignancies and benign hematological cases. NGS helped to define the allelic ratio of FLT3+ mutations and helped to accurately define the ELN risk of AML. Mutations that were detected in the cases with dysplastic bone marrow findings were concordant that were reported in the literature. Larger case series are needed in order to define the therapeutic and prognostic implications.

JP Sharman, JM Melear, A Yacoub et al.

Objectives: The combination of lenalidomide + rituximab (R2) has shown complementary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (NHL), as well as mantle cell lymphoma (MCL), an uncommon but aggressive form of NHL. The MAGNIFY phase 3 trial previously reported an ORR of 54% in patients with R/R MCL (Sharman J, et al. Hematol Oncol. 2019). Presented here are updated analyses from this trial. Materials and methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL, marginal zone lymphoma, and MCL. Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in patients with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group (IWG) criteria. Secondary end points include safety, CR rate, duration of response (DOR), duration of CR (DOCR), time-to-response (TTR), time-to-next antilymphoma therapy, and overall survival. This analysis evaluates the interim primary endpoint of overall response rate (ORR) by 1999 IWG criteria and safety of R2 induction in patients with MCL in the induction intention-to-treat population. Results: As of August 28, 2020, 73 patients with MCL were enrolled (median age, 70.0 y [range, 51–88]); 89% had stage III/IV disease, and 41% had bulky disease (> 7 cm or > 3 cm ×3 lymph nodes). All patients had received prior rituximab-containing therapy, with 25 (34%) rituximab refractory (progression ≤ 6 mo after last rituximab dose). Seven patients (10%) had received prior ibrutinib. Median follow-up was 31.7 mo for patients still alive. ORR was 51%, with 34% CR rate (CR + CRu). Response rates were similar in patients refractory to rituximab (ORR = 48%, CR/CRu = 32%) and patients not refractory to rituximab (ORR = 52%, CR/CRu = 35%). Median DOR was 31.6 mo; median DOCR was not reached; median TTR was 2.8 mo, and median PFS was 28.0 mo, with 1-year PFS rate of 57%. The most common treatment emergent adverse events (TEAEs) of any grade were neutropenia (51%), fatigue (44%), diarrhea (32%), constipation (28%), cough (28%), dyspnea (26%), and nausea (26%). Grade 3/4 neutropenia was 46%; all other grade 3/4 TEAEs were ≤ 11%. Discussion: R2 is an active and tolerated regimen with durable responses among patients with R/R MCL and mostly naive to Bruton tyrosine kinase inhibitor therapy. Conclusions: These results suggest that R2 should be considered as a therapeutic option for patients with R/R MCL.

Robert J. Kreitman, Claire Dearden, Pier Luigi Zinzani et al.

Abstract Background Moxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL). Methods Eligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days. Results Eighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported. Conclusions Moxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy. Trial registration ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

Theodor Tirilomis

Atte Nikkilä, Jani Raitanen, Olli Lohi et al.

Julio Delgado, Itziar Salaverria, Tycho Baumann et al.

Adil A Othman, Adil A Eissa, Raji D Markous et al.

Background and Aim: Owing to the scarcity of data on hepatitis C virus (HCV) genotypes in Iraq and due to their epidemiological as well as therapy implications, this study was initiated aiming at determining these genotypes in Northern Iraq. Materials and Methods: A total of 70 HCV antibody positive multi transfused patients with hemoglobinopathies, who had detectable HCV ribonucleic acid, were recruited for genotyping using genotype-specific nested polymerase chain reaction. Results: The most frequent genotype detected was genotype 4 (52.9%) followed by 3a (17.1%), 1b (12.9%) and 1a (1.4%), while mixed genotypes (4 with either 3a or 1b) were detected in 7.1%. Conclusion: The predominance of genotype 4 is similar to other studies from surrounding Eastern Mediterranean Arab countries and to the only earlier study from central Iraq, however the significant high proportion of 3a and scarcity of 1a, are in contrast to the latter study and may be explainable by the differing population interactions in this part of Iraq. This study complements previous studies from Eastern Mediterranean region and demonstrates relative heterogeneity of HCV genotype distribution within Iraq and should trigger further studies in other parts of the country.

Olga Meltem Akay, Eren Gündüz, Ercan Kaya et al.

Poul Bennekou, Henrik Harbak, Lars Ole Simonsen

Koulieris Efstathios, Panayiotidis Panayiotis, Harding Stephen J et al.

<p>Abstract</p> <p>Background</p> <p>HevyLite™ is a new, recently developed method that facilitates separate quantification of the kappa- and lambda-bounded amounts of a given immunoglobulin (Ig). Using this method, we measured intact immunoglobulin (heavy/light chain; HLC) IgG-kappa, IgG-lambda, IgA-kappa, IgA-lambda individually, as well as their deriving ratios (HLCR) in a series of IgG or IgA multiple myeloma (MM) patients, to investigate and assess the contribution of these tests to disease evaluation.</p> <p>Patients and methods</p> <p>HevyLite™ assays were used in sera from 130 healthy individuals (HI) and 103 MM patients, at time of diagnosis. In patients, the level of paraprotein was IgG in 78 (52 IgG-kappa, 26 IgG-lambda) and IgΑ in 25 (13 IgΑ-kappa, 12 IgΑ-lambda). Durie-Salmon and International Staging System stages were evenly distributed. Symptomatic patients (n = 77) received treatment while asymptomatic ones (n = 26) were followed. Patients' median follow-up was at 32.6 months. HLCR was calculated with the involved Ig (either G or A) as numerator.</p> <p>Results</p> <p>In HI, median IgG-kappa was 6.85, IgG-lambda 3.81, IgA-kappa 1.19 and IgA-lambda 0.98 g/L. The corresponding median involving HLC values in MM patients were 25.8, 23.45, 28.9 and 36.4 g/L. HLC-IgG related to anemia, high serum free light chain ratio and extensive bone marrow infiltration, while high HLCR correlated with the same plus increased β2-microglobulin. In addition, increased HLCR and the presence of immunoparesis correlated with time to treatment. Patients with high HLCR had a significantly shorter survival (<it>p </it>= 0.022); HLCR retained its prognostic value in multivariate analysis.</p> <p>Conclusions</p> <p>HLC and HLCR quantify the precise amount of the involved immunoglobulin more accurately than other methods; moreover, they carry prognostic information regarding survival in MM patients.</p>