{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:06:39Z","timestamp":1791245199915,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Baxalta GmbH, now part of Takeda","award":["Investigator-Initiated Research grant no. IISR-2019-104350\/ IIR-DE-002696"],"award-info":[{"award-number":["Investigator-Initiated Research grant no. IISR-2019-104350\/ IIR-DE-002696"]}]},{"name":"aio-studien-ggmbh of the german cancer society","award":["AIO-SUP-0119\/ass"],"award-info":[{"award-number":["AIO-SUP-0119\/ass"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Support Care Cancer"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>In secondary immunodeficiency, immunoglobulin replacement therapy (IgRT) is recommended by guidelines (GL) for patients with IgG level\u2009&lt;\u20094\u00a0g\/l and more than 3 infections or a severe infection. IgRT may be appropriate if IgG level\u2009&lt;\u20094\u00a0g\/l and\/or 1\u20133 less severe infections (\u2264\u2009grade 2).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This was a retrospective sample analysis representative for practices and hospitals in Germany. The treatments and infection data were collected from patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). GL adherence (GLAD) was analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Data from 1086 patients (CLL 490, MM 596) were collected from 86 centers. Of all patients, 34.8% developed IgG deficiency during therapy (CLL 35.5%; MM 34.2%). IgRT was given in 23.5% of CLL and 14.4% of MM patients. GLAD in hypogammaglobulinemia and indication to IgRT was 23.3% of 86 CLL and 22.1% of 77 MM patients. Without GLAD, the hazard ratio (HR) for any infection was 4.49 (95% CI 3.72\u20135.42; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and for severe infections (grade\u2009\u2265\u20093) 10.64 (95% CI 7.54\u201315.00; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Significant independent risk factors for infections were a higher Charlson Comorbidity Index, IgG deficiency, and 3<jats:sup>rd<\/jats:sup>\u2009+\u2009line treatment, as well as therapy with BTK inhibitors or chemotherapy in CLL. Multivariable analysis showed a significantly lower risk of severe infections after start of IgRT with a HR of 0.47 (95% CI 0.28\u20130.77; <jats:italic>p<\/jats:italic>\u2009=\u20090.003).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Guideline adherence correlated with fewer and less severe infections but was low in patients with indication to IgRT. Risk factors for infection can be identified. Risk of severe infections was significantly lower in patients with IgRT.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00520-022-06920-y","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T19:06:43Z","timestamp":1646680003000},"page":"5187-5200","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunoglobulin substitution in patients with secondary antibody deficiency in chronic lymphocytic leukemia and multiple myeloma: a representative analysis of guideline adherence and infections"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-0265","authenticated-orcid":false,"given":"Hartmut","family":"Link","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Kerkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Holtmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Working Groups Supportive Care (AGSMO)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Medical Oncology (AIO) of the German Cancer Society (DKG)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"6920_CR1","doi-asserted-by":"publisher","unstructured":"Wang Y, Achenbach SJ, Rabe KG, Shanafelt TD, Call T, Ding W et al 2020 Cause of death in patients with newly diagnosed chronic lymphocytic leukemia (CLL) stratified by the CLL-International Prognostic Index (CLL-IPI). J Clin Oncol 38(15_suppl):8026-. https:\/\/doi.org\/10.1200\/JCO.2020.38.15_suppl.8026","DOI":"10.1200\/JCO.2020.38.15_suppl.8026"},{"issue":"1","key":"6920_CR2","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3324\/haematol.2014.107714","volume":"100","author":"C Blimark","year":"2015","unstructured":"Blimark C, Holmberg E, Mellqvist UH, Landgren O, Bjorkholm M, Hultcrantz M et al (2015) Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica 100(1):107\u2013113. https:\/\/doi.org\/10.3324\/haematol.2014.107714","journal-title":"Haematologica"},{"issue":"7","key":"6920_CR3","doi-asserted-by":"publisher","first-page":"e300","DOI":"10.3324\/haematol.2017.182006","volume":"103","author":"MA Andersen","year":"2018","unstructured":"Andersen MA, Eriksen CT, Brieghel C, Biccler JL, Cunha-Bang CD, Helleberg M et al (2018) Incidence and predictors of infection among patients prior to treatment of chronic lymphocytic leukemia: a Danish nationwide cohort study. Haematologica 103(7):e300\u2013e303. https:\/\/doi.org\/10.3324\/haematol.2017.182006","journal-title":"Haematologica"},{"key":"6920_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3389\/fimmu.2019.00033","volume":"10","author":"SY Patel","year":"2019","unstructured":"Patel SY, Carbone J, Jolles S (2019) The expanding field of secondary antibody deficiency: causes, diagnosis, and management. Front Immunol 10:33. https:\/\/doi.org\/10.3389\/fimmu.2019.00033","journal-title":"Front Immunol"},{"issue":"4","key":"6920_CR5","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/s41375-019-0388-x","volume":"33","author":"G Maschmeyer","year":"2019","unstructured":"Maschmeyer G, De Greef J, Mellinghoff SC, Nosari A, Thiebaut-Bertrand A, Bergeron A et al (2019) Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections in Leukemia (ECIL). Leukemia 33(4):844\u201362. https:\/\/doi.org\/10.1038\/s41375-019-0388-x","journal-title":"Leukemia"},{"issue":"5","key":"6920_CR6","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1586\/1744666X.2014.902314","volume":"10","author":"SS Duraisingham","year":"2014","unstructured":"Duraisingham SS, Buckland MS, Grigoriadou S, Longhurst HJ (2014) Secondary antibody deficiency. Expert Rev Clin Immunol 10(5):583\u2013591. https:\/\/doi.org\/10.1586\/1744666X.2014.902314","journal-title":"Expert Rev Clin Immunol"},{"key":"6920_CR7","doi-asserted-by":"publisher","unstructured":"Dropulic LK, Lederman HM (2016) Overview of infections in the immunocompromised host. Microbiol Spectr 4(4). https:\/\/doi.org\/10.1128\/microbiolspec.DMIH2-0026-2016","DOI":"10.1128\/microbiolspec.DMIH2-0026-2016"},{"issue":"1","key":"6920_CR8","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/17474086.2018.1407645","volume":"11","author":"T Tadmor","year":"2018","unstructured":"Tadmor T, Welslau M, Hus I (2018) A review of the infection pathogenesis and prophylaxis recommendations in patients with chronic lymphocytic leukemia. Expert Rev Hematol 11(1):57\u201370. https:\/\/doi.org\/10.1080\/17474086.2018.1407645","journal-title":"Expert Rev Hematol"},{"issue":"11","key":"6920_CR9","doi-asserted-by":"publisher","first-page":"e499","DOI":"10.1038\/bcj.2016.105","volume":"6","author":"C da Cunha-Bang","year":"2016","unstructured":"da Cunha-Bang C, Simonsen J, Rostgaard K, Geisler C, Hjalgrim H, Niemann CU (2016) Improved survival for patients diagnosed with chronic lymphocytic leukemia in the era of chemo-immunotherapy: a Danish population-based study of 10455 patients. Blood Cancer J 6(11):e499. https:\/\/doi.org\/10.1038\/bcj.2016.105","journal-title":"Blood Cancer J"},{"issue":"14","key":"6920_CR10","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1056\/NEJM198810063191403","volume":"319","author":"RP Gale","year":"1988","unstructured":"Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic L, Gale RP, Chapel HM, Bunch C, Rai KR, Foon K et al (1988) Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. N Engl J Med 319(14):902\u20137. https:\/\/doi.org\/10.1056\/NEJM198810063191403","journal-title":"N Engl J Med"},{"issue":"8905","key":"6920_CR11","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/s0140-6736(94)90180-5","volume":"343","author":"HM Chapel","year":"1994","unstructured":"Chapel HM, Lee M, Hargreaves R, Pamphilon DH, Prentice AG (1994) Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. The UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma. Lancet 343(8905):1059\u201363. https:\/\/doi.org\/10.1016\/s0140-6736(94)90180-5","journal-title":"Lancet"},{"issue":"5","key":"6920_CR12","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1080\/10428190902856824","volume":"50","author":"P Raanani","year":"2009","unstructured":"Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O (2009) Immunoglobulin prophylaxis in chronic lymphocytic leukemia and multiple myeloma: systematic review and meta-analysis. Leuk Lymphoma 50(5):764\u2013772. https:\/\/doi.org\/10.1080\/10428190902856824","journal-title":"Leuk Lymphoma"},{"key":"6920_CR13","doi-asserted-by":"publisher","first-page":"626","DOI":"10.3389\/fimmu.2014.00626","volume":"5","author":"N Compagno","year":"2014","unstructured":"Compagno N, Malipiero G, Cinetto F, Agostini C (2014) Immunoglobulin replacement therapy in secondary hypogammaglobulinemia. Front Immunol 5:626. https:\/\/doi.org\/10.3389\/fimmu.2014.00626","journal-title":"Front Immunol"},{"issue":"8","key":"6920_CR14","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1002\/eji.201444700","volume":"44","author":"WAC Sewell","year":"2014","unstructured":"Sewell WAC, Kerr J, Behr-Gross ME, Peter HH, Kreuth Ig Working G (2014) European consensus proposal for immunoglobulin therapies. Eur J Immun 44(8):2207\u201314. https:\/\/doi.org\/10.1002\/eji.201444700","journal-title":"Eur J Immun"},{"key":"6920_CR15","unstructured":"Na I-K, Hensel M, Maschmeyer G, Scheibenbogen C, Wehr C, Wolff D, et al.: Immundefekte, sekund\u00e4r, Schwerpunkt: Therapieinduzierte Immundefekte in der H\u00e4matologie und Onkologie. Onkopedia-Leitlinie. https:\/\/www.onkopedia.com\/de\/onkopedia\/guidelines\/immundefekte-sekundaer\/@@guideline\/html\/index.html#ID0EFYAE (2019). Accessed 30.12.2020 2019"},{"key":"6920_CR16","unstructured":"CHMP: Guideline on core SmPC for human normal immunoglobulin for intravenous administration (IVIg). https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-core-smpc-human-normal-immunoglobulin-intravenous-administration-ivig-rev-5_en.pdf (2018). Accessed EMA\/CHMP\/BPWP\/94038\/2007 Rev. 5"},{"key":"6920_CR17","unstructured":"Wissenschaftlicher-Beirat-der-Bundes\u00e4rztekammer: Querschnitts-Leitlinien (B\u00c4K) zur Therapie mit Blutkomponenten und Plasmaderivaten. http:\/\/www.bundesaerztekammer.de\/downloads\/QLL_Haemotherapie_2014.pdf (2014). Accessed"},{"issue":"1","key":"6920_CR18","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.annonc.2020.09.019","volume":"32","author":"B Eichhorst","year":"2021","unstructured":"Eichhorst B, Robak T, Montserrat E, Ghia P, Niemann CU, Kater AP et al (2021) Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 32(1):23\u201333. https:\/\/doi.org\/10.1016\/j.annonc.2020.09.019","journal-title":"Ann Oncol"},{"issue":"8","key":"6920_CR19","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1038\/s41375-020-0876-z","volume":"34","author":"E Terpos","year":"2020","unstructured":"Terpos E, Engelhardt M, Cook G, Gay F, Mateos MV, Ntanasis-Stathopoulos I et al (2020) Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia 34(8):2000\u20132011. https:\/\/doi.org\/10.1038\/s41375-020-0876-z","journal-title":"Leukemia"},{"issue":"1","key":"6920_CR20","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s00520-015-2779-5","volume":"24","author":"H Link","year":"2016","unstructured":"Link H, Nietsch J, Kerkmann M, Ortner P, Supportive Care Group of the German Cancer S (2016) Adherence to granulocyte-colony stimulating factor (G-CSF) guidelines to reduce the incidence of febrile neutropenia after chemotherapy\u2013a representative sample survey in Germany. Support Care Cancer 24(1):367\u201376. https:\/\/doi.org\/10.1007\/s00520-015-2779-5","journal-title":"Support Care Cancer"},{"issue":"4","key":"6920_CR21","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/s00520-018-4481-x","volume":"27","author":"H Link","year":"2019","unstructured":"Link H, Kerkmann M, Holtmann L, Ortner P, Working Groups Supportive C, Medical Oncology within the German Cancer S (2019) G-CSF guideline adherence in Germany, an update with a retrospective and representative sample survey. Support Care Cancer 27(4):1459\u201369. https:\/\/doi.org\/10.1007\/s00520-018-4481-x","journal-title":"Support Care Cancer"},{"issue":"5","key":"6920_CR22","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1007\/s00520-019-05018-2","volume":"28","author":"H Link","year":"2020","unstructured":"Link H, Diel I, Ohlmann CH, Holtmann L, Kerkmann M, Associations Supportive Care in Oncology MOUOwtGCS et al (2020) Guideline adherence in bone-targeted treatment of cancer patients with bone metastases in Germany. Support Care Cancer 28(5):2175\u201384. https:\/\/doi.org\/10.1007\/s00520-019-05018-2","journal-title":"Support Care Cancer"},{"key":"6920_CR23","unstructured":"R_Core_Team (2020) R: A Language and Environment for Statistical Computing. Organisation: R Foundation for Statistical Computing, Vienna, Austria"},{"issue":"4","key":"6920_CR24","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1214\/aos\/1176345976","volume":"10","author":"PK Andersen","year":"1982","unstructured":"Andersen PK, Gill RD (1982) Cox\u2019s regression model for counting processes: a large sample study. Ann Statist 10(4):1100\u20131120. https:\/\/doi.org\/10.1214\/aos\/1176345976","journal-title":"Ann Statist"},{"issue":"1","key":"6920_CR25","doi-asserted-by":"publisher","first-page":"289","DOI":"10.2307\/2346101","volume":"57","author":"Y Benjamini","year":"1995","unstructured":"Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B (Methodol) 57(1):289\u2013300. https:\/\/doi.org\/10.2307\/2346101 (citeulike-article-id:1042553)","journal-title":"J Roy Stat Soc Ser B (Methodol)"},{"key":"6920_CR26","unstructured":"CTEP: Common Terminology Criteria for Adverse Events (CTCAE) v5.0. https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/CTCAE_v5_Quick_Reference_5x7.pdf (2017)"},{"issue":"5","key":"6920_CR27","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","volume":"40","author":"ME Charlson","year":"1987","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373\u2013383. https:\/\/doi.org\/10.1016\/0021-9681(87)90171-8","journal-title":"J Chronic Dis"},{"issue":"4","key":"6920_CR28","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1111\/ejh.13580","volume":"106","author":"S Jolles","year":"2021","unstructured":"Jolles S, Michallet M, Agostini C, Albert MH, Edgar D, Ria R et al (2021) Treating secondary antibody deficiency in patients with haematological malignancy: European expert consensus. Eur J Haematol 106(4):439\u2013449. https:\/\/doi.org\/10.1111\/ejh.13580","journal-title":"Eur J Haematol"},{"issue":"12","key":"6920_CR29","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/s1470-2045(19)30506-6","volume":"20","author":"MT Drayson","year":"2019","unstructured":"Drayson MT, Bowcock S, Planche T, Iqbal G, Pratt G, Yong K et al (2019) Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol 20(12):1760\u20131772. https:\/\/doi.org\/10.1016\/s1470-2045(19)30506-6","journal-title":"Lancet Oncol"},{"issue":"8","key":"6920_CR30","doi-asserted-by":"publisher","first-page":"4867","DOI":"10.1007\/s00520-020-05982-0","volume":"29","author":"L Moore","year":"2021","unstructured":"Moore L, Bartels T, Persky DO, Abraham I, Kumar A, McBride A (2021) Outcomes of primary and secondary prophylaxis of chemotherapy-induced and febrile neutropenia in bendamustine plus rituximab regimens in patients with lymphoma and chronic lymphocytic leukemia: real-world, single-center experience. Support Care Cancer 29(8):4867\u20134874. https:\/\/doi.org\/10.1007\/s00520-020-05982-0","journal-title":"Support Care Cancer"},{"issue":"1","key":"6920_CR31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.3324\/haematol.2012.070755","volume":"98","author":"E Bouvet","year":"2013","unstructured":"Bouvet E, Borel C, Ob\u00e9ric L, Compaci G, Cazin B, Michallet A-S et al (2013) Impact of dose intensity on outcome of fludarabine, cyclophosphamide, and rituximab regimen given in the first-line therapy for chronic lymphocytic leukemia. Haematologica 98(1):65\u201370. https:\/\/doi.org\/10.3324\/haematol.2012.070755","journal-title":"Haematologica"},{"issue":"2","key":"6920_CR32","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.clml.2012.11.011","volume":"13","author":"C Casulo","year":"2013","unstructured":"Casulo C, Maragulia J, Zelenetz AD (2013) Incidence of hypogammaglobulinemia in patients receiving rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk 13(2):106\u2013111. https:\/\/doi.org\/10.1016\/j.clml.2012.11.011","journal-title":"Clin Lymphoma Myeloma Leuk"},{"issue":"12","key":"6920_CR33","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1016\/j.leukres.2015.10.013","volume":"39","author":"F De Angelis","year":"2015","unstructured":"De Angelis F, Tosti ME, Capria S, Russo E, D\u2019Elia GM, Annechini G et al (2015) Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: A retrospective cohort study. Leuk Res 39(12):1382\u20131388. https:\/\/doi.org\/10.1016\/j.leukres.2015.10.013","journal-title":"Leuk Res"},{"issue":"8","key":"6920_CR34","doi-asserted-by":"publisher","first-page":"713","DOI":"10.2217\/imt-2017-0178","volume":"10","author":"KA Sacco","year":"2018","unstructured":"Sacco KA, Abraham RS (2018) Consequences of B-cell-depleting therapy: hypogammaglobulinemia and impaired B-cell reconstitution. Immunotherapy 10(8):713\u2013728. https:\/\/doi.org\/10.2217\/imt-2017-0178","journal-title":"Immunotherapy"},{"issue":"7","key":"6920_CR35","doi-asserted-by":"publisher","first-page":"e184169","DOI":"10.1001\/jamanetworkopen.2018.4169","volume":"1","author":"S Barmettler","year":"2018","unstructured":"Barmettler S, Ong MS, Farmer JR, Choi H, Walter J (2018) Association of Immunoglobulin levels, infectious risk, and mortality with rituximab and hypogammaglobulinemia. JAMA Netw Open 1(7):e184169. https:\/\/doi.org\/10.1001\/jamanetworkopen.2018.4169","journal-title":"JAMA Netw Open"},{"issue":"7","key":"6920_CR36","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.3109\/10428194.2016.1142082","volume":"57","author":"MA Andersen","year":"2016","unstructured":"Andersen MA, Vojdeman FJ, Andersen MK, Brown Pde N, Geisler CH, Weis Bjerrum O et al (2016) Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. Leuk Lymphoma 57(7):1592\u20131599. https:\/\/doi.org\/10.3109\/10428194.2016.1142082","journal-title":"Leuk Lymphoma"},{"issue":"6","key":"6920_CR37","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1128\/cvi.00021-11","volume":"18","author":"J Karlsson","year":"2011","unstructured":"Karlsson J, Andr\u00e9asson B, Kondori N, Erman E, Riesbeck K, Hogevik H et al (2011) Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom\u2019s macroglobulinemia, and monoclonal gammopathy of undetermined significance. Clin Vaccine Immunol 18(6):969\u2013977. https:\/\/doi.org\/10.1128\/cvi.00021-11","journal-title":"Clin Vaccine Immunol"},{"issue":"6","key":"6920_CR38","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3324\/haematol.2013.096792","volume":"99","author":"V Goede","year":"2014","unstructured":"Goede V, Cramer P, Busch R, Bergmann M, Stauch M, Hopfinger G et al (2014) Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German Chronic Lymphocytic Leukemia Study Group trials. Haematologica 99(6):1095\u20131100. https:\/\/doi.org\/10.3324\/haematol.2013.096792","journal-title":"Haematologica"},{"issue":"5","key":"6920_CR39","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.3324\/haematol.2019.242958","volume":"105","author":"M Engelhardt","year":"2020","unstructured":"Engelhardt M, Ihorst G, Duque-Afonso J, Wedding U, Sp\u00e4t-Schwalbe E, Goede V et al (2020) Structured assessment of frailty in multiple myeloma as a paradigm of individualized treatment algorithms in cancer patients at advanced age. Haematologica 105(5):1183\u20131188. https:\/\/doi.org\/10.3324\/haematol.2019.242958","journal-title":"Haematologica"},{"issue":"5","key":"6920_CR40","doi-asserted-by":"publisher","first-page":"910","DOI":"10.3324\/haematol.2016.162693","volume":"102","author":"M Engelhardt","year":"2017","unstructured":"Engelhardt M, Domm AS, Dold SM, Ihorst G, Reinhardt H, Zober A et al (2017) A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica 102(5):910\u2013921. https:\/\/doi.org\/10.3324\/haematol.2016.162693","journal-title":"Haematologica"},{"issue":"13","key":"6920_CR41","doi-asserted-by":"publisher","first-page":"2068","DOI":"10.1182\/blood-2014-12-615187","volume":"125","author":"A Palumbo","year":"2015","unstructured":"Palumbo A, Bringhen S, Mateos M-V, Larocca A, Facon T, Kumar SK et al (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 125(13):2068\u20132074. https:\/\/doi.org\/10.1182\/blood-2014-12-615187","journal-title":"Blood"},{"issue":"10","key":"6920_CR42","doi-asserted-by":"publisher","first-page":"e296","DOI":"10.1371\/journal.pmed.0040296","volume":"4","author":"E von Elm","year":"2007","unstructured":"von Elm E, Altman DG, Egger M, Pocock SJ, G\u00f8tzsche PC, Vandenbroucke JP et al (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med 4(10):e296. https:\/\/doi.org\/10.1371\/journal.pmed.0040296","journal-title":"PLoS Med"},{"issue":"3","key":"6920_CR43","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10654-019-00500-x","volume":"34","author":"W Hoffmann","year":"2019","unstructured":"Hoffmann W, Latza U, Baumeister SE, Br\u00fcnger M, Buttmann-Schweiger N, Hardt J et al (2019) Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology. Eur J Epidemiol 34(3):301\u2013317. https:\/\/doi.org\/10.1007\/s10654-019-00500-x","journal-title":"Eur J Epidemiol"}],"container-title":["Supportive Care in Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-022-06920-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00520-022-06920-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00520-022-06920-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T10:50:53Z","timestamp":1651056653000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00520-022-06920-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["6920"],"URL":"https:\/\/doi.org\/10.1007\/s00520-022-06920-y","relation":{},"ISSN":["0941-4355","1433-7339"],"issn-type":[{"value":"0941-4355","type":"print"},{"value":"1433-7339","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]},"assertion":[{"value":"10 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"An opinion has been obtained from the Ethics Committee of Rhineland-Palatinate, Mainz, Germany, in accordance with the guidelines and recommendations for ensuring Good Epidemiological Practice (GEP) []. Due to the nature of the study, no additional opinions from ethics committees were required.All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Professor Hartmut Link received research funding and honoraria, acted on speakers\u2019 bureau, and\/or consulted for Takeda. Markus Kerkmann and Laure Holtmann have no conflicts of interest to declare that are relevant to the content of this article.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The guidelines for Observational Studies in Epidemiology (STROBE) were taken into account as far as applicable [].","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Standard of reporting"}}]}}