An Extended Prognostic Index of the ISSWM Score Based on Thyroid Complications in Waldenström Macroglobulinemia/Lymphoplasmacytoid Lymphoma

Waldenström macroglobulinemia/lymphoplasmacytoid lymphoma (WM/LPL) is a rare lymphoproliferative neoplasm characterized by clonally related lymphocytes, lymphoplasmacytic cells, and plasma cell proliferation. WM/LPL patients commonly present with elevated immunoglobulin, predominantly immunoglobulin M (IgM). Previous studies reported that thyroid dysfunction was associated with the development and progression of solid tumors. However, only limited information is available on the correlation between thyroid complications and lymphoid malignancies. The aim of our study was to explore the prognostic significance of thyroid complications in WM/LPL. Herein, 13.3% of WM/LPL patients were diagnosed with thyroid complications, which were significantly associated with unfavorable progression-free survival (PFS), overall survival (OS), and adverse treatment response. Co-existing thyroid disease was significantly related to alleviated serum IgM levels, providing an answer to practical problems. Furthermore, the presence of thyroid complications was identified as an independent prognostic indicator for PFS in WM/LPL. Incorporating the ISSWM score with thyroid complications was superior to ISSWM alone in risk stratification and prognostic prediction. Furthermore, subgroup analyses of WM/LPL patients revealed that subclinical hypothyroidism predicted undesirable outcomes at the early stage. These results were also supported by independent microarray dataset analyses. In conclusion, the primary strength of this study is that it provides robust real-world evidence on the prognostic role of thyroid complications, highlighting further clinical concerns in the management of WM/LPL patients.

[1]  R. Davis,et al.  Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma , 2022, Blood advances.

[2]  Sheeba K. Thomas,et al.  Waldenström Macroglobulinemia - 2021 Update on Management and Future Directions. , 2021, Clinical lymphoma, myeloma & leukemia.

[3]  Chao Leng,et al.  Hypothyroidism is a predictive factor of superior antitumour efficacy of programmed death 1 inhibitors in hepatocellular carcinoma , 2021, International journal of cancer.

[4]  T. Kipps,et al.  Long-term Follow-up of Patients with Relapsed or Refractory Non–Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study , 2021, Clinical Cancer Research.

[5]  A. Cappola,et al.  Autoimmune Thyroid Disease in Women. , 2021, JAMA.

[6]  D. Colomer,et al.  Defining an Ultra-Low Risk Group in Asymptomatic IgM Monoclonal Gammopathy , 2021, Cancers.

[7]  B. Sauer,et al.  Treatment Patterns and Outcomes in a Nationwide Cohort of Older and Younger Veterans with Waldenström Macroglobulinemia, 2006–2019 , 2021, Cancers.

[8]  M. Espéli,et al.  Hematological disorder associated Cxcr4-gain-of-function mutation leads to uncontrolled extrafollicular immune response. , 2021, Blood.

[9]  M. Gertz.  Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management , 2020, American journal of hematology.

[10]  S. Treon,et al.  Management of Waldenström macroglobulinemia in 2020. , 2020, Hematology. American Society of Hematology. Education Program.

[11]  R. Advani,et al.  Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia. , 2020, The Lancet. Haematology.

[12]  C. Buske,et al.  Targeting of CXCR4 by the Naturally Occurring CXCR4 Antagonist EPI-X4 in Waldenström’s Macroglobulinemia , 2020, bioRxiv.

[13]  Lei Chen,et al.  Trends in Incidence and Mortality of Waldenström Macroglobulinemia: A Population-Based Study , 2020, Frontiers in Oncology.

[14]  Xu Wang,et al.  MYD88 L265P Elicits Mutation-specific Ubiquitination to Drive NF-κB Activation and Lymphomagenesis. , 2020, Blood.

[15]  S. Treon,et al.  Epigenomics in Waldenström macroglobulinemia. , 2020, Blood.

[16]  S. Rubinstein,et al.  Hyperviscosity Syndrome in Paraprotein Secreting Conditions Including Waldenstrom Macroglobulinemia , 2020, Frontiers in Oncology.

[17]  M. Schulze,et al.  Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition , 2019, International journal of cancer.

[18]  M. Dimopoulos,et al.  How I treat Waldenström's Macroglobulinemia. , 2019, Blood.

[19]  A. Paulus,et al.  Updates in prognostication and treatment of Waldenström's macroglobulinemia. , 2019, Hematology/oncology and stem cell therapy.

[20]  S. Treon,et al.  What is new in the treatment of Waldenstrom macroglobulinemia? , 2019, Leukemia.

[21]  J. Castillo,et al.  Lymphoplasmacytic Lymphoma and Marginal Zone Lymphoma. , 2019, Hematology/oncology clinics of North America.

[22]  V. Mai,et al.  R-CHOP-Associated Graves' Hyperthyroidism , 2019, Case Reports in Oncology.

[23]  M. Huibers,et al.  CXCR4 mutations in lymphoplasmacytic lymphoma lead to altered CXCR4 expression , 2019, British journal of haematology.

[24]  T. Habermann,et al.  Predictors of symptomatic hyperviscosity in Waldenström macroglobulinemia , 2018, American journal of hematology.

[25]  M. Kersten,et al.  Waldenström's macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2018, Annals of oncology : official journal of the European Society for Medical Oncology.

[26]  E. Kimby,et al.  Prognostic factors and primary treatment for Waldenström macroglobulinemia – a Swedish Lymphoma Registry study , 2018, British journal of haematology.

[27]  N. Rothman,et al.  Serologic markers of viral infection and risk of non‐Hodgkin lymphoma: A pooled study of three prospective cohorts in China and Singapore , 2018, International journal of cancer.

[28]  M. Dimopoulos,et al.  Treatment and outcome patterns in European patients with Waldenström's macroglobulinaemia: a large, observational, retrospective chart review. , 2018, The Lancet. Haematology.

[29]  S. Treon,et al.  The real world of Waldenström's macroglobulinaemia. , 2018, The Lancet. Haematology.

[30]  S. Rajkumar,et al.  How I manage monoclonal gammopathy of undetermined significance. , 2018, Blood.

[31]  S. Treon,et al.  Serum IgM level as predictor of symptomatic hyperviscosity in patients with Waldenström macroglobulinaemia , 2017, British journal of haematology.

[32]  M. Gertz,et al.  Secondary malignancies in patients with multiple myeloma, Waldenström macroglobulinemia and monoclonal gammopathy of undetermined significance , 2017, Leukemia & lymphoma.

[33]  Timothy R. Smith,et al.  Preoperative low tri-iodothyronine concentration is associated with worse health status and shorter five year survival of primary brain tumor patients , 2016, Oncotarget.

[34]  Yingli Liu,et al.  Prevalence and Clinical Significance of Low T3 Syndrome in Non-Dialysis Patients with Chronic Kidney Disease , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[35]  H. Einsele,et al.  Targeting B-cell non Hodgkin lymphoma: New and old tricks. , 2016, Leukemia research.

[36]  Lifang Zhao,et al.  Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia , 2016, Scientific Reports.

[37]  Pingan Chen,et al.  Free Triiodothyronine Levels and Short-Term Prognosis in Chronic Heart Failure Patients With Type 2 Diabetes , 2015, The American journal of the medical sciences.

[38]  A. Papagianni,et al.  Low T3 syndrome and long-term mortality in chronic hemodialysis patients. , 2015, World journal of nephrology.

[39]  A. Bunevičius,et al.  Neuroprotective actions of thyroid hormones and low-T3 syndrome as a biomarker in acute cerebrovascular disorders , 2015, Expert review of neurotherapeutics.

[40]  U. Yılmaz,et al.  Can Non-Thyroid Illness Syndrome Predict Mortality in Lung Cancer Patients? A Prospective Cohort Study , 2014, Hormones and Cancer.

[41]  R. Advani,et al.  Treatment recommendations for patients with Waldenström's Macroglobulinemia (WM) and related disorders: consensus from the Seventh International Workshop on WM , 2014 .

[42]  G. Ren,et al.  Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine , 2013, BMC Cancer.

[43]  N. Harris,et al.  MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. , 2012, The New England journal of medicine.

[44]  B. Biondi,et al.  Subclinical thyroid disease , 2012, The Lancet.

[45]  M. Stone,et al.  Evidence-based focused review Evidence-based focused review of management of hyperviscosity syndrome , 2012 .

[46]  Dong Won Lee,et al.  The prevalence of low triiodothyronine according to the stage of chronic kidney disease in subjects with a normal thyroid-stimulating hormone. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[47]  J. Koshiol,et al.  Chronic immune stimulation and subsequent Waldenström macroglobulinemia. , 2008, Archives of internal medicine.

[48]  P. Berchialla,et al.  Low triiodothyronine serum levels as a predictor of poor prognosis in burn patients. , 2008, Burns : journal of the International Society for Burn Injuries.

[49]  S. Montoto,et al.  Lymphoplasmacytic lymphoma-Waldenstrom's macroglobulinemia. , 2008, Critical reviews in oncology/hematology.

[50]  W. Su,et al.  Euthyroid sick syndrome in trauma patients with severe inflammatory response syndrome. , 2006, Chinese journal of traumatology = Zhonghua chuang shang za zhi.

[51]  S. Monti,et al.  Low triiodothyronine (T3) state: a predictor of outcome in respiratory failure? Results of a clinical pilot study. , 2004, European journal of endocrinology.

[52]  S. Monti,et al.  Low triiodothyronine ( T 3 ) state : a predictor of outcome in respiratory failure ? Results of a clinical pilot study , 2004 .

[53]  M. Dimopoulos,et al.  Clinicopathological definition of Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. , 2003, Seminars in oncology.

[54]  A. L'Abbate,et al.  Low-T3 Syndrome: A Strong Prognostic Predictor of Death in Patients With Heart Disease , 2003, Circulation.

[55]  A. L'Abbate,et al.  Low-T 3 Syndrome A Strong Prognostic Predictor of Death in Patients With Heart Disease , 2003 .

[56]  S. Leeder,et al.  A population based study , 1993, The Medical journal of Australia.

[57]  D. Allen,et al.  Thyroiditis , 1989, Clinical pediatrics.

[58]  F. Trimarchi,et al.  Immunoglobulin binding of thyroid hormones in a case of Waldenstrom's macroglobulinemia. , 1982, The Journal of clinical endocrinology and metabolism.