Description of TEMPI syndrome in Waldenström‘s macroglobulinemia

Czech version

Authors: Z. Adam ¹; L. N. Leová ^2,3; M. Patočková ⁴; S. Rajecká ⁵; S. Nehyba ⁶; M. Borský ⁷; J. Kotašková ⁷; V. Kubeš ⁸; J. Kissová ^1,9; J. Vaníček ¹⁰; Z. Pazdičová ¹¹; Z. Řehák ¹²; J. Foukal ¹¹; A. Čermák ¹³; Z. Adamová ¹⁴; L. Zdražilová-Dubská ^15,16; K. Starý ¹⁷; I. Boichuk ¹; L. Pour ¹
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Radiodia gnostické oddělení, FTN Praha ²; RadioMed spol. s r. o., Praha ³; Oddělení následné péče, Nemocnice Tišnov ⁴; Oddělení klinické hematologie, FN u sv. Anny v Brně ⁵; Interní kardiologická klinika LF MU a FN Brno ⁶; Centrum molekulární bio logie a genetiky, Interní hematologická a onkologická klinika LF MU a FN Brno ⁷; Ústav patologie LF MU a FN Brno ⁸; Oddělení klinické hematologie, FN Brno ⁹; Klinika zobrazovacích metod LF MU a FN u sv. Anny v Brně ¹⁰; Klinika radiologie a nukleární medicíny LF MU a Brno ¹¹; Oddělení nukleární medicíny, MOU Brno ¹²; Urologická klinika LF MU a FN Brno ¹³; Chirurgické oddělení, Nemocnice Frýdek Místek ¹⁴; Ústav laboratorní medicíny LF MU a FN Brno ¹⁵; Katedra laboratorních metod LF MU Brno ¹⁶; Interní gastroenterologická klinika LF MU a FN Brno ¹⁷
Published in: Klin Onkol 2025; 38(4): 283-301
Category: Original Articles
doi: https://doi.org/10.48095/ccko2025283

Overview

Background: TEMPI syndrome (telangiectasia, erythrocytosis with increased erythropoietin, monoclonal gammopathy, perinephritic fluid collections, and intrapulmonary shunts) was described by David Sykes in 2011. By the end of March 2025, we have found descriptions of 35 cases of TEMPI syndrome in the literature. Non-IgM monoclonal gammopathy of clinical significance was diagnosed in 23 patients, multiple myeloma in 10 patients and Waldenström‘s macroglobulinemia in only 2 cases. Sykes estimated the median interval from the first symptoms to the diagnosis at 10 years. For many years, these patients were treated for a misdiagnosis of secondary erythrocytosis or primary polycythemia. Observation: In 2015, an increase in hemoglobin and hematocrit concentrations was found in the patient. The diagnosis was concluded as secondary erythrocytosis in obstructive bronchopulmonary disease. Telangiectasias, which appeared soon after the detection of erythrocytosis, were misinterpreted as a manifestation of hepatopathy. The patient was treated with therapeutic phlebotomy. In 2024, symptoms of pleural effusion, ascites, swelling of the perineum and genitals appeared. This was the reason for admission to the hospital. Results: CT scan in 2024 revealed pleural effusions, large perinephritic fluid collections and confirmed clinically evident swelling of the perineum and genitals (pelvic effusion). This gave rise to the suspicion of TEMPI syndrome. The results of morphological, flow-cytometric and molecular biological examination of the bone marrow and high concentrations of total immunoglobulin type IgM (40.6 g/L) and monoclonal immunoglobulin type IgM (23.6 g/L) with cryoglobulin properties corresponded to Waldenström‘s macroglobulinemia. Contrast echocardiography confirmed the existence of arteriovenous shunts, which could not be localized by other methods. Other abnormalities included very low levels of vitamin B12 and folic acid. Laboratory examination did not show significant endocrinopathy. After therapeutic plasmapheresis, treatment with rituximab, bendamustine and dexamethasone was started in December 2024. Conclusion: In each differential diagnosis of secondary erythrocytosis, it is necessary to examine monoclonal immunoglobulin to exclude its cause in TEMPI or POEMS syndrome. A large perinephritic fluid collection is diagnostic of only two diagnoses, TEMPI syndrome or renal lymphangiomatosis, while other renal diseases can cause a smaller volume of perirenal fluid collection.

Keywords:

monoclonal gammopathy – venous thrombosis – TEMPI syndrome – telangiectasia – erythrocytosis – perinephritic fluid collection – intrapulmonary arteriovenous shunts – Waldenström‘s macroglobulinemia – monoclonal gammopathy of clinical significance

Sources

1. Faber E. Základy hematologické diagnostiky. Praha: Grada Publishing 2024.

2. Ščudla V, Horák P, Karásek D. Základy diferenciální diagnostiky ve vnitřním lékařství. Olomouc: Univerzita Palackého 2021.

3. Kučerová J, Horváthová M, Pospíšilová D et al. Vrozené polycytemie. Trans Hematol Dnes 2009; 15 (4): 216–222.

4. Indrák K. Diferenciální diagnostika a léčba polyglobulií. Hematol Transfuz 1992; 2 (3): 12–21.

5. Podstavková N, Weinbergerová B, Palová M et al. Ph negativní myeloproliferativní neoplázie na českých hematologických centrech –⁠ analýza dat MIND. Trans Hematol Dnes 2021; 27 (3): 242–253. doi: 10.48095/cctahd20 21242.

6. Bělohlávková P, Hluší A, Ráčil Z et al. Ph-negativní myeloproliferativní choroby (esenciální trombocytémie, pravá polycytémie, primární myelofibróza). Léčebné postupy v hematologii 2020. Praha: ČLS JEP 2020 : 153–172.

7. Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 2023; 98 (9): 1465–1487. doi: 10.1002/ ajh.27002.

8. Song J, Sundar KM, Horvathova M et al al. Increased blood reactive oxygen species and hepcidin in obstructive sleep apnea precludes expected erythrocytosis. Am J Hematol 2023; 98 (8): 1265–1276. doi: 10.1002/ajh. 2699.

9. Gašperšič J, Kristan A, Kunej T et al. Erythrocytosis: genes and pathways involved in disease development. Blood Transfus 2021; 19 (6): 518–532. doi: 10.2450/2020.0197-20.

10. McMullin MF. Genetic background of congenital erythrocytosis. Genes (Basel) 2021; 12 (8): 1151. doi: 10.3390/genes12081151.

11. Opíchalová D, Ščudla V, Vomáčka J et al. Multifokální osteosklerotický plazmocytom s polyneuropatií –⁠ POEMS syndrom. Cesk Revmatol 2001; 9 (1): 31–34.

12. Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol 2023; 98 (12): 1934–1950. doi: 10.1002/ajh.27081.

13. Chang H, Shih LY. Concurrence of multiple myeloma and idiopathic erythrocytosis. Acta Clin Belg 2009; 64 (5): 434–435. doi: 10.1179/acb.2009.071.

14. Bazari H, Attar EC, Dahl DM et al. Case records of the Massachusetts General Hospital. Case 23-2010. A 49-year-old man with erythrocytosis, perinephric fluid collections, and renal failure. N Engl J Med 2010; 363 (5): 463–475. doi: 10.1056/NEJMcpc1004086.

15. Sykes DB, Schroyens W, O‘Connell C. The TEMPI syndrome –⁠ a novel multisystem disease. N Engl J Med 2011; 365 (5): 475–477. doi: 10.1056/NEJMc1106670.

16. Rosado FG, Oliveira JL, Sohani AR et al. Bone marrow findings of the newly described TEMPI syndrome: when erythrocytosis and plasma cell dyscrasia coexist. Mod Pathol 2015; 28 (3): 367–372. doi: 10.1038/modpathol.2014.117.

17. Lipsker D. Monoclonal gammopathy of cutaneous significance: review of a relevant concept. J Eur Acad Dermatol Venereol 2017; 31 (1): 45–52. doi: 10.1111/jdv.13847.

18. Merlini G, Stone MJ. Dangerous small B-cell clones. Blood 2006; 108 (8): 2520–2530. doi: 10.1182/blood-2006-03-001164.

19. Fermand JP,  Bridoux F, Dispenzieri A et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications Blood 2018; 132 (14): 1478–1485. doi: 10.1182/blood-2018-04-839480.

20. Dispenzieri A. Monoclonal gammopathies of clinical significance. Hematology Am Soc Hematol Educ Program 2020; 2020 (1): 380–388. doi: 10.1182/hematology.2020000122.

21. Hájek R. Diagnostika a léčba mnohočetného myelomu: doporučení vypracované Českou myelomovou skupinou, Myelomovou sekcí České hematologické společnosti a Slovenskou myelómovou spoločností pro diagnostiku a léčbu mnohočetného myelomu. Trans Hematol Dnes 2009; 15 (Suppl 2): 49–80.

22. Adam Z, Harvanová L, Pour L et al. Monoklonální gamapatie klinického významu a další nemoci. Praha: Grada 2023.

23. Alaggio R, Amador C, Anagnostopoulos I et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia 2022; 36 (7): 1720–1748. doi: 10.1038/s41375-022-01620-2.

24. Schroyens W, O’Connell C, Sykes D. Complete and partial responses of the TEMPI syndrome to bortezomib. N Engl J Med 2012; 367 (8): 778–780. doi:  10.1056/NEJMc1205806.

25. Mohammadi F, Wolverson M, Bastani B. A new case of TEMPI syndrome. Clin Kidney J 2012; 5 (6): 556–558. doi:  10.1093/ckj/sfs139.

26. Jasim S, Mahmud G, Bastani B et al. Subcutaneous bortezomib for treatment of TEMPI syndrome. Clin Lymphoma Myeloma Leuk 2014; 14 (6): e221–e223. doi: 10.1016/j.clml.2014.07.004.

27. Kwok M, Korde N, Landgren O. Bortezomib to treat the TEMPI syndrome. N Engl J Med 2012; 366 (19): 1843–1845. doi:  10.1056/NEJMc1202649.

28. Viglietti D, Sverzut JM, Peraldi MN. Perirenal fluid collections and monoclonal gammopathy. Nephrol Dial Transplant 2012; 27 (1): 448–449. doi: 10.1093/ndt/ gfr433.

29. Ryden A, Wei K, Rodriguez R et al. Too much blood: a case of the newly described TEMPI syndrome. Chest 2013; 144 (4): 2. doi:  10.1378/chest.1701121.

30. Kenderian S, Rosado F, Sykes D et al. Long-term complete clinical and hematological responses of the TEMPI syndrome after autologous stem cell transplantation. Leukemia 2015; 29 (12): 2414–2416. doi:  10.1038/leu.2015.298.

31. Belizaire R, Sykes D, Chen Y et al. Difficulties in hematopoietic progenitor cell collection from a patient with TEMPI syndrome and severe iatrogenic iron deficiency. Transfusion 2015; 55 (9): 2142–2148. doi:  10.1111/trf.13125.

32. Pascart T, Herbaux C, Lemaire A et al. Coexistence of rheumatoid arthritis and TEMPI syndrome: new insight in microangiogenic-related diseases. Joint Bone Spine 2016; 83 (5): 587–588. doi:  10.1016/j.jbspin.2015.06.011.

33. Debbaneh M, Chong K. A case of atrophie blanche in a patient with TEMPI syndrome. J Am Acad Dermatol 2018; 79 (3): AB5–AB. doi: 10.1016/j.jaad.2018.05.065.

34. Liang S, Yeh S. Relapsed multiple myeloma as TEMPI syndrome with good response to salvage lenalidomide and dexamethasone. Ann Hematol 2019; 98 (10): 2447–2450. doi: 10.1007/s00277-019-03761-4.

35. Shizuku T, Matsui K, Yagi S et al. The first case of TEMPI syndrome in Japan. Intern Med 2020; 59 (14): 1741–1744. doi:  10.2169/internalmedicine.3547-19.

36. Manek G, Gupta M, Thomas VM et al. Hunting for the shunting: a rare case of intrapulmonary shunting due to TEMPI syndrome causing hypoxia. Am J Respir Crit Care Med 2020; 201: A7234. doi: 10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A7234.

37. Diral E, Parma M, Renso R et al. A fatal case of TEMPI syndrome, refractory to proteasome inhibitors and autologous stem cell transplantation. Leuk Res 2020; 97 : 106441. doi:  10.1016/j.leukres.2020.106441.

38. Lor M, Cheng M, Liang B et al. TEMPI syndrome with progressive telangiectasias associated with pulmonary deterioration. JAMA Dermatol 2020; 156 (12): 1379–1380. doi:  10.1001/jamadermatol.2020.2668.

39. Guo H, Chen Y, Wu Y et al. Case 528: skin pruritus-polycythemia-M proteinemia. Natl Med J China 2020; 100 (46): 3727–3730. doi:  10.3760/cma.j.cn112137-20200409-01144.

40. Ruan Y, Zhao X, Pan M. Diffuse telangiectasia: a clue to the TEMPI syndrome. JAAD Case Rep 2021; 10 : 99–101. doi:  10.1016/j.jdcr.2021.02.022.

41. Liu J, Li Z, Fan H et al. A case of TEMPI syndrome. Natl Med J China 2021; 101 (13): 966–967. doi:  10.3760/cma.j.cn112137-20200817-02405.

42. Sun C, Xu J, Zhang B et al. Whole-genome sequencing suggests a role of MIF in the pathophysiology of TEMPI syndrome. Blood Adv 2021; 5 (12): 2563–2568. doi: 10.1182/bloodadvances.2020003783.

43. Strobl J, Sinz C, Heil PM et al. Cutaneous ulceration as primary presentation of TEMPI syndrome. J Eur Acad Dermatol Venereol 2021; 35 (12): e891–e894. doi:  10.1111/jdv.17539.

44. Kubik T, Minoo P. TEMPI syndrome associated with IgM monoclonal gammopathy. Blood 2022; 39 (8): 1254. doi:  10.1182/blood.2021014393.

45. Asimakopoulou S, Malandrakis P, Kamiliou A et al. A rare case of TEMPI syndrome (telangiectasias, erythrocytosis, monoclonal gammopathy and ascites) associated with IgM monoclonal gammopathy. Leuk Lymphoma 2024; 65 (6): 857–859. doi: 10.1080/10428194.2024. 2323084.

46. Kalomeris TA, Grossman ME, Tepler J et al. TEMPI syndrome: a clinical, light-microscopic and phenotypic evaluation with review of the literature. J Cutan Pathol 2024; 51 (4): 299–305. doi: 10.1111/cup.14572.

47. Fotiou D, Solia E, Theodorakakou F et al. TEMPI syndrome: difficult to diagnose, „easy“ to treat? Ann Hematol 2024; 103 (9): 3787–3793. doi: 10.1007/s00277-024-05893-8.

48. Undar L, Atas U, Iltar U et al. Long-term complete clinical and hematological response with bortezomib: the report of a case with TEM (P) I syndrome and a review of the literature. Clin Lymphoma Myeloma Leuk 2022; 22 (9): 702–707. doi: 10.1016/j.clml.2022.04.018.

49. Wu JH, Viruni N, Chun J et al. Ocular involvement in TEMPI syndrome. Am J Ophthalmol Case Rep 2022; 26 : 101534. doi: 10.1016/j.ajoc.2022.101534.

50. Kawamura S, Tamaki M, Nakamura Y et al. Successful treatment of the TEMPI syndrome with pomalidomide plus dexamethasone followed by autologous stem cell transplantation. Acta Haematol 2022; 145 (5): 553–559. doi: 10.1159/000525056.

51. Sansen PY, Montfort L, Nanquette A et al. Complete remission in a TEMPI syndrome treated with a daratumumab, lenalidomide, and dexamethasone-based regimen: a case report. Case Rep Oncol 2024; 17 (1): 175–179. doi: 10.1159/000535551.

52. Sykes DB, Schroyens W. Teclistamab as successful treatment of relapsed TEMPI syndrome. N Engl J Med 2024; 391 (22): 2173–2175. doi: 10.1056/NEJMc2411016.

53. Melincovici CS, Boşca AB, Şuşman S et al. Vascular endothelial growth factor (VEGF) –⁠ key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018; 59 (2): 455–467.

54. Bokhari SMZ, Hamar P. Vascular Endothelial Growth Factor-D (VEGF-D): an angiogenesis bypass in malignant tumors. Int J Mol Sci 2023; 24 (17): 13317. doi: 0.3390/ijms241713317.

55. Nunes Rosado FG, Lekovic D, Gagan J et al. Comprehensive next-generation sequencing testing in a patient with TEMPI syndrome. Lab Med 2023; 54 (5): 546–549. doi: 10.1093/labmed/lmad003.

56. Zhao M, Liu J, Yu Q et al. IRF4-BLOC1S5: the first rearrangement gene identified in TEMPI syndrome. Haematologica 2024; 109 (8): 2701–2705. doi: 10.3324/haematol.2023.284727.

57. Zhang X, Fang M. TEMPI syndrome: erythrocytosis in plasma cell dyscrasia. Clin Lymphoma Myeloma Leuk 2018; 18 (11): 724–730. doi:  10.1016/j.clml.2018.07.284.

58. Kolařík L, Horáková D, Matoušková I. Deskriptivní epidemiologie vybraných hematoonkologických onemocnění v České republice. Trans Hematol Dnes 2024; 30 (1): 26–40. doi: 10.48095/cctahd2024prolekare.cz3.

59. Bradáčová M, Faber E, Minařík J et al. Hereditární hemoragická teleangiektázie (syndrom Rendu-Osler-Weber). Trans Hematol Dnes 2023; 29 (3): 171–176. doi: 10.48095/cctahd2023prolekare.cz5.

60. Rongioletti F, Failla MC, Atzori L et al. Skin manifestations of POEMS and AESOP syndrome in the same patient revealing plasma cell dyscrasia. J Cutan Pathol 2016; 43 (12): 1167–1171. doi: 10.1111/cup.12798.

61. Dagrosa AT, Cowdrey MCE, LeBlanc RE et al. Adenopathy and extensive skin patch overlying a plasmacytoma with unusual histologic findings in a patient with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes syndrome and Castleman disease. J Cutan Pathol 2019; 46 (10): 784–789. doi: 10.1111/cup.13514.

62. Annese T, Tamma R, Ruggieri S et al. Erythropoietin in tumor angiogenesis. Exp Cell Res 2019; 374 (2): 266–273. doi:  10.1016/j.yexcr.2018.12.013.

63. Mossuz P, Girodon F, Donnard M et al. Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis. Haematologica 2004; 89 (10): 1194–1198.

64. Stetler-Stevenson M, Paiva B, Stoolman L et al. Consensus guidelines for myeloma minimal residual disease sample staining and data acquisition. Cytometry B Clin Cytom 2016; 90 (1): 26–30. doi: 10.1002/cyto.b.21249.

65. Tsao TF, Liang KW, Huang HH et al. Sonography of perinephric fluid collections: a pictorial essay. J Clin Ultrasound 2019; 47 (3): 150–160. doi: 10.1002/jcu.22680.

66. Haddad MC, Medawar WA, Hawary MM et al. Perirenal fluid in renal parenchymal medical disease („floating kidney“): clinical significance and sonographic grading. Clin Radiol 2001; 56 (12): 979–983. doi: 10.1053/crad.2001.0631.

67. Aliasgari M, Atabak S, Lashay A et al. Bilateral perirenal subcapsular fluid collection: a rare presentation of renal parenchymal disease. Urol J 2010; 7 (1): 61–62.

68. Balci NC, Akun E, Erturk M et al. Renal-related perinephric fluid collections: MRI findings. Magn Reson Imaging 2005; 23 (5): 679–684. doi: 10.1016/j.mri.2005.04.003.

69. Moretto S, Gradilone U, Costanzi Porrini G et al. Clinical significance of perinephric fluid collection in patients with renal colic and urolithiasis: a retrospective analysis. J Clin Med 2024; 13 (20): 6118. doi: 10.3390/jcm13206118.

70. Hakeem A, Gojwari TA, Reyaz S et al. Computed tomography findings in bilateral perinephric lymphangiomatosis. Urol Ann 2010; 2 (1): 26–28. doi: 10.4103/0974-7796.62922.

71. Abualrub AM, Malhes WM, Shehadeh MH et al. Bilateral renal lymphangiomatosis: a case report and literature review. Cureus 2024; 16 (4): e58180. doi: 10.7759/cureus.58180.

72. Král Z, Krejčí J, Červinková I e al. Lymphangiomatosis –⁠ very rare disease of the lymphatic vessels. Vnitr Lek 2021; 67 (E–4): 9–12.

73. Ma J, Chen Y, Qin X et al. POEMS syndrome: a rare cause of ascites and pelvic effusion. Clin Case Rep 2022; 10 (11): e6603. doi: 10.1002/ccr3.6603.

74. Buncová M, Málek I. Pravolevý zkrat při perfuzní scintigrafii plic 99mTc-MAA. Cesk Radiol 2002; 56 (5): 299–302.

75. Xu ZF, Ruan J, Chang L et al. Case report: TEMPI syndrome: report of three cases and treatment follow-up. Front Oncol 2022; 12 : 949647. doi: 10.3389/fonc.2022. 949647.

76. Pasquesoone H, Callaud A, Carsuzaa T et al. First use of 18F-FDG PET in TEMPI syndrome: can it be used for treatment assessment? A case report. Front Nucl Med 2023; 3 : 1273967. doi: 10.3389/fnume.2023.1273967.

77. Adam Z, Zdražilová-Dubská L, Pour L et al. Kryoglobulinémie z úhlu pohledu jednotlivých medicínských odborností. Trans Hematol Dnes 2024; 30 (4): 213–223. doi: 10.48095/cctahd2024prolekare.cz19.

78. Sykes DB, O‘Connell C, Schroyens W. The TEMPI syndrome. Blood 2020; 135 (15): 1199–1203. doi: 10.1182/blood.2019004216.

79. Bohoněk M, Hrabánek J, Kořánková M et al. Venepunkční a aferetická léčba polyglobulií. Trans Hematol Dnes 2013; 19 (4): 216–222.

80. Sykes DB, Schroyens W. Complete responses in the TEMPI syndrome after treatment with daratumumab. N Engl J Med 2018; 378 (23): 2240–2242. doi: 10.1056/NEJMc1804415.

81. Verma SP, Singh B, Kushwaha R et al. Polycythaemia following treatment of lymphoplasmacytic lymphoma. BMJ Case Rep 2020; 13 (10): e235687. doi: 10.1136/bcr-2020-235687.

82. Adam Z, Pour L, Zeman D et al. Waldenström‘s macroglobulinemia –⁠ clinical symptoms and review of therapy yesterday, today and tomorrow. Klin Onkol 2023; 36 (3): 177–191. doi: 10.48095/ccko2023177.

83. Hájek R. Diagnostika a léčba Waldenströmovy makroglobulinémie: doporučení vypracovaná Českou myelomovou skupinou (CMG), myelomovou sekcí České hematologické společnosti ČLS JEP a Kooperativní lymfomovou skupinou, lymfomovou sekcí České hematologické společnosti ČLS JEP. Trans Hematol Dnes 2022; 28 (Suppl 1): 42–74.

84. Flodr P, Adam Z, Navrátilová M et al., Poškození způsobená depozity monoklonálního imunoglobulinu typu IgM a lehkými řetězci u Waldenströmovy makroglobulinémie –⁠ popis případu a přehled literatury. Trans Hematol Dnes 2024; 30 (2): 99–111. doi: 10.48095/cctahd2024prolekare.cz8.

85. Adam Z, Krejčí M, Pour L et al. Successful treatment of relapsed Waldenström’s macroglobulinemia with proteasome inhibitors (bortezomib and subsequently ixazomib) in combination with rituximab and dexamethasone. A case report and review of the of proteasome inhibitors in Waldenström’s macroglobulinemia. Klin Onkol 2024; 37 (6): 451–462. doi: 10.48095/ccko2024451.

86. Adam Z, Pour L, Krejčí M et al. The treatment combination of obinutuzumab, bendamustine and dexamethasone achieved a deeper response than the previous line of treatment in five patients with Waldenström’s macroglobulinemia. Klin Onkol 2024; 37 (6): 427–432. doi: 10.48095/ccko2024427.