Das Medizinportal


Diagnostik des Multiplen Myeloms – von Erstdiagnose bis zum Nachweis der minimalen Resterkrankung (S. 10–15)
Stefanie Huhn, Katharina Kriegsmann, Mark Kriegsmann, Maximilian Merz 

  1. Rosenthal DS., Schrier SL, Rosmarin AG. Evaluation of bone marrow aspirate smears. 2017 21.06.2017 29.01.2018]; Available from: www.uptodate.com/contents/evaluation-of-bone-marrow-aspirate-smears
  2. Landgren O and SV Rajkumar. New Developments in Diagnosis, Prognosis, and Assessment of Response in Multiple Myeloma. Clin Cancer Res 2016; 22(22): 5428–5433
  3. Group IMW, International Myeloma Working Group (IMWG) Criteria for the Diagnosis of Multiple Myeloma
  4. Fend Fand L Quintanilla-Martinez, [B-cell neoplasms with plasmacellular and plasmablastic differentiation]. Pathologe 2013; 34(3): 198–209
  5. Tzankov A, S Dirnhofer, and C Beham-Schmid, [Normal bone marrow and common reactive alterations]. Pathologe 2012; 33(6): 496–507
  6. Wei A and S Juneja, Bone marrow immunohistology of plasma cell neoplasms. J Clin Pathol 2003; 56(6): 406–11
  7. Lorsbach RB, et al. Plasma cell myeloma and related neoplasms. Am J Clin Pathol 2011; 136(2): 168–82
  8. Slotta-Huspenina J, et al. Cyclin D1 positive multiple myeloma: predominance of the short, 3'UTR-deficient transcript is associated with high cyclin D1 mRNA levels in cases with t(11;14) translocation, but does not correlate with proliferation rate or genomic deletions. Leuk Res 2008; 32(1): 79–88
  9. Jelinek T, et al. Current applications of multiparameter flow cytometry in plasma cell disorders. Blood Cancer J 2018; 8(1): e621
  10. Rawstron AC, et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008; 93(3): 431–8
  11. Paiva B, et al. Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients. Leukemia 2012; 26(8): 1862–9
  12. Moreau P, et al. Lack of CD27 in myeloma delineates different presentation and outcome. Br J Haematol 2006; 132(2): 168–70
  13. Guikema JE, et al. CD27 is heterogeneously expressed in multiple myeloma: low CD27 expression in patients with high-risk disease. Br J Haematol 2003; 121(1): 36–43
  14. Sherrod AM, et al. Minimal residual disease testing after stem cell transplantation for multiple myeloma. Bone Marrow Transplant 2016; 51(1): 2–12
  15. Paiva B, JJ van Dongen, and A Orfao. New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood 2015; 125(20): 3059–68
  16. Vogel W, et al. Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation. J Cancer Res Clin Oncol 2005; 131(4): 214–8
  17. Galimberti S, et al. Peripheral blood stem cell contamination evaluated by a highly sensitive molecular method fails to predict outcome of autotransplanted multiple myeloma patients. Br J Haematol 2003; 120(3): 405–12
  18. Soh KT, JD Tario Jr, and PK Wallace. Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry. Clin Lab Med 2017; 37(4): 821–853
  19. Takamatsu H. Comparison of Minimal Residual Disease Detection by Multiparameter Flow Cytometry, ASO-qPCR, Droplet Digital PCR, and Deep Sequencing in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation. J Clin Med 2017; 6(10)
  20. Bai Y, A Orfao, and CS. Chim. Molecular detection of minimal residual disease in multiple myeloma. Br J Haematol 2017
  21. Nowakowski GS, et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005; 106(7): 2276–9
  22. Paiva B, et al. Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile. Blood 2013; 122(22): 3591–8
  23. Sherrod AM, et al. Minimal residual disease testing after stem cell transplantation for multiple myeloma. Bone Marrow Transplant 2015
  24. Kumar S, T Kimlinger, and W Morice. Immunophenotyping in multiple myeloma and related plasma cell disorders. Best Pract Res Clin Haematol 2010; 23(3): 433–51
  25. Mailankody S, et al. Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol 2015; 12(5): 286–95
  26. Landgren O, et al. Flow cytometry detection of minimal residual disease in multiple myeloma: Lessons learned at FDA-NCI roundtable symposium. Am J Hematol 2014; 89(12): 1159–60
  27. van Dongen JJ, A Orfao, and C EuroFlow. EuroFlow: Resetting leukemia and lymphoma immunophenotyping. Basis for companion diagnostics and personalized medicine. Leukemia 2012; 26(9): 1899–907
  28. Hart AJ, et al. Minimal residual disease in myeloma: are we there yet? Biol Blood Marrow Transplant 2012; 18(12): 1790–9
  29. Paiva B, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom 2010; 78(4): 239–52
  30. Flores-Montero J, et al. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia 2017; 31(10): 2094–2103
  31. Paiva B, et al. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood 2016; 127(25): 3165–74
  32. Rawstron AC, et al. Minimal residual disease assessed by multiparameter flow cytometry in multiple myeloma: impact on outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol 2013; 31(20): 2540–7
  33. Paiva B, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol 2011; 29(12): 1627–33
  34. Paiva B, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 2008; 112(10): 4017–23
  35. Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17(8): e328–e346
  36. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15(12): e538–48
  37. Avet-Loiseau H, et al. Minimal Residual Disease in Multiple Myeloma: Final Analysis of the IFM2009 Trial. ASH 2017. Abstract 435
  38. De Tute RM, et al. Minimal Residual Disease in the Maintenance Setting in Myeloma: Prognostic Significance and Impact of Lenalidomide. ASH 2017. Abstract 904
  39. Paiva B,  Puig N, Cedena Romero MTT, Cordon L, Vidriales M-B, Burgos L, et al. Impact of Next-Generation Flow (NGF) Minimal Residual Disease (MRD) Monitoring in Multiple Myeloma (MM): Results from the PETHEMA/GEM2012 Trial. AHS 2017. Abstract 905
  40. Chakraborty R, et al. Serial measurements of circulating plasma cells before and after induction therapy have an independent prognostic impact in patients with multiple myeloma undergoing upfront autologous transplantation. Haematol 2017; 102(8): 1439–45
  41. Gonsalves WI, et al. Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: implications for redefining high-risk myeloma. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK 2014; 28(10): 2060–5
  42. Huhn S, et al. Circulating tumor cells as a biomarker for response to therapy in multiple myeloma patients treated within the GMMG-MM5 trial. Bone Marrow Transplant 2017; 52(8): 1194–8
  43. Huhn S, et al. Circulating Tumor Cells As a Surrogate Marker for Bone Marrow Minimal Residual Disease and an Adverse Prognostic Factor for Patients with Multiple Myelom. ASH 2017. Abstract 4359
  44. Hillengass J, et al. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group. Blood Cancer J 2017 Aug 25; 7(8): e599
  45. Hillengass J et al. Prognostic significance of focal lesions in whole-body magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 2010; 28: 1606–10
  46. Kastritis E et al. The prognostic importance of the presence of more than one focal lesion in spine MRI of patients with asymptomatic (smoldering) multiple myeloma. Leukemia 2014; 28: 2402–3
  47. Merz M et al. Predictive value of longitudinal whole-body magnetic resonance imaging in patients with smoldering multiple myeloma. Leukemia 2014; 28: 1902–8
  48. Zamagni E et al. 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease. Leukemia 2016; 30: 417–22
  49. Siontis B et al. Positron emission tomography-computed tomography in the diagnostic evaluation of smoldering multiple myeloma: Identification of patients needing therapy. Blood Cancer J 2015; 5: e364
  50. Moreau P et al. Prospective evaluation of MRI and PET-CT at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial. Blood 2015; 126: 395

Therapie des fitten Patienten (S. 21–25)
Hartmut Goldschmidt, Marc-Steffen Raab, Elias Karl Mai, Katja Weisel  

  1. Palumbo A, Bringhen S, Mateos M-V, Larocca A, Facon T, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma: an International Myeloma Working Group report. Blood 2015
  2. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, et al.  International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014 Nov; 15(12): e538–48
  3. Moreau P, Attal M, Facon T. Frontline therapy of multiple myeloma. Blood 2015 May 14; 125(20): 3076–84
  4. Einsele H, Engelhardt M, Tapprich C, Müller J, Liebisch P, et al.  Phase II study of Bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial. Br J Haematol 2017 Nov; 179(4): 586–597
  5. Mai EK, Bertsch U, Dürig J, Kunz C, Haenel M, et al. Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma. Leukemia 2015 Aug; 29(8): 1721–9
  6. Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017 Jul; 28(Suppl_4): iv52–iv61
  7. Sahin U, Demirer T. Current strategies for the management of autologous peripheral blood stem cell mobilization failures in patients with multiple myeloma. J Clin Apher 2017 Oct: 1 [Epub ahead of print] 
  8. Cheng J, Schmitt M, Wuchter P, Buss EC, Witzens-Harig M, et al. Plerixafor is effective given either preemptively or as a rescue strategy in poor stem cell mobilizing patients with multiple myeloma. Transfusion 2015, 55(2): 275–83
  9. Mateos MV, San Miguel JF. Management of multiple myeloma in the newly diagnosed patient. Hematology Am Soc Hematol Educ Program 2017 Dec 8; 2017(1): 498–507
  10. Jackson G, Davies F, Pawlyn C, Cairns D, Striha A, et al. Lenalidomide Maintenance Significantly Improves Outcomes compared to Observation Irrespective of Cytogenetic Risk: Results of the Myeloma XI Trial.  ASH 2017, Abstract 436
  11. Goldschmidt H, Mai EK, Dürig J, Scheid C, Weisel K, et al. Response-Adapted Lenalidomide Maintenance in Newly Diagnosed, Transplant-Eligible Multiple Myeloma: Results from the Multicenter Phase III GMMG-MM5 Trial.  ASH 2017, Abstract 400
  12. Goldschmidt H, Lokhorst HM, Mai EK et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia 2017 Jul 4
  13. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016 Aug; 17(8): e328–e346
  14. Terpos E, Kleber M, Engelhardt M et al. European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications. Haematologica 2015 Oct; 100(10): 1254–66 

UPDATE: Update zum Basalzellkarzinom (S. 41–48)
Manuel Krieter, Erwin Schultz, Dirk Debus 

  1. Ting PT, Kasper R, Arlette JP. Metastatic basal cell carcinoma: report of two cases and literature review. Journal of cutaneous medicine and surgery 2005; 9: 10–15
  2. Jacob A. Observations respecting an ulcer of peculiar character, which attacks the eyelids and other parts of the face. Dublin Hospital Representative 1824; 4: 232–239 
  3. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, Awmf): S3-Leitlinie Prävention von Hautkrebs, Langversion 1.1, 2014, Awmf Registernummer: 032/052ol
  4. Samarasinghe V, Madan V, Lear JT. Focus on Basal cell carcinoma. J Skin Cancer 2011; 2011: 328615
  5. Hauschild A, Breuninger H, Kaufmann R et al. Kurzleitlinie - Basalzellkarzinom der Haut (Update 2012). 2013
  6. Youssef KK, van Keymeulen A, Lapouge G et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nature cell biology 2010; 12: 299–305
  7. Dessinioti C, Antoniou C, Katsambas A et al. Basal cell carcinoma: What’s new under the sun. Photochem and Photobiol 2010; 86(3): 481–491
  8. Rosso S, Zanetti R, Martinez C et al. The multicentre south European study ‘Helios’. II. Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin. British journal of cancer 1996; 73: 1447–1454
  9. Makarova A, Wang G, Dolorito JA et al. Vitamin D3 Produced by Skin Exposure to UVR Inhibits Murine Basal Cell Carcinoma Carcinogenesis. J Invest Dermatol 2017; 137(12): 2613–2619
  10. Kricker A, Armstrong BK, English DR et al. Does intermittent sun exposure cause basal cell carcinoma? a case-control study in Western Australia. Int J Cancer 1995 Feb 8; 60(4): 489–94
  11. Roewert-Huber J, Lange-Asschenfeldt B, Stockfleth E et al. Epidemiology and aetiology of basal cell carcinoma. Br J Dermatol 2007 Dec; 157 Suppl 2: 47–51
  12. Madan V, Hoban P, Strange RC et al. Genetics and risk factors for basal cell carcinoma. Br J Dermatol 2006; 154: 5–7
  13. Johnson RL, Rothman AL, Xie J et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996; 272: 1668–1671
  14. Goppner D, Leverkus M. Basal cell carcinoma – from the molecular understanding of the pathogenesis to targeted therapy of progressive disease. J Skin Cancer 2011; 2011: 650258
  15. Nedved D, Tonkovic-Capin V, Hunt E et al. Diagnostic concordance rates in the subtyping of basal cell carcinoma by different dermatopathologists. J Cutan Pathol 2014;  41: 9–13
  16. Batra RS, Kelley LC. Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery. Arch Der¬matol 2002;  138: 1043–1051
  17. Felder S, Rabinovitz H, Oliviero M, Kopf A. Dermoscopic differentiation of a superficial basal cell carcinoma and squamous cell carcinoma in situ. Dermatol Surg 2006; 32: 423–425
  18. Nori S, Rius-Díaz F, Cuevas J, et al. Sensitivity and specificity of reflectance-mode confocal microscopy for in vivo diagnosis of basal cell carcinoma: a multicenter study. J Am Acad Dermatol 2004; 51(6): 923–30
  19. Cheng HM, Guitera P. Systematic review of optical coherence tomography usage in the diagnosis and management of basal cell carcinoma. Br J Dermatol 2015 Dec; 173(6): 1371–80
  20. Gilbody JS, Aitken J, Green A. What causes basal cell carcinoma to be the commonest cancer? Aust J Public Health 1994; 18: 218–221
  21. Walling HW, Fosko SW, Geraminejad PA et al. Aggressive basal cell arcinoma: presentation, pathogenesis, and management. Cancer Metastasis Rev 2004; 23(3-4): 389–402 
  22. Kopf AW, Bart RS, Schrager D et al. Curettage-electrodesiccation treatment of basal cell carcinomas. Arch Dermatol 1977; 113: 439–443
  23. Thissen MR, Nieman FH, Ideler AH et al. Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 2000; 26: 759–764
  24. Wang I, Bendsoe N, Klinteberg CA et al. Photodynamic therapy vs. Cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol 2001; 144: 832–840
  25. Morton CA, McKenna KE, Rhodes LE. Guidelines for topical photodynamic therapy: update. Br J Dermatol. 2008; 159: 1245–1266
  26. Rhodes LE, de Rie M, Enstrom Y et al. Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol 2004; 140: 17–23
  27. Basset-Seguin N, Ibbotson S, Emtestam L. Photodynamic therapy using Metvix is as efficacious as cryotherapy in BCC, with better cosmetic results. J Eur Acad Dermatol Venereol 2004; 18: 412
  28. Marks R, Gebauer K, Shumack S et al. Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol 2001; 44: 807–813
  29. Geisse JK, Rich P, Pandya A et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002; 47: 390–398
  30. Geisse J, Caro I, Lindholm J et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 2004; 50: 722–733
  31. Gollnick H, Barona CG, Frank RG et al. Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe. Eur J Dermatol 2008; 18: 677–682
  32. Roozeboom MH, Arits AH, Mosterd K et al. Three-Year Follow-Up Results of Photodynamic Therapy vs. Imiquimod vs. Fluorouracil for Treatment of Superficial Basal Cell Carcinoma: A Single-Blind, Noninferiority, Randomized Controlled Trial. J Invest Dermatol 2016; 136(8): 1568–74 
  33. Jansen MHE, Mosterd K, Arits AHMM et al. Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma. J Invest Dermatol 2018 Mar; 138(3): 527–533
  34. Skvara H, Kalthoff F, Meingassner JG, et al. Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 2011; 131: 1735–44
  35. Emilie Lauressergues, Peter Heusler, Fabrice Lestienne et al. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model. Pharmacol Res Perspect 2016; 4(2): e00214
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  39. Ballester-Sánchez R, Pons-Llanas O, Candela-Juan C, et al. Two years results of electronic brachytherapy for basal cell carcinoma. J Contemp Brachytherapy 2017; 9(3): 251–255
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  42. Lear JT, Migden MR, Lewis KD, et al. Long-term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30-month analysis of the randomized phase 2 BOLT study. J Eur Acad Dermatol Venereol 2018 Mar; 32(3): 372–381
  43. Alcalay J, Tauber G, Fenig E, et al. Vismodegib as a Neoadjuvant Treatment to Mohs Surgery for Aggressive Basal Cell Carcinoma. J Drugs Dermatol 2015; 14(3): 219–223
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  47. Lin, J.S., Eder M, Weinmann S. Behavioral counseling to prevent skin cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2011; 154(3): 190–201
  48. Ulrich C, Jurgensen JS, Degen A et al. Prevention of non-melanoma skin cancer in organ transplant patients by regular use of a sunscreen: a 24 months, prospective, case-control study. Br J Dermatol 2009; 161: 78–84
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  53. Kreul SM, Havighurst T, Kim K, et al. A phase III skin cancer chemoprevention study of DFMO: long-term follow-up of skin cancer events and toxicity. Cancer Prev Res (Phila) 2012; 5(12): 1368–1374
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Radiojodrefraktäres differenziertes Schilddrüsenkarzinom: Rasche und langanhaltende Tumorreduktion mit Lenvatinib (S. 54–55) 

  1. Fachinformation Lenvima®, Stand Juni 2017
  2. DKK Programm: www.dkk2018.de/programm.html (eingesehen am 05.02.2018)
  3. Schlumberger M et al. N Engl J Med 2015; 372: 621–30
  4. Gianoukakis AG et al. ASCO Annual Meeting 2016, Abstract #6089
  5. Brose MS et al. J Clin Oncol 2017 Aug 10; 35(23): 2692–2699
  6. Robinson B et al. J Clin Endocrinol Metab Nov 2016; 101(11): 4103–4109
  7. Tuttle RM et al. Best Pract Res Clin Endocrinol Metab 2017 Jun; 31(3): 295–305
  8. Wirth LJ et al. Ann Oncol 2014; 25 (Supplement 4): iv340–iv356
  9. Haddad RI et al. Endocrine 2017 Apr; 56(1): 121–128
  10. lenvima.de/dtc-perspective/