Clinical applicability and prognostic significance of molecular response assessed by fluorescent-PCR of immunoglobulin genes in multiple myeloma: Results from a GEM/PETHEMA study

British Journal of Haematology

Volumn 163, Issue 5, 2013, Pages 581-589

  Martinez Lopez, Joaquin ^a   Fernández Redondo, Elena ^a   García Sánz, Ramón ^b   Montalbán, María Angeles ^a   Martínez Sánchez, Pilar ^a   Pavia, Bruno ^b   Mateos, María Victoria ^b   Rosiñol, Laura ^c   Martín, Marisa ^a   Ayala, Rosa ^a   Martínez, Rafael ^d   Blanchard, María Jesus ^e   Alegre, Adrian ^f   Besalduch, Joan ^g   Bargay, Joan ^h   Hernandez, Miguel T ⁱ   Sarasquete, María Eugenia ^b   Sanchez Godoy, Pedro ^j   Fernández, Manuela ^a   Blade, Joan ^c   San Miguel, Jesús F ^b   Lahuerta, Juan Jose ^a   more..

^a HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

^b HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^c INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^d HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^e HOSPITAL RAMÓN Y CAJAL   (Spain)

^f HOSPITAL UNIVERSITARIO DE LA PRINCESA   (Spain)

^g HOSPITAL UNIVERSITARIO SON ESPASES   (Spain)

^h HOSPITAL SON LLÀTZER   (Spain)

ⁱ HOSPITAL UNIVERSITARIO DE CANARIAS   (Spain)

^j HOSPITAL SEVERO OCHOA   (Spain)

more..

Author keywords

Flow cytometry; Fluorescent PCR; IGH; Minimal residual disease; Multiple myeloma

Indexed keywords

IMMUNOGLOBULIN HEAVY CHAIN;

ADULT; AGED; ARTICLE; CANCER PROGNOSIS; CANCER SURVIVAL; CONTROLLED STUDY; DISEASE ASSOCIATION; FEMALE; FLOW CYTOMETRY; FLUORESCENT POLYMERASE CHAIN REACTION; GENE; GENE FUNCTION; GENE IDENTIFICATION; GENE REARRANGEMENT; HEALTH CARE COST; HUMAN; IGL GENE; IMMUNOGLOBULIN GENE; IMMUNOGLOBULIN HEAVY CHAIN GENE; IMMUNOPHENOTYPING; MAJOR CLINICAL STUDY; MALE; MINIMAL RESIDUAL DISEASE; MOLECULAR DYNAMICS; MULTIPLE MYELOMA; MULTIPLEX POLYMERASE CHAIN REACTION; OVERALL SURVIVAL; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; SURVIVAL RATE; SURVIVAL TIME;

FLOW CYTOMETRY; FLUORESCENT-PCR; IGH; MINIMAL RESIDUAL DISEASE; MULTIPLE MYELOMA;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLINICAL TRIALS, PHASE III AS TOPIC; DIAGNOSTIC TESTS, ROUTINE; DNA, NEOPLASM; FEMALE; FLOW CYTOMETRY; FLUOROMETRY; GENE REARRANGEMENT, B-LYMPHOCYTE, HEAVY CHAIN; GENE REARRANGEMENT, B-LYMPHOCYTE, LIGHT CHAIN; GENES, IMMUNOGLOBULIN; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOPHENOTYPING; MALE; MIDDLE AGED; MULTICENTER STUDIES AS TOPIC; MULTIPLE MYELOMA; NEOPLASM, RESIDUAL; POLYMERASE CHAIN REACTION; PROGNOSIS; SENSITIVITY AND SPECIFICITY; TRANSPLANTATION, AUTOLOGOUS;

EID: 84887607810     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12576     Document Type: Article

References (39)

1. Billadeau, D., Quam, L., Thomas, W., Kay, N., Greipp, P., Kyle, R., Oken, M.M. & Van Ness, B. (1992) Detection and quantitation of malignant cells in the peripheral blood of multiple myeloma patients. Blood, 80, 1818-1824.
2. Blade, J., Samson, D., Reece, D., Apperley, J., Bjorkstrand, B., Gahrton, G., Gertz, M., Giralt, S., Jagannath, S. & Vesole, D. (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. British Journal of Haematology, 102, 1115-1123.
3. Chee, C.E., Kumar, S., Larson, D.R., Kyle, R.A., Dispenzieri, A., Gertz, M.A., Colby, C.L. & Rajkumar, S.V. (2009) The importance of bone marrow examination in determining complete response to therapy in patients with multiple myeloma. Blood, 114, 2617-2618.
4. Compagno, M., Mantoan, B., Astolfi, M., Boccadoro, M. & Ladetto, M. (2005) Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in myeloma. Methods in Molecular Medicine, 113, 145-163.
5. Davies, F.E., Forsyth, P.D., Rawstron, A.C., Owen, R.G., Pratt, G., Evans, P.A., Richards, S.J., Drayson, M., Smith, G.M., Selby, P.J., Child, J.A. & Morgan, G.J. (2001) The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. British Journal of Haematology, 112, 814-819.
6. Davies, F.E., Rawstron, A.C., Owen, R.G. & Morgan, G.J. (2002) Minimal residual disease monitoring in multiple myeloma. Best Practice & Research Clinical Haematology, 15, 197-222.
7. van Dongen, J.J., Langerak, A.W., Bruggemann, M., Evans, P.A., Hummel, M., Lavender, F.L., Delabesse, E., Davi, F., Schuuring, E., Garcia-Sanz, R., van Krieken, J.H., Droese, J., Gonzalez, D., Bastard, C., White, H.E., Spaargaren, M., Gonzalez, M., Parreira, A., Smith, J.L., Morgan, G.J., Kneba, M. & Macintyre, E.A. (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia, 17, 2257-2317.
8. van Dongen, J.J., Lhermitte, L., Bottcher, S., Almeida, J., van der Velden, V.H., Flores-Montero, J., Rawstron, A., Asnafi, V., Lecrevisse, Q., Lucio, P., Mejstrikova, E., Szczepanski, T., Kalina, T., de Tute, R., Bruggemann, M., Sedek, L., Cullen, M., Langerak, A.W., Mendonca, A., Macintyre, E., Martin-Ayuso, M., Hrusak, O., Vidriales, M.B. & Orfao, A. (2012) euroflow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes. Leukemia, 26, 1908-1975.
9. Durie, B.G.M., Harousseau, J.L., Miguel, J.S., Blade, J., Barlogie, B., Anderson, K., Gertz, M., Dimopoulos, M., Westin, J., Sonneveld, P., Ludwig, H., Gahrton, G., Beksac, M., Crowley, J., Belch, A., Boccadaro, M., Turesson, I., Joshua, D., Vesole, D., Kyle, R., Alexanian, R., Tricot, G., Attal, M., Merlini, G., Powles, R., Richardson, P., Shimizu, K., Tosi, P., Morgan, G. & Rajkumar, S.V. (2006) International uniform response criteria for multiple myeloma. Leukemia, 20, 1467-1473.
10. Galimberti, S., Benedetti, E., Morabito, F., Papineschi, F., Callea, V., Fazzi, R., Stelitano, C., Andreazzoli, F., Guerrini, F., Ciabatti, E., Martino, M., Nobile, F., Iacopino, P. & Petrini, M. (2005) Prognostic role of minimal residual disease in multiple myeloma patients after non-myeloablative allogeneic transplantation. Leukemia Research, 29, 961-966.
11. Harousseau, J.L., Attal, M. & Avet-Loiseau, H. (2009) The role of complete response in multiple myeloma. Blood, 114, 3139-3146.
12. Kapoor, P., Rajkumar, S.V., Lacy, M., Russell, S., Dingli, D., Hayman, S., Buadi, F., Kyle, R., Greipp, P., Dispenzieri, A., Gertz, M. & Kumar, S. (2011) Impact of immunofixation and clonality assessments in patients obtaining complete response in multiple myeloma [abstract]. Haematologica, 96, S39.
13. Kumar, S., Kimlinger, T. & Morice, W. (2010) Immunophenotyping in multiple myeloma and related plasma cell disorders. Best Practice & Research Clinical Haematology, 23, 433-451.
14. Ladetto, M., Pagliano, G., Ferrero, S., Cavallo, F., Drandi, D., Santo, L., Crippa, C., De Rosa, L., Pregno, P., Grasso, M., Liberati, A.M., Caravita, T., Pisani, F., Guglielmelli, T., Callea, V., Musto, P., Cangialosi, C., Passera, R., Boccadoro, M. & Palumbo, A. (2010) Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. Journal of Clinical Oncology, 28, 2077-2084.
15. Ladetto, M., Ferrero, S., Drandi, D., Cavallo, F., Monitillo, L., Ghione, P., Barbiero, S., Grasso, M., Rossini, F., Guglielmelli, T., Cangialosi, C., Liberati, A.M., Callea, V., Caravita, T., De Rosa, L., Pisani, F., Falcone, A.P., Pregno, P., Rocci, A., Passera, R., Boccadoro, M. & Palumbo, A. (2011) Long term of the gimema VTD consolidation trial in autografted multiple myeloma patients (VEL-03-096): impact of minimal residual disease detection by real time quantitative PCR on late recurrences and overall survival. Blood (ASH Annual Meeting Abstracts), 118, 827.
16. Lahuerta, J.J., Martinez-Lopez, J., Serna, J.D., Blade, J., Grande, C., Alegre, A., Vazquez, L., Garcia-Larana, J., Sureda, A., Rubia, J.D., Conde, E., Martinez, R., Perez-Equiza, K., Moraleda, J.M., Leon, A., Besalduch, J., Cabrera, R., Miguel, J.D., Morales, A., Garcia-Ruiz, J.C., Diaz-Mediavilla, J. & San-Miguel, J. (2000) Remission status defined by immunofixation versus Electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients. British Journal of Haematology, 109, 438-446.
17. Lahuerta, J.J., Mateos, M.V., Martinez-Lopez, J., Rosinol, L., Sureda, A., de la Rubia, J., Garcia-Larana, J., Martinez-Martinez, R., Hernandez-Garcia, M.T., Carrera, D., Besalduch, J., de Arriba, F., Ribera, J.M., Escoda, L., Hernandez-Ruiz, B., Garcia-Frade, J., Rivas-Gonzalez, C., Alegre, A., Blade, J. & San Miguel, J.F. (2008) Influence of pre- and post-transplantation responses on outcome of patients with multiple myeloma: sequential improvement of response and achievement of complete response are associated with longer survival. Journal of Clinical Oncology, 26, 5775-5782.
18. Langerak, A.W., Groenen, P.J., Bruggemann, M., Beldjord, K., Bellan, C., Bonello, L., Boone, E., Carter, G.I., Catherwood, M., Davi, F., Delfau-Larue, M.H., Diss, T., Evans, P.A., Gameiro, P., Garcia Sanz, R., Gonzalez, D., Grand, D., Hakansson, A., Hummel, M., Liu, H., Lombardia, L., Macintyre, E.A., Milner, B.J., Montes-Moreno, S., Schuuring, E., Spaargaren, M., Hodges, E. & van Dongen, J.J. (2012) euroclonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia, 26, 2159-2171.
19. Martinez-Lopez, J., Blade, J., Mateos, M.V., Grande, C., Alegre, A., Garcia-Larana, J., Sureda, A., de la Rubia, J., Conde, E., Martinez, R., de Arriba, F., Viguria, M.C., Besalduch, J., Cabrera, R., Gonzalez-San Miguel, J.D., Guzman-Zamudio, J.L., Gomez del Castillo, M.C., Moraleda, J.M., Garcia-Ruiz, J.C., San Miguel, J. & Lahuerta, J.J. (2011) Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood, 118, 529-534.
20. Martinez-Sanchez, P., Montejano, L., Sarasquete, M.E., Garcia-Sanz, R., Fernandez-Redondo, E., Ayala, R., Montalban, M.A., Martinez, R., Garcia Larana, J., Alegre, A., Hernandez, B., Lahuerta, J.J. & Martinez-Lopez, J. (2008) Evaluation of minimal residual disease in multiple myeloma patients by fluorescent-polymerase chain reaction: the prognostic impact of achieving molecular response. British Journal of Haematology, 142, 766-774.
21. Mateos, M.V., Oriol, A., Martinez-Lopez, J., Gutierrez, N., Teruel, A.I., de Paz, R., Garcia-Larana, J., Bengoechea, E., Martin, A., Mediavilla, J.D., Palomera, L., de Arriba, F., Gonzalez, Y., Hernandez, J.M., Sureda, A., Bello, J.L., Bargay, J., Penalver, F.J., Ribera, J.M., Martin-Mateos, M.L., Garcia-Sanz, R., Cibeira, M.T., Ramos, M.L., Vidriales, M.B., Paiva, B., Montalban, M.A., Lahuerta, J.J., Blade, J. & Miguel, J.F. (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. The Lancet Oncology, 11, 934-941.
22. Moreau, P. (2011) PET-CT in MM: a new definition of CR. Blood, 118, 5984-5985.
23. Munshi, N.C. & Anderson, K.C. (2013) Minimal residual disease in multiple myeloma. Journal of Clinical Oncology, 31, 2523-2526.
24. Paiva, B., Vidriales, M.B., Cervero, J., Mateo, G., Perez, J.J., Montalban, M.A., Sureda, A., Montejano, L., Gutierrez, N.C., Garcia de Coca, A., de Las Heras, N., Mateos, M.V., Lopez-Berges, M.C., Garcia-Boyero, R., Galende, J., Hernandez, J., Palomera, L., Carrera, D., Martinez, R., de la Rubia, J., Martin, A., Blade, J., Lahuerta, J.J., Orfao, A. & San Miguel, J.F. (2008) Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood, 112, 4017-4023.
25. Paiva, B., Vidriales, M.B., Perez, J.J., Mateo, G., Montalban, M.A., Mateos, M.V., Blade, J., Lahuerta, J.J., Orfao, A. & San Miguel, J.F. (2009) Multiparameter flow cytometry quantification of bone marrow plasma cells at diagnosis provides more prognostic information than morphological assessment in myeloma patients. Haematologica, 94, 1599-1602.
26. Paiva, B., Almeida, J., Perez-Andres, M., Mateo, G., Lopez, A., Rasillo, A., Vidriales, M.B., Lopez-Berges, M.C., Miguel, J.F. & Orfao, A. (2010) Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry Part B: Clinical Cytometry, 78, 239-252.
27. Paiva, B., Martinez-Lopez, J., Vidriales, M.B., Mateos, M.V., Montalban, M.A., Fernandez-Redondo, E., Alonso, L., Oriol, A., Teruel, A.I., de Paz, R., Larana, J.G., Bengoechea, E., Martin, A., Mediavilla, J.D., Palomera, L., de Arriba, F., Blade, J., Orfao, A., Lahuerta, J.J. & San Miguel, J.F. (2011a) Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. Journal of Clinical Oncology, 29, 1627-1633.
28. Paiva, B., Gutierrez, N.C., Rosinol, L., Vidriales, M.B., Montalban, M.A., Martinez-Lopez, J., Mateos, M.V., Cibeira, M.T., Cordon, L., Oriol, A., Terol, M.J., Echeveste, M.A., de Paz, R., de Arriba, F., Palomera, L., de la Rubia, J., Diaz-Mediavilla, J., Sureda, A., Gorosquieta, A., Alegre, A., Martin, A., Hernandez, M.T., Lahuerta, J.J., Blade, J. & San Miguel, J.F. (2011b) High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood, 119, 687-691.
29. Paiva, B., Gutierrez, N.C., Rosinol, L., Vidriales, M.B., Montalban, M.A., Martinez-Lopez, J., Mateos, M.V., Cibeira, M.T., Cordon, L., Oriol, A., Terol, M.J., Echeveste, M.A., de Paz, R., de Arriba, F., Palomera, L., de la Rubia, J., Diaz-Mediavilla, J., Sureda, A., Gorosquieta, A., Alegre, A., Martin, A., Hernandez, M.T., Lahuerta, J.J., Blade, J. & San Miguel, J.F. (2012a) High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood, 119, 687-691.
30. Paiva, B., Vidriales, M.B., Montalban, M.A., Perez, J.J., Gutierrez, N.C., Rosinol, L., Martinez-Lopez, J., Mateos, M.V., Cordon, L., Oriol, A., Terol, M.J., Echeveste, M.A., De Paz, R., De Arriba, F., Palomera, L., la Rubia, J.D., Diaz-Mediavilla, J., Sureda, A., Gorosquieta, A., Alegre, A., Martin, A., Lahuerta, J.J., Blade, J., Orfao, A. & San Miguel, J.F. (2012b) Multiparameter Flow Cytometry Evaluation of Plasma Cell DNA Content and Proliferation in 595 Transplant-Eligible Patients with Myeloma Included in the Spanish GEM2000 and GEM2005<65y. American Journal of Pathology, 181, 1870-1878.
31. Raab, M.S., Cremer, F.W., Breitkreutz, I.N., Gerull, S., Luft, T., Benner, A., Goerner, M., Ho, A.D., Goldschmidt, H. & Moos, M. (2005) Molecular monitoring of tumour load kinetics predicts disease progression after non-myeloablative allogeneic stem cell transplantation in multiple myeloma. Annals of Oncology, 16, 611-617.
32. Rajkumar, S.V., Harousseau, J.L., Durie, B., Anderson, K.C., Dimopoulos, M., Kyle, R., Blade, J., Richardson, P., Orlowski, R., Siegel, D., Jagannath, S., Facon, T., Avet-Loiseau, H., Lonial, S., Palumbo, A., Zonder, J., Ludwig, H., Vesole, D., Sezer, O., Munshi, N.C. & San Miguel, J. (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood, 117, 4691-4695.
33. Rawstron, A., De Tute, R., Child, A., Davies, F., Gregory, W., Bell, S., Szubert, A., Navarro-Coy, N., Drayson, M., Feyler, S., Ross, F., Cook, G., Jackson, G., Morgan, G. & Owen, R. (2011) Minimal residual disease (MRD) assessment using multiparameter flow cytometry (MCF) predicts outcome in both intensively and non-intensively treated patients: results from the MRC myeloma IX trial. Haematologica, 96, S30.
34. Rosinol, L., Oriol, A., Teruel, A.I., Hernandez, D., Lopez-Jimenez, J., de la Rubia, J., Granell, M., Besalduch, J., Palomera, L., Gonzalez, Y., Etxebeste, M.A., Diaz-Mediavilla, J., Hernandez, M.T., de Arriba, F., Gutierrez, N.C., Martin-Ramos, M.L., Cibeira, M.T., Mateos, M.V., Martinez, J., Alegre, A., Lahuerta, J.J., San Miguel, J. & Blade, J. (2012) Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood, 120, 1589-1596.
35. Sarasquete, M.E., Garcia-Sanz, R., Gonzalez, D., Martinez, J., Mateo, G., Martinez, P., Ribera, J.M., Hernandez, J.M., Lahuerta, J.J., Orfao, A., Gonzalez, M. & San Miguel, J.F. (2005) Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleotide real-time quantitative polymerase chain reaction and flow cytometry. Haematologica, 90, 1365-1372.
36. Singhal, S., Powles, R., Milan, S., Raje, N., Viner, C., Treleaven, J., Raymond, J., Cunningham, D. & Mehta, J. (1995) Kinetics of paraprotein clearance after autografting for multiple myeloma. Bone Marrow Transplantation, 16, 537-540.
37. Tricot, G.J. (2007) What is the significance of molecular remission in multiple myeloma? Clinical Advances in Hematology and Oncology, 5, 91-95.
38. van de Velde, H.J., Liu, X., Chen, G., Cakana, A., Deraedt, W. & Bayssas, M. (2007) Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma. Haematologica, 92, 1399-1406.
39. van der Velden, V.H., Willemse, M.J., van der Schoot, C.E., Hahlen, K., van Wering, E.R. & van Dongen, J.J. (2002) Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR. Leukemia, 16, 928-936.