FLOW CYTOMETRY

Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma.
Blood. 2005 Oct 1;106(7):2276-9.
Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ, Lust JA, Dispenzieri A, Greipp PR, Kyle RA, Rajkumar SV.
This study evaluated prognosis according to the number of circulating plasma cells tested by flow cytometry of peripheral blood in 302 myeloma patients.
Circulating plasma cells per 50,000 mononuclear cells were:
  - 0 circulating plasma cells in 80 (27%) patients
  - 1-10 circulating plasma cells in 106 (35%) patients
  - >10 circulating plasma cells in 115 (38%) patients
Median overall survival was:
  - 47 months for the whole group
  - 59 months for patients with 10 or fewer circulating plasma cells
  - 37 months for patients with >10 circulating PCs
Multivariate analysis showed that the number of circulating plasma cells was an independent predictor of survival. Its prognostic value was independent of other known prognostic factors, such as albumin and b2m.

Minimal residual disease monitoring in multiple myeloma: a comparison between allelic-specific oligonucleoide real-time quantitative polymerase chain reaction and flow-cytometry.
Haematologica. 2005 Oct;90(10):1365-72.
Sarasquete ME, García-Sanz R, González D, Martínez J, Mateo G, Martínez P, Ribera JM, Hernández JM, Lahuerta JJ, Orfão A, González M, San Miguel JF.
This study compared quantitative PCR and flow cytometry (FCM) for the detection of minimal residual disease in multiple myeloma. The authors analyzed 32 bone marrow samples of patients in complete remission after stem cell transplant both by PCR and flow cytometry. Because of technical reasons, PCR was feasible in 75% of patients, while flow cytometry was feasible in up to 90% of patients. Therefore, both tests were obtained simultaneously in only 24 patients. PCR was more sensitive than flow cytometry, because it detected residual myeloma cells in 17 patients, whereas floww cytometry detected residual cells in 11 patients. The authors concluded that both PCR and flow cytometry are acceptable methods and provide equivalent prognostic information. PCR was more sensitive, but it was time-consuming and technically feasible in a lower proportion of patients.

Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy.
J Clin Oncol. 2008 Jun 1;26(16):2737-44.
Mateo G, Montalbán MA, Vidriales MB, Lahuerta JJ, Mateos MV, Gutiérrez N, Rosiñol L, Montejano L, Bladé J, Martínez R, de la Rubia J, Diaz-Mediavilla J, Sureda A, Ribera JM, Ojanguren JM, de Arriba F, Palomera L, Terol MJ, Orfao A, San Miguel JF; PETHEMA Study Group; GEM Study Group.
This prospective study in 685 patients with newly diagnosed multiple myeloma evaluated the prognostic impact of several antigenic markers, assessed by flow cytometry. Worse prognosis, with shorter PFS and OS, was seen with expression of both CD19 and CD28 and absence of CD117. CD28 expression was associated with t(14;16) and del(17p), and the absence of CD117 was associated with t(4;14) and del(13q). Patients could be stratified into 3 risk categories:
  - Good risk: CD28 negative, CD117+
  - Intermediate risk: either both markers negative or both positive
  - Poor risk: CD28+, CD117 negative
Progression-free survival was 45, 37, and 30 months, respectively.

Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation.
Blood. 2008 Nov 15;112(10):4017-23.
Paiva B, Vidriales MB, Cerveró J, Mateo G, Pérez JJ, Montalbán MA, Sureda A, Montejano L, Gutiérrez NC, García de Coca A, de Las Heras N, Mateos MV, López-Berges MC, García-Boyero R, Galende J, Hernández J, Palomera L, Carrera D, Martínez R, de la Rubia J, Martín A, Bladé J, Lahuerta JJ, Orfao A, San Miguel JF; GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups.
This is a prospective study which evaluates the prognostic significance of flow cytometry in detecting minimal residual disease after stem cell transplant. 295 patients with newly diagnosed myeloma underwent autologous stem cell transplant, and disease remission was evaluated at day 100 after transplant. In the group of patients with minimal residual disease by flow cytometry, the median progression-free survival was 37 months, whereas in the group of patients with negative flow cytometry (two-thirds of patients), the median PFS was 71 months. Overall survival was also different between the two groups (89 months vs not reached. The authors demonstrated a prognostic significance even when they defined CR by immunofixation status, but at multivariate analysis the presence of minimal residual disease detected by flow cytometry was the most important independent prognostic factor.

Quantification of clonal circulating plasma cells in relapsed multiple myeloma.
Br J Haematol. 2014 Nov;167(4):500-5.
Gonsalves WI, Morice WG, Rajkumar V, Gupta V, Timm MM, Dispenzieri A, Buadi FK, Lacy MQ, Singh PP, Kapoor P, Gertz MA, Kumar SK.
Circulating plasma cells were quantified by multi-parameter flow cytometry in 647 patients with relapsed multiple myeloma. Circulating plasma cells were absent in patients in coimplete remission, whereas the presence of 100 or more circulating plasma cells (per 150,000 gated mononuclear events) was associated with an inferior median survival (12 months vs 33 months). The adverse impact on prognosis was maintained at multivariate analysis.

Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction.
Blood. 2015 Mar 19;125(12):1932-5.
Rawstron AC, Gregory WM, de Tute RM, Davies FE, Bell SE, Drayson MT, Cook G, Jackson GH, Morgan GJ, Child JA, Owen RG.
The authors assessed the presence of minimal residual disease (MDR) by flow cytometry in 397 patients with multiple myeloma, treated in the Medical Research Council Myeloma IX study (this included autologous stem cell transplant). They found that median overall survival increased for each log depletion in the MDR level:
  -     >10%  : 1    year
  -    1-10%  : 4    years
  -  0.1-1%   : 5.9  years
  - 0.01-0.1% : 6.8  years
  -     <0.01%: >7.5 years

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.
J Clin Oncol. 2017 Sep 1;35(25):2900-2910.
Lahuerta JJ, Paiva B, Vidriales MB, Cordón L, Cedena MT, Puig N, Martinez-Lopez J, Rosiñol L, Gutierrez NC, Martín-Ramos ML, Oriol A, Teruel AI, Echeveste MA, de Paz R, de Arriba F, Hernandez MT, Palomera L, Martinez R, Martin A, Alegre A, De la Rubia J, Orfao A, Mateos MV, Blade J, San-Miguel JF; GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group.
These authors analyzed data of flow cytometry to assess minimal residual disease (MRD) in 609 patients enrolled in previous clinical trials. They found that the achievement of a stringent complete remission by flow cytometry was associated with a superior long-term survival. The achievement of MRD-negative status had a better prognostic value than the achievement of CR (complete remission, traditionally defined as a negative immunofixation and <5% plasma cells in the bone marrow). The authors conclude that MRD negativity should one of the most important end point for the treatment of multiple myeloma in eligible patients (i.e., those who can undergo a stem cell transplant or those without major comorbidities that prevent the administration of adequate chemotherapy regimens).

 

CYTOGENETICS

See specific section.

Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants.
J Clin Oncol. 1997 Jul;15(7):2659-66.
Tricot G, Sawyer JR, Jagannath S, Desikan KR, Siegel D, Naucke S, Mattox S, Bracy D, Munshi N, Barlogie B.

Poor prognosis in multiple myeloma is associated only with partial or complete deletions of chromosome 13 or abnormalities involving 11q and not with other karyotype abnormalities.
Blood. 1995 Dec 1;86(11):4250-6.
Tricot G, Barlogie B, Jagannath S, Bracy D, Mattox S, Vesole DH, Naucke S, Sawyer JR.

CT-guided biopsy of focal lesions in patients with multiple myeloma may reveal new and more aggressive cytogenetic abnormalities.
AJNR Am J Neuroradiol. 2001 Apr;22(4):781-5.
Avva R, Vanhemert RL, Barlogie B, Munshi N, Angtuaco EJ.
78 myeloma patients underwent CT-guided FNA biopsy of focal lesions visualized at MRI of spine and pelvis, and specimens were sent for cytogenetic analysis. Results were compared with those obtained from bone marrow biopsies. CT-guided FNA showed cytogenetic abnormalities in 21% of patients. In 10-20% of cases, the results were more informative than those obtained with a standard bone marrow biopsy.

Both hypodiploidy and deletion of chromosome 13 independently confer poor prognosis in multiple myeloma.
Br J Haematol. 2002 Sep;118(4):1041-7.
Fassas AB, Spencer T, Sawyer J, Zangari M, Lee CK, Anaissie E, Muwalla F, Morris C, Barlogie B, Tricot G.

MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants.
Br J Haematol. 2003 Aug;122(3):430-40.
Jacobson J, Barlogie B, Shaughnessy J, Drach J, Tricot G, Fassas A, Zangari M, Giroux D, Crowley J, Hough A, Sawyer J.

Abnormal cytogenetics and significant bone marrow plasmacytosis are predictive of early progression and short survival in patients with low tumor mass asymptomatic multiple myeloma.
Leuk Lymphoma. 2004 Dec;45(12):2481-4.
Depil S, Leleu X, Micol JB, Berthon C, Laï JL, Bauters F, Quesnel B, Facon T.

Suppression of abnormal karyotype predicts superior survival in multiple myeloma.
Leukemia. 2008 Apr;22(4):850-5.
Arzoumanian V, Hoering A, Sawyer J, van Rhee F, Bailey C, Gurley J, Shaughnessy JD Jr, Anaissie E, Crowley J, Barlogie B.
Cytogenetic studies were reviewed in 2041 patients with multiple myeloma. Cytogenetic abnormalities were found in one-third of patients at baseline, in 14% after induction therapy, 10% after stem cell transplantation, and 28% at relapse. The presence of cytogenetic abnormalities, either at baseline or at relapse, was associated with poor prognosis, whereas their disappearance after the induction therapy had a favorable impact on prognosis.

 

FISH

Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy.
Blood. 2002 Sep 1;100(5):1579-83.
Moreau P, Facon T, Leleu X, Morineau N, Huyghe P, Harousseau JL, Bataille R, Avet-Loiseau H; Intergroupe Francophone du Myélome.
Analysis of chromosomal abnormalities in 168 myeloma patients at baseline showed poor outcome in patients with t(4;14), good outcome in patients with t(11;14), and intermediate outcome in patients with neither t(4;14) nor t(11;14).

Clinical and biologic implications of recurrent genomic aberrations in myeloma.
Blood. 2003 Jun 1;101(11):4569-75. Epub 2003 Feb 6.
Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA, Dewald GW, Van Ness B, Van Wier SA, Henderson KJ, Bailey RJ, Greipp PR.
FISH in 351 myeloma patients treated with conventional chemotherapy allowed to identify 3 risk categories:
 1 - High risk: median survival 24.7 months
         t(4; 14) (42 patients)
         t(14;16) (15 patients)
         -17p13 (37 patients)
  2 - Intermediate risk: median survival 42.3 months
         -13q14 (176 patients)
  3 - Good risk: median survival 50.5 months
         All others

Clinical implications of t(11;14)(q13;q32), t(4;14)(p16.3;q32), and -17p13 in myeloma patients treated with high-dose therapy.
Blood. 2005 Oct 15;106(8):2837-40.
Gertz MA, Lacy MQ, Dispenzieri A, Greipp PR, Litzow MR, Henderson KJ, Van Wier SA, Ahmann GJ, Fonseca R.
This study evaluated the prognostic impact of FISH in 238 myeloma patients treated with stem cell transplantation. The t(11;14) translocation did not influence prognosis, but patients with the t(4;14) translocation or -17p had a shorter progression-free survival (only 8.2 months with t4;14) and shorter overall survival. The risk ratio for t(4;14) was greater than for Del13. Patients with both t(4;14) and Del13 had a shorter overall survival than patients with Del13 alone (19 vs 27 months).

Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis.
Leukemia. 2007 Jan;21(1):143-50.
Gutiérrez NC, Castellanos MV, Martín ML, Mateos MV, Hernández JM, Fernández M, Carrera D, Rosiñol L, Ribera JM, Ojanguren JM, Palomera L, Gardella S, Escoda L, Hernández-Boluda JC, Bello JL, de la Rubia J, Lahuerta JJ, San Miguel JF; GEM/PETHEMA Spanish Group.
260 myeloma patients were analyzed by FISH. Patients with t(4;14), Rb or p53 deletions had a shorter overall survival than patients without these abnormalities, but patients with Rb deletions without other abnormalities had a similar outcome to patients with negative FISH (46 vs 54 months, p= 0.3).

Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.
Blood. 2007 Apr 15;109(8):3489-95.
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C.
FISH was obtained in 1064 patients with newly diagnosed myeloma, screening for -13, -17p, t(11;14), t(4;14), hyperdiploidy, and MYC translocations. After multivariate analysis, only t(4;14) (14% of patients) and -17p (11% of patients) retained a negative prognostic value for both event-free survival and overall survival.

Long-term analysis of the IFM 99 trials for myeloma: cytogenetic abnormalities [t(4;14), del(17p), 1q gains] play a major role in defining long-term survival.
J Clin Oncol. 2012 Jun 1;30(16):1949-52.
Avet-Loiseau H, Attal M, Campion L, Caillot D, Hulin C, Marit G, Stoppa AM, Voillat L, Wetterwald M, Pegourie B, Voog E, Tiab M, Banos A, Jaubert J, Bouscary D, Macro M, Kolb B, Traulle C, Mathiot C, Magrangeas F, Minvielle S, Facon T, Moreau P.

Chromosome 8q24.1/c-MYC abnormality: a marker for high-risk myeloma.
Leuk Lymphoma. 2015 Mar;56(3):602-7.
Glitza IC, Lu G, Shah R, Bashir Q, Shah N, Champlin RE, Shah J, Orlowski RZ, Qazilbash MH.
The oncogene c-MYC is rearranged in about 15% of patients with multiple myeloma. In this study, 23 patients with myeloma and c-MYC rearrangement had an aggressive clinical course, because of the high incidence of plasma cell leukemia and/or extramedullary disease either at diagnosis or upon progression (12 patients, 52%), and a short median survival (only 20 months).

Longitudinal fluorescence in situ hybridization reveals cytogenetic evolution in myeloma relapsing after autologous transplantation.
Haematologica. 2017 Aug;102(8):1432-1438.
Merz M, Jauch A, Hielscher T, Mai EK, Seckinger A, Hose D, Bertsch U, Neben K, Raab MS, Salwender H, Blau IW, Lindemann HW, Schmidt-Wolf I, Scheid C, Haenel M, Weisel K, Goldschmidt H, Hillengass J.
This is a retrospective study which compared FISH results in the bone marrow of 128 patients with multiple myeloma at baseline and at relapse, after an upfront autologous stem cell transplant. The results confirmed the presence of clonal evolution of myeloma over time: high-risk cytogenetic features, such as 17p- and 1q21+, were present more often at the time of relapse, and they were associated with a very poor outcome.

FISH - t(11;14)

t(11;14) does not predict long-term survival in myeloma.
Leukemia. 2005 Jun;19(6):1078-9.
Chang H, Qi XY, Stewart AK.

FISH - t(4;14)

In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression.
Blood. 2003 Feb 15;101(4):1520-9.
Keats JJ, Reiman T, Maxwell CA, Taylor BJ, Larratt LM, Mant MJ, Belch AR, Pilarski LM.
This study found the t(4;14) translocation in 31 of 208 (14.9%) patients with multiple myeloma, and 1 of 52 (1.9%) patients with MGUS. Breakpoint analysis of the IgH-MMSET showed that in 68% of cases, the protein produced by the t(4;14) was a hybrid transcript encoding full-length MMSET. The rest of cases lacked amino terminal exons. RT-PCR detected expression of FGFR3 in only 23 of 31 (74%) patients with t(4;14) MM. The presence of t(4;14) predicted a poor response to induction therapy, and poor prognosis: median survival was about 21 months (vs about 43 months), even in patients who did not have expression of FGFR.

The t(4;14) is associated with poor prognosis in myeloma patients undergoing autologous stem cell transplant.
Br J Haematol. 2004 Apr;125(1):64-8.
Chang H, Sloan S, Li D, Zhuang L, Yi QL, Chen CI, Reece D, Chun K, Keith Stewart A.

128 myeloma patients treated with autologous stem cell transplantation were studied for the t(11;14) and t(4;14) translocations. t(11;14) was present in 16 of 125 (12.8%) and t(4;14) in 15 of 120 (12.5%) patients. The t(11;14) translocation had a neutral impact on prognosis, whereas patients with t(4;14) had a shorter median progression-free survival (9.9 vs 25.8 months, p= 0.0003) and shorter median overall survival (18.3 vs 48.1 months, p <0.0001) than the rest of the patients.

Clinical outcomes in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance.
J Clin Oncol. 2005 Oct 1;23(28):7069-73.
Jaksic W, Trudel S, Chang H, Trieu Y, Qi X, Mikhael J, Reece D, Chen C, Stewart AK.
This study clarified that the poor prognosis associated with the t(4;14) translocation is not due to primary drug resistance, but instead to a rapid relapse of the disease. t(4;14) was present in 19 of 131 (14.5%) myeloma patients treated with stem cell transplantation. Patients with t(4;14) had a predominance of IgA isotype (53%). After induction chemotherapy, 90% of the 19 patients achieved a partial response, but disease progression occurred rapidly, as 26% of patients progressed before the stem cell transplant, and median progression-free survival after transplant was only 14 months. Median overall survival after stem cell transplantation was 24 months. Duration of response to salvage therapy was short (median: 4.7 months).

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.
Leukemia. 2007 Sep;21(9):2020-4.
Moreau P, Attal M, Garban F, Hulin C, Facon T, Marit G, Michallet M, Doyen C, Leyvraz S, Mohty M, Wetterwald M, Mathiot C, Caillot D, Berthou C, Benboubker L, Garderet L, Chaleteix C, Traullé C, Fuzibet JG, Jaubert J, Lamy T, Casassus P, Dib M, Kolb B, Dorvaux V, Grosbois B, Yakoub-Agha I, Harousseau JL, Avet-Loiseau H; SAKK; IFM Group.
Among 100 myeloma patients treated with tandem transplants, patients with t(4;14) had worse outcomes than patients without t(4:14): median event-free survival was 21 vs 37 months, and median overall survival was 41.4 vs 65 months.

Clinical and biological features of t(4;14) multiple myeloma: a prospective study.
Leuk Lymphoma. 2011 Feb;52(2):238-46.
Karlin L, Soulier J, Chandesris O, Choquet S, Belhadj K, Macro M, Bouscary D, Porcher R, Ghez D, Malphettes M, Asli B, Brouet JC, Bories JC, Hermine O, Fermand JP, Arnulf B.
This is a report of 102 consecutive patients with myeloma expressing the t(4;14). Prognosis was poor, with median progression-free survival of 12 months, and median overall survival after transplantation of 31 months.

FISH - t(14;16)

Translocation t(14;16) and multiple myeloma: is it really an independent prognostic factor?
Blood. 2011 Feb 10;117(6):2009-11.
Avet-Loiseau H, Malard F, Campion L, Magrangeas F, Sebban C, Lioure B, Decaux O, Lamy T, Legros L, Fuzibet JG, Michallet M, Corront B, Lenain P, Hulin C, Mathiot C, Attal M, Facon T, Harousseau JL, Minvielle S, Moreau P; Intergroupe Francophone du Myélome.
This study is a retrospective analysis of 32 patients with t914;16), found among 1003 patients with newly diagnosed myeloma (3%). Patients with t(14;16) had an overall survival similar to that of patients without the translocation.

FISH - 17p-

Bortezomib plus dexamethasone induction improves outcome of patients with t(4;14) myeloma but not outcome of patients with del(17p).
J Clin Oncol. 2010 Oct 20;28(30):4630-4.
Avet-Loiseau H, Leleu X, Roussel M, Moreau P, Guerin-Charbonnel C, Caillot D, Marit G, Benboubker L, Voillat L, Mathiot C, Kolb B, Macro M, Campion L, Wetterwald M, Stoppa AM, Hulin C, Facon T, Attal M, Minvielle S, Harousseau JL.
This is a retrospective study of 507 patients with newly diagnosed myeloma who were treated with either bortezomib-dexamethasone x 4 cycles or VAD, as induction therapy before autologous stem cell transplantation. Results:
  - When compared with VAD chemotherapy, bortezomib improved both EFS and OS in patients with t(4;14), but not in patients with del(17p)
  - del(17p) was an adverse prognostic factor only if present in >60% plasma cells
  - t(4;14) and del(17p-) remained poor prognostic factors, and bortezomib did not overcome their prognostic impact (at least, when given for 4 cycles as induction therapy)

FISH - +1q

Outcome of Patients with Multiple Myeloma and CKS1B Gene Amplification after Autologous Hematopoietic Stem Cell Transplantation.
Biol Blood Marrow Transplant. 2016 Dec;22(12):2159-2164.
Bock F, Lu G, Srour SA, Gaballa S, Lin HY, Baladandayuthapani V, Honhar M, Stich M, Shah ND, Bashir Q, Patel K, Popat U, Hosing C, Korbling M, Delgado R, Rondon G, Shah JJ, Thomas SK, Manasanch EE, Isermann B, Orlowski RZ, Champlin RE, Qazilbash MH.
This is a retrospective study comparing post-transplant outcomes of patients with multiple myeloma with 1q21+ (gain/amplification of the CKS1B gene on the chromosome 1q21 region) (58 patients) vs those without it (58 patients). Median follow-up after the autolous stem cell transplant was 25.4 months. The results showed the adverse prognostic impact of 1q21+:
  - Median progression-free survival: 15 months with 1q21+, and 33 months without it (p=0.002)
  - Overall survival at 2 years: 62% with 1q21+, and 91% without it (p=0.02)

Gain of chromosome 1q portends worse prognosis in multiple myeloma despite novel agent-based induction regimens and autologous transplantation.
Leuk Lymphoma. 2017 Aug;58(8):1823-1831.
Shah GL, Landau H, Londono D, Devlin SM, Kosuri S, Lesokhin AM, Lendvai N, Hassoun H, Chung DJ, Koehne G, Jhanwar SC, Landgren O, Levine R, Giralt SA.
In this retrospective study of 95 patients with multiple myeloma treated with an autologous stem cell transplant, 21% of them had gains of chromosome 1 (+1q). These patients had a worse median progression-free survival (2.1 vs 4.3 years), even with the transplant, confirming the high-risk nature of this chromosomal abnormality.

 

GEP

Testing standard and genetic parameters in 220 patients with multiple myeloma with complete data sets: superiority of molecular genetics.
Br J Haematol. 2007 Jun;137(6):530-6.
Shaughnessy JD Jr, Haessler J, van Rhee F, Anaissie E, Pineda-Roman M, Cottler-Fox M, Hollmig K, Zangari M, Mohiuddin A, Alsayed Y, Grazziutti M, Epstein J, Crowley J, Barlogie B
.

 

OTHER

Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantation.
Br J Haematol. 2006 Nov;135(4):486-91.
Chang H, Qi X, Trieu Y, Xu W, Reader JC, Ning Y, Reece D.
This study evaluated frequency and prognostic impact of CKS1B (chromosome 1q21 region) amplification by FISH in 99 myeloma patients treated with autologous stem cell transplantation. 3-8 CKS1B signals were found in 31 of 99 (31%) patients, and were associated with a worse outcome than in patients without CKS1B amplification: progression-free survival was 18.5 vs. 25.7 months (p= 0.035), and overall survival was 44.8 months vs not reached (p= 0.20, not statistically significant).

The presence of DRB1*01 allele in multiple myeloma patients is associated with an indolent disease.
Tissue Antigens. 2008 Jun;71(6):548-51.
Alcoceba M, Marín L, Balanzategui A, Sarasquete ME, Martín-Jiménez P, Chillón MC, Corral R, Pérez-Persona E, Fernández-Calvo FJ, Hernández JM, Bladé J, Lahuerta JJ, González M, San Miguel JF, García-Sanz R.
This study evaluated the HLA-DRB1 phenotypic frequencies in 53 patients with smoldering/indolent myeloma and 128 patients with symptomatic myeloma. Frequency of DRB1*01 was higher in patients with smoldering myeloma than in those with symptomatic myeloma (38% vs 14%, p= 0.001) or healthy individuals (38% vs 22%, p= 0.01). The authors proposed that HLA-DRB1*01 confers a better ability to present myeloma-related antigens to immunocompetent cells, favoring a better immune response against the myeloma.

 

 


Giampaolo Talamo, M.D.