Primary plasma cell leukemia (PCL) is a rare plasma cell malignancy. Consequently, few large reports have been published. Presented is a cytogenetic analysis of 40 patients with primary PCL compared with 247 newly diagnosed patients with stage III multiple myeloma (MM). Cytogenetic abnormalities were observed in 23 of 34 patients, with usually complex hypodiploid or pseudodiploid karyotypes. Analysis of rearrangements of the 14q32 region revealed significant differences with high cell mass MM—a higher incidence of t(11;14) (33% vs 16%; P < .025) and of t(14;16) (13% vs 1%;P < .002) though incidences of t(4;14) were identical and a higher incidence of monosomy 13 (68% vs 42%;P = .005). Hypodiploid karyotypes and monosomy 13 may explain, at least in part, the poorer prognosis of primary PCL. In contrast, significantly longer survival was observed in patients displaying t(11;14) in comparison with those lacking this translocation (P = .001).

Subjects:
Brief Reports, Neoplasia
Topics:
cytogenetics, fluorescent in situ hybridization, interphase, karyotype determination procedure, leukemia, plasma cell, ptsd checklist, cytogenetic analysis, posterior cruciate ligament, cancer, multiple myeloma

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells (PC) within the bone marrow. On rare occasions, PCs are observed in the peripheral blood and mimic acute leukemia. Kyle et al1 defined strict criteria for the diagnosis of plasma cell leukemia (PCL): an absolute PC number greater than 2 × 109/L or a relative number greater than 20% of peripheral white blood cells. PCL is rarely encountered; it represents less than 5% of malignant PC disorders.1-4 Consequently, few series have been reported, and only 3 series clinically analyzing more than 20 patients have been published.2-4 We now report on the largest series of primary PCL (35 patients with primary PCL and 5 patients with a primary PCL-like condition) analyzed by cytogenetics or interphase and multicolor fluorescence in situ hybridization (FISH). Interphase FISH results were then compared to those obtained in a series of 247 newly diagnosed patients with a stage III MM, as previously reported.5 6 

Between 1992 and 2000, 35 patients with primary PCL and 5 patients with a PCL-like disease (less than 2 × 109PC/L; range, 1 × 109-1.9 × 109) were analyzed by FISH in our laboratory. Twenty of these patients were directly analyzed in Nantes, whereas the other 20 patients were diagnosed in other institutions, and metaphase preparations were secondarily sent to us for FISH analysis. Most patients received melphalan-based conventional dosage chemotherapy, and 13 patients were treated using high-dose chemotherapy followed by autologous (10 patients) or allogeneic (3 patients) stem cell rescue. These patients have been compared with 247 patients with newly diagnosed stage III MM, analyzed in the same conditions (most of them have been previously reported5 6).

Bone marrow (34 patients) or peripheral blood (6 patients) cells were cultured without mitogens for 24 to 72 hours, using standard conditions. Cytogenetic analysis was attempted in 34 patients. Patients with abnormal karyotype were analyzed using multicolor FISH. Briefly, metaphase spreads were hybridized with a multicolor painting probe panel (SpectraVysion; Vysis, Voisins-le-Bretonneux, France), and analyzed using the software (Vysis). Each chromosome was pseudocolored in a specific color, enabling an accurate identification of marker chromosomes. Finally, we performed interphase FISH experiments in all 40 patients for the analysis of 14q32 and 13q14 rearrangements, as previously reported.5 6 Other FISH analyses were performed using specific probes to confirm some abnormalities in 11 patients.

Median age was 62 years (range, 35-89 years). Five patients did not fulfill the criteria for PCL but resembled true PCL patients in other factors and thus were included in this series. The median absolute number of circulating PC in PCL patients was 9.2 × 109/L (range, 2-64 × 109). Osteolytic lesions were present in 17 of 29 patients (59%) with available clinical data. Overall survival was brief, with a median survival of 7 months (range, 5 days-38 months). This poor survival is in agreement with previously reported series and confirms the poor prognosis of primary PCL.3-5 7 However, a detailed analysis of survival shows that 11 of 40 patients died within the first month of diagnosis and that, in contrast, some patients are alive 2 to 3 years after diagnosis.

An abnormal karyotype was obtained in 23 of 34 patients (Table1). Most were complex and pseudodiploid or hypodiploid. Only 3 patients had hyperdiploidy (48, 49, and 51 chromosomes). These results are in contrast with those published in MM,8-10 in which hyperdiploidy is observed in approximately 60% of patients, but they confirm previously published analyses.3,4 Multicolor FISH analysis was performed in 21 of 23 patients with an abnormal karyotype (no available metaphases for patients 34 and 36). In several patients, it enabled the identification of marker chromosomes. Some markers were extremely complex, containing sequences from up to 6 chromosomes, and could not be identified by cytogenetics (Figure 1). Among all the abnormalities revealed by multicolor FISH analysis, t(6;8)(q12-q15;q24) was identified in 2 patients (patients 3 and 37; Figure 1). The involvement of c-myc was confirmed by other FISH experiments using specific probes located on each side of thec-myc locus (manuscript submitted), which showed a separation of both probes. This specific abnormality has been reported.11 No other translocation involvingc-myc has been identified, neither by conventional karyotyping nor by interphase or multicolor FISH. These results contrast with those recently reported by Shou et al12describing c-myc rearrangements in almost 100% of myeloma cell lines and 50% of patients with MM. No satisfactory answer can be proposed to explain these discrepancies.

Table 1.

Cytogenetic characteristics and survival of the 40 patients

PatientAgeKaryotype14q32 Partner*Monosomy 13Survival†
 1 34 46,XY,t(9;14)(p13;q32) 9p13 No 1 wk  
 2 64 ND 11q13 Yes 18 mos+ 
 3 51 46,XX,t(1;20)(p11;p11),t(6;8)(q14;q24),+7,−13,der(17)t(17;21)(q10;p10) 16q23 Yes 7 mos  
 4 56 Unsuccessful UI Yes 12 mos 
 5 70 45,XY,der(5)t(5;20)(p10;p10),t(11;14)(q13;q32),der(11)t(1;11)(q12;q23),−13,der(20)t(5;20)
(q10;qter→dup(5)(?);p10) 		11q13 Yes 1 wk 
 6 55 40,XY,−1,del(1)(q11q41),der(2)t(1;2)(q12;q22),der(5)t(4;5)(?;q12),t(5;22)(q13;q11),der(6)t(1;6)
(?;q26),del(7)(q10q21),der(8)t(6;8;X;1;8),der(8)t(1;8)(p?;p10),der(9)t(4;9)(p16;q34),der(11)
t(11;13)(p12;q14),−12,−13,del(13)(q12q32),−14,dic(15;19)(p10;q13),der(16)t(1;16)(?;q24),
der(17)t(13;17)(?;p13),−19,−20,der(21)t(1;21)(?;p13) 		4p16 and UI Yes 3 mos  
 7 69 ND None No 9 mos 
 8 56 Unsuccessful 11q13 No 38 mos 
 9 68 ND 11q13 and UI Yes 3 mos 
10 73 45,XY,del(1)(p13),ins(3;14)(p21;q32),der(6)t(1;6)(?;q24),del(10)(p11),der(11)t(X;11;14)(?;q24;?),
der(12)t(X;12)(?;q24),−13,del(14)(?)x2 		3p21 Yes 2 mos 
11 37 43,X,−Y,der(6)t(6;10)(q21;?),der(7)t(7;12)(p21;?),−8,der(9)t(9;11;14)(q32;q13;q32),−10,
del(13)(q?),del(17)(p12),der(21)t(8;21)(?;q22) 		11q13 Yes 17 mos  
12 65 Unsuccessful UI No 2 mos 
13 50 48-51,XY,der(1)t(1;14)(p11;q11)x2,+3,der(4)t(4;22)(p13;q11),−4,der(5)t(5;22)(q32;q11),−6,
+dup(7)(?),+der(9)t(9;16)(p11;?),+11,der(12)t(6;12)(?;q12),−14,−14,der(15)t(11;15)(q13;q22),
−16,der(16)t(16;21)(p11;q11),der(17)t(1;17)(p12;p12),+18,+19,+der(21)t(8;21)(?;q22)x2,
der(21)t(1;21)(?;q22),−22 		UI No 3 wks  
14 74 46,XY,der(14)t(11;14)(q13;q32) 11q13 No 3 mos  
15 54 Normal None No 29 mos+ 
16 50 40-47,X,−Y,−1,−1,+3,t(3;14)(q27;q32),der(4)t(4;22)(p10;q10),der(7)t(2;7)(q22;q31),t(8;18)
(p10;q10),+der(8)t(8;18)(p10;q10),+9,+10,der(11)t(1;11)(p21;q23),der(11)t(11;16)(?;?),
der(12)t(X;11;8;12;7;1),+der(12)t(7;12;8),del(14)(?),der(16)t(16;?)(q10;?),der(16)t(16;?)(q22;?),
der(17)t(11;17)(q11;p11),−18,−18,der(19)t(12;19)(?;p13),−20,der(20)t(1;20)(?;p12),−21,−22 		3q27 Yes 3 mos  
17 56 ND 11q13 Yes 22 mos 
18 46 43,X,der(X)(?),−1,der(2)t(1;2)(?;q36),der(4)t(4;16)(q35;?),der(6)t(1;6;17),del(8)(p?),der(10)
t(6;10)(p13;p11),der(11)t(11;18)(q25;?),+der(12)(?),−13,der(14)t(14;16)(q32;q23),der(15)
t(15;16)(p11;q11),−17,−18,der(19)t(16;19)(?;?),der(21)t(16;21)(?;q13) 		16q23 Yes 7 mos  
19 61 Unsuccessful 16q23 Yes 4 mos 
20 83 ND UI No 1 wk 
21 63 30,X,+der(1)(?)+3,+7,+9,+11,del(13)(q13),+18,+19 None Yes 6 mos  
22 78 Unsuccessful UI Yes 5 wks 
23 79 Unsuccessful 4p16 Yes 1 mo 
24 72 ND None No 8 mos 
25 57 Unsuccessful UI Yes 7 mos+ 
26 53 44,−X,der(X)t(X;1)(p23;q12),der(8)t(8;13)(q24;q14),del(12)(p11),−13,del(13)(q14),der(14)
t(1;14)(q12;p11) 		4p16 Yes 13 mos 
27 52 45,XY,der(10)t(7;10)(?;q21),t(14;20)(q32;q12),−22 20q12 Yes 8 mos  
28 85 Unsuccessful 11q13 No 1 wk 
29 50 Unsuccessful 11q13 No 29 mos+ 
30 55 Unsuccessful 11q13 Yes 15 mos+ 
31 35 49,XY,+8,+9,−13,t(14;16)(q32;q23),+18,+mar 16q23 Yes 7 mos 
32 85 44,XX,del(1)(p21p31),del(1)(p32p34),der(2)t(2;3)(q26;?),del(2)(q31q34),t(3;4;14)(p11;p16;q32),
ins(3;7)(q12;?),dup(7)(?),−13,der(13)t(7;13)(p10;q10),−20 		4p16 Yes 1 mo 
33 48 48,XY,t(1;3)(q21;p12),t(11;14)(q13;q32),+der(18)(?)x2 11q13 No 28 mos+ 
34 70 42,X,−X,der(1)dic(1;?)(?;?),t(2;14)(p23;q32),add(2)(q37),add(3q26),add(6q24),add(7)(p13),
add(10)(q24),−12,−13,del(14)(q23q32),dic(16;?)(q13;?),del(17)(p12),−21,+r 		2p23 Yes 1 wk 
35 69 44,X,−X,del(1)(p13p31),der(5)t(5;?)(q31;?),der(6)t(6;?)(q26;?),−8,t(11;14)(q13;q32),−13,+21 11q13 Yes 29 mos 
36‡ 62 44,XY,−1,del(3)(p23),add(2)(q37),der(6)t(1;6)(p22;p22),−8,add(9)(p24),add(10)(q26),−13,−14,
der(16)t(1;16)(q10;p10),+2mar 		None Yes 21 mos 
37‡ 67 44,XY,−1,del(1)(p21p31),der(2)t(1;2)(q12;q36),der(2)t(2;7)(p12;q11),t(6;8)(q15;q24),der(6)t(3;6)
(q21;q15),−7,del(9)(p11),del(12)(q22q23),del(13)(q14),t(16;20)(q10;p10),der(20)t(1;20)(p12;q12) 		None Yes 3 wks 
38‡ 60 44,XY,del(2)(p13),dic(X;5)(p?;p11),−7,der(8)t(8;?)(p23;?),der(10)t(10;21),t(11;14)(q13;q32),−16 11q13 No 17 mos 
39‡ 74 45,X,−X,t(1;2;8)(p13;?;q24),der(2)t(2;7)(q24;q21),der(8)t(8;13)(p22;q14),−13,der(14)t(1;14)
(q12;q32)x2 		4p16 and 1q12 Yes 2 wks 
40‡ 79 41,X,der(X)t(X;17)(p11.3;q11),der(1)t(1;7)(p21;q21),der(2)t(1;2)(p?;p13?),der(4)t(4;9)(p10;q10),
−4,der(5)t(5;12)(p10;q21),der(5)t(5;6)(q31;p21),der(6)t(6;7)(q12;q11.2),−7,t(8;8)(p23;q21),−9,
+der(12)t(5;12)(q31;q13.1),−13,del(13)(q13q21),t(15;22)(p10;q11),−16,−17,der(18)t(X;18)
(p11.3;p11),der(20)t(2;20)(p1?1;p1?3) 		None Yes 1 wk 
PatientAgeKaryotype14q32 Partner*Monosomy 13Survival†
 1 34 46,XY,t(9;14)(p13;q32) 9p13 No 1 wk  
 2 64 ND 11q13 Yes 18 mos+ 
 3 51 46,XX,t(1;20)(p11;p11),t(6;8)(q14;q24),+7,−13,der(17)t(17;21)(q10;p10) 16q23 Yes 7 mos  
 4 56 Unsuccessful UI Yes 12 mos 
 5 70 45,XY,der(5)t(5;20)(p10;p10),t(11;14)(q13;q32),der(11)t(1;11)(q12;q23),−13,der(20)t(5;20)
(q10;qter→dup(5)(?);p10) 		11q13 Yes 1 wk 
 6 55 40,XY,−1,del(1)(q11q41),der(2)t(1;2)(q12;q22),der(5)t(4;5)(?;q12),t(5;22)(q13;q11),der(6)t(1;6)
(?;q26),del(7)(q10q21),der(8)t(6;8;X;1;8),der(8)t(1;8)(p?;p10),der(9)t(4;9)(p16;q34),der(11)
t(11;13)(p12;q14),−12,−13,del(13)(q12q32),−14,dic(15;19)(p10;q13),der(16)t(1;16)(?;q24),
der(17)t(13;17)(?;p13),−19,−20,der(21)t(1;21)(?;p13) 		4p16 and UI Yes 3 mos  
 7 69 ND None No 9 mos 
 8 56 Unsuccessful 11q13 No 38 mos 
 9 68 ND 11q13 and UI Yes 3 mos 
10 73 45,XY,del(1)(p13),ins(3;14)(p21;q32),der(6)t(1;6)(?;q24),del(10)(p11),der(11)t(X;11;14)(?;q24;?),
der(12)t(X;12)(?;q24),−13,del(14)(?)x2 		3p21 Yes 2 mos 
11 37 43,X,−Y,der(6)t(6;10)(q21;?),der(7)t(7;12)(p21;?),−8,der(9)t(9;11;14)(q32;q13;q32),−10,
del(13)(q?),del(17)(p12),der(21)t(8;21)(?;q22) 		11q13 Yes 17 mos  
12 65 Unsuccessful UI No 2 mos 
13 50 48-51,XY,der(1)t(1;14)(p11;q11)x2,+3,der(4)t(4;22)(p13;q11),−4,der(5)t(5;22)(q32;q11),−6,
+dup(7)(?),+der(9)t(9;16)(p11;?),+11,der(12)t(6;12)(?;q12),−14,−14,der(15)t(11;15)(q13;q22),
−16,der(16)t(16;21)(p11;q11),der(17)t(1;17)(p12;p12),+18,+19,+der(21)t(8;21)(?;q22)x2,
der(21)t(1;21)(?;q22),−22 		UI No 3 wks  
14 74 46,XY,der(14)t(11;14)(q13;q32) 11q13 No 3 mos  
15 54 Normal None No 29 mos+ 
16 50 40-47,X,−Y,−1,−1,+3,t(3;14)(q27;q32),der(4)t(4;22)(p10;q10),der(7)t(2;7)(q22;q31),t(8;18)
(p10;q10),+der(8)t(8;18)(p10;q10),+9,+10,der(11)t(1;11)(p21;q23),der(11)t(11;16)(?;?),
der(12)t(X;11;8;12;7;1),+der(12)t(7;12;8),del(14)(?),der(16)t(16;?)(q10;?),der(16)t(16;?)(q22;?),
der(17)t(11;17)(q11;p11),−18,−18,der(19)t(12;19)(?;p13),−20,der(20)t(1;20)(?;p12),−21,−22 		3q27 Yes 3 mos  
17 56 ND 11q13 Yes 22 mos 
18 46 43,X,der(X)(?),−1,der(2)t(1;2)(?;q36),der(4)t(4;16)(q35;?),der(6)t(1;6;17),del(8)(p?),der(10)
t(6;10)(p13;p11),der(11)t(11;18)(q25;?),+der(12)(?),−13,der(14)t(14;16)(q32;q23),der(15)
t(15;16)(p11;q11),−17,−18,der(19)t(16;19)(?;?),der(21)t(16;21)(?;q13) 		16q23 Yes 7 mos  
19 61 Unsuccessful 16q23 Yes 4 mos 
20 83 ND UI No 1 wk 
21 63 30,X,+der(1)(?)+3,+7,+9,+11,del(13)(q13),+18,+19 None Yes 6 mos  
22 78 Unsuccessful UI Yes 5 wks 
23 79 Unsuccessful 4p16 Yes 1 mo 
24 72 ND None No 8 mos 
25 57 Unsuccessful UI Yes 7 mos+ 
26 53 44,−X,der(X)t(X;1)(p23;q12),der(8)t(8;13)(q24;q14),del(12)(p11),−13,del(13)(q14),der(14)
t(1;14)(q12;p11) 		4p16 Yes 13 mos 
27 52 45,XY,der(10)t(7;10)(?;q21),t(14;20)(q32;q12),−22 20q12 Yes 8 mos  
28 85 Unsuccessful 11q13 No 1 wk 
29 50 Unsuccessful 11q13 No 29 mos+ 
30 55 Unsuccessful 11q13 Yes 15 mos+ 
31 35 49,XY,+8,+9,−13,t(14;16)(q32;q23),+18,+mar 16q23 Yes 7 mos 
32 85 44,XX,del(1)(p21p31),del(1)(p32p34),der(2)t(2;3)(q26;?),del(2)(q31q34),t(3;4;14)(p11;p16;q32),
ins(3;7)(q12;?),dup(7)(?),−13,der(13)t(7;13)(p10;q10),−20 		4p16 Yes 1 mo 
33 48 48,XY,t(1;3)(q21;p12),t(11;14)(q13;q32),+der(18)(?)x2 11q13 No 28 mos+ 
34 70 42,X,−X,der(1)dic(1;?)(?;?),t(2;14)(p23;q32),add(2)(q37),add(3q26),add(6q24),add(7)(p13),
add(10)(q24),−12,−13,del(14)(q23q32),dic(16;?)(q13;?),del(17)(p12),−21,+r 		2p23 Yes 1 wk 
35 69 44,X,−X,del(1)(p13p31),der(5)t(5;?)(q31;?),der(6)t(6;?)(q26;?),−8,t(11;14)(q13;q32),−13,+21 11q13 Yes 29 mos 
36‡ 62 44,XY,−1,del(3)(p23),add(2)(q37),der(6)t(1;6)(p22;p22),−8,add(9)(p24),add(10)(q26),−13,−14,
der(16)t(1;16)(q10;p10),+2mar 		None Yes 21 mos 
37‡ 67 44,XY,−1,del(1)(p21p31),der(2)t(1;2)(q12;q36),der(2)t(2;7)(p12;q11),t(6;8)(q15;q24),der(6)t(3;6)
(q21;q15),−7,del(9)(p11),del(12)(q22q23),del(13)(q14),t(16;20)(q10;p10),der(20)t(1;20)(p12;q12) 		None Yes 3 wks 
38‡ 60 44,XY,del(2)(p13),dic(X;5)(p?;p11),−7,der(8)t(8;?)(p23;?),der(10)t(10;21),t(11;14)(q13;q32),−16 11q13 No 17 mos 
39‡ 74 45,X,−X,t(1;2;8)(p13;?;q24),der(2)t(2;7)(q24;q21),der(8)t(8;13)(p22;q14),−13,der(14)t(1;14)
(q12;q32)x2 		4p16 and 1q12 Yes 2 wks 
40‡ 79 41,X,der(X)t(X;17)(p11.3;q11),der(1)t(1;7)(p21;q21),der(2)t(1;2)(p?;p13?),der(4)t(4;9)(p10;q10),
−4,der(5)t(5;12)(p10;q21),der(5)t(5;6)(q31;p21),der(6)t(6;7)(q12;q11.2),−7,t(8;8)(p23;q21),−9,
+der(12)t(5;12)(q31;q13.1),−13,del(13)(q13q21),t(15;22)(p10;q11),−16,−17,der(18)t(X;18)
(p11.3;p11),der(20)t(2;20)(p1?1;p1?3) 		None Yes 1 wk 

ND indicates not done; FISH, fluorescence in situ hybridization.

Karyotypes have been written according to conventional cytogenetics, multicolor FISH, and interphase FISH results.

*

UI, an illegitimate 14q32 rearrangement has been recognized, but the partner chromosomal region has not been identified.

†

Plus sign means that the patient is still alive.

‡

These five patients did not fulfill the criteria defined by Kyle et al1 but absolute plasma cell counts between 1 × 109 and 2 × 109.

View Large
Fig. 1.
Fig. 1. Multicolor FISH analysis. / (A) Partial multicolor FISH karyotype showing both derivatives of t(6;8)(q15;q24) (patient 37). (B) Complex chromosomal marker identified by multicolor FISH (patient 6), containing 5 different chromosomal fragments (from chromosomes 6, 8, X, 1, and 8). (C) Complex chromosomal marker identified by multicolor FISH (patient 16), containing 6 different chromosomal fragments (from chromosomes X, 11, 8, 12, 7, and 1).
View largeDownload PPT

Multicolor FISH analysis.

(A) Partial multicolor FISH karyotype showing both derivatives of t(6;8)(q15;q24) (patient 37). (B) Complex chromosomal marker identified by multicolor FISH (patient 6), containing 5 different chromosomal fragments (from chromosomes 6, 8, X, 1, and 8). (C) Complex chromosomal marker identified by multicolor FISH (patient 16), containing 6 different chromosomal fragments (from chromosomes X, 11, 8, 12, 7, and 1).

Fig. 1.
Fig. 1. Multicolor FISH analysis. / (A) Partial multicolor FISH karyotype showing both derivatives of t(6;8)(q15;q24) (patient 37). (B) Complex chromosomal marker identified by multicolor FISH (patient 6), containing 5 different chromosomal fragments (from chromosomes 6, 8, X, 1, and 8). (C) Complex chromosomal marker identified by multicolor FISH (patient 16), containing 6 different chromosomal fragments (from chromosomes X, 11, 8, 12, 7, and 1).
View largeDownload PPT

Multicolor FISH analysis.

(A) Partial multicolor FISH karyotype showing both derivatives of t(6;8)(q15;q24) (patient 37). (B) Complex chromosomal marker identified by multicolor FISH (patient 6), containing 5 different chromosomal fragments (from chromosomes 6, 8, X, 1, and 8). (C) Complex chromosomal marker identified by multicolor FISH (patient 16), containing 6 different chromosomal fragments (from chromosomes X, 11, 8, 12, 7, and 1).

Close modal

Interphase FISH experiments were performed in all 40 patients and closely analyzed the 14q32 and 13q14 chromosomal bands, as previously described.5,6 An illegitimate rearrangement of theIGH gene was observed in 32 of 40 (80%) patients; in 3 patients, 2 different rearrangements were identified (Table 1). This incidence of 14q32 abnormalities is significantly higher than that observed in a control series of 247 patients newly diagnosed with stage III MM (60%) (P = .024). Of note, 3 (7.5%) patients displayed 2 different 14q32 rearrangements, whereas only 1 of 247 stage III patients showed this configuration. Three partners were recurrently identified, either with metaphase or interphase FISH: 11q13, 4p16, and 16q23, in 13, 5, and 4 patients, respectively. No case of t(8;14) was identified. Compared with the control stage III MM population, t(11;14) and t(14;16) were significantly more frequent in primary PCL than in stage III MM (33% and 13% vs 16% and 1%;P = .025 and P = .002, respectively). Such a high incidence of t(11;14) has never been reported in patients with PC malignancies. Regarding the t(14;16), one study based on multicolor spectral karyotyping reported a 12% (6 of 50) incidence.11 However, clinical data were not described, and some PCL patients may have been included. Finally, the 12% (11 of 53) incidence of t(4;14) observed in primary PCL and MM is in agreement with that recently reported by Malgeri et al.13 Few cytogenetic analyses of patients with primary PCL have been published. In one study,3 9 patients were analyzed and 1 patient with t(11;14) was described. However, a detailed analysis of karyotypes in this study reveals 3 patients with “add (16q24),” which may correspond to unidentified t(14;16). This abnormality is cryptic and could be missed by conventional cytogenetics. Another study of 4 patients reported 1 with t(11;14).14 In contrast, no differences were observed for t(4;14) between primary PCL and stage III MM. These results clearly highlight specific associations between some 14q32 rearrangements and the type of presentation of plasma cell dyscrasias rather than a random occurrence. Whereas t(11;14) is observed in all types of plasma cell dyscrasia (ie, MGUS,15 MM,5 primary PCL, and myeloma cell lines16), t(4;14) appears to be specifically associated with MM,5,15 primary PCL, and cell lines,16but not with MGUS, t(14;16) is mostly observed in primary PCL and cell lines,17 and t(8;14) is specifically associated with myeloma cell lines.12 

Then we focused on chromosome 13 loss. This abnormality has been recently identified as a poor prognostic factor.18-20Interphase FISH analysis was performed using a probe specific for the D13S319 locus, at 13q14. Although monosomy 13 is observed in 42% of patients with stage III MM, 27 of 40 (68%) patients with primary PCL displayed this abnormality (P = .005). Thus, the cytogenetic profile presented by patients with primary PCL—hypodiploidy or pseudodiploidy and monosomy 13—may explain the poor survival observed in these patients. However, some patients younger than 65 years without monosomy 13 may benefit from intensive therapy and enjoy longer survival. In addition, a detailed analysis of 5 patients with a primitive PCL-like disease revealed a profile similar to that of PCL patients (pseudodiploid or hypodiploid karyotypes, high incidence of monosomy 13, short survival). These similarities with PCL may suggest a reappraisal of the diagnostic criteria, empirically defined by Kyle et al1 25 years ago.

Despite a marked heterogeneity in treatment modalities, we performed multiple statistical analyses on overall survival using several end-points. The only significant difference was the survival at 12 months between patients with or without t(11;14)—t(11;14) was associated with significantly longer survival (P = .001; Fisher exact test). These data contrast with previously published reports concluding the opposite finding.21 22 Larger prospective studies are necessary to establish definitive conclusions.

Supported in part by grants from the Fondation de France and from the Association de Recherche contre le Cancer.

The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 U.S.C. section 1734.

1
Kyle
 
RA
Maldonado
 
JE
Bayrd
 
ED
Plasma cell leukemia: report on 17 cases.
Arch Intern Med.
133
1974
813
818
Google Scholar
Crossref
Search ADS
PubMed
 
2
Noel
 
P
Kyle
 
RA
Plasma cell leukemia: an evaluation of response to therapy.
Am J Med.
83
1987
1062
1068
Google Scholar
Crossref
Search ADS
PubMed
 
3
Dimopoulos
 
MA
Palumbo
 
A
Delasalle
 
KB
Alexanian
 
R
Primary plasma cell leukemia.
Br J Haematol.
88
1994
754
759
Google Scholar
Crossref
Search ADS
PubMed
 
4
Garcia-Sanz
 
R
Orfao
 
A
Gonzalez
 
M
et al
Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics.
Blood.
93
1999
1032
1037
Google Scholar
Crossref
Search ADS
PubMed
 
5
Avet-Loiseau
 
H
Li
 
JY
Facon
 
T
et al
High incidence of translocations t(11;14)(q13;q32) and t(4,14)(p16;q32) in patients with plasma cell malignancies.
Cancer Res.
58
1998
5640
5645
Google Scholar
PubMed
 
6
Avet-Loiseau
 
H
Li
 
JY
Morineau
 
N
et al
Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma.
Blood.
94
1999
2583
2589
Google Scholar
Crossref
Search ADS
PubMed
 
7
Pruzanski
 
W
Platts
 
ME
Ogryzlo
 
MA
Leukemic form of immunocytic dyscrasia (plasma cell leukemia): a study of ten cases and a review of the literature.
Am J Med.
47
1969
60
74
Google Scholar
Crossref
Search ADS
PubMed
 
8
Laı̈
 
JL
Zandecki
 
M
Mary
 
JY
et al
Improved cytogenetics in multiple myeloma: a study of 151 patients including 117 patients at diagnosis.
Blood.
85
1995
2490
2497
Google Scholar
Crossref
Search ADS
PubMed
 
9
Sawyer
 
JR
Waldron
 
JA
Jagannath
 
S
Barlogie
 
B
Cytogenetic findings in 200 patients with multiple myeloma.
Cancer Genet Cytogenet.
82
1995
41
49
Google Scholar
Crossref
Search ADS
PubMed
 
10
Smadja
 
NV
Fruchart
 
C
Isnard
 
F
et al
Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.
Leukemia.
12
1998
960
969
Google Scholar
Crossref
Search ADS
PubMed
 
11
Sawyer
 
JR
Lukacs
 
JL
Munshi
 
N
et al
Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping.
Blood.
92
1998
4269
4278
Google Scholar
Crossref
Search ADS
PubMed
 
12
Shou
 
Y
Martelli
 
ML
Gabrea
 
A
et al
Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma.
Proc Natl Acad Sci U S A.
97
2000
228
233
Google Scholar
Crossref
Search ADS
PubMed
 
13
Malgeri
 
U
Baldini
 
L
Perfetti
 
V
et al
Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by reverse transcription-polymerase chain reaction analysis of IGH-MMSET fusion transcripts.
Cancer Res.
60
2000
4058
4061
Google Scholar
PubMed
 
14
Jonveaux
 
P
Berger
 
R
Chromosome studies in plasma cell leukemia and multiple myeloma in transformation.
Genes Chromosomes Cancer.
4
1992
321
325
Google Scholar
Crossref
Search ADS
PubMed
 
15
Avet-Loiseau
 
H
Facon
 
T
Daviet
 
A
et al
14q32 Translocations and monosomy 13 observed in monoclonal gammopathy of undetermined significance delineate a multistep process for the oncogenesis of multiple myeloma.
Cancer Res.
59
1999
4546
4550
Google Scholar
PubMed
 
16
Bergsagel
 
PL
Chesi
 
M
Nardini
 
E
Brents
 
LA
Kirby
 
SL
Kuehl
 
WM
Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.
Proc Natl Acad Sci U S A.
93
1996
13931
13936
Google Scholar
Crossref
Search ADS
PubMed
 
17
Chesi
 
M
Bergsagel
 
PL
Shonukan
 
OO
et al
Frequent dysregulation of the c-maf proto-oncogene at 16q23 by translocation to an Ig locus in multiple myeloma.
Blood.
91
1998
4457
4463
Google Scholar
Crossref
Search ADS
PubMed
 
18
Tricot
 
G
Barlogie
 
B
Jagannath
 
S
et al
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.
86
1995
4250
4256
Google Scholar
Crossref
Search ADS
PubMed
 
19
Zojer
 
N
Königsberg
 
R
Ackermann
 
J
et al
Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization.
Blood.
95
2000
1925
1930
Google Scholar
Crossref
Search ADS
PubMed
 
20
Desikan
 
R
Barlogie
 
B
Sawyer
 
J
et al
Results of high dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities.
Blood.
96
2000
4008
4010
Google Scholar
Crossref
Search ADS
 
21
Fonseca
 
R
Witzig
 
TE
Gertz
 
MA
et al
Multiple myeloma and the translocation t(11;14)(q13;q32): a report on 13 cases.
Br J Haematol.
101
1998
296
301
Google Scholar
Crossref
Search ADS
PubMed
 
22
Laı̈
 
JL
Michaux
 
L
Dastugue
 
N
et al
Cytogenetics in multiple myeloma: a multicenter study of 24 patients with t(11;14)(q13;q32) or its variant.
Cancer Genet Cytogenet.
104
1998
133
138
Google Scholar
Crossref
Search ADS
PubMed
 

Author notes

Hervé Avet-Loiseau and Régis Bataille, Laboratoire d'Hématologie, Institut de Biologie, 9 quai Moncousu, 44093 Nantes Cedex 1, France; e-mail:havetloiseau@chu-nantes.fr or frb@sante.univ-nantes.fr.

Copyright © 2001 The American Society of Hematology
2001
Sign in via your Institution