World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 3, Number 4, August 2012, pages 147-157

Detection of Skeletal Lesions by Whole Body Multidetector Computed Tomography in Multiple Myeloma has no Impact on Long-Term Outcomes Post Autologous Hematopoietic Cell Transplantation

Figure 1. Rib, sternal, and vertebral body myelomatous lesions seen by WBCT (arrows) (b, c) but not conventional skeletal radiography (a).

Figure 2. Incidental finding of a non-cystic, exophytic left renal mass in a patient with multiple myeloma (arrow). This mass was later found to be a renal cell carcinoma.

Figure 3. Kaplan-Meier overall survival (OS) and progression-free survival (PFS) curves for the different groups of patients. P values are displayed within the figure for each comparison. Group 1: Patients who had more myelomatous bone disease detected on WBCT than CSS. Group 2: Patients without any differences between CSS and WBCT in the detection of myelomatous bone diseaseGroup 3: Patients without any myelomatous bone disease detected by either modality. Group 4: Patients with myelomatous bone lesions detected by WBCT but not by CSS.Group 5: patients in groups 3 and 4 together.

**Table 1.** Patient and Disease Characteristics
Characteristics	Group 1 (n = 41)	Group 2 (n = 31)
Abbreviations: HCT: hematopoietic cell transplant; FISH: fluorescence in situ hybridization; ISS: international staging system; B2M: beta 2 microglobulin; WBCT: whole body computerized tomography; CSS: conventional skeletal survey; Group 1: Patients who had more myelomatous bone disease detected on WBCT than CSS; Group 2: Patients without any differences between CSS and WBCT in the detection of myelomatous bone disease.
Male/female	22/19	17/14
Age, median (range) years	58 (25 - 75)	59 (43 - 75)
Durie-Salmon/ ISS
I A/I	2/19	3/11
II A/I	12/11	9/11
III A/IIIB/III	23/4/5	13/6/5
B2M, mg/L, median (range)	2.27 (0.84 - 14.1)	2.6 (1.45 - 69.6)
Median follow-up (range), months	36 (6 - 84)	31 (11 - 73)
Lines of therapy before HCT
1	28	20
2	9	7
3	4	4
Conditioning for first autologous HCT
Melphalan	32	18
Busulfan/cyclophosphamide +/- etoposide	9	13
Cytogenetics/FISH
Normal	25	24
Complex/hyperdiploid and del 13 by cytogenetics	4	1
Hyperdiploid without deletions	6	3
FISH + chromosomes 13,14, or 17	3	3
Del Y	2	1
Time to first auto HCT: median (range) months	7 (3 - 60)	7 (3 - 39)
Tandem autologous/autologous HCT	5	4
Tandem autologous/allogeneic HCT	5	6
Salvage autologous/autologous HCT	4	1
Salvage autologous/allogeneic HCT	6	2
Maintenance lenalidomide	4	1
Maintenance thalidomide/interferon	5	6

Table 1. Patient and Disease Characteristics

Characteristics

Group 1 (n = 41)

Group 2 (n = 31)

Abbreviations: HCT: hematopoietic cell transplant; FISH: fluorescence in situ hybridization; ISS: international staging system; B2M: beta 2 microglobulin; WBCT: whole body computerized tomography; CSS: conventional skeletal survey; Group 1: Patients who had more myelomatous bone disease detected on WBCT than CSS; Group 2: Patients without any differences between CSS and WBCT in the detection of myelomatous bone disease.

Male/female

22/19

17/14

Age, median (range) years

58 (25 - 75)

59 (43 - 75)

Durie-Salmon/ ISS

I A/I

2/19

3/11

II A/I

12/11

9/11

III A/IIIB/III

23/4/5

13/6/5

B2M, mg/L, median (range)

2.27 (0.84 - 14.1)

2.6 (1.45 - 69.6)

Median follow-up (range), months

36 (6 - 84)

31 (11 - 73)

Lines of therapy before HCT

Conditioning for first autologous HCT

Melphalan

Busulfan/cyclophosphamide +/- etoposide

Cytogenetics/FISH

Normal

Complex/hyperdiploid and del 13 by cytogenetics

Hyperdiploid without deletions

FISH + chromosomes 13,14, or 17

Del Y

Time to first auto HCT: median (range) months

7 (3 - 60)

7 (3 - 39)

Tandem autologous/autologous HCT

Tandem autologous/allogeneic HCT

Salvage autologous/autologous HCT

Salvage autologous/allogeneic HCT

Maintenance lenalidomide

Maintenance thalidomide/interferon

**Table 2.** Patient and Disease Characteristics of Group 5 (Negative Conventional Skeletal Survey) Compared to all Other Groups
Characteristic	Group 5 (n = 14)	All Other Patients (n = 58)
Abbreviations: HCT: hematopoietic cell transplant; FISH: fluorescence in situ hybridization; ISS: international staging system.
Male/female	5/9	34/24
Age, median (range) years	59 (47 - 75)	56 (35 - 75)
Durie-Salmon stage
I A	1	4
II A	7	14
III A/IIIB	3/3	33/7
International staging system
I	3	26
II	6	16
III	3	7
missing	2	9
Lines of therapy before HCT
1	10	38
2	3	13
3	1	7
Cytogenetics/FISH
Normal	11	38
Complex/hyperdiploid and del 13 by cytogenetics	0	5
Hyperdiploid without deletions	1	8
FISH + chromosomes 13,14, or 17	2	4
Del Y	0	3
Time to first autologous HCT: median (range) months	6 (4 - 24)	7 (3 - 60)
Tandem autologous/autologous HCT	2	7
Tandem autologous/allogeneic HCT	5	6
Salvage autologous/autologous HCT	0	5
Salvage autologous/allogeneic HCT	0	8
Maintenance lenalidomide	0	5
Maintenance thalidomide/interferon	2	9

Table 2. Patient and Disease Characteristics of Group 5 (Negative Conventional Skeletal Survey) Compared to all Other Groups

Characteristic

Group 5 (n = 14)

All Other Patients (n = 58)

Abbreviations: HCT: hematopoietic cell transplant; FISH: fluorescence in situ hybridization; ISS: international staging system.

Male/female

5/9

34/24

Age, median (range) years

59 (47 - 75)

56 (35 - 75)

Durie-Salmon stage

I A

II A

III A/IIIB

3/3

33/7

International staging system

III

missing

Lines of therapy before HCT

Cytogenetics/FISH

Normal

Complex/hyperdiploid and del 13 by cytogenetics

Hyperdiploid without deletions

FISH + chromosomes 13,14, or 17

Del Y

Time to first autologous HCT: median (range) months

6 (4 - 24)

7 (3 - 60)

Tandem autologous/autologous HCT

Tandem autologous/allogeneic HCT

Salvage autologous/autologous HCT

Salvage autologous/allogeneic HCT

Maintenance lenalidomide

Maintenance thalidomide/interferon

**Table 3.** Risk Factor Analysis for Progression Free Survival
Variable	Univariate	Multivariate
Abbreviations: DS: Durie-Salmon stage; ISS: International staging system; FISH: fluorescence in situ hybridization; Definitions of cytogenetics: 1-poor prognosis, complex abnormalities with del 13, 17p, or t(4:14), or any of these abnormalities; 2- Intermediate prognosis, normal chromosomes, Del 13 by FISH only; 3- Good prognosis, hyperdiploidy, t(11,14).
Disease stage DS
IIA vs IA	0.884	0.292 - 2.675	0.8274	1.166	0.342 - 3.972	0.8058
IIIA vs IA	1.337	0.465 - 3.845	0.2898	1.722	0.575 - 5.157	0.3311
IIIB vs IA	1.439	0.420 - 4.930	0.3350	4.219	0.994 - 17.902	0.0509
Disease stage ISS
II vs I	1.467	0.800 - 2.692	0.2156	1.41	0.699 - 2.845	0.3376
III vs I	0.742	0.304 - 1.808	0.5110	0.533	0.189 - 1.508	0.2358
Cytogenetics/FISH
3 vs 1	1.178	0.496 - 2.797	0.7107	0.997	0.391 - 2.44	0.9598
2 vs 1	1.750	0.483 - 6.254	0.3894	2.411	0.638 - 9.109	0.1943
Negative vs Positive conventional skeletal survey	0.522	0.253 - 1.077	0.0784	0.396	0.172 - 0.910	0.0291
Gender
Male vs Female	0.998	0.577 - 1.726	0.9944	1.088	0.603 - 1.963	0.7795
Age	1.005	0.977 - 1.033	0.7452	1.005	0.973 - 1.039	0.7534

Table 3. Risk Factor Analysis for Progression Free Survival

Variable

Univariate

Multivariate

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Abbreviations: DS: Durie-Salmon stage; ISS: International staging system; FISH: fluorescence in situ hybridization; Definitions of cytogenetics: 1-poor prognosis, complex abnormalities with del 13, 17p, or t(4:14), or any of these abnormalities; 2- Intermediate prognosis, normal chromosomes, Del 13 by FISH only; 3- Good prognosis, hyperdiploidy, t(11,14).

Disease stage DS

IIA vs IA

0.884

0.292 - 2.675

0.8274

1.166

0.342 - 3.972

0.8058

IIIA vs IA

1.337

0.465 - 3.845

0.2898

1.722

0.575 - 5.157

0.3311

IIIB vs IA

1.439

0.420 - 4.930

0.3350

4.219

0.994 - 17.902

0.0509

Disease stage ISS

II vs I

1.467

0.800 - 2.692

0.2156

1.41

0.699 - 2.845

0.3376

III vs I

0.742

0.304 - 1.808

0.5110

0.533

0.189 - 1.508

0.2358

Cytogenetics/FISH

3 vs 1

1.178

0.496 - 2.797

0.7107

0.997

0.391 - 2.44

0.9598

2 vs 1

1.750

0.483 - 6.254

0.3894

2.411

0.638 - 9.109

0.1943

Negative vs Positive conventional
skeletal survey

0.522

0.253 - 1.077

0.0784

0.396

0.172 - 0.910

0.0291

Gender

Male vs Female

0.998

0.577 - 1.726

0.9944

1.088

0.603 - 1.963

0.7795

Age

1.005

0.977 - 1.033

0.7452

1.005

0.973 - 1.039

0.7534

**Table 4.** Risk Factor Analysis for Overall Survival
Variable	Univariate	Multivariate
Abbreviations: DS: Durie-Salmon stage; ISS: International staging system; FISH: fluorescence in situ hybridization; Definitions of cytogenetics: 1- poor prognosis,complex abnormalities with del 13, 17p, or t(4:14), or any of these abnormalities; 2- Intermediate prognosis, normal chromosomes, Del 13 by FISH only; 3- good prognosis, hyperdiploidy, t(11,14).
Disease stage DS
IIA vs IA	0.754	0.083 - 6.876	0.8026	1.27	0.111 - 14.485	0.8472
IIIA vs IA	2.116	0.275 - 16.264	0.4715	4.57	0.534 - 39.147	0.1655
IIIB vs IA	3.839	0.461 - 31.947	0.2133	11.972	1.196 - 116.23	0.0346
Disease stage ISS
II vs I	7.70	2.765 - 21.837	0.0001	7.234	2.179 - 24.015	0.0012
III vs I	4.579	1.321 - 15.872	0.0164	3.426	0.809 - 14.516	0.0946
Cytogenetics/FISH
3 vs 1	1.044	0.308 - 3.539	0.9452	0.26	0.058 - 1.154	0.0763
2 vs 1	1.089	0.181 - 6.54	0.9257	0.232	0.031 - 1.724	0.1532
Negative vs Positive conventional skeletal survey	0.136	0.018 - 1.01	0.051	0.061	0.007 - 0.554	0.013
Gender Male vs Female	0.803	0.358 - 1.798	0.593	0.875	0.37 - 2.069	0.761
Age	1.03	0.987 - 1.074	0.1809	1.047	0.987 - 1.111	0.126

Table 4. Risk Factor Analysis for Overall Survival

Variable

Univariate

Multivariate

Hazard ratio

95% CI

P value

Hazard ratio

95% CI

P value

Abbreviations: DS: Durie-Salmon stage; ISS: International staging system; FISH: fluorescence in situ hybridization; Definitions of cytogenetics: 1- poor prognosis,complex abnormalities with del 13, 17p, or t(4:14), or any of these abnormalities; 2- Intermediate prognosis, normal chromosomes, Del 13 by FISH only; 3- good prognosis, hyperdiploidy, t(11,14).

Disease stage DS

IIA vs IA

0.754

0.083 - 6.876

0.8026

1.27

0.111 - 14.485

0.8472

IIIA vs IA

2.116

0.275 - 16.264

0.4715

4.57

0.534 - 39.147

0.1655

IIIB vs IA

3.839

0.461 - 31.947

0.2133

11.972

1.196 - 116.23

0.0346

Disease stage ISS

II vs I

7.70

2.765 - 21.837

0.0001

7.234

2.179 - 24.015

0.0012

III vs I

4.579

1.321 - 15.872

0.0164

3.426

0.809 - 14.516

0.0946

Cytogenetics/FISH

3 vs 1

1.044

0.308 - 3.539

0.9452

0.26

0.058 - 1.154

0.0763

2 vs 1

1.089

0.181 - 6.54

0.9257

0.232

0.031 - 1.724

0.1532

Negative vs Positive conventional skeletal survey

0.136

0.018 - 1.01

0.051

0.061

0.007 - 0.554

0.013

Gender Male vs Female

0.803

0.358 - 1.798

0.593

0.875

0.37 - 2.069

0.761

Age

1.03

0.987 - 1.074

0.1809

1.047

0.987 - 1.111

0.126

**Table 5.** Comparison of Survival Curves Using the Logrank Test
Groups of patients	Median PFS (months)	Median OS (months)	Hazard ratio	95% confidence interval	P value
Abbreviations: Group 1: Patients who had more myelomatous bone disease detected on WBCT than CSS; Group 2: Patients without any differences between CSS and WBCT in the detection of myelomatous bone disease; Group 3: Patients without any myelomatous bone disease detected by either modality; Group 4: Patients with myelomatous bone lesions detected by WBCT but not by CSS; Group 5: patients in groups 3 and 4 together.
Groups 1 vs. 2	17 vs. 27	84 vs. not yet reached	PFS: 0.627 OS 1.001	PFS: 0.36 - 1.1 OS: 0.43 - 2.34	PFS: 0.09 OS: 0.997
Groups 3 vs. 4	28 vs. 36.5	Not yet reached vs. 60	PFS: 1.544 OS: 0.00	PFS: 0.41 - 6.66 OS: 0.0008 - 3.18	PFS: 0.487 OS: 0.157
Groups 5 vs. all others	32 vs. 17	Not yet reached vs. 84	PFS: 0.47 OS: 0.145	PFS: 0.28 - 0.93 OS: 0.13 - 0.87	PFS: 0.0292 OS: 0.0258

Table 5. Comparison of Survival Curves Using the Logrank Test

Groups of patients

Median PFS (months)

Median OS (months)

Hazard ratio

95% confidence interval

P value

Abbreviations: Group 1: Patients who had more myelomatous bone disease detected on WBCT than CSS; Group 2: Patients without any differences between CSS and WBCT in the detection of myelomatous bone disease; Group 3: Patients without any myelomatous bone disease detected by either modality; Group 4: Patients with myelomatous bone lesions detected by WBCT but not by CSS; Group 5: patients in groups 3 and 4 together.

Groups 1 vs. 2

17 vs. 27

84 vs. not yet reached

PFS: 0.627
OS 1.001

PFS: 0.36 - 1.1
OS: 0.43 - 2.34

PFS: 0.09
OS: 0.997

Groups 3 vs. 4

28 vs. 36.5

Not yet reached vs. 60

PFS: 1.544
OS: 0.00

PFS: 0.41 - 6.66
OS: 0.0008 - 3.18

PFS: 0.487
OS: 0.157

Groups 5 vs. all others

32 vs. 17

Not yet reached vs. 84

PFS: 0.47
OS: 0.145

PFS: 0.28 - 0.93
OS: 0.13 - 0.87

PFS: 0.0292
OS: 0.0258