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 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 4008-4010
BRIEF REPORT
Results of high-dose therapy for 1000 patients with multiple
myeloma: durable complete remissions and superior survival in the
absence of chromosome 13 abnormalities
Raman Desikan,
Bart Barlogie,
Jeffrey Sawyer,
Dan Ayers,
Guido Tricot,
Ashraf Badros,
Maurizio Zangari,
Nikhil C. Munshi,
Elias Anaissie,
Dan Spoon,
David Siegel,
Sundar Jagannath,
David Vesole,
Joshua Epstein,
John Shaughnessy,
Athanasios Fassas,
Seah Lim,
Paula Roberson, and
John Crowley
From the Myeloma and Transplantation Research Center and Division of
Biometry, University of Arkansas for Medical Sciences, Little Rock, AR;
and the Southwest Oncology Group Statistical Center, Fred Hutchinson
Cancer Center, Seattle, WA.
 |
Abstract |
High-dose therapy (HDT) has increased complete remission (CR) rates
and survival in multiple myeloma (MM). We now report on continuous CR
(CCR) and associated prognostic factors in 1000 consecutive patients
receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 ( 13) abnormalities and with
beta-2-microglobulin  2.5 mg/L, C-reactive protein 4 mg/L, and
pre-HDT standard chemotherapy 12 months. Of all 390 CR patients
without 13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with 13 abnormalities. 13 abnormalities, present in overall 16%,
reduced 5-year event-free survival from 20% to 0% and overall
survival from 44% to 16% (both P < .0001). CR and a
second HDT cycle applied within 6 months both extended event-free and
overall survival significantly, justifying further pursuit of HDT,
especially toward curing non-13 MM.
(Blood. 2000;95:4008-4010)
© 2000 by The American Society of Hematology.
| |
Introduction |
In newly diagnosed multiple myeloma (MM), melphalan
(MEL) dose escalation has increased complete response (CR) rates to
~50% and overall survival (OS) to > 5 years.1-5 After
accruing 1000 consecutive patients into MEL-based tandem high-dose
therapy (HDT) trials with autologous hematopoietic stem cell (AHSC)
support, we now report on their long-term outcome with emphasis on
5-year continuous CR (CCR) and the associated prognostic factors.
| |
Study design |
Between September 1989 and June 1998, 1000 consecutive eligible
patients with MM were enrolled in MEL HDT trials. Patients had to have
adequate cardiopulmonary and hepatic functions, whereas renal
insufficiency and advanced age ( 65 years) were not exclusion criteria. Comprehensive initial work-up included cytogenetic analysis of Giemsa-banded chromosomes6 and data on duration of and
response to prior standard-dose therapy (SDT). Primary SDT resistance
and resistant relapse were distinguished.7 AHSCs were
mobilized prior to first HDT, either with granulocyte
colony-stimulating factor alone (99 patients)8 or with
high-dose cyclophosphamide (6 g/m2) plus
granulocyte-macrophage colony-stimulating factor9 (462 patients) or granulocyte colony-stimulating factor (179 patients); the
remaining 260 patients received other mobilization regimens.
All 1000 patients received MEL 200 mg/m2 as the first HDT
cycle; 76% received a second HDT cycle (94% within 12 months). Major second HDT regimens were MEL 200 mg/m2 in 39%, MEL 140 mg/m2 + total body irradiation (850-1020 cGy) in 15%, MEL
200 mg/m2 + cyclophosphamide 120 mg/kg in 8%,
BEAM10 (carmustine 300 mg/m2,
etoposide 200 mg/m2 × 4 days, cytarabine 400 mg/m2 × 4 days, melphalan 140 mg/m2) in 2%,
and other regimens in the remainder; 10% received allotransplants.
Serial laboratory parameters and clinical follow-up visits were
scheduled at 3- to 6-month intervals during the initial 2 years and
subsequently at least annually to document MM and clinical status. All
patients provided written informed consent indicating their awareness
of the investigational nature of treatment programs and alternative
therapies available. All HDT trials were approved by the Institutional
Review Board.
Study end points included treatment-related mortality (TRM) within 60 days of HDT, CR incidence and duration (from onset of CR) and
event-free survival (EFS), and OS. Data were analyzed on an
intent-to-treat basis. Response and relapse criteria were previously
reported.5
Survival distributions (Kaplan and Meier)11 were compared,
using the log rank test.12 Multivariate modeling of TRM and CR were performed, using stepwise selection methods and logistic regression. Similarly, multivariate modeling of CR duration, EFS, and
OS employed stepwise selection in proportional hazard regression models.13 Of the many cytogenetic abnormalities affecting
EFS and OS, those of chromosome 13 ( 13) were the
dominant adverse anomaly on multivariate analysis, hence considered as
the sole cytogenetic variable evaluated along with standard prognostic factors. Time-dependent covariates (CR, second HDT) were used to model
parameters measured after first HDT.14
| |
Results and discussion |
Patient characteristics included the following median values
(ranges): age, 53 years (14-82 years); prior SDT, 10 months (0.5-222 months); beta-2-microglobulin (B2M), 2.3 mg/L (0.8-70 mg/L); and C-reactive protein (CRP), 4.1 mg/L (0.3-237 mg/L). Fifty-six percent had Durie-Salmon stage III at initiation of SDT; 38% had resistant MM
(primary resistance, 24%; resistant relapse, 14%); and immunoglobulin isotypes were IgG in 53%; IgA in 21%; and light-chain only,
IgD, or nonsecretory MM in the remainder. Cytogenetic abnormalities were present pre-HDT in 34%, including 16% with 13 abnormalities (monosomy 13, 109 patients; deletion 13q in 58, translocations involving 13q in 18; many had several abnormalities).
TRM was low (2.7% with first, 4.8% with second
AHSCT-supported HDT); 44% achieved CR, which lasted a median of 2.4 years. Projected EFS and OS at 5 years were 25% (SE 2%) and 40% (SE
2%), respectively. According to multivariate analysis, CR rates were higher when SDT was still effective (sensitive MM) (OR: 3.2, P < .0001) and did not exceed 12 months (OR: 2.0, P < .0001); in the absence of 13 abnormalities (OR: 2.0, P < .0005) and with IgA isotype (OR: 1.8, P = .001). Both EFS and OS were significantly longer in the
absence of 13 abnormalities; with low pre-HDT B2M and CRP levels;
SDT 12 months; sensitive disease; and, in contrast to CR, in the
absence of IgA isotype (Table
1). Primary resistance versus
resistant relapse did not independently affect EFS or OS. CR was more
durable without 13 abnormalities (RR: 0.6, P = .01), SDT 12 months (RR: 0.6, P < .0001), CRP 4.0 mg/L (RR:
0.7, P = .02), and B2M 2.5 mg/L (RR: 0.8, P = .03).
With the use of the 3 dominant standard prognostic factors
readily available in most trials (B2M, CRP, SDT duration), 4 distinct risk groups were defined (Figure 1).
Whereas plateaus of EFS, OS, and CR duration were noted at 5 years in
the presence of only favorable factors, prognosis worsened
progressively as the number of risk features increased. Within almost
all standard prognostic factor-defined risk groups, 13 abnormalities
identified a cohort with dismal prognosis with no 5-year CCR or EFS
(Table 2; Figure 1).
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| Fig 1.
Clinical outcome according to risk.
Influence of the dominant standard prognostic factors
( -2-microglobulin, C-reactive protein, duration of standard therapy
prior to high-dose therapy) on event-free survival (A); overall
survival (B); and CR duration (C). Four distinct risk groups can be
distinguished on the basis of the number of unfavorable features
present (for details, see text). Ratios denote the fraction of patients
experiencing an event among those presenting with chromosome 13 deletion. Events and at risk values are for curves with 0 unfavorable
characteristics.
|
|
By using time-dependent covariate analysis, both CR and
application of a second HDT cycle in a timely fashion were
favorable variables in addition to pre-HDT features (see Table 1).
Indeed, regardless of 13 abnormalities, EFS and OS were longer when
a second HDT cycle was applied within 6 months (landmark
analysis).15
These data indicate that (1) 13 MM should be considered as
a separate incurable disease entity even after tandem HDT; (2) 5-year
CCR of 52% in the best risk group (no 13 abnormalities; low B2M and
CRP; SDT 12 months) is compatible with cure; and (3) dose intensity
(timely administration of a second HDT cycle) contributes to extending
EFS and OS.16-18 Consequently, programs aimed at curing MM
should strive to increase CR rates and apply the key CR-inducing
intervention (MEL 200) promptly and probably repeatedly to minimize
further mutations and hence additional drug resistance during tumor
regrowth. The shorter time-to-null effect (when benefit wears
off)19 of a second MEL-based HDT cycle in 13 compared
with non-13 MM ( 3 months vs. 6-12 months, data not shown)
indicates that 13 MM requires more frequent intensive chemotherapy
as in acute leukemia, such as DT-PACE (dexamethasone 40 mg × 4 days, thalidomide 400 mg daily; 4-day continuous IV infusions of cisplatin 10 mg/m2, adrianycin
[doxorubicin] 10 mg/m2, cyclophosphamide 400 mg/m2, etoposide 40 mg/m2),20
that includes thalidomide as a new active agent in MM.21 Thalidomide between HDT cycles and DCEP (dexamethasone 40 mg × 4 days, 4-day continuous IV infusions of cyclophosphamide 400 mg/m2, etoposide 40 mg/m2,
cisplatin 10 mg/m2) after tandem HDT may
prevent relapses.22 The improved tolerance of
non-myeloablative MEL-based allotransplant regimens23 is currently being explored as an important adjunct to exploit a graft-versus-myeloma effect.24 The lack of adverse
implications of advanced age and renal insufficiency after controlling
for the key biological variables justifies inclusion of such
patients in HDT trials.25
| |
Footnotes |
Submitted October 13, 1999; accepted February 2, 2000.
Supported in part by grants CA55819 and NCI 5 U10 CA38926-15
from the National Cancer Institute, Bethesda, Maryland.
Dedicated to all myeloma patients toward achieving cure.
Reprints: Bart Barlogie, Myeloma and Transplantation Research
Center, University of Arkansas for Medical Sciences, 4301 West Markham,
Slot 623, Little Rock, AR 72205.
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.
| |
References |
1.
McElwain T, Powles R.
High-dose intravenous melphalan for plasma-cell leukemia and myeloma.
Lancet.
1983;2:822-824[Medline]
[Order article via Infotrieve].
2.
Barlogie B, Alexanian R, Dicke K, et al.
High dose chemoradiotherapy and autologous bone marrow transplantation for resistant multiple myeloma.
Blood.
1987;70:869-872[Abstract/Free Full Text].
3.
Harousseau J, Attal M, Divine M, et al.
Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: a report of the French registry on autologous transplantation in multiple myeloma.
Blood.
1995;85:3077-3085[Abstract/Free Full Text].
4.
Attal M, Harousseau J, Stoppa A, et al.
A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma.
N Engl J Med.
1996;335:91-97[Abstract/Free Full Text].
5.
Barlogie B, Jagannath S, Desikan KR, et al.
Total therapy with tandem transplants for newly diagnosed multiple myeloma.
Blood.
1999;93:55-65[Abstract/Free Full Text].
6.
Sawyer J, Waldron J, Jagannath S, Barlogie B.
Cytogenetics findings in 200 patients with multiple myeloma.
Cancer Genet Cytogenet.
1995;82:41-49[Medline]
[Order article via Infotrieve].
7.
Alexanian R, Dimopoulos M.
The treatment of multiple myeloma.
N Engl J Med.
1994;7:484-489.
8.
Desikan K, Barlogie B, Jagannath S, et al.
Comparable engraftment kinetics following peripheral blood stem cell infusion mobilized with G-CSF with or without cyclophosphamide in multiple myeloma.
J Clin Oncol.
1998;16:1547-1553[Abstract/Free Full Text].
9.
Barlogie B, Jagannath S, Vesole D, et al.
Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma.
Blood.
1997;89:789-793[Abstract/Free Full Text].
10.
Linch DC, Winfield D, Goldstone AH, et al.
Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial.
Lancet.
1993;341:1051-1054[Medline]
[Order article via Infotrieve].
11.
Kaplan EL, Meier P.
Nonparametric estimation from incomplete observations.
J Am Stat Assoc.
1958;53:457-481.
12.
Mantel N.
Evaluation of survival data and two new rank order statistics arising in its consideration.
Cancer Chemother Rep.
1966;50:163-170[Medline]
[Order article via Infotrieve].
13.
Cox DR.
Regression models and life-tables [with discussion].
J Royal Stat Soc, Series B.
1972;34:187-220.
14.
Crowley J, Hu M.
Covariance analysis of heart transplant survival data.
J Am Stat Assoc.
1977;72:27-36.
15.
Anderson JR, Cain CC, Gelber RD, Gelman RS.
Analysis and interpretation of the comparison of survival by treatment outcome variables in cancer clinical trials.
Cancer Treat Rep.
1985;69:1139-1146[Medline]
[Order article via Infotrieve].
16.
Attal M, Harousseau L, Facon T, et al.
Single versus double transplant in myeloma: a randomized trial of the "Inter Groupe Francais Du Myelome" (IFM).
Blood.
1999;94:714a.
17.
Bjorkstrand BT, Svensson H, Goldschmidt H, et al.
5489 Autotransplants in multiple myeloma a registry study from the European Group for Blood and Marrow Transplantation (EBMT).
Blood.
1999;94:714a.
18.
Tosi P, Cavo M, Zamagni E, Ronconi S, Benni M, Tura S.
A multicentric randomized clinical trial comparing single vs double autologous peripheral blood stem cell transplantation for patients with newly diagnosed multiple myeloma: results of an interim analysis.
Blood.
1999;94:715a.
19.
Finke J, Bertz H, Veelken H, et al.
In vivo T cell depletion with ATG reduces GVHD in unrelated donor stem cell transplantation.
Blood.
1999;94:713a.
20.
Barlogie B, Desikan R, Munshi N, et al.
Single course D.T. PACE anti-angiochemotherapy affects CR in plasma cell leukemia and fulminant multiple myeloma (MM).
Blood.
1998;92:4180a.
21.
Singhal S, Mehta J, Desikan R, et al.
Antitumor activity of thalidomide in refractory multiple myeloma.
N Engl J Med.
1999;341:1565-1571[Abstract/Free Full Text].
22.
Desikan R, Munshi N, Zangari M, et al.
DCEP consolidation chemotherapy (CC) after 2 cycles of melphalan-based high dose therapy (HDT)high incidence of CR and superior outcome in comparison with matched historical controls.
Blood.
1999;94:316a.
23.
Khouri IF, Keating M, Korbling M, et al.
Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.
J Clin Oncol.
1998;16:2817-2824[Abstract].
24.
Tricot G, Vesole D, Jagannath S, Hilton J, Munshi N, Barlogie B.
Graft-versus-myeloma effect: proof of principle.
Blood.
1996;87:1196-1198[Abstract/Free Full Text].
25.
Barlogie B, Desikan R, Munshi N, et al.
Durable CR in multiple myeloma (MM) in the absence of chromosome 13 deletion (13) and with tandem melphalan-based high dose therapy (HDT)the Arkansas Experience with 1000 consecutive patients.
Blood.
1999;94:714a.
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[PDF]
|
|
|
|
|
|
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B. Barlogie, J. Shaughnessy, G. Tricot, J. Jacobson, M. Zangari, E. Anaissie, R. Walker, and J. Crowley
Treatment of multiple myeloma
Blood,
January 1, 2004;
103(1):
20 - 32.
[Abstract]
[Full Text]
[PDF]
|
|
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J. Blade, D. H. Vesole, and M. Gertz
Transplantation for multiple myeloma: who, when, how often?
Blood,
November 15, 2003;
102(10):
3469 - 3477.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kaufmann, J. Ackermann, H. Greinix, T. Nosslinger, H. Gisslinger, A. Keck, H. Ludwig, N. Worel, P. Kalhs, C. Zielinski, et al.
Beneficial effect of high-dose chemotherapy in multiple myeloma patients with unfavorable prognostic features
Ann. Onc.,
November 1, 2003;
14(11):
1667 - 1672.
[Abstract]
[Full Text]
[PDF]
|
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D. G. Maloney, A. J. Molina, F. Sahebi, K. E. Stockerl-Goldstein, B. M. Sandmaier, W. Bensinger, B. Storer, U. Hegenbart, G. Somlo, T. Chauncey, et al.
Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma
Blood,
November 1, 2003;
102(9):
3447 - 3454.
[Abstract]
[Full Text]
[PDF]
|
|
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A Wei and S Juneja
Bone marrow immunohistology of plasma cell neoplasms
J. Clin. Pathol.,
June 1, 2003;
56(6):
406 - 411.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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J. Shaughnessy, J. Jacobson, J. Sawyer, J. McCoy, A. Fassas, F. Zhan, K. Bumm, J. Epstein, E. Anaissie, S. Jagannath, et al.
Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression
Blood,
May 15, 2003;
101(10):
3849 - 3856.
[Abstract]
[Full Text]
[PDF]
|
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H. M. Lokhorst, C. M. Segeren, L. F. Verdonck, B. van der Holt, R. Raymakers, M. H.J. van Oers, R. M.Y. Barge, H. C. Schouten, P. H.M. Westveer, M. M.C. Steijaert, et al.
Partially T-Cell-Depleted Allogeneic Stem-Cell Transplantation for First-Line Treatment of Multiple Myeloma: A Prospective Evaluation of Patients Treated in the Phase III Study HOVON 24 MM
J. Clin. Oncol.,
May 1, 2003;
21(9):
1728 - 1733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
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M. Filipits, G. Pohl, T. Stranzl, H. Kaufmann, J. Ackermann, H. Gisslinger, H. Greinix, A. Chott, and J. Drach
Low p27Kip1 Expression Is an Independent Adverse Prognostic Factor in Patients with Multiple Myeloma
Clin. Cancer Res.,
February 1, 2003;
9(2):
820 - 826.
[Abstract]
[Full Text]
[PDF]
|
|
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|
|
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L. Laterveer, L. F. Verdonck, T. Peeters, E. Borst, A. C. Bloem, and H. M. Lokhorst
Graft versus myeloma may overcome the unfavorable effect of deletion of chromosome 13 in multiple myeloma
Blood,
February 1, 2003;
101(3):
1201 - 1201.
[Full Text]
[PDF]
|
|
|
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R. A. Kyle, M. A. Gertz, T. E. Witzig, J. A. Lust, M. Q. Lacy, A. Dispenzieri, R. Fonseca, S. V. Rajkumar, J. R. Offord, D. R. Larson, et al.
Review of 1027 Patients With Newly Diagnosed Multiple Myeloma
Mayo Clin. Proc.,
January 1, 2003;
78(1):
21 - 33.
[Abstract]
[PDF]
|
|
|
|
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M. J. Robertson, D. Pelloso, R. Abonour, R. A. Hromas, R. P. Nelson Jr., L. Wood, and K. Cornetta
Interleukin 12 Immunotherapy after Autologous Stem Cell Transplantation for Hematological Malignancies
Clin. Cancer Res.,
November 1, 2002;
8(11):
3383 - 3393.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Peggs, S. Mackinnon, K. Yong, and A. Badros
Reduced Intensity Conditioning and Allogeneic Stem-Cell Transplantation: Determining Its Role in Multiple Myeloma
J. Clin. Oncol.,
October 15, 2002;
20(20):
4268 - 4269.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. V. Rajkumar, M. A. Gertz, R. A. Kyle, P. R. Greipp, and Mayo Clinic Myeloma, Amyloid, and Dysproteinemia G
Current Therapy for Multiple Myeloma
Mayo Clin. Proc.,
August 1, 2002;
77(8):
813 - 822.
[Abstract]
[PDF]
|
|
|
|
|
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M. Chiriva-Internati, Z. Wang, E. Salati, K. Bumm, B. Barlogie, and S. H. Lim
Sperm protein 17 (Sp17) is a suitable target for immunotherapy of multiple myeloma
Blood,
July 18, 2002;
100(3):
961 - 965.
[Abstract]
[Full Text]
[PDF]
|
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|
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A. Badros, B. Barlogie, E. Siegel, M. Cottler-Fox, M. Zangari, A. Fassas, C. Morris, E. Anaissie, F. Van Rhee, and G. Tricot
Improved Outcome of Allogeneic Transplantation in High-Risk Multiple Myeloma Patients After Nonmyeloablative Conditioning
J. Clin. Oncol.,
March 1, 2002;
20(5):
1295 - 1303.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Zhan, J. Hardin, B. Kordsmeier, K. Bumm, M. Zheng, E. Tian, R. Sanderson, Y. Yang, C. Wilson, M. Zangari, et al.
Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells
Blood,
March 1, 2002;
99(5):
1745 - 1757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
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K. C. Anderson, J. D. Shaughnessy Jr., B. Barlogie, J.-L. Harousseau, and G. D. Roodman
Multiple Myeloma
Hematology,
January 1, 2002;
2002(1):
214 - 240.
[Abstract]
[Full Text]
|
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|
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|
|
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H. Avet-Loiseau, F. Gerson, F. Magrangeas, S. Minvielle, J.-L. Harousseau, and R. Bataille
Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors
Blood,
November 15, 2001;
98(10):
3082 - 3086.
[Abstract]
[Full Text]
[PDF]
|
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|
|
|
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N. V. Smadja, C. Bastard, C. Brigaudeau, D. Leroux, and C. Fruchart
Hypodiploidy is a major prognostic factor in multiple myeloma
Blood,
October 1, 2001;
98(7):
2229 - 2238.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Stewart, R. Vescio, G. Schiller, O. Ballester, S. Noga, H. Rugo, C. Freytes, E. Stadtmauer, S. Tarantolo, F. Sahebi, et al.
Purging of Autologous Peripheral-Blood Stem Cells Using CD34 Selection Does Not Improve Overall or Progression-Free Survival After High-Dose Chemotherapy for Multiple Myeloma: Results of a Multicenter Randomized Controlled Trial
J. Clin. Oncol.,
September 1, 2001;
19(17):
3771 - 3779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. A. Zaidi and D. H. Vesole
Multiple Myeloma: An Old Disease with New Hope for the Future
CA Cancer J Clin,
September 1, 2001;
51(5):
273 - 285.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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F. Bullrich, H. Fujii, G. Calin, H. Mabuchi, M. Negrini, Y. Pekarsky, L. Rassenti, H. Alder, J. C. Reed, M. J. Keating, et al.
Characterization of the 13q14 Tumor Suppressor Locus in CLL: Identification of ALT1, an Alternative Splice Variant of the LEU2 Gene
Cancer Res.,
September 1, 2001;
61(18):
6640 - 6648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Strother, D. Ashley, S. J. Kellie, A. Patel, D. Jones-Wallace, S. Thompson, R. Heideman, E. Benaim, R. Krance, L. Bowman, et al.
Feasibility of Four Consecutive High-Dose Chemotherapy Cycles With Stem-Cell Rescue for Patients With Newly Diagnosed Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor After Craniospinal Radiotherapy: Results of a Collaborative Study
J. Clin. Oncol.,
May 15, 2001;
19(10):
2696 - 2704.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Badros, B. Barlogie, C. Morris, R. Desikan, S. R. Martin, N. Munshi, M. Zangari, J. Mehta, A. Toor, M. Cottler-Fox, et al.
High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions
Blood,
May 1, 2001;
97(9):
2574 - 2579.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Avva, R. L. Vanhemert, B. Barlogie, N. Munshi, and E. J. Angtuaco
CT-guided Biopsy of Focal Lesions in Patients with Multiple Myeloma May Reveal New and More Aggressive Cytogenetic Abnormalities
AJNR Am. J. Neuroradiol.,
April 1, 2001;
22(4):
781 - 785.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
N. C. Munshi
Arsenic Trioxide: An Emerging Therapy for Multiple Myeloma
Oncologist,
April 1, 2001;
6(90002):
17 - 21.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. Facon, H. Avet-Loiseau, G. Guillerm, P. Moreau, F. Genevieve, M. Zandecki, J.-L. Lai, X. Leleu, J.-P. Jouet, F. Bauters, et al.
Chromosome 13 abnormalities identified by FISH analysis and serum {beta}2-microglobulin produce a powerful myeloma staging system for patients receiving high-dose therapy
Blood,
March 15, 2001;
97(6):
1566 - 1571.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Lim, Z. Wang, M. Chiriva-Internati, and Y. Xue
Sperm protein 17 is a novel cancer-testis antigen in multiple myeloma
Blood,
March 1, 2001;
97(5):
1508 - 1510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. S. Dalton, P. L. Bergsagel, W. M. Kuehl, K. C. Anderson, and J. L. Harousseau
Multiple Myeloma
Hematology,
January 1, 2001;
2001(1):
157 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
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Top
Abstract
Introduction