Autologous Stem Cell Transplantation: An Effective Salvage
Therapy in Multiple Myeloma
, Cyrille Hulin
, Denis Caillot
, Stéphanie Tardy
, Jessica Michel
, Thomas Gastinne
, Cédric Rossi
, Cyrille Touzeau
, Lucie Planche
, Marion Loirat
, Philippe Moreau
1Hematology Department, University Hospital, Montreal, Canada 2Hematology Department, University Hospital, Nancy, France 3Hematology Department, University Hospital, Dijon, France 4Hematology Department, University Hospital, Metz, France 5Hematology Department, University Hospital, Nantes, France
Article history: Received 5 September 2012 Accepted 19 November 2012 Key Words: Multiple myeloma Salvage therapy Autologous stem cell transplantation
a b s t r a c t
Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between theﬁrst and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of theﬁrst ASCT to the date of theﬁrst relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to theﬁrst ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after theﬁrst ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.
Ó 2013 American Society for Blood and Marrow Transplantation.
Autologous stem cell transplantation (ASCT) after
high-dose melphalan is the treatment of choice for patients with
symptomatic multiple myeloma (MM) who are younger than
65 years of age
. The incorporation of novel agents into
this strategy has markedly improved progression-free
survival (PFS) and overall survival (OS) of this group of
patients over the last decade
. Nevertheless, almost all
patients ultimately relapse, and no plateau is observed in the
survival curves. At the time of disease recurrence, no one
standard salvage approach is available; instead, various
therapeutic options are used, including novel agentebased
therapy, administered for a
ﬁxed duration of time or until
In a pivotal trial for the approval of bortezomib as
mon-otherapy in patients with relapsed and refractory MM, the
median PFS was 7 months
, whereas in pivotal trials for
the approval of lenalidomide in combination with
dexa-methasone in the same group of patients, the median time to
progression was approximately 11 months
. A recent
prospective, randomized, phase III study showed that
a triplet combination of bortezomib, thalidomide, and
dexamethasone achieved superior results compared with
thalidomideedexamethasone alone in patients relapsing
after ASCT, with a median time to progression of 19.5 versus
13.8 months, respectively
. This study suggested that
combinations consisting of both an immunomodulatory drug
and a proteasome inhibitor are a valuable option at the time
of relapse. However, when a frozen graft is available, it is also
possible to repeat high-dose therapy in patients who
previ-ously responded to the frontline application of high-dose
melphalan and ASCT
. Over time, many reports have
demonstrated the feasibility of this salvage strategy
Most data are available from retrospective studies and are
based on single-center experiences with small numbers of
selected patients. In this setting, PFS has been shown to
range from 7 to 22 months, and treatment-related mortality
was acceptable, ranging from 0% to 8%. Various prognostic
factors for prolonged PFS have been described, such as
the duration of response to the
ﬁrst high-dose therapy
or the number of lines of therapy before
. Here, we report the results of a
retro-spective analysis of salvage ASCT conducted in three French
centers. Our goals were to identify prognostic factors for
prolonged PFS and OS.
In this retrospective analysis, all consecutive patients treated between 1995 and 2009 at centers of Nancy, Dijon, and Nantes with high-dose therapy and ASCT as part of salvage therapy after a frontline single or tandem ASCT and a subsequent relapse were included. To have a reliable
American Society for Blood
and Marrow Transplantation
Financial disclosure: See Acknowledgments on page 449.
* Correspondence and reprint requests: Philippe Moreau, MD, Hema-tology Department, University Hospital Hôtel-Dieu, Place Ricordeau, 44093 Nantes, France.
E-mail address:email@example.com(P. Moreau).
y E. Lemieux and C. Hulin equally contributed to this work.
1083-8791/$ e see front matter Ó 2013 American Society for Blood and Marrow Transplantation.
follow-up time, patients who received salvage ASCT after January 1, 2010, were not included in the present analysis. The choice of salvage ASCT instead of other options was left to the treating physician and was also dependent on stem cell availability. In addition, patients had to present with adequate cardiac, lung, liver, or renal function, according to each center’s policy.
Response and progression were deﬁned according to the International Myeloma Working Group criteria. Brieﬂy, a complete response was deﬁned as negative immunoﬁxation of serum and urine, disappearance of soft tissue plasmacytoma, and5% plasma cells in the bone marrow. Very good partial response (VGPR) was deﬁned as serum and urine M-protein detectable only by immunoﬁxation or as a 90% or greater reduction in serum M-protein plus a urine M-protein level of<100 mg per 24 hours. Partial response (PR) was deﬁned as a reduction in serum M-protein of at least 50% and by a reduction of at least 90% or an absolute value of<200 mg per 24 hours in urine M-protein. Stable disease was deﬁned as not meeting any response criteria, and progressive disease was deﬁned as a conﬁrmed increase of25% of M-protein from baseline. Relapse was deﬁned as the reappearance of serum or urine M-protein or the development of new bone lesions, plasmacytoma, or hypercalcemia. Response post-ASCT was assessed at a maximum 100 days post transplantation, and patients were followed approximately every 3 months thereafter.
PFS1 was deﬁned from the date of the ﬁrst ASCT to the date of ﬁrst relapse or progression. PFS2 was deﬁned from the date of salvage ASCT to the date of subsequent relapse or progression. OS rates were estimated from the date of diagnosis or from the date of relapse to the date of death or to the date of the last follow-up for patients who were still alive. Kaplan-Meier curves for PFS and OS were plotted and compared using a log-rank test. Predictive factors were determined by univariate analysis using Kaplan-Meier curves and the log-rank test. Only predictive factors with a signiﬁ-cant result (P< .05) in univariate analysis entered multivariate analysis, using Cox regression. Statistical analysis was performed using SAS 9.3 (SAS Institute, Cary, NC).
From January 1995 to December 2009, 81 patients were
treated with salvage ASCT. Patient characteristics at the time
of diagnosis of symptomatic MM are shown in
median time from diagnosis to the
ﬁrst ASCT was 4 months.
Thirty-six percent of patients received tandem ASCT, 95%
responded to high-dose therapy, and 58% received some
form of maintenance therapy, the median duration of which
was 16 months (range, 1 to 64).
Patient characteristics at the time of salvage ASCT are
. The median time between the
ﬁrst and the
salvage ASCT was 47 months (range, 13 to 168). Ninety-
percent of patients received induction therapy before
salvage ASCT, which consisted of novel agentebased regimen
in half, and four patients proceeded to ASCT without any
salvage chemotherapy. Only 26 patients (32%) received
more than 2 lines of therapy before salvage ASCT. At the
time of salvage ASCT, 67 patients (83%) had achieved at
least a PR to induction therapy, 10 (12%) had not responded
to induction, and 4 were in an untreated relapse.
Fifty-eight of 81 patients (72%) received stem cells that had
been harvested before the
ﬁrst ASCT. For 23 patients (28%),
stem cells were harvested after the
ﬁrst relapse using
granulocyte colony-stimulating factor alone (13 patients),
þ granulocyte colony-stimulating factor
(6 patients), or plerixafor
þ granulocyte colony-stimulating
factor (4 patients). After salvage ASCT, 75 patients (93%)
achieved at least a PR, including 67% VGPR, and no toxic
death was reported. Sixteen patients (20%) received
consol-idation therapy, whereas 30 (37%) received some form of
maintenance therapy after salvage ASCT.
Survival and Prognostic Factors
The median follow-up time for living patients was 7 years
(range, 2.1 to 16.6). The median OS was 10 years from
diag-nosis and 4 years from salvage ASCT (
). The median
PFS1 was 40 months (range, 10 to 152), and the median PFS2
was 18 months (range, 2 to 64) (
The duration of the second response was found to be
related to PFS1: The median PFS2 was 26.4 months in
patients experiencing their
ﬁrst relapse more than 40
months after the
ﬁrst ASCT versus 14 months in patients
relapsing within the
ﬁrst 40 months after their ﬁrst ASCT,
¼ .001 (
). A cut-off value of 24 months for relapse
ﬁrst ASCT was also found to signiﬁcantly affect PFS2,
with a duration of second response of 9 versus 18 months
¼ .0096) for patients relapsing within 24 months versus
those with a relapse more than 24 months after the
ASCT. The analysis was not performed for a shorter duration
ﬁrst response due to the small number of patients
relapsing within 18 months after their
ﬁrst ASCT. In addition,
the duration of response after the
ﬁrst ASCT also affected OS.
The median OS rate from salvage therapy was longer in
patients relapsing 24 or 40 months after their
versus others (median 7.2 and 7.3 versus 2.4 and 3.4 years,
The duration of response after salvage ASCT was also
ﬁcantly affected by the use of maintenance therapy
). Results of the univariate analysis of prognostic
factors are presented in
. In the multivariate analysis,Table 1
Patient Characteristics at Diagnosis and First High-Dose Therapy Step
Variable Patients (N¼ 81)
Median age at diagnosis (range) 55 (30-67)
Male 47 (58%) Female 34 (42%) Durie-Salmon stage I 4 (5%) II 9 (11%) III 68 (84%)
International Staging System
1 40 (49%) 2 22 (27%) 3 14 (17%) Missing data 5 (7%) Isotype IgG 53 (65%) IgA 10 (12%) Light chain 18 (23%)
Induction regimen beforeﬁrst ASCT
VAD 69 (85%)
VMCP-VBAP 4 (5%)
Bortezomib-dexamethasone 8 (10%)
Conditioning regimen beforeﬁrst ASCT
Melphalan 200 mg/m2 40 (49%)
Melphalan 140 mg/m2 23 (28%)
Melphalan 140þ 8 Gy total body irradiation 12 (15%)
Other 6 (7%)
Tandem ASCT 29 (36%)
Response afterﬁrst high-dose therapy
VGPR 58 (72%)
PR 19 (23%)
SD 4 (5%)
Maintenance therapy afterﬁrst high-dose therapy
Interferon-a 24 (30%)
Thalidomide 13 (16%)
Lenalidomide 6 (7%)
Other 4 (5%)
None 34 (42%)
VAD indicates vincristine, adriamycin, dexamethasone; VMCP-VBAP, vincristine, melphalan, cyclophosphamide, prednisone-vincristine, carmus-tine, doxorubicin, prednisone; SD, stable disease.
three independent factors unfavorably affected PFS: a short
duration of response to the
ﬁrst ASCT, a response less than
a VGPR after salvage therapy, and no maintenance treatment
after salvage ASCT. Age over 60 years and a short duration of
response after the
ﬁrst ASCT were the two factors adversely
affecting OS from the time of diagnosis and OS from the
time of salvage ASCT (
Currently, there is no broadly accepted standard
treat-ment for patients with relapsed/refractory MM
. For the
selection of an appropriate treatment strategy at this stage,
both disease-related and patient-related factors and,
impor-tantly, the type of previous therapy need to be considered
. Disease-related factors include the quality and
duration of response to previous therapies and the
aggres-siveness of the relapse, whereas patient-related factors
quality of life, age, and performance status
previous therapies, it is important to take into account if the
patient has been exposed to alkylators or to the novel agents,
immunomodulatory drugs and proteasome inhibitors, and if
this was alone or in combination, to de
ﬁne the best strategy
Intensive therapy can always be considered at this stage
. Although allogeneic transplantation shows limited
ﬁt for the treatment of patients with relapsed/
, available data suggest that a second
autologous transplantation may be bene
ﬁcial and well
tolerated for some patients in this setting
. The overall
response rates in studies range from 55% to 69%, with a
100-day mortality rate
. However, the small sample
size used in these studies complicates the identi
the ideal candidate for this treatment approach. Most reports
suggest that the duration of the
ﬁrst response to ASCT is the
major prognostic factor
In the current retrospective study, we con
salvage ASCT at the time of relapse is a valuable and feasible
option. Response rates were high, with more than 90% ofFigure 2. Progression-free survival rates after salvage ASCT according to the duration of response after theﬁrst ASCT (<40 or >40 months).
Figure 3. Progression-free survival rates after salvage ASCT according to maintenance therapy.
Figure 1. Progression-free and overall survival rates. Table 2
(N¼ 81) Median age at the time of salvage ASCT (range) 58 (35-71) Novel induction regimen before salvage ASCT
VAD 23 (29%) Bortezomib-dexamethasone or lenalidomide-dexamethasone or thalidomide-lenalidomide-dexamethasone 26 (32%) VTD or VRD 10 (12%) Others 18 (22%) None 4 (5%)
Conditioning regimen before salvage ASCT
Melphalan 220 mg/m2 12 (15%)
Melphalan 200 mg/m2 45 (56%)
Melphalan 140 mg/m2 9 (11%)
Melphalanþ busulphan 2 (2%)
Others 13 (16%)
Response after salvage ASCT
VGPR 54 (67%)
PR 21 (26%)
SD 5 (6%)
PD 1 (1%)
Transplantation-related death 0
Consolidation therapy after salvage ASCT
Bortezomib-dexamethasone 6 (7%)
VTD 2 (3%)
VRD 4 (5%)
Lenalidomide-dexamethasone 4 (5%)
None 65 (80%)
Maintenance therapy after salvage ASCT
Thalidomide 11 (14%)
Lenalidomide 12 (15%)
Bortezomib 3 (4%)
Other 4 (5%)
None 51 (63%)
VAD indicates vincristine, adriamycin, dexamethasone; VTD, bortezomib-thalidomide-dexamethasone; VRD, bortezomib-lenalidomide-dexamethasone; SD, stable disease; PD, progressive disease.
patients achieving at least a PR, with no
transplantation-related mortality. Our results thereby con
re-ported by various groups
. In addition, similar to what
has previously been described, we show that the duration of
response to the
ﬁrst ASCT is the major prognostic factor for
both PFS and OS. In our series, a duration of response of at
least 24 months to the
ﬁrst intensive therapy was associated
with a longer PFS and OS. This cut-off value of 24 months was
also described in a series of 81 patients treated at the
Prin-cess Margaret Hospital, Toronto, Ontario, Canada
Different cut-off values, ranging from 12 to 24 months,
have already been proposed by several investigators
. Interestingly, we found that a response of less than
VGPR after salvage ASCT was an independent adverse
prog-nostic factor for PFS. It is only the second time this factor,
which is a known prognostic factor in the frontline ASCT
, has been described to be important in the context
of salvage ASCT
. Of note, we were able to analyze the
impact of maintenance therapy after salvage ASCT and
showed for the
ﬁrst time that maintenance might
signiﬁ-cantly prolong the duration of response. The role of
main-tenance in the frontline setting is a matter of controversy
, despite the overwhelming strong evidence of an
improvement in PFS when immunomodulatory drugs are
administered after upfront ASCT
feed the debate on the role of maintenance in the setting of
salvage ASCT. Of note in our analysis is that some patients
received an autograft that had been cryopreserved and
stored for 10 years before the salvage ASCT
There are a number of limitations to our study. First, it
was not an intent-to-treat analysis, and we lack precise data
on how many patients were excluded from salvage ASCT
because of comorbidity, an insuf
ﬁcient amount of stem cells,
or progressive and/or refractory disease. This selection bias is
the most important shortcoming. Second, the study is related
to the long period of accrual, which explains the
heteroge-neity in the treatment received by the patients, both as part
of frontline therapy and at the time of relapse. Clearly, the
role of salvage ASCT has to be re-examined in the context of
novel agents. Moreover, we collected cytogenetic data in only
some patients, and salvage therapies have to be evaluated, if
possible, with this information available.
Nevertheless, our data show that salvage ASCT is
a feasible option that should be routinely considered at the
time of relapse for patients with a response duration of more
than 2 years to frontline high-dose therapy. The feasibility of
salvage ASCT might also be improved in the future with novel
strategies of stem cell collection, such as the use of plerixafor,
which allows the collection of stem cells in patients
previ-ously exposed to high-dose therapy
Multivariate Cox Regression Analysis of Variables Unfavorably Affecting Progression-Free and Overall Survival Rates
Variable (P< .05) HR 95% CI P Value
Progression-free survival after salvage ASCT
Duration of response afterﬁrst ASCT < 24 mo 2.25 [1.02, 4.98] .04
Duration of response afterﬁrst ASCT < 40 mo 2.46 [1.40, 4.32] .001
Response after salvage ASCT< VGPR 1.97 [1.02, 3.80] .04
No maintenance therapy after salvage ASCT 3.40 [1.72, 6.69] .0004
Overall survival from diagnosis
Age> 60 y 4.00 [1.50, 10.71] .006
Duration of response afterﬁrst ASCT < 24 mo 14.90 [3.98, 55.70] <.0001
Duration of response afterﬁrst ASCT < 40 mo 4.67 [2.04, 10.70] .0003
Overall survival from salvage ASCT
Age> 60 y 3.62 [1.39, 9.42] .008
Duration of response afterﬁrst ASCT < 24 mo 8.25 [2.93, 23.22] <.0001
Duration of response afterﬁrst ASCT < 40 mo 4.45 [1.93, 10.24] .0004
HR indicates hazard ratio; CI, conﬁdence interval. Table 3
Univariate Analysis of Variables Unfavorably Affecting Progression-Free and Overall Survival Rates
Variable (P< .05) HR 95% CI P Value
Progression-free survival after salvage ASCT
Duration of response afterﬁrst ASCT < 24 mo 2.40 [1.21, 4.76] .01
Duration of response afterﬁrst ASCT < 40 mo 2.78 [1.62, 4.77] .0002
Response after salvage ASCT< VGPR 2.48 [1.42, 4.10] .001
No maintenance therapy after salvage ASCT 3.32 [1.76, 6.29] .0002
Overall survival from diagnosis
Age> 60 y 5.09 [2.33, 11.10] <.0001
b2-microglobulin at diagnosis> 3.5 mg/L 2.21 [1.12, 4.35] .02
Duration of response afterﬁrst ASCT < 24 mo 6.85 [3.27, 14.86] <.0001
Duration of response afterﬁrst ASCT < 40 mo 7.08 [3.35, 14.99] <.0001
Response afterﬁrst ASCT < VGPR 2.80 [1.48, 5.28] .00015
Response after salvage ASCT< VGPR 3.81 [2.00, 7.23] <.0001
No maintenance therapy after salvage ASCT 2.83 [1.23, 6.49] .01
Overall survival from salvage ASCT
Age> 60 y 2.89 [1.43, 5.86] .003
Duration of response afterﬁrst ASCT < 24 mo 3.65 [1.77, 7.53] .0004
Duration of response afterﬁrst ASCT < 40 mo 3.47 [1.68, 7.18] .0008
Response afterﬁrst ASCT < VGPR 2.25 [1.18-4.29] .01
Response after salvage ASCT< VGPR 2.76 [1.43, 5.31] .002
Financial disclosure: The authors have nothing to disclose.
1. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med. 1996;3335:91-97.
2. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875-1883.
3. Moreau P, Avet-Loiseau H, Harousseau JL, Attal M. Current trends in autologous stem cell transplantation for myeloma in the era of novel therapies. J Clin Oncol. 2011;29:1898-1906.
4. Richardson PG, Sonneveld P, Schuster M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: ﬁnal time-to-event results of the APEX trial. Blood. 2007;110:3557-3560.
5. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexametha-sone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133-2142.
6. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexa-methasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123-2132.
7. Garderet L, Iacobelli S, Moreau P, et al. Superiority of the triple combination of bortezomib-thalidomide-dexamethasone over the dual combination of thalidomide-dexamethasone in patients with multiple myeloma progressing or relapsing after autologous transplantation: the MMVAR/IFM 2005-04 randomized phase III trial from the chronic leukemia working party of the European Group for Blood and Marrow Transplantation. J Clin Oncol. 2012;30:2475-2482.
8. Gertz MA. Stem cell transplant: an effective salvage therapy for multiple myeloma. Leuk Lymph. 2011;52:1413-1414.
9. Olin RL, Vogl DT, Porter DL, et al. Second auto-SCT is safe and effective salvage therapy for relapsed multiple myeloma. Bone Marrow Trans-plant. 2009;43:417-422.
10. Shah N, Ahmed F, Bashir Q, et al. Durable remission with salvage second autotransplants in patients with multiple myeloma. Cancer. 2012;118:3549-3555.
11. Elice F, Raimondi R, Tosetto A, et al. Prolonged overall survival with second on-demand autologous transplant in multiple myeloma. Am J Hematol. 2006;81:426-431.
12. Qazilbash MH, Saliba R, De Lima M, et al. Second autologous or allo-geneic transplantation after the failure ofﬁrst autograft in patients with multiple myeloma. Cancer. 2006;106:1084-1089.
13. Chow AW, Lee CH, Hiwase DK, et al. Relapsed multiple myloma: who beneﬁts from salvage autografts? Blood (ASH Annual Meeting Abstracts) 2011;118:abstr 3059.
14. Saad AA, Vesole DH, Le-Rademacher J, et al. Second autologous plants for multiple myeloma relapse after a prior autologous trans-plantda report from the Center for International Blood and Marrow Transplant Research. Blood (ASH Annual Meeting Abstracts) 2011;118:abstr 504.
15. Alvares CL, Davies FE, Horton C, et al. The role of second autografts in the management of myeloma atﬁrst relapse. Haematologica. 2006;91: 141-142.
16. Jimenez-Zepeda VH, Mikhael J, Winter A, et al. Second autologous stem cell transplantation as salvage therapy for multiple myeloma: impact on progression-free and overall survival. Biol Blood Marrow Transplant. 2012;18:773-779.
17. Burzynski JA, Toro JJ, Patel RC, et al. Toxicity of a second autologous peripheral blood stem cell transplant in patients with relapsed or recurrent multiple myeloma. Leuk Lymph. 2009;50:1442-1447. 18. Freytes CO, Vesole DH, Zhong X, et al. Second transplants in relapsed
multiple myeloma: autologous versus non-myeloablative/reduced intensity allogenic transplantation. Blood (ASH Annual Meeting Abstracts) 2011;118:abstr 824.
19. Fenk R, Liese V, Neubauer F, et al. Predictive factors for successful salvage high-dose therapy in patients with multiple myeloma relapsing after autologous blood stem cell transplantation. Leuk Lymph. 2011;52:1455-1462.
20. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20: 1467-1473.
21. Jakubowiak A. Management strategies for relapsed/refractory multiple myeloma: current clinical perspectives. Semin Hematol. 2012;49(suppl 1): S16-S32.
22. Bird JM, Owen RG, D’Sa S, et al. Guidelines for the diagnosis and management of multiple myeloma. Br J Haematol. 2011;154:32-75. 23. Ofﬁdani M, Corvatta L, Morabito F, et al. How to treat patients with
relapsed/refractory multiple myeloma: evidence-based information and opinions. Expert Opin Invest Drugs. 2011;20:779-793.
24. Lonial S, Mitsiades CS, Richardson PG. Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res. 2011;17: 1264-1277.
25. Shah N, Lonial S. Evidence-based mini-review: treatment options for patients with relapsed/refractory myeloma previously treated with novel-agents and high-dose chemotherapy and autologous stem-cell transplantation. Hematol Am Soc Hematol Educ Progr. 2010;1: 310-313.
26. Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and retreatment approaches in the era of novel agents. Leukemia. 2012; 26:73-85.
27. Lokhorst H, Einsele H, Vesole D, et al. International Myeloma Working Group consensus statement regarding the current status of allogeneic stem-cell transplantation for multiple myeloma. J Clin Oncol. 2010;28: 4521-4530.
28. Ludwig H, Durie BG, McCarthy P, et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood. 2012;119: 3003-3015.
29. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782-1791.
30. McCarthy PL, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366: 1770-1781.
31. Giralt S, Stadtmauer EA, Harousseau JL, et al. International Myeloma Working Group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100). Leukemia. 2009;23:1904-1912.