International Journal of Myeloma 5(3): 23–29, 2015
©日本骨髄腫学会

ORIGINAL

Outcome of allogeneic hematopoietic stem-cell transplantation for
multiple myeloma: retrospective analysis of 16 patients
Akinori NISHIKAWA1(*), Shinobu TAMURA1,2(*), Kazuo HATANAKA1,3, Kodai KURIYAMA1,
Hiroki HOSOI1, Shogo MURATA1, Nobuyoshi HANAOKA1, Noboru YONETANI4,
Toshiharu TAMAKI3, Hideki NAKAKUMA1 and Takashi SONOKI1
The role of allogeneic hematopoietic stem cell transplantation (allo-SCT) for multiple myeloma (MM) has not yet
been established. We performed allo-SCT on 16 patients with MM in our hospital and an associated center, andretrospectively evaluated its efficacy. The median age at allo-SCT was 47 years. Eight patients underwent allo-SCT asa front-line therapy. Non-myeloablative treatment was provided for 14 patients. The overall survival (OS) andprogression-free survival (PFS) rates 3 years after transplantation were 72.9% and 37.5%, respectively, in patients
who received front-line therapy, and were significantly higher than those in patients who received allo-SCT assalvage therapy (both P < 0.05). Transplant-related mortality at 3 years was 31.3%. Seven out of the 16 patientssurvived, and 4 patients who underwent allo-SCT as front-line therapy without maintenance showed relapse as an
extramedullary mass, which was controlled by external radiation, and survived long-term, having a mean OS of 7.8
years. In our study, the OS and PFS recieved allo-SCT were not superior to those recieved more common therapies,
such as autologous stem cell transplantation or combined chemotherapy with new agents. We need to have moreprogress in allo-SCT for MM while establishing safe and effective procedures.
Key words:

multiple myeloma, allogeneic hematopoietic stem cell transplantation, graft-versus-myeloma effect

1. Introduction

outcomes due to the various combinations of new drugs­
being reported in the literature 2,3). In spite of these drug

New drugs (bortezomib, thalidomide, and lenalidomide)­combinations, multiple myeloma still has no cure due tohave become available in recent years, and the guidelines forthe development of chemotherapy resistance during thetreating multiple myeloma are radically changing 1). Further-course of prolonged treatments.

more, achieving deeper remission before autologous periph-

Allogeneic hematopoietic stem cell transplantation (allo-

eral blood stem cell transplantation (auto-SCT) has led toSCT) with myeloablative conditioning is no longer recom-

improvements in overall survival (OS), and more favorable

mended in daily clinical medicine due to high treatmentrelated mortality (TRM) 4–6). However, some clinical studies

Received: March 16, 2015, accepted: July 5, 2015
1
Department of Hematology/Oncology, Wakayama Medical
University
2
Department of Hematology/Oncology, Social Insurance Kinan
Hospital, Japan3
Department of Hematology, Rinku General Medical Center
4
Department of Hematology, Kobe City Medical Center General
Hospital(*) equally contributed
Corresponding author: Akinori NISHIKAWA, M.D.
Department of Hematology/Oncology, Wakayama Medical
University, 811-1 Kimiidera, Wakayama, Wakayama 641-8509, Japan
TEL: 81-73-441-0665, FAX: 81-73-441-0653
E-mail: nishikaw@wakayama-med.ac.jp

reported a 7-year progression-free survival (PFS) rate of
approximately 20% among patients with multiple myeloma
who underwent allo-SCT using myeloablative conditioning,
and a plateau was reached in the survival curve 4–6). These findings suggest that allo-SCT may prolong OS and be curative
therapy for some multiple myeloma patients.
A non-myeloablative conditioning regimen, the so-called
reduced-intensity stem cell transplantation (RIST), has recently
been applied to MM patients. In 2011, two groups performed
prospective studies in which therapies with auto-SCT alone
versus auto-SCT followed by RIST were compared in patientswith de novo myeloma, and favorable outcomes wereobserved in patients undergoing RIST 7,8). However, allo-SCT for
the treatment of multiple myeloma has not yet been estab-

International Journal of Myeloma

vol. 5 no. 3 (2015)

23

NISHIKAWA et al.

lished because of a high relapse rate (RR) and TRM, even with

(Saitama Medical Center, Jichi Medical University), which is a

RIST.

graphical user interface for R (The R Foundation for Statistical

We retrospectively investigated the efficacy of allo-SCT in

Computing). More precisely, it is a modified version of R com-patients with MM treated in our hospital and an associatedmander designed to add statistical functions frequently used

center for 11 years. We herein describe the outcomes of 16

in biostatistics 11).

patients with MM who underwent allo-SCT, and discuss the

3. Resultsrole of allo-SCT in the new drugs era.

2. Materials and Methods

3.1. Patient characteristics
Patient characteristics are summarized in Table 1. Median

2.1. Patientsage at allo-SCT was 47 (range 31–64) years. Sixteen patients

We retrospectively reviewed 16 patients with multiple

were classified by diagnosis (IgG, n = 5; IgA, n = 2; Bence-Jones

myeloma treated with allo-SCT at two institutes (Wakayama

protein, n = 8; non-secretory, n = 1). In addition, 12 patients

Medical University and Rinku General Medical Center) between

had light chain κ, while 2 had light chain λ. All patients had

June 2001 and December 2012. Patients with multiple

received induction chemotherapy with vincristine, doxorubi-

myeloma were diagnosed using IMWG criteria 9). We selected

cin, and dexamethasone or new drugs (bortezomib or thalido-

MM patients who expected to survive long time and to avoidmide). Fourteen patients had received one or two treatment

TRM as following criteria. The inclusion criteria were: high-regimens before allo-SCT. Only two had received more thanrisk or refractory myeloma, under 60 years old and HCT-CI

three regimens. Eight patients had undergone high-dose(Hematopoietic Cell Transplantation-Comorbidity Index) score­therapy with auto-SCT. Eight patients with refractory/relapsed≤ 2. We fully explained the risks and benefits of allo-SCT tomultiple myeloma had received allo-SCT as salvage therapy,

patients. After their informed consent, we provided allo-SCT

while we performed it as a front-line strategy in 8 newly diag-for MM patients.

nosed patients. Three patients were found to have the deletionof chromosome 13 (del(13)) by G-banding. Seven patients had

2.2. Definitions

progressive disease (PD) at allo-SCT.

We evaluated their responses and progression according to
the international uniform response criteria 10). Briefly, a partial

Table 1.

Clinical characteristics of patients at diagnosis (n = 16)

response (PR) was defined as ≥50% reduction in serum M-

Characteristics

Value

protein or ≥200 mg reduction in the 24-hour excretion ofMale/female
Median age (range, years)
Myeloma subtype
IgG
IgA
Bence-Jones protein
Non-secretory
κ/λDeletion 13 abnormality
Median time between diagnosis and allo-SCT(month)Number of therapies before allo-SCT
1–2
3
4–5
Prior auto-SCT
Yes/NoStrategy
Front-line/Salvage
Disease status at allo-SCT
Non-PDPD

11/5
47 (31–64)

Bence Jones protein (BJP) urea. A very good partial response(VGPR) was defined as ≥90% reduction in serum M-protein or≥100 mg reduction in the 24-hour excretion of BJP urea. A com­plete response (CR) was defined as the complete disappearance of serum and urine M-protein using immune fixation. In
addition, remission was defined as the absence of myeloma
cells by morphology in marrow specimens. Cytogenetic­studies were performed on bone marrow.
2.3. Statistical analysis
OS was calculated from the day of allo-SCT until death or
the last follow-up. PFS was calculated from the day of allo-SCT
until relapse or progression, death from any cause, or the last
follow-up. The probabilities of OS and PFS were estimatedusing the Kaplan-Meier method. TRM and RR were estimatedusing the cumulative incidence method. These analyses were
performed with the log-rank test to compare OS, PFS, TRM,
and RR between groups. All P-values were 2 sided and P < 0.05
was considered significant. A univariate Cox regression analysis was used to determine the prognostic value of various variables for OS. All statistical analyses were performed with EZR
24

International Journal of Myeloma

vol. 5 no. 3 (2015)

5 (31%)
2 (13%)
8 (50%)
1 (6%)
12/2 (75/13%)
3 (19%)
22
14 (85%)
1 (6%)
1 (6%)
8/8 (50/50%)
8*/8 (50/50%)
9 (56%)
7 (44%)

allo-SCT, allogenic stem cell transplantation; auto-SCT, autologous stem
cell transplantation; PD, progression disease.
(*) 6 patients received tandem auto/mini-allo-SCT, 2 patients received
myeloablative allo-SCT.

Allogeneic hematopoietic stem-cell transplantation for multiple myeloma

3.2. Transplantation
Transplantation characteristics are listed in Table 2. Humanleukocyte antigen (HLA) compatibility was determined bymedium resolution molecular methods for HLA-A, -B, C, and-DRB1. Eight patients were transplanted from HLA-matcheddonors. The stem cell source in eight patients was from siblings. Fourteen allogeneic transplant patients received RIST
regimens. In the post-transplantation period, all patientswere treated with immunosuppressive drug tacrolimus- or
cyclosporine A-based regimens for prophylaxis of graft-­versus-host disease (GVHD). Half of the patients were treatedwith tacrolimus and short-term methotrexate. The HCT-CI of
most recipients was good.
3.3. Graft-versus-host disease and transplantation-related
mortality
The cumulative incidences of grades II–IV acute and chronic
GVHD were 41.7% and 72.8%, respectively. TRM for all patientswas 25.0% at 100 days and 31.3% at 3 years (Fig. 1A). Regarding strategies, 3-year TRM was 12.5% in the front-line groupand 50.0% in the salvage group (Fig. 1B). The outcome wasunfavorable in the salvage group, but not significantly so (P =0.19).

Table 2. Transplantation characteristics of patients (n = 16)
Characteristics
SourceSibling/Unrelated
HLA (Allele level)
Matched1 mismatched
2 mismatched
3 mismatched
Conditioning regimen
Myeloablative
Reduced-intensity conditioning
Flu + L-PAM
Flu + Cy + TBI
L-PAM + TBI
2CdA + Bu
GVHD prophylaxis
TAC-based
CSP-based
HCT-CI
0
1, 2

Value
8/8 (50/50%)
8 (50%)
5 (31%)
1 (6%)
2 (13%)
2 (12%)
14 (88%)9 (56%)
4 (25%)
2 (13%)
1 (6%)
10 (63%)6 (37%)
11 (69%)4 (31%)HLA, human leukocyte antigen; Flu, fludarabine; L-PAM, melphalan;Cy, cyclophosphamide; TBI, total body irradiation; 2CdA,
2-chlorodeoxyadenosine; Bu, busulfan; GVHD, graft-versus-hostdisease; TAC, tacrolimus; CSP, cyclosporin A; HCT-CI, Hematopoietic
Cell Transplant Co-morbidity Index.

Figure 1. Cumulative incidence of TRM in all patients who underwent allo-SCT (A), and a comparison between front-line and ­salvage therapies (B).
Cumulative incidence of RR in all patients who underwent allo-SCT (C), and a comparison between front-line and salvage therapies (D).

International Journal of Myeloma

vol. 5 no. 3 (2015)

25

NISHIKAWA et al.

Figure 2. PFS (A) and OS (B) curves of 16 patients who underwent allo-SCT.

Figure 3. PFS (A) and OS (B) after allo-SCT are shown based on the donor type. PFS (C) and OS (D) after allo-SCT are also shown based on thetreatment strategy.

3.4. Causes of deathmonths after allo-SCT and, despite re-transplantation, had

Causes of death within 100 days after allo-SCT were multi-

transplantation-related death.

organ failure in 2 patients and sepsis, myocardial infarction,and graft failure in 1 patient each. After 100 days, bacterial

3.5. Response after transplantation and survival

pneumonia and obstructive bronchitis resulted in the death of

RR for all patients was 72.8% at 3 years (Fig. 1C). The 3-year

1 patient each. One patient died due to primary disease pro-

RR in the front-line group (57.2%) was significantly lower thangression 8 months after allo-SCT. One patient relapsed 10that in the salvage group (100.0%) (Fig. 1D, P = 0.006). In this26

International Journal of Myeloma

vol. 5 no. 3 (2015)

Allogeneic hematopoietic stem-cell transplantation for multiple myeloma

Table 3. Analysis of pretransplantation factors predicting overall
survival
FactorAge at transplant<50≥50
Disease status at allo-SCT
Non-PD
PD
Strategy
Front-line
Salvage
Prior auto-SCTNo
Yes
Conditioning regimen
Myeloablative
Reduced-intensity
conditioning
SourceSibling
Unrelated
Donor
HLA-Matched
HLA-mismatched
Chronic GVHD
Yes
No

N

Hazard Ratio(95% CI)

P
0.67

9
7

1.00
1.35 (0.35–5.27)

9
7

1.00
4.73 (1.15–19.5)

8
8

1.00
0.30 (0.07–1.27)

2
14

1.00
0.38 (0.07–1.99)

items was detected by this retrospective analysis because of

4. Discussion
The indication of allo-SCT has been expanded since the RIST
regimen was developed. Compared with other hematologicaldiseases, multiple myeloma develops in older patients who

0.51

cannot tolerate myeloablative conditioning. Previous studies
reported that TRM and RR were both high in patients with

1.00
0.62 (0.16–2.51)

multiple myeloma undergoing allo-SCT with myeloablative
0.27

1.00
2.21 (0.55–8.88)

conditioning; therefore, this regimen has not been recommended in evidence-based medicine 4–6). Several prospective

0.78
7
4

strategy (front-line vs salvage) showed a trend toward signifi-

the small number of patients.

0.26

8
8

status at allo-SCT (non-PD vs PD) was significant (hazard ratio,

P = 0.06). However, no significant difference in the other

0.10

8
8

source, HLA match, and chronic GVHD (Table 3). Only diseasecance (hazard ratio, 0.26; 95% confidence interval, 0.06–1.08;
0.06

1.00
0.26 (0.06–1.08)

strategy, prior auto-SCT, conditioning regimen, stem cell

4.73; 95% confidence interval, 1.15–19.5; P = 0.03), whereas
0.03

8
8

A univariate analysis was performed for various items
including age at transplantation, disease status at allo-SCT,

1.00
1.38 (0.14–13.5)

allo-SCT, allogenic stem cell transplantation; PD, progression disease;auto-SCT, autologous stem cell transplantation; HLA, human leukocyte
antigen; GVHD, graft-versus-host disease.

studies have been conducted using RIST, which can reduce
TRM, in patients with relapsed/refractory multiple mye­loma 12–14). TRM was improved, but remained high, ranging
from 20% to 30%, and RIST did not result in an improvementin OS in relapsed/refractory multiple myeloma. New drugs
such as bortezomib and immunomodulating drugs became
available at around the same time. These drugs with low TRM

study, the 3-year RR was high, even in the front-line group. Of

have largely contributed to prolonged OS, leading to allo-SCT

the 10 patients with recurrence, 4 showed relapse as an extra-

no longer being recommended as salvage therapy 15). Our

medullary mass, which was controlled well by external radia-

study also demonstrated the poor outcome of salvage therapy

tion, and subsequently sustained CR over 1 year. One patient

and was consistent with previous findings.

with recurrence was treated with lenalidomide, whereas theSome prospective studies used allo-SCT as front-line therapy

others did not receive new drugs such as bortezomib andfor multiple myeloma 7,8). Of particular interest are studies byimmunomodulating drugs. The 4 patients with extramedullarygroups from Sweden and Italy who performed auto-SCT fol-

relapse were all in the front-line group, and survived long-

lowed by RIST on patients with de novo multiple myeloma. OS

term, having a mean OS of 7.8 years.

and PFS in these patients were both significantly higher thanThe 3-year PFS in 16 patients with multiple myeloma wasthose in patients undergoing auto-SCT alone 7,8). Furthermore,

18.8%, whereas the 3-year OS was 54.7% (Fig. 2A, B). No signifi-

the outcomes achieved with auto-SCT followed by allo-SCT incant difference was observed between sources in either thefront-line therapy were more favorable than those with sal-

3-year PFS (12.5% for siblings vs 25% for unrelated donors;

vage therapy 12–14). However, TRM was still higher with this regi-

P = 0.58; Fig. 3A) or 3-year OS (50% for siblings vs 62.5% for

men than with auto-SCT alone 7,8). Gahrton et al. also recently

unrelated donors; P = 0.50; Fig. 3B). The 3-year PFS was sig­

reported that long-term survival outcomes (8 years) after auto-nificantly higher in patients undergoing allo-SCT as front-line

SCT followed by RIST for new multiple myeloma were signifi-

therapy than in those receiving transplantation as salvage

cantly better than those after auto-SCT alone 16). TRM and RR

therapy (37.5% in the front-line group vs 0% in the salvage

were higher in the front-line group in our study, whereas OSgroup; P = 0.003; Fig. 3C). The 3-year OS was also significantly

was similar to the findings reported by these two groups. Our

higher in the front-line group than in the salvage groupresults also revealed some long-term survivors of multiple(72.9% vs 37.5%; P = 0.05; Fig. 3D).

myeloma in the front-line group, which suggest that thoseInternational Journal of Myeloma

vol. 5 no. 3 (2015)

27

NISHIKAWA et al.

who underwent allo-SCT as front-line therapy had markedly

such as autologous stem cell transplantation or combined

better prognoses.

chemotherapy with new agents. We need to have more prog-

More patients can achieve CR before auto-SCT due to thedevelopment of new drugs. A previous study showed that

ress in allo-SCT for MM while establishing safe and effective
procedures.

patients achieving CR before auto-SCT were more likely tohave improved prognoses 3). In addition, Crawley et al. 17)

5. Conflicts of Interest Disclosures

reported that CR/VGPR/PR, but not PD, prior to RIST was associated with improved OS. In our study, a univariate analysis fordisease status also revealed that myeloma patients with PD

The authors declare no competing financial interests related
to this work.

were not expected to have prolonged OS, which was consistent with previous findings. Allo-SCT may only be effective

References

for myeloma patients with a well-controlled disease status.
Serum-free light chain analyses have enabled the detailed
18)

evaluation of disease statuses . Therefore, the identificationof stringent CR by this analysis will be of importance in the
success of allo-SCT.
Greater difficulties are associated with obtaining the­graft-versus-myeloma (GVM) effect in multiple myeloma thanin other hematological malignancies 4,5). Previous studies
reported that patients with multiple myeloma had higher RR
than those with other diseases. On the other hand, patientswith chronic GVHD were shown to have a reduced risk ofrecurrence, which indicated the presence of the GVM effect,
and there was no contribution to extended OS 19–21). Although
the presence of chronic GVHD in this study did not contributeto prolonged OS, some recurrent cases had an extramedullarymass, which was controlled well by external radiation, andsubsequently sustained CR over 1 year. A chimerism analysis at
the onset of recurrence showed a full donor-cell population,
which supported the GVM effect being expected in bone marrow. Hereafter, longer survival can be expected in our recurrent patients receiving new drugs such as bortezomib andimmunomodulating drugs. Our results showed that only disease status at allo-SCT (non-PD vs PD) was significant, whereas
strategy (front-line vs salvage) showed a trend for significancefor overall survival. However, no significant difference was
detected in the other items by this retrospective analysis
because of the small number of patients.
Multiple myeloma is currently very hard to cure with new
drugs and/or auto-SCT. Furthermore, the findings of previous
studies and the results of the present study demonstrated that
allo-SCT is not desirable as salvage therapy. New drugs have
improved the treatment options for myeloma patients; therefore, allo-SCT remains a controversial treatment because ofhigh RR and TRM. In our study, some patients who underwent
allo-SCT as front-line therapy without maintenance survived
as long as those in a previous study 16). This result suggests that
the GVM effect contributed, at least in part, to disease control.
According to our study, the OS and PFS recieved allo-SCT
were not superior to those recieved more common therapies,
28

International Journal of Myeloma

vol. 5 no. 3 (2015)

1) Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Bladé J, etal. International Myeloma Working Group: International Myeloma
Working Group consensus approach to the treatment of multiple
myeloma patients who are candidates for autologous stem celltransplantation. Blood. 2011; 117: 6063–73.
2) Kim JS, Kim K, Cheong JW, Min YH, Suh C, Kim H, et al. Korean
Multiple Myeloma Working Party: Complete remission status
before autologous stem cell transplantation is an important prognostic factor in patients with multiple myeloma undergoing
upfront single autologous transplantation. Biol Blood Marrow
Transplant. 2009; 15: 463–70.
3) Harousseau JL, Attal M, Avet-Loiseau H. The role of complete
response in multiple myeloma. Blood. 2009; 114: 3139–46.
4) Lokhorst H, Einsele H, Vesole D, Bruno B, San Miguel J, PérezSimon JA, et al. International Myeloma Working Group: Inter­national Myeloma Working Group consensus statement regarding
the current status of allogeneic stem-cell transplantation for­multiple myeloma. J Clin Oncol. 2010; 28: 4521–30.
5) Gahrton G. Progression in allogeneic transplantation for multiple
myeloma. Eur J Haematol. 2010; 85: 279–89.
6) Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd
DD, et al. Standard chemotherapy compared with high-dose
chemoradiotherapy for multiple myeloma: final results of phase III
US Intergroup Trial S9321. J Clin Oncol. 2006; 24: 929–36.
7) Björkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L,
et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation
in myeloma: long-term follow-up. J Clin Oncol. 2011; 29: 3016–22.
8) Giaccone L, Storer B, Patriarca F, Rotta M, Sorasio R, Allione B, et al.
Long-term follow-up of a comparison of nonmyeloablative allografting with autografting for newly diagnosed myeloma. Blood.
2011; 117: 6721–7.
9) International Myeloma Working Group. Criteria for the classi­
fication of monoclonal gammopathies, multiple myeloma andrelated disorders: a report of the International Myeloma Working
Group. Br J Haematol. 2003; 121: 749–57.
10) Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson
K, et al. International Myeloma Working Group: International uniform response criteria for multiple myeloma. Leukemia. 2006; 20:
1467–73.
11) Kanda Y. Investigation of the freely-available easy-to-use software“EZR” (Easy R) for medical statistics. Bone Marrow Transplant.
2013; 48: 452–8.
12) Efebera YA, Qureshi SR, Cole SM, Saliba R, Pelosini M, Patel RM, etAllogeneic hematopoietic stem-cell transplantation for multiple myelomaal. Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma. Biol Blood Marrow
Transplant. 2010; 16: 1122–9.
13) Shimoni A, Hardan I, Ayuk F, Schilling G, Atanackovic D, Zeller W,
et al. Allogenic hematopoietic stem-cell transplantation with
reduced-intensity conditioning in patients with refractory andrecurrent multiple myeloma. Cancer. 2010; 116: 3621–30.
14) Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C, et al.
Allogeneic stem cell transplantation in multiple myeloma
relapsed after autograft: a multicenter retrospective study basedon donor availability. Biol Blood Marrow Transplant. 2012; 18:
617–26.
15) Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi
FK, et al. Improved survival in multiple myeloma and the impact
of novel therapies. Blood. 2008; 111: 2516–20.
16) Gahrton G, Iacobelli S, Björkstrand B, Hegenbart U, Gruber A,
Greinix H, et al. EBMT Chronic Malignancies Working Party Plasma
Cell Disorders Subcommittee: Autologous/reduced-intensity allogeneic stem cell transplantation versus autologous transplantation in multiple myeloma: long-term results of the EBMTNMAM2000 study. Blood. 2013; 121: 5055–63.

17) Crawley C, Lalancette M, Szydlo R, Gilleece M, Peggs K, Mackinnon
S, et al. Chromic Leukaemia Working Party of the EBMT: Outcomesfor reduced-intensity allogeneic transplantation for multiple
myeloma: an analysis of prognostic factors from the Chronic­Leukaemia Working Party of the EBMT. Blood. 2005; 105: 4532–9.
18) Kyrtsonis MC, Vassilakopoulos TP, Kafasi N, Sachanas S, Tzenou T,
Papadogiannis A, et al. Prognostic value of serum free light chain
ratio at diagnosis in multiple myeloma. Br J Haematol. 2007; 137:
240–3.
19) Baron F, Storb R. The immune system as a foundation for immunologic therapy and hematologic malignancies: a historical perspective. Best Pract Res Clin Haematol. 2006; 19: 637–53.
20) Pérez-Simón JA, Díez-Campelo M, Martino R, Brunet S, Urbano A,
Caballero MD, et al. Influence of the intensity of the conditioning
regimen on the characteristics of acute and chronic graft-versushost disease after allogeneic transplantation. Br J Haematol. 2005;
130: 394–403.
21) Ringdén O, Shrestha S, da Silva GT, Zhang MJ, Dispenzieri A,­Remberger M, et al. Effect of acute and chronic GVHD on relapse
and survival after reduced-intensity conditioning allogeneic trans­
plantation for myeloma. Bone Marrow Transplant. 2012; 47: 831–7.

International Journal of Myeloma

vol. 5 no. 3 (2015)29