doi:10.1182/blood-2007-07-101212Prepublished online September 17, 2007;2008 111: 1805-1810   

 Hechmi Louzir, Koussay Dellagi and Abdeladhim Ben AbdeladhimKsouri, Assia Ben Hassen, Fahmi Msadek, Ali Saad, Mohamed Hsaïri, Kamel Boukef, Ahlem Amouri,Romdhane, Halima El Omri, Moez Elloumi, Hatem Belaaj, Ramzi Jeddi, Lamia Aissaouï, Habib Abderrahman Abdelkefi, Saloua Ladeb, Lamia Torjman, Tarek Ben Othman, Amel Lakhal, Neila Ben randomized clinical trialtransplantation in multiple myeloma: results of a multicentertherapy with thalidomide is superior to double autologous Single autologous stem-cell transplantation followed by maintenance

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CLINICAL TRIALS AND OBSERVATIONS

Single autologous stem-cell transplantation followed by maintenance therapy withthalidomide is superior to double autologous transplantation in multiple myeloma:results of a multicenter randomized clinical trial

Abderrahman Abdelkefi,1 Saloua Ladeb,1 Lamia Torjman,1 Tarek Ben Othman,1 Amel Lakhal,1 Neila Ben Romdhane,2

Halima El Omri,3 Moez Elloumi,4 Hatem Belaaj,4 Ramzi Jeddi,5 Lamia Aissaouı,5 Habib Ksouri,1 Assia Ben Hassen,1

Fahmi Msadek,6 Ali Saad,7 Mohamed Hsaıri,8 Kamel Boukef,9 Ahlem Amouri,10 Hechmi Louzir,10 Koussay Dellagi,10 andAbdeladhim Ben Abdeladhim,1 on behalf of the Tunisian Multiple Myeloma Study Group

1Centre National de Greffe de Moelle Osseuse, Tunis; 2Hopital La Rabta, Tunis; 3Hopital Farhat Hached, Sousse; 4Hopital Hedi Chaker, Sfax; 5Hopital AzizaOthmana, Tunis; 6Hopital militaire, Tunis; 7Laboratoire de cytogenetique, Hopital Farhat Hached, Sousse; 8Institut National de la Sante Publique, Tunis; 9CentreNational de Transfusion Sanguine, Tunis; and 10Institut Pasteur de Tunis, Tunisia

From April 2003 to December 2006, 195patients with de novo symptomatic my-eloma and younger than 60 years of agewere randomly assigned to receive eithertandem transplantation up front (arm A,n � 97) or one autologous stem-cell trans-plantation followed by a maintenancetherapy with thalidomide (day � 90,100 mg per day during 6 months) (arm B,n � 98). Patients included in arm B re-ceived a second transplant at diseaseprogression. In both arms, autologousstem-cell transplantation was preceded

by first-line therapy with thalidomide-dexamethasone and subsequent collec-tion of peripheral blood stem cells withhigh-dose cyclophosphamide (4 g/m2) andgranulocyte colony stimulating factor.Data were analyzed on an intent-to-treatbasis. With a median follow-up of33 months (range, 6-46 months), the3-year overall survival was 65% in arm Aand 85% in arm B (P � .04). The 3-yearprogression-free survival was 57% in armA and 85% in arm B (P � .02). Up-frontsingle autologous transplantation fol-

lowed by 6 months of maintenancetherapy with thalidomide (with secondtransplant in reserve for relapse or pro-gression) is an effective therapeutic strat-egy to treat multiple myeloma patientsand appears superior to tandem trans-plant in this setting. This study was regis-tered at www.ClinicalTrials.gov as (NCT00207805). (Blood. 2008;111:1805-1810)

© 2008 by The American Society of Hematology

Introduction

Two prospective randomized studies have shown that recipients ofhigh-dose chemotherapy with autologous stem cell transplantation(ASCT) have superior survival when compared with patientstreated with conventional therapy.1,2 In both studies, patients wereyounger than 65 years, and as a result, single ASCT is nowconsidered a standard option in younger patients.1-3

The Intergroupe Francophone du Myelome (IFM) was the firstto demonstrate that 2 sequential ASCTs improved 7-year event-freesurvival (EFS) and overall survival (OS) rates in comparison with asingle ASCT.4 Recently, the Bologna 96 clinical study has shownthat in comparison with a single ASCT as up-front therapy fornewly diagnosed multiple myeloma (MM), double ASCT effectedsuperior complete response (CR) rate and EFS but failed tosignificantly prolong OS. Benefits offered by double ASCT wereparticularly evident among patients who did not achieve at least avery good partial response (VGPR) after one autotransplantation.5

Second ASCT given after relapse following a single ASCT hasbeen used as a salvage therapy in many centers.6-11 Recently, aretrospective study has compared tandem ASCT up front with astrategy including planned second ASCT at relapse or progres-

sion.12 In this retrospective study, Morris et al12 showed that asecond ASCT performed before relapse and within 6 to 12 monthsof the first ASCT improved survival.

While there have been no randomized trials to evaluate thebenefit of second ASCT following relapse, it has been suggestedthat ASCT (after first relapse) may achieve the same outcome astransplantation following initial therapy.13-15 Indeed, Fermand etal13 showed that early transplantation improved EFS but did notaffect OS when compared with delayed transplantation.

Although MM remains incurable with conventional treatments,management of the disease recently has been transformed with theintroduction of 3 novel agents: bortezomib,16 thalidomide,17 andlenalidomide.18 These agents represent a new generation of treat-ments for MM that affect both specific intracellular signalingpathways and the tumor microenvironment.19 Thalidomide is anagent with immunomodulatory and antiangiogenic properties.Thalidomide plus dexamethasone20-22 is currently approved asfrontline treatment of MM. Furthermore, several studies haveshown that thalidomide is an effective maintenance therapy afterASCT in patients with MM.23-25

Submitted July 14, 2007; accepted September 13, 2007. Prepublished onlineas Blood First Edition paper, September 17, 2007; DOI 10.1182/blood-2007-07-101212.

An Inside Blood analysis of this article appears at the front of this issue.

The online version of this article contains a data supplement.

The publication costs of this article were defrayed in part by page chargepayment. Therefore, and solely to indicate this fact, this article is herebymarked ‘‘advertisement’’ in accordance with 18 USC section 1734.

© 2008 by The American Society of Hematology

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We therefore performed a multicenter, randomized trial de-signed to compare tandem ASCT up front with one ASCT followedby maintenance therapy with thalidomide and a second ASCT afterrelapse or progression.

Methods

Requirements for patient enrollment

Eligibility criteria included age younger than 60 years, a Durie-Salmon stage II orIII myeloma, and previously untreated patients. Patients were excluded if theyhad one of the following criteria: prior malignancy, pregnant or nursing women,refusal of contraception, patients with ECOG performance score of 4, positiveHIV test, psychiatric disease, severe abnormalities of cardiac (systolic ejectionfraction � 50%), pulmonary (vital capacity or carbon monoxide diffusion� 50% of normal), liver (serum bilirubin � 35 �M or ALAT, ASAT � 4 timesnormal), and renal functions (serum creatinine level of more than 300 �M). Thestudy protocol was approved by the national medical ethical committee, and awritten informed consent was obtained from the patients, in accordance with theDeclaration of Helsinki. This study was registered at www.ClinicalTrials.gov asnumber NCT 00207805.

Study protocol

Initial enrollment. Between April 2003 and December 2006, patientswere registered by the coordinating center (Centre National de Greffe deMoelle Osseuse, Tunis), and a centralized analysis of �-2 microglobulin(Institut Pasteur, Tunis) and conventional cytogenetics were performed(Sousse, and Institut Pasteur, Tunis).

Induction therapy. During the first-line therapy, thalidomide was adminis-tered at a dose of 200 mg per day for 75 consecutive days, and dexamethasonewas administered at a dose of 20 mg/m2 body surface area on days 1 to 4, 9 to12, and 17 to 20 on the first and the third month of therapy and at 20 mg/m2 ondays 1 to 4, the second month. During the first-line therapy, patients receivedtherapeutic doses of prophylactic anticoagulation with acenocoumarol (interna-tional normalized ratio of the prothrombin time: 2-3).

Stem cell collection. After first-line therapy, patients who proceeded toperipheral blood stem cell (PBSC) collection received high-dosecyclophosphamide (4 g/m2) and granulocyte colony stimulating factor(GCSF, 5 �g/kg/day). A minimum of 6 million CD34 cells per kilogramwas collected.

Randomization. After PBSC, patients were randomly assigned toreceive one of the following treatment arms: arm A, 2 successive ASCTs.The conditioning regimen of the first ASCT consisted of melphalan at adose of 200 mg/m2. The second ASCT was administered within 6 months ofthe first ASCT, with the same conditioning regimen. In case of diseaseprogression or relapse after second ASCT, patients included in arm Areceived thalidomide as salvage therapy (200 mg/day); arm B, one ASCTwith a conditioning regimen with melphalan 200 mg/m2 followed bymaintenance therapy with thalidomide at a dose of 100 mg per day,starting 3 months after the ASCT. The duration of maintenancethalidomide was 6 months. Patients included in arm B received a secondASCT in case of disease progression or relapse.

Assessments

The response criteria of the European Group for Blood and MarrowTransplantation proposed in 1998 were used in this study,26 with theaddition of a VGPR.27 A CR was defined as the lack of detectableparaprotein by serum and urine immunofixation and 5% or fewer plasmacells with normal morphological features in a bone marrow aspirate.A VGPR was defined as a 90% decrease in the serum paraprotein level; apartial response (PR) as a 50% decrease in the paraprotein level or a90% decrease in the level of Bence Jones protein (including patients withBence Jones protein alone) or both; a minimal response (MR) was definedas a 25% decrease in the serum paraprotein level; stable disease as nochange in the paraprotein level; a progression as a 25% increase in the

serum paraprotein level; and a relapse as the reappearance of the parapro-tein and/or the recurrence of bone marrow infiltration in a patient with aprior CR. A skeletal survey was performed according to the guideline of theUnited Kingdom myeloma forum.28

Statistical analysis

The proportion of patients with a given characteristic were compared bychi-square test or Fisher exact test. Differences in the means of continuousmeasurements were tested by Student t test and checked with the use of theMann-Whitney U test. The duration of progression-free survival (PFS) wascalculated for patients randomly assigned from the date of randomassignment to the time of progression, relapse, or death. The primary endpoint of this study was OS from randomization. Secondary end point wasPFS. The expected OS in arm A is approximately 60% at 5 years. To have an80% chance of detecting a 20% difference in OS (ie, an OS of 80% in armB) at 5 years with an alpha value of 5% using a 2-sided test required184 patients to be randomized. All comparisons were performed on anintention-to-treat basis. Survival curves were estimated by the Kaplan-Meiermethod and compared with the use of the log-rank test, using June 1, 2007, as thereference date. Prognostic factors for survival were determined by means ofthe Cox proportional-hazards model for covariate analysis. The study wascompleted after 195 patients had been randomly assigned.

Results

Patient flow (Figure 1)

During this 49-month study, 202 patients were enrolled andreceived first-line therapy with thalidomide and dexamethasone.We observed 4 deaths due to infections during first-line therapy.

Figure 1. Flow diagram.

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The first 13 patients who received dexamethasone-thalidomidewere not given prophylaxis of deep venous thrombosis (DVT).Among these first 13 patients, 2 (15%) had symptomatic DVT.Because of the high rate of DVT observed in this first group,therapeutic doses of prophylactic anticoagulation with acenocou-marol were given for the remaining 189 patients. No further DVTswere observed subsequent to the addition of anticoagulant.

A peripheral blood stem-cell collection was performed in198 patients. A median number of 8 million CD34 cells perkilogram was collected (range, 6.5-36).

Three patients were excluded, because of one death and2 refusals of randomization. Ultimately, 195 patients were random-ized: 97 patients were allocated to arm A, and 98 patients wereallocated to arm B. The median time from enrollment to randomiza-tion was 3 months (range, 2-4 months).

Completion of assigned therapy

In arm A, 90% of patients underwent the first transplantation, and82% underwent the second transplantation. The median time fromthe first to the second transplantation was 5 months (range,3-6 months). In arm B, 87% of patients underwent the firsttransplantation and 80% of patients received maintenancethalidomide.

Baseline characteristics

The baseline characteristics of the 195 patients randomly assignedis shown in Table 1. No significant differences were found betweenthe 2 treatment groups.

Response rate

The response rate at each step of the study is shown in Table 2.At 3 months after the first ASCT, on an intention-to-treat basis

the overall rates of CR and VGPR in arms A and B were 40%and 41%, respectively (P � .8).

After second ASCT and 6 months of maintenance thalidomide,the overall rates of CR and VGPR in arms A and B were 54% and68%, respectively (P � .04).

Table 2. Response rate

Arm A (n � 95) Arm B (n � 97) P

CR and VGPR 3 mo after

first transplantation

38 (40) 40 (41) NS

PR 3 mo after first

transplantation

42 (44) 41 (42) NS

MR 3 mo after first

transplantation

9 (10) 9 (10) NS

PD 3 mo after first

transplantation

6 (6) 7 (7) NS

CR and VGPR .04

6 mo after second

transplantation

50 (54) NA

3 mo after maintenance

thalidomide

NA 66 (68)

PR NS

6 mo after second

transplantation

36 (39) NA

3 mo after maintenance

thalidomide

NA 26 (27)

MR NS

6 mo after second

transplantation

3 (3) NA

3 mo after maintenance

thalidomide

NA 3 (3)

PD NS

6 mo after second

transplantation

4 (4) NA

3 mo after maintenance

thalidomide

NA 2 (2)

Data are numbers (%). Response rate based on intention-to-treat analysis.PD indicates progressive disease; NA, not applicable; and NS, not significant.

Figure 2. Progression-free survival according to treatment arm. The probabilitiesof progression-free survival (95% CI) are shown below each time point. Tandemtransplantation up front (arm A: —); single autologous followed by maintenancethalidomide and second autologous in case of relapse/progression (arm B: �). Theprobability of progression-free survival (95% CI) after randomization at 3 years in armA is 57% (37-76) and in arm B is 85% (77-94).

Table 1. Baseline characteristics of the patients

Arm A (n � 97) Arm B (n � 98)

Sex, M/F, no. of patients 49/48 50/48

Age, y (range) 53 (35-59) 54 (34-59)

DS stage II/III, no. of patients 15/82 14/84

M component, no. of patients

IgG 59 57

IgA 16 17

Bence Jones 22 24

Hemoglobin, g/L (range) 93 (53-121) 94 (64-120)

Serum calcium, mmol/L (range) 2.4 (2-4) 2.5 (2.1-4)

Serum albumin, g/L (range) 35 (20-42) 34 (18-43)

Serum �-2 microglobulin,

nmol/L (range)

255 (85-1700) 246.5 (93.5-1190)

Serum creatinine, �mol/L

(range)

100 (46-220) 95 (43-226)

Bone marrow plasmocytosis,

% of cells (range)

35 (20-90) 39 (25-80)

Chromosome 13, no. of patients

(conventional

cytogenetics)

No deletion 56 58

Deletion 13 16

Unknown 28 24

International Staging System,

no. of patients

I 27 29

II 31 30

III 39 39

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Progression-free survival and overall survival

With a median follow-up of 33 months (range, 6-46 months), the3-year probability of OS was 65% in arm A and 85% in arm B(P � .04). The 3-year PFS was 57% in arm A and 85% in arm B(P � .02; Figures 2,3).

Prognostic factors for progression-free survival

In a multivariate analysis of all 195 patients randomly assigned, PFSwas significantly related to deletion of chromosome 13 (P � .05), �-2microglobulin ( � 3 mg/L; P � .01), and treatment assignment(arm A or arm B; P � .04).

In arm B, the effect of thalidomide on PFS differed according tothe response achieved at 3 months after the first transplantation.

Patients who had at least a VGPR did not benefit from thalidomide(P � .5). Patients who did not have at least a VGPR had asignificant benefit from thalidomide (P � .003).

Treatment-related toxicity

Treatment-related toxicity in each treatment group is shown inTable 3. Of the 19 deaths observed in arm A, 4 were attributed tothe toxic effects of ASCT and 15 to disease progression. Of the9 deaths observed in arm B, 2 were attributed to the toxic effects ofASCT and 7 to disease progression.

In arm B, 78 patients (80%) received maintenance treatmentwith thalidomide for a median of 6 months (range, 2-6 months) at afixed dose of 100 mg/day. The adverse events (as defined by theNational Cancer Institute Common Toxicity Criteria, version 2)during maintenance treatment with thalidomide are shown in Table4. Drug-related adverse events led to discontinuation of thalido-mide in 7 patients (7 of 78, 9%). Peripheral neuropathy was themain reason for discontinuation.

In arm A, 18 patients received thalidomide as salvage therapyafter second ASCT for a median of 4 months (range, 1-6 months),at a fixed dose of 200 mg per day. The adverse events (as defined bythe National Cancer Institute Common Toxicity Criteria, version 2)during salvage therapy with thalidomide are shown in Table 4.Drug-related adverse events led to discontinuation of thalidomidein 4 patients (4 of 18, 23%), with peripheral neuropathy as the mainreason for discontinuation. Currently, 3 patients (3 of 18, 17%)continue on thalidomide and remain alive and progression free. Theremaining 15 patients died due to disease progression.

Discussion

To our knowledge, no randomized studies have examined if it isnecessary to perform 2 ASCTs within a limited period or ifadvantage can be obtained by performing a second ASCT only afterthe patient has relapsed. In a retrospective study, Morris et al12

showed that a second ASCT performed before relapse and within6 to 12 months of the first ASCT improved survival.

We compared tandem ASCT with single ASCT followed bymaintenance treatment with thalidomide and a second ASCT ifneeded due to progression or relapse in adults with MM. This studywas predicated on previous work published by Fermand et al,13

who showed that early transplantation improved EFS but did notaffect OS when compared with delayed transplantation.

We found a higher quality of response with the delayed ASCTstrategy versus the standard up-front tandem strategy, as well as a betterPFS and OS. The best quality of response observed in arm B withmaintenance thalidomide could explain the better PFS in this group. The

Table 3. Treatment-related toxicity

Arm A (n � 97) Arm B (n � 98) P

First autologous transplant

Patients, no. (%) 87 (90) 85 (87) NS

Median duration of

neutropenia,* days (range)

8 (4-12) 8 (5-13) NS

Median duration of

thrombocytopenia,† days

(range)

9 (2-19) 10 (2-20) NS

Platelet transfusions, no.

(range)

4 (0-10) 3 (0-11) NS

Treatment-related deaths, no. 2 1 NS

Second autologous transplant

Patients, no. (%) 80 (82) 9 (9) NA

Median duration of

neutropenia,* days (range)

9 (4-14) 10 (6-14) NS

Median duration of

thrombocytopenia,† days

(range)

12 (4-22) 13 (6-23) NS

Platelet transfusions, no.

(range)

5 (1-12) 5 (1-11) NS

Treatment-related deaths, no. 2 1 NS

NS indicates not significant; and NA, not applicable.* Neutropenia: � 0.5 � 109 white cells/L.†Thrombocytopenia: � 50 � 109 platelets/L.

Table 4. Adverse events during treatment with thalidomide

Arm A(salvage)

Arm B(maintenance)

Peripheral neuropathy 2 (11) 3 (4)

Fatigue 1 (6) 2 (3)

Constipation 1 (6) 1 (1)

Neutropenia 0 0

Cardiac 0 0

Thrombosis 0 0

Thrombocytopenia 0 0

Anemia 0 0

Infection 0 1 (1)

Data are percentages of adverse events (% grades 3-4).

Figure 3. Overall survival according to treatment arm. The probabilities of overallsurvival (95% CI) are shown below each time point. Tandem transplantation up front(arm A: —); single autologous followed by maintenance thalidomide and secondautologous in case of relapse/progression (arm B: �). The probability of overallsurvival (95% CI) after randomization at 3 years in arm A is 65% (49-80) and in arm Bis 85% (76-95).

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benefit of maintenance thalidomide was observed only in patients whohad not achieved a VGPR following high-dose therapy, suggesting thatthalidomide induced a direct cytoreductive effect and additional re-sponse, rather than maintaining responses already achieved by ASCT.One hypothesis derived from this observation would be that stoppingmaintenance thalidomide as soon as a VGPR has been reached could bea more effective strategy to reduce side effects and decrease thalidomideresistance and/or intolerance at time of relapse. These findings warrantfurther study.

In our study, patients received thalidomide and dexamethasoneas induction therapy.29 In the future, it will be important to definewhether prior exposure and response to thalidomide inductiontherapy will have an impact on its use as maintenance treatment.30

This study provides a precedent for use of novel therapies suchas thalidomide to help prepare patients for ASCT and as mainte-nance to sustain a posttransplantation response. However, onecaveat in this study is that patients in the tandem ASCT group didnot receive thalidomide maintenance therapy. The recently pub-lished IFM study by Attal et al has shown that maintenancethalidomide provides a clinical benefit following double ASCT.23

At least the first two-thirds of the curves in Figures 2,3(progression-free survival vs overall survival) are almost superim-posable. Indeed, in most cases we have observed very aggressiverelapses, often accompanied with rapid death despite salvageattempts. One explanation could be that many of our patientspostpone consulting long after the first clinical symptoms ofrelapse, and show an advanced state at admission. Anotherexplanation could be the limited options of salvage therapy in ourcountry (eg, Velcade is not available in Tunisia).

In our trial, maintenance therapy with thalidomide was notfound to increase the risk of thromboembolic complications. Wethus confirm that this risk is mainly observed if thalidomide isgiven during induction therapy when the tumor burden is high.31,32

It is also in the context of the addition of dexamethasone that therisk of thromboembolic disease increases.33

Recently, Mileshkin et al34 have shown that thalidomide shouldbe limited to fewer than 6 months to minimize the risk ofneurotoxicity. In our trial, the incidence of severe neuropathy(grade 3-4) was acceptable (4%). Nine percent of patients had todiscontinue thalidomide because of drug-related adverse events,and peripheral neuropathy was the main reason for discontinuation.In our study, the dose of maintenance thalidomide was 100 mg/dayfor a median duration of 6 months.

In contrast, Attal et al23 reported that 39% of patients had todiscontinue thalidomide because of drug-related adverse events.

In their study, median duration of maintenance thalidomide was15 months, with a mean dose of 200 mg/day.

Stewart et al35 reported that the adverse effects of thalidomide,when used as maintenance therapy after transplantation, were doserelated. Others studies in the posttransplantation setting have alsosuggested cumulative effects.36

Because responses may occur with doses of 50 to 100 mg/day,37

maintenance therapy with lower doses should be studied. Ourresults suggest that the use of low-dose thalidomide (100 mg/day)for maintenance after ASCT is an active treatment approach withacceptable toxicity and improved survival.

In conclusion, up-front single ASCT followed by 6 months ofmaintenance therapy with thalidomide (with second ASCT inreserve for relapse or progression) is an effective therapeuticstrategy to treat MM patients and appears superior to tandemtransplantation in this setting.

Acknowledgments

We thank Mr Jean-Luc Harousseau for his critical reading of themanuscript. We are indebted to the patients who participated inthe trial, to the attending physicians who referred their patientsto our center, and to Mr Naceur Gharbi for his support.

This work was supported by the Ministry of Research (03/UR/08-03) and the Association Tunisienne des Greffes de la MoelleOsseuse (ATGMO).

Authorship

Contributions: A.A., L.T., T.B.O., S.L., A.L., N.B.R., H.E.O., M.E.,H.B., R.J., L.A., H.K., A.B.H., F.M., A.S., M.H., K.B., A.A., H.L.,K.D., and A.B.A. participated in designing and performing theresearch; A.A. analyzed the data and wrote the paper, and allauthors checked the final version of the manuscript.

A complete list of the members of the Tumisian MultipleMyeloma Study Group is provided in Document S1 (available onthe Blood website; see the Supplemental Materials link at the top ofthe online article).

Conflict-of-interest disclosure: The authors declare no compet-ing financial interests.

Correspondence: Abderrahman Abdelkefi, Centre National deGreffe de Moelle Osseuse, Rue Jebel Lakhdar, 1006 Bab Saadoun,Tunis, Tunisia; e-mail: aabdelkefi@yahoo.fr.

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1810 ABDELKEFI et al BLOOD, 15 FEBRUARY 2008 � VOLUME 111, NUMBER 4

THIS ARTICLE WAS RETRACTED

ON JUNE 11, 2009.

For personal use only. by guest on June 12, 2013. bloodjournal.hematologylibrary.orgFrom

Retraction

Abdelkefi A, Ladeb S, Torjman L, Ben Othman T, Lakhal A, Ben Romdhane N, El Omri H,Elloumi M, Belaaj H, Jeddi R, Aissaouı L, Ksouri H, Ben Hassen A, Msadek F, Saad A, Hsaıri M,Boukef K, Amouri A, Louzir H, Dellagi K, Ben Abdeladhim A, on behalf of the Tunisian MultipleMyeloma Study Group. Single autologous stem-cell transplantation followed by maintenancetherapy with thalidomide is superior to double autologous transplantation in multiplemyeloma: results of a multicenter randomized clinical trial. Blood. 2008;111:1805-1810.

The authors wish to retract the February 15, 2008, article citedabove. The initial data available at the time the paper was publishedwere inappropriately collected. The first author, AbderrahmanAbdelkefi, was solely responsible for the errors. The authorspresent their deepest apologies to the scientific community and tothe readers, reviewers, and editors of Blood for publishing these

data. The undersigned agreed to the retraction by notifying thejournal.

Abderrahman Abdelkefi, Saloua Ladeb, Lamia Torjman, Tarek BenOthman, Amel Lakhal, Neila Ben Romdhane, Moez Elloumi, Ramzi Jeddi,Lamia Aissaouı, Assia Ben Hassen, Fahmi Msadek, Ali Saad, andMohamed Hsaıri

6265BLOOD, 11 JUNE 2009 � VOLUME 113, NUMBER 24

For personal use only. by guest on June 12, 2013. bloodjournal.hematologylibrary.orgFrom