Validation and reliability of a disease-specific quality of life measure (the TranQol) in adults and children with thalassaemia major.

This study aimed to demonstrate the validity, reliability and responsiveness of a new disease-specific quality of life (QoL) questionnaire for children and adults with thalassaemia major, the Transfusion-dependent QoL questionnaire (TranQol). 106 participants (51 adults and 55 children) were recruited from six North American thalassaemia treatment centres with a mean age of 20·7 years (standard deviation [SD] 9, range 7-51 years). The mean total TranQol score was 71 (SD 17, 32-97) on a scale of 0-100. Patients with co-morbidities had significantly lower scores (63 vs. 75, P = 0·001). TranQol scores showed substantial agreement (P < 0·001) with the Health Utilities Index Mark 3 (all patients, r = 0·65), the Pediatric QoL (children, r = 0·77) and the Short Form (36) physical (adults, r = 0·69) and mental summary scores (r = 0·76). In the subgroup who rated their QoL as better, there was a 4·0 point (SD 9·0) improvement in TranQol scores, from baseline of 67·1-71·1 one week later (P = 0·008). Test-retest reliability was excellent (intra-class correlation coefficient, 0·93). The TranQol was valid, with acceptable correlation for all administered measures and was reliable and responsive to change. The TranQol can be incorporated into future studies of thalassaemia major.

A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia.

The benefit of adding rituximab to standard treatment in nonsplenectomized patients with primary immune thrombocytopenia (ITP) is uncertain. We performed a pilot randomized trial to determine the feasibility of recruitment, protocol adherence, and blinding of a larger trial of rituximab versus placebo; and to evaluate the potential efficacy of adjuvant rituximab in ITP. Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving standard ITP therapy for a platelet count below 30 × 10(9)/L were randomly allocated to receive 4 weekly infusions of 375 mg/m(2) rituximab or saline placebo. Sixty patients were recruited over 46 months, which was slower than anticipated. Protocol adherence and follow-up targets were achieved, and blinding was successful for research staff but not for patients. After 6 months, there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L, significant bleeding or rescue treatment once standard treatment was stopped (21/32 [65.6%] vs 21/26 [80.8%]; relative risk = 0.81, 95% confidence intervals, 0.59%-1.11%). Timely accrual poses a challenge to the conduct of a large randomized trial of rituximab for presplenectomy ITP. No difference in the frequency of the composite outcome was observed in this pilot trial (registered at www.clinicaltrials.gov NCT00372892).

Improved survival in red blood cell transfusion dependent patients with primary myelofibrosis (PMF) receiving iron chelation therapy.

Many patients with primary myelofibrosis (PMF) become red blood cell (RBC) transfusion dependent (TD), risking iron overload (IOL). Iron chelation therapy (ICT) may decrease the risk of haemosiderosis associated organ dysfunction, though its benefit in PMF is undefined. To assess the effect of TD and ICT on survival in PMF, we retrospectively reviewed 41 patients. Clinical data were collected from the database and by chart review. The median age at PMF diagnosis was 64 (range 43-86) years. Median white blood cell (WBC) count at diagnosis was 7.6 (range 1.2-70.9) x 10(9)/L; haemoglobin 104 (62-145) G/L; platelets 300 (38-2088) x 10(9)/L. Lille, Strasser, Mayo and International Prognostic System (IPS) scores were: low risk, n = 15, 8, 11, 3; intermediate, n = 15, 19, 9, 16; high, n = 5, 11, 5, 7; respectively. Primary PMF treatment was: supportive care, n = 23; hydroxyurea, n = 10; immunomodulatory, n = 4; splenectomy, n = 2. Sixteen patients were RBC transfusion independent (TI) and 25 TD; of these 10 received ICT for a median of 18.3 (0.1-117) months. Pre-ICT ferritin levels were a median of 2318 (range 263-8400) and at follow up 1571 (1005-3211 microg/L (p = 0.01). In an analysis of TD patients, factors significant for overall survival (OS) were: WBC count at diagnosis (p = 0.002); monocyte count (p = 0.0001); Mayo score (p = 0.05); IPS (p = 0.02); number of RBC units (NRBCU) transfused (p = 0.02) and ICT (p = 0.003). In a multivariate analysis, significant factors were: NRBCU (p = 0.001) and ICT (p = 0.0001). Five year OS for TI, TD-ICT and TD-NO ICT were: 100, 89 and 34%, respectively (p = 0.003). The hazard ratio (HR) for receiving >20 RBCU was 7.6 (95% Confidence Intervals [CI] 1.2-49.3) and for ICT was 0.15 (0.03-0.77). In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted.

Two new examples of Hb St. Etienne [beta 92(F8)HisGln] in association with venous thrombosis.

Hb St. Etienne [beta92(F8)HisGln] (also known as Hb Istanbul) is a rare unstable beta-globin chain variant that has been described in only three reports involving four patients. We report two individuals in a family of Scottish extraction whose members had been erroneously diagnosed to have hereditary spherocytosis (HS) and have now been shown to be heterozygotes for Hb St. Etienne. They also had venous thrombotic events with minimal provocation. This family illustrates the difficulties in identifying the cause of chronic hemolytic anemia and highlights the possible contribution of chronic hemolysis to increased risk of thrombosis.

Iron overload in myelodysplastic syndromes: a Canadian consensus guideline.

In December 2005, 11 Canadian hematologists met to develop an evidence-based clinical practice guideline that would address the diagnosis, monitoring, management, and rationale for the treatment of transfusional iron overload in patients with myelodysplastic syndromes (MDS). This Expert Panel consisted of hematologists from across Canada, each with an active practice in a major population centre or a rural area. Based on an extensive literature search and years of clinical experience, their mandate was to address common clinical practice questions, particularly why treat, whom to treat, when to initiate treatment, and how to treat iron overload in patients with MDS.

Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.

BACKGROUND: Whether to continue oral anticoagulant therapy beyond 6 months after an "unprovoked" venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants. METHODS: In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5-7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule. RESULTS: We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%-11.3%). Men had a 13.7% (95% CI 10.8%-17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer > or = 250 microg/L while taking warfarin; body mass index > or = 30 kg/m(2); or age > or = 65 years. These women had an annual risk of 1.6% (95% CI 0.3%-4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%-17.3%). INTERPRETATION: Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men.

Residual pulmonary embolism as a predictor for recurrence after a first unprovoked episode: Results from the REVERSE cohort study.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first, unprovoked venous thromboembolism is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. Risk stratification tools may assist in decision making. OBJECTIVES: We sought to determine the relationship between residual pulmonary embolism assessed by baseline ventilation-perfusion scan after completion of 5-7months of oral anticoagulant therapy and the risk of recurrent venous thromboembolism in patients with the first episode of unprovoked pulmonary embolism. METHODS: We conducted a multicentre prospective cohort study of participants with a first, unprovoked venous thromboembolism enrolled after the completion of 5-7months of oral anticoagulation therapy. The participants completed a mean 18-month follow-up. Participants with pulmonary embolism had baseline ventilation-perfusion scan before discontinuation of oral anticoagulant therapy and the percentage of vascular obstruction on baseline ventilation-perfusion scan was determined. During follow-up after discontinuation of oral anticoagulant therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated with reference to baseline imaging. MEASUREMENTS AND MAIN RESULTS: During follow-up, 24 of 239 (10.0%) participants with an index event of isolated pulmonary embolism or pulmonary embolism associated with deep vein thrombosis and central assessment of percentage of vascular obstruction on baseline ventilation-perfusion scan had confirmed recurrent venous thromboembolism. As compared to participants with no residual pulmonary embolism on baseline ventilation-perfusion scan, the hazard ratio for recurrent venous thromboembolism was 2.0 (95% CI 0.5-7.3) for participants with percentage of vascular obstruction of 0.1%-4.9%, 2.1 (95% CI 0.5-7.8) for participants with percentage vascular obstruction of 5.0%-9.9% and 5.3 (95% CI 1.8-15.4) for participants with percentage vascular obstruction greater than or equal to 10%. CONCLUSIONS: Residual pulmonary embolism assessed by pulmonary vascular obstruction on baseline ventilation-perfusion performed after 5-7months of oral anticoagulant therapy for the first episode of unprovoked pulmonary embolism was associated with a statistically significant higher risk of subsequent recurrent venous thromboembolism. Percentage of pulmonary vascular obstruction assessment by ventilation-perfusion scans maybe a useful tool to help guide the duration of oral anticoagulant therapy after a first unprovoked pulmonary embolism. TRIAL REGISTRATION: Registered at www.clinicaltrials.gov identifier: NCT00261014.

Clinical progression and outcome of patients with monoclonal B-cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) is a clonal lymphoproliferation with the immunophenotype of chronic lymphocytic leukemia (CLL) but a B-lymphocyte count of less than 5 x 10(9)/l and no lymphadenopathy, organomegaly, cytopenias or symptoms. We performed a retrospective analysis of patients with MBL (n = 46), Rai stage 0 CLL (n = 112) and Rai stage > or =1 CLL (n = 54). Median follow-up and range was 30 (0.1-120) months for MBL, 60 (0.1-309) months for stage 0 CLL and 54 (0.1-309) months for stage > or =1 CLL. None of the MBL patients required treatment compared with 24 of 112 (21%) stage 0 CLL and 28 of 54 (52%) stage > or =1 CLL patients (p < 0.0003). No MBL underwent aggressive transformation compared with 1 of 112 (0.8%) stage 0 CLL and 6 of 54 (11%) stage > or =1 CLL patients (p < 0.0003). Progression-free survival (PFS) appeared improved in MBL compared to stage 0 CLL, although this did not reach statistical significant (p = 0.07) due to the relatively short follow-up in the MBL group; two year PFS was 97.2% for MBL, 93.1% for stage 0 CLL, and 68% for stage > or =1 CLL patients (p < 0.0001 for stage > or =1 CLL compared with MBL and stage 0 CLL). This is the first study of outcome in MBL which demonstrates that patients have an improved disease course compared to stage 0 CLL patients. Over a median 2.5 years of follow-up, no MBL patients required treatment or died of CLL-related causes.

Massive bleeding on a bladder protectant: a case report of pentosan polysulfate sodium-induced coagulopathy.

Pentosan polysulfate sodium (Elmiron; Alza Pharmaceuticals, Mountain View, Calif) is an oral preparation of pentosan polysulfate used in the symptomatic management of interstitial cystitis. While pentosan polysulfate has a known heparin-like effect in its parenteral form, there have been no previous reports of coagulopathy with oral use. We present an interesting case of inadvertent systemic anticoagulation resulting in serious bleeding complications in a young woman taking oral pentosan polysulfate for interstitial cystitis.

Improved outcome of human immunodeficiency virus-associated plasmablastic lymphoma of the oral cavity in the era of highly active antiretroviral therapy: a report of two cases.

Plasmablastic lymphoma (PBL) is a recently described type of non-Hodgkin's lymphoma (NHL) that occurs in up to 3% of patients with HIV infection. Although the clinical-pathological features of several patients with HIV-associated plasmablastic lymphoma are documented, detailed description of clinical outcome is limited to isolated case reports. Generally, the response to lymphoma therapy is poor and survival is short. Response to highly active anti-retroviral therapy (HAART), however, has also been described. In this report, we describe the clinical course of two patients diagnosed with HIV-associated PBL in the era of HAART. One patient had a complete response to HAART, with a response-duration of 14 months, followed by relapse in the gastrointestinal tract several months after an anti-retroviral holiday. He is currently in complete remission (CR) eight months from diagnosis of relapse after receiving a full course of combination chemotherapy with modified CHOP, and 25 months from initial diagnosis. A second patient responded to brief chemotherapy in conjunction with HAART and is in clinical CR ten months from diagnosis. These cases illustrate that immunologic and virologic control with HAART may be beneficial for treating PBL and may possibly maintain continued CR. We advocate a high index of suspicion for primary PBL or its recurrence in patients with HIV infection, a history of low CD4 counts or high viral load, and oral or gastrointestinal symptoms.

Combination hemodialysis and centrifugal therapeutic plasma exchange: 18 years of Canadian experience.

Hemodialysis (HD) and therapeutic plasma exchange (TPE) are extracorporeal treatments that may both be required in the same patient. When provided separately, 7-8 hours of therapy time is required. Simultaneous administration of both therapies can reduce time and personnel requirements. We report our 18-year institutional experience with combination HD and centrifugal TPE therapy. During combination therapy, the TPE circuit is attached to the HD circuit through an extension blood line connected to the HD venous return line, allowing simultaneous operation of both circuits. The HD circuit is anticoagulated with heparin and the TPE circuit with regional citrate. Blood flow rates through the HD circuit can reach 350 mL/min with plasma removal rates in the TPE circuit up to 60 mL/min. Ninety-two patients received a total of 621 treatments between December 1993 and July 2011. All treatments were completed within 4 hours. No major treatment-related adverse events occurred and less than 10% of treatments were complicated by minor events. Main indications for treatment were ANCA (anti-neutrophilic cytoplasmic antibody) vasculitis (n = 25), Goodpasture's/antiglomerular basement membrane disease (n = 24), adult thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (n = 24), and acute antibody-mediated renal transplant rejection (n = 8). Overall rates of renal recovery, in-hospital mortality, and overall mortality at 18-year follow-up were 45% (41/ 92), 2% (2/92), and 21% (19/ 92), respectively, compatible with published literature. Combination HD and TPE is safe, efficient, and requires less human resources and time than conventional sequential therapy. It should be considered in patients whose treatment regimen includes HD and TPE.

Improved survival with iron chelation therapy for red blood cell transfusion dependent lower IPSS risk MDS may be more significant in patients with a non-RARS diagnosis.

Retrospective analyses suggest iron overload is associated with inferior survival (OS) in lower risk MDS and iron chelation therapy (ICT) with improvement. However, an analysis of RARS patients found no such association. We analyzed subtypes of lower risk MDS. Median OS for non-RARS without and with ICT was 44 months and not reached (P<0.001), and for RARS 99 and 134.4 months (P=NS); in red blood cell (RBC) transfusion dependent RARS patients not receiving ICT, median OS was 73.8 months (P=0.025). These results suggest a stronger association between ICT and OS in non-RARS MDS than in RARS, with significantly superior OS in transfusion dependent patients receiving ICT.

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

Functional analysis of three recombinant A1-VWF domain mutants in comparison to wild type and plasma-derived VWF facilitates subtyping in type 2 von Willebrand disease.

Phenotypic diagnosis of VWD, in particular type 2, is challenging. Molecular diagnosis may fail to provide clarity since mutations within a short stretch of the same domain may cause various phenotypes, and since even experts will ascribe different subtypes to similar mutations. We assessed diagnostic difficulty in VWD by investigating five cases where phenotypic data was unclear. We identified 3 novel mutations within the A1 domain of the VWF gene: L1460F (2 related patients), Y1363C (1 patient), E1389K (2 related patients). These were not found in 100 normal individuals or documented in the VWF mutation database. Detailed functional analysis of recombinant mutants included VWF multimers, VWF:Ag, VWF:RCo, VWF:CB, and Platelet-VWF binding studies, and results assessed against recombinant WT and plasma derived (pd) VWF. Multimer analysis showed clear loss of HMW VWF with E1389K only, consistent with coincident low relative CB/Ag ratio. VWF-platelet binding studies using two independent approaches showed enhanced activity for L1460F, but reduced activity for E1389K and Y1363C. A novel finding was that WT rVWF showed enhanced platelet binding in RIPA analysis compared to pdVWF with this being dependent on the dilution material used. Through these extensive studies, we assigned L1460F to type 2B, E1389K to 2A, and Y1363C to 2M VWD. Thus, although molecular analysis is not required to classify VWD patient subtypes, a thorough and combined phenotypic, genotypic and functional analysis will assist assignment of the VWD subtype.

Red blood cell transfusion independence following the initiation of iron chelation therapy in myelodysplastic syndrome.

Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC). A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

Risk of recurrent venous thromboembolism after a first oestrogen-associated episode. Data from the REVERSE cohort study.

The use of exogenous oestrogen in women with otherwise unprovoked venous thromboembolism (VTE) could be considered sufficient explanation to classify VTE as provoked if the risk of recurrent VTE after 3-6 months of anticoagulant treatment is similar to the risk of recurrent VTE observed after a surgery or prolonged immobilisation. Our objective was to assess the risk of recurrent VTE in women after a first unprovoked episode on oestrogen. The REVERSE study is a cohort study of patients with a first unprovoked VTE treated with anticoagulant treatment for 5-7 months. The risk of recurrent VTE during follow-up was compared between women users and non users of oestrogen at the time of index VTE. Among the 646 patients included, 314 were women, of them 67 were current users of oestrogen at the time of their VTE: 49 were on oral contraceptives and 18 on post-menopausal hormone replacement therapy (HRT). No significant association was found between oestrogen exposure, either oral contraceptives or HRT, and a lower risk of recurrent VTE after adjustment for age, or analysis restricted to women in the same age range as oestrogen contraceptives and HRT users, respectively. The risk of recurrent VTE is low in women after a first otherwise unprovoked oestrogen-associated VTE. However, this risk is not significantly lower than in women whose VTE was not related to oestrogen use.

Supportive care and chelation therapy in MDS: are we saving lives or just lowering iron?

The myelodysplastic syndromes (MDS) are characterized by cytopenias and risk of transformation to acute myeloid leukemia (AML). Although new treatments are available, a mainstay in MDS remains supportive care, which aims to minimize the impact of cytopenias and transfusion of blood products. Red blood cell (RBC) transfusions place patients at risk of iron overload (IOL). In beta-thalassemia major (BTM), IOL from chronic RBC transfusions inevitably leads to organ dysfunction and death. With iron chelation therapy (ICT), survival in BTM improved from the second decade to near normal and correlated with ICT compliance. Effects of ICT in BTM include reversal of cardiac arrhythmias, improvement in left ventricular ejection fraction, arrest of hepatic fibrosis, and reduction of glucose intolerance. It is not clear whether these specific outcomes are applicable to MDS. Although retrospective, recent studies in MDS suggest an adverse effect of transfusion dependence and IOL on survival and AML transformation, and that lowering iron minimizes this impact. These data raise important points that warrant further study. ICT is potentially toxic and cumbersome, is costly, and in MDS patients should be initiated only after weighing potential risks against benefits until further data are available to better justify its use. Since most MDS patients eventually require RBC transfusions, the public health implications both of transfusion dependence and ICT in MDS are considerable. This paper summarizes the impact of cytopenias in MDS and treatment approaches to minimize their impact, with a focus on RBC transfusions and their complications, particularly with respect to iron overload.

Acute leukemia in patients sixty years of age and older: a twenty year single institution review.

OBJECTIVES: Acute leukemia, particularly acute myeloid leukemia, occurs more frequently in the elderly, a growing segment of the North American population. To evaluate our progress in the diagnosis, treatment and outcome of this condition, we reviewed our experience of all patients > or =60 years of age diagnosed with acute leukemia over a 20-year period at Saint Paul's Hospital, a university-based hospital in Vancouver, Canada. METHODS: A retrospective chart review was performed of 103 patients > or =60 years of age diagnosed with acute leukemia (acute myeloid leukemia-81; acute lymphoid leukemia-15; acute leukemia not otherwise specified-7). RESULTS: Median age was 72 (range 60-88) years. Bone marrow aspirate yielded cytogenetic information on 57 patients and 18 (31.6%) had an unfavourable karyotype. Fifty-three (51%) patients received induction chemotherapy (treated) and 50 (49%) were palliated (untreated). Treated patients were younger [median 67 years (range 60-79)] than untreated patients [76 years (61-88)], (P < 0.0001). Of the treated patients, 33 (62%) achieved a complete remission. The median overall survival for the group was 104 (1-2689) days, and for treated versus untreated patients-219 (1-2689) and 39 (2-1229) days, respectively (P = 0.0021). Univariate variables predictive of prolonged survival included induction chemotherapy (P = 0.0027), de novo leukemia (P = 0.0420), and younger age, with a relative increase in death in older subgroups (60-69, 70-79, 80+), (P = 0.0311). Induction chemotherapy was the only predictor of prolonged survival in multivariate analysis (P = 0.0027). CONCLUSIONS: The prognosis of acute leukemia in older patients remains poor, and even though induction chemotherapy seem to prolong survival in patients able to receive treatment, most ultimately die of leukemia.

A randomised comparison of melphalan with prednisone or dexamethasone as induction therapy and dexamethasone or observation as maintenance therapy in multiple myeloma: NCIC CTG MY.7.

The effectiveness of melphalan plus dexamethasone (M-Dex) with melphalan plus prednisone (MP) as induction therapy and dexamethasone with observation as maintenance therapy was compared in 585 older patients with multiple myeloma. Randomization to the M-Dex arm was stopped as a result of an analysis performed which met a predetermined event-related criterion. Of 466 patients randomised to MP or M-Dex, no differences were detected in the respective median progression-free survivals (PFS) [1.8 vs. 1.9 years; Hazard Ratio (HR) = 0.88, 95% CI 0.72-1.07; P = 0.2] or overall survivals (OS) (2.5 vs. 2.7 years; HR = 0.91, 95% CI 0.74-1.11; P = 0.3). Of the initial 585 patients, 292 remained evaluable for maintenance therapy. Patients randomised to maintenance dexamethasone had a superior median PFS (2.8 years vs. 2.1 years; HR = 0.61, 95% CI 0.47-0.79; P = 0.0002). No difference in median OS was detected (4.1 years vs. 3.8 years; HR = 0.88, 95% CI 0.65-1.18; P = 0.4). The maintenance therapy results were robust when analysed by using two additional methodologies. Dexamethasone did not improve clinical outcome when combined with melphalan during induction; maintenance dexamethasone improved PFS, but this did not translate into a detectable survival advantage.