Abstract 2615
The first EORTC-CLG AML pilot study (58872) demonstrated the efficacy of Mitoxantrone (MTZ), substituted for daunorubicin, in the treatment of childhood AML. The subsequent trial ...(58921) aimed to compare MTZ and Idarubicin (IDA), an anthracycline with a favorable pharmacokinetic profile (such as good CSF penetration) and suggested to be more efficacious than daunorubicin in adult AML trials performed in the last two decades.
Between March 1993 and December 2002, 227 eligible patients (pts) <18y of age with newly diagnosed AML (N=216) or high risk MDS (RAEB & RAEBt, N=11) were randomized in the EORTC phase III 58921 trial to receive either IDA or MTZ in induction and 1st intensification course, each at a dose of 10 mg/m2/d for 3 days in both courses. Concomitant chemotherapy consisted of standard dose Cytarabine (AraC) and Etoposide (Eto) in induction and high-dose AraC (18–36 g/m2) in 1st intensification. Allogeneic stem cell transplantation after 1st intensification was recommended for pts who achieved CR and had an HLA-identical sibling donor. Patients in CR without donor had to receive a 2nd (DCTER = continuous infusion of standard dose AraC, Daunorubicin 4x 20 mg/m2/d, Eto, Dexamethasone, 6-thioguanine) and 3rd intensification course (high dose AraC 12 g/m2 + Eto), followed by maintenance therapy (6-Thioguanine daily + AraC 4 days/month) for 12 months. CNS irradiation after the 3rd intensification for patients with initial WBC counts >=70×10E9/L was abandoned from November 1994 on. Randomization was done centrally. The primary endpoint was EFS; secondary endpoints were OS, CR rate after induction/1st intensification, DFS and toxicity. Intention-to-treat analysis was used.
A total of 112 and 115 eligible pts were randomly assigned to receive IDA and MTZ, respectively. The rate of CR after two courses was 79.5% (IDA) vs 85.2% (MTZ). At an overall median follow-up of 9.9 y (range 0.25–16 y), there were 65 vs 59 events in the IDA vs MTZ group: failure to achieve CR (23 vs 17), relapse (35 vs 40), and death without relapse (7 vs 2). The 5-year EFS rate was 42.0% (SE 4.7%) in the IDA group and 48.4% (SE 4.7%) in the MTZ group (hazard ratio (HR) = 1.20, 95% CI 0.84–1.71, 2-sided log rank p=0.29). The 5-year OS rate was comparable in both treatment arms: 59.8% (SE 4.6%) in the IDA group and 57.5% (SE 4.7%) in the MTZ group (HR = 1.03, 95% CI 0.70–1.54, 2-sided log rank p=0.87).
In CR patients with (N=46/187) or without (N=141/187) an HLA-identical sibling donor, the 5-year DFS rate from CR was 65.1% (SE 7.1%) and 51.5% (SE 4.2%) respectively (HR=0.65, 95% CI 0.37–1.11, 2-sided log rank p=0.11) and the 5-year OS rate 78.0% (SE 6.1%) and 60.7% (SE 4.1%) respectively (HR=0.53, 95% CI 0.28–1.01, 2-sided log rank p=0.048). This advantage for patients with a donor remained important regarding both DFS (HR=0.60, p=0.07) and OS (HR=0.49, p=0.03), even after adjustment for WBC count at diagnosis, age, cytogenetic features and randomized arm.
The interval between start of induction and start of 1st intensification was similar in both arms (median 5.2 weeks). Grade 3–4 infection following the induction course was 37.5% (IDA) vs 25.4% (MTZ); incidence of fever grade 3–4 was 25% (IDA) vs 22.8% (MTZ). In this trial, the cumulative anthracycline dosage (conversion factor 5) was 380 mg/m2. Acute and late-onset cardiotoxicity was comparable in both treatment arms.
There was no significant difference in efficacy and in toxicity between the two randomized treatment groups, IDA versus MTZ, although grade 3–4 infection rate following the induction course was slightly higher in the IDA arm. Patients who reached CR and who had a HLA compatible sibling donor had a longer DFS and OS than pts without a donor.
No relevant conflicts of interest to declare.
Abstract 133▪▪This icon denotes a clinically relevant abstract
T-cell acute lymphoblastic leukemia (ALL) accounts for 15% of ALL cases in children and has been associated with a higher risk for ...central nervous system (CNS) relapse and a worse prognosis. In EORTC trials 58831 and 2, standard risk (SR) patients (pts) were not irradiated but received intermediate dose methotrexate (MTX) courses; for medium and high risk pts, high dose (HD) MTX was added to the treatment regimen and the administration of cranial radiotherapy (RT) was randomised. The omission of RT didn't result in an increase of CNS or systemic relapse and consequently, CNS-directed chemotherapy was substituted for RT in all following trials. The long-term outcome of T-ALL pts in the subsequent phase III trials (58881 and 58951) are presented here.
The BFM backbone for ALL treatment was applied to all EORTC-CLG trials since 1983. As CNS treatment in study 58881, SR pts received 4 HD MTX courses (5 g/m2) in interval therapy and 10 IT MTX injections during the intensive treatment phases. Pts with CNS-3 status at diagnosis received 2 additional IT injections during induction, 2 during consolidation and 6 HD MTX courses + IT during maintenance. T-ALL pts with poor prephase response (PPR) at day 8 or who didn’t achieve complete remission (CR) after induction were included in the very high risk (VHR) group. VHR CNS-directed chemotherapy included 10 IT MTX injections, 6 IT triple and 10 HD MTX courses during intensive treatment phases, followed by 4 IT MTX injections during maintenance (the latter for CNS-3 pts only). In the 58951 trial, all T-ALL pts had an intensified induction. The CNS-directed therapy of all average risk T-ALL pts was intensified to 11 HD MTX courses, 1 IT with MTX and 15 triple IT. MRD ≥ 1% at the end of induction was added as VHR criterium. All non-transplanted VHR pts received 1 IT MTX injection, 19 IT triple and 9 HD MTX courses. Several randomized questions were addressed in both trials of which most relevant for T-ALL pts: in study 58881 the comparison E.coli asparaginase (ASP) Medac versus (vs) “other ASP” (= Erwinia ASP or E.coli ASP Bayer); in trial 58951 1) the comparison dexamethasone (DEX 6 mg/m2/d) vs prednisolone (PRED 60 mg/m2/d) in induction and 2) conventional vs prolonged E.coli ASP for non-VHR pts.
303 and 296 T-ALL pts were included in trials 58881 and 58951 resp, representing 14.5% and 15.2% of all pts. Outcome results and type of events for the entire 58881 and 58951 cohorts and according to several subgroups are presented in the table. The 8-year isolated and overall CNS relapse incidences were 6.8% and 10.9% in study 58881, 5.3% and 8.5% in study 58951. The 8-year EFS, DFS and OS improved remarkably in study 58951. In the latter trial, outcome improvement was particularly seen in pts with initial WBC<100x10E9/L and in the good prephase responders (GPR) which had a significant better outcome than those with PPR. 58881 pts assigned to the “other ASP” arm had an inferior outcome. Concerning the DEX/PRED comparison in the 58951 T-ALL cohort, no advantage was seen for EFS (hazard ratio (HR) (99%CI): 1.26 (0.70;2.27)) or OS. There even was a trend towards worse EFS for pts with initial WBC>100x10E9/L and for pts with PPR treated in the DEX arm (HR (99%CI): 1.52 (0.63;3.64) and 1.47 (0.64;3.35)). Prolonged ASP treatment did not improve outcome of the whole T-ALL 58951 cohort.
Prophylactic and therapeutic RT can safely be omitted from frontline treatment of children with T-ALL. Adequate ASP therapy, intensified induction treatment and CNS directed therapy can result in a significant improvement of the outcome of at least 2/3rd of T-ALL pts, particularly those with initial WBC<100x10E9/L and GPR.5888158951Other ASPE.coli ASP MedacAllPREDDEXAllAll EFSN=94N=209N=303N=151N=145N=2968-yr %52.1%71.6%65.1%76.7%71.3%74.0%WBC<100N=53N=110N=163N=101N=87N=1888-yr %58.4%71.8%66.9%79.7%77.8%78.8%WBC>=100N=41N=99N=140N=50N=58N=1088-yr %43.9%71.2%63.0%70.5%61.6%65.6%GPRN=59N=126N=185N=101N=91N=1928-yr %57.6%76.8%70.3%81.6%80.7%81.2%PPRN=35N=82N=117N=48N=54N=1028-yr %42.9%64.6%57.5%67.6%55.6%61.4%All CRsN=89N=204N=293N=145N=141N=286DFS55.0%73.3%67.3%78.2%73.3%75.8%Isolated CNS relapse11.1%5.4%6.8%5.5%5.0%5.3%CNS relapse16.9%8.4%10.9%9.8%7.1%8.5%Non-CNS relapse20.3%14.4%16.5%10.5%15.3%12.9%Death in CR7.9%3.9%5.3%1.5%4.3%2.9%OSN=94N=209N=303N=151N=145N=2968-yr %59.6%77.7%71.9%84.1%74.2%78.2%
No relevant conflicts of interest to declare.
Abstract 134
Asparaginase (ASP) is an essential component in combination chemotherapy for childhood ALL and NHL, as indicated by several randomized trials. However, the optimal number of ASP ...administrations is still unknown. We conducted a randomized phase III trial comparing conventional E.coli ASP regimen (short-ASP, 12 doses) with prolonged E.coli ASP therapy (long-ASP, 24 doses).
The European Organization for Research and Treatment of Cancer Children’s Leukemia Group (EORTC-CLG) phase III 58951 trial was open to de novo ALL or NHL patients (pts) < 18 y. This BFM-based study addressed 2 main randomized questions. The first evaluated the value of dexamethasone (DEX, 6mg/m2/d) vs prednisolone (PRED, 60mg/m2/d) in induction for all pts. In the second question all non-very high risk (VHR) pts were randomized for either short- or long-ASP. All patients had to receive 8×10000 U/m2 in induction. In the short-ASP arm pts had to receive 4×10000 U/m2 in late intensification; pts in the long-ASP arm had to receive 8×5000 U/m2E.coli ASP injections in consolidation and 8 (4×10000 U/m2 + 4×5000U/m2) in late intensification. Patients with grade ≥2 allergy to E.coli ASP had to be switched to equivalent doses of Erwinia or PEG ASP. Central randomization was stratified by the 1st randomized arm, risk group (VLR, AR1, AR2) and center. The primary endpoint of the study was disease-free survival (DFS), secondary endpoints were overall survival (OS) and toxicity. Intention-to-treat analysis was performed.
Between December 1998 and August 2008, 2038 patients were randomized for the 1st question and 1552 pts, ALL (n=1481) and NHL (n=71), were randomly assigned to receive long-ASP (n=775) or short-ASP (n=777). At a median follow-up of 7 years there were 97 vs 112 events in the long- vs short-ASP group (see table). The 8-year DFS rate was 87.0% in the long-ASP and 84.2% in short-ASP group (hazard ratio (HR) = 0.87, 95% CI 0.66–1.14, 2-sided logrank p=0.30). The 8-year OS rate was comparable in both treatment arms: 92.6% in the long-ASP group and 91.3% in the short-ASP group (HR = 0.89, 95% CI 0.61–1.29, 2-sided log rank p=0.53). Similar treatment differences were observed in each risk group, in randomized arm (PRED vs DEX), and B- and T-lineage ALL pts.
The incidence of grade 3–4 infection was higher in the long- vs short-ASP group during consolidation (25.2% vs 14.5%) and late intensification (22.6% vs 15.9%). This difference was more pronounced in pts who were randomly assigned to DEX (see table). In the long- vs short-ASP group grade 2–4 allergy to ASP was 22.5% vs 0.3% in consolidation and 10.3% vs 21.5% in late intensification. During the whole treatment period, the incidence of grade 2–4 allergy was 30.5% in the long-ASP arm and 21.7% in the short-ASP arm. In the long- vs short-ASP arm approximately 67% vs 95% pts received at least the total number of E.coli or equivalent ASP administrations as planned according to the treatment arm.
At long follow-up (median= 7 yrs) prolonged E.coli asparaginase therapy in consolidation and late intensification for VLR and AR pts did not improve significantly the outcome. Intensive ASP treatment did increase infection rate in consolidation and late intensification and resulted in more grade 2–4 allergic reactions. In the future, we aim to improve outcome rates by the use of PEG ASP and monitoring of asparaginase activity and antibody formation.EndpointLong-ASP (N=775)Short-ASP (N=777)DFS8-yr % (SE%)87.0% (1.3%)84.2% (1.4%)DFS status, NCCR678665Events97112NoCR02Relapse87103CNS relapse1011Non-CNS7792Death CR107OS8-yr % (SE%)92.6% (1.0%)91.3% (1.2%)Grade 3-4 InfectionConsolidation25.2%14.5%DEX/PRED27.3%/23.1%11.6%/17.3%Late intensification22.6%15.9%DEX/PRED23.9%/21.4%13.9%/18%Grade 2-4 allergy22.5%0.3%Consolidation10.3%21.5%Late intensification30.5%21.7Total23.0%0.5%Switch ASP10.8%24.8%ConsolidationLate intensification
No relevant conflicts of interest to declare.
Abstract 565▪FN2▪This icon denotes a clinically relevant abstract
Hyperdiploidy >50 chromosomes (HD>50) has long been recognized as favorable group in childhood B-ALL but there is still debate on the ...factors contributing to heterogeneity of prognosis observed within this entity. Better outcome has been reported for patients (pts) presenting DNA index (DI) >1.16 (Blood 1985;10:213), ≥56 chromosomes (Leukemia 1996;10:213), triple trisomies (TT) +4,+10,+17, double trisomies +4,+10 (Leukemia 2005;19:734) and trisomy 18 (Blood 2003;102:2756) but there is no consensus between the reports and these factors are differently applied in current protocols.
We studied these factors in the pts with HD>50 enrolled in the ALL 58951 trial, BFM related. HD>50 were detected by cytogenetics (karyotype/FISH) and/or flow cytometry (DI). In order to analyze the outcome of HD>50 itself, pts with recurrent unfavorable translocations t(9;22), 11q23/MLL+, with t(1;19), t(12;21) or Down Syndrome were excluded, as well as near-triploidies/duplication of hypodiploidies 30–39 chromosomes.
Pts were stratified into 4 risk groups (VLR/AR1/AR2/VHR) according to DI, Modal Number of Chromosomes (MNC), WBC, CNS/gonadal involvement, presence of VHR features (unfavorable translocations, poor response to prephase, residual disease (MRD) at the end of induction >10-2). VLR was defined as: DI>1.16 or MNC>50, WBC<10×109/L, no CNS/gonadal involvement and no VHR features.
Overall Results: Out of 1651 B-lineage pts registered in the 58951 study over a 10-year period (1998-2008), a total of 541 pts had HD>50. Median age was 3 years and median WBC was 5.6×109/L. After prephase, 3% (N=17) were poor responders; initial risk group distribution into VLR/AR1/AR2/VHR was 45%/47%/5%/3%. After induction, 540 (99.8%) reached complete remission, 455 of whom had an MRD evaluation: MRD<10-3 (N=416;91%), MRD <10-2 and >10-3 (N=26;6%) or MRD≥10-2 (N=13;2%). At median follow-up of 6 years, 48 pts (9%) relapsed, 22 pts (4%) died and 6 (1%) died without relapse. The 6-yr EFS was 89% (SE=1.5%).
MNC was assessed in 446 pts (82%) with successful karyotypes, MNC ranged from 51 to 66 chromosomes and peaked at 55–56; 87 pts had 51 to 53 chromosomes (HD51-53), 258 pts had 54 to 57 (HD54-57) and 101 pts had ≥58 chromosomes (HD≥58). In these 3 groups, VLR regimen was given to 16%, 50% and 64% respectively. Structural abnormalities were detected in 46% of pts and associated with all MNCs. DI, assessed in 460 pts was <1.16 (N=146), 1.16 to 1.24 (N=240) and ≥1.24 (N=104). There was no strict overlap between the HD≥58 and DI ≥1.24 groups.
Prognostic Factors: The only significant prognostic factors for EFS were MNC, DI, TT, DT and MRD.
EFS was clearly improved (p<0.001) when the MNC was ≥58 chromosomes: 6-yr EFS was 80% (HD51-53) vs 89% (HD54-57) vs 99% (HD’58). In the last group, all pts had a good response to prephase, only 3 pts had detectable MRD after induction (1pt: MRD>10-2 and 2 pts: MRD≥10-3) and only 1 pt (MNC=58) relapsed. No specific profile of chromosome gains was identified in HD ≥58 since all chromosomes contributed to tri/tetrasomies, except chromosome 1. Likewise, the higher the DI the better the outcome (p=0.01): 6-yr EFS was 83% (DI<1.16) vs 90% (DI≥ 1.16 and <1.24) vs 95% (DI ≥1.24).
TT were detected in 168 out of 468 pts, and DT in 242 out of 466 pts. There was no overlap with HD ≥58 since TT and DT were distributed from 52 to 66 chromosomes. One third of TT and of DT had MNC≥58. TT and DT were also of prognostic importance for outcome: the 6-yr EFS rate was 96% (TT) vs 86% (non-TT) (p=0.005) and 94% (DT) vs 84% (non-DT) (p=0.003). A hierarchical variable based on presence of HD≥58, TT or DT showed that HD ≥58 (N=101; 6-yr EFS: 99%) group had a better outcome than TT without HD≥58 (N=115; 6-yr EFS: 93%) and DT without HD≥58 and without +17 (N=55; 6-yr EFS: 84%) groups (p=0.04). We can infer from our results that the good outcome observed for all of the TT and DT was partially due to their association with HD ’58. Consequently, the best indicator for excellent outcome was a high MNC (≥58 chromosomes).
From our 58951 trial, we can assume that among children with B-ALL and HD>50, those with ≥58 chromosomes, stand every chance of being cured. Our results stress the necessity of karyotype for identifying them since this is the only way to assess MNC. They can also be detected (less accurately) by DI (DI ≥1.24). Therefore, both MNC and DI should be used for stratifying pts in the very low risk groups.
No relevant conflicts of interest to declare.
The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric ...Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) patients with chemotherapy-responsive disease.
From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M.
Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively. Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (n=8), mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3).
The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.
Abstract 909▪▪This icon denotes an abstract that is clinically relevant.
T-ALL accounts for approximately 15% of childhood ALL. Despite major improvement of treatments, relapses still occur with ...dramatic prognosis. Efforts made in the past decade to understand T-ALL oncogenesis led to the identification of a number of oncogenes deregulated by genomic abnormalities, including TAL1, HOX11/TLX1, HOX11L2/TLX3, CALM-AF10, NUP214-ABL1, and MYB, some of them determining subtypes with distinct biological profiles. However, in EORTC trials, using BFM-derived protocols, these various genetic lesions have no prognostic impact, with the exception of a trend toward a favourable outcome for SIL-TAL1 fusion or HOX11 over expression (Cavé et al. 2004). Thus, risk-stratification remained based on early response to chemotherapy, as assessed by poor response to the (corticosteroid) prephase (PPR) and, in addition (58951 trial), on a high level (>10-2) of minimal residual disease (MRD) at completion of induction therapy. Hyperactivation of the NOTCH pathway by mutations of NOTCH1 or FBXW7 has been recently demonstrated in T-ALL. We investigated whether NOTCH1 and/or FBXW7 status could help to improve risk-stratification in T-ALL. We screened NOTCH1 and FBXW7 mutations by direct sequencing in 133 children with T-ALL enrolled in EORTC-CLG trials 58881 and 58951. Activating NOTCH1 mutations were found in 75 (56%) patients. Inactivating FBXW7 mutations were found in 20 (14%) patients, mostly in association with NOTCH1 mutations. Overall, 78 (59%) patients were considered NOTCH+ (NOTCH1 and/or FBXW7 mutated) whereas 55 (41%) were NOTCH- (NOTCH1 and FBXW7 wild type). NOTCH+ patients were distributed through all genetic subgroups. No significant relationships between NOTCH status and sex, age, WBC count, CNS or mediastinal involvement were observed. However, NOTCH+ had more often a cortical immunophenotype (53% vs 28%; p=0.02). NOTCH+ patients had a better early response to chemotherapy vs NOTCH- patients: lower PPR rate (20% vs 42%; p=0.02), and a lower incidence of high MRD level (13% (6/45) versus 30% (9/30); p=0.14). This led to less frequent switch to a very high risk (VHR) protocol for NOTCH+ versus NOTCH- patients (29% vs 49%, p=0.05). After a median follow-up of 4.6 years, 3 patients did not reach CR, 25 relapsed, 1 died in CR and 84 remained alive in CR; a total of 18 patients died. The outcome of NOTCH+ patients was similar to that of NOTCH- patients. The 5-yr EFS were 74% and 69% (p=0.8), respectively, and the 5-yr overall survival were 82% and 80% (p=0.7), respectively. However, prognostic importance of NOTCH status differed according to early response to treatment. In patients with a PPR, the NOTCH+ patients had a worse outcome than NOTCH- patients (5-yr EFS was 44% vs 58%; HR=1.54, p=0.43), whereas in non-PPR subgroup a reverse trend was observed (5-yr EFS was 83% vs 76%; HR=0.94, p=0.91). Similarly, in patients with high MRD levels the outcome was worse in NOTCH+ vs NOTCH- patients (5-yr EFS was 0% vs 47%, HR=11.7, p=0.03) whereas in MRD- patients the trend was reversed (5-yr EFS was 79% vs 71%, HR=0.88, p=0.83). Thus, although NOTCH1+ patients responded earlier and better to chemotherapy as compared to NOTCH1- patients, they did not show, overall, a better EFS. This was due to the poor outcome of NOTCH+ patients who had VHR features. In the German BFM trials, NOTCH1 mutations were also associated with lower rate of “poor response” to chemotherapy but this translated into a favourable outcome (see the ASH 2009 abstract of Kox et al.) NOTCH1- patients had a similar outcome in EORTC and BFM studies (5-yr EFS: 69% vs 74%) whereas NOTCH1+ patients had a lower 5-yr EFS in EORTC than in BFM studies (74% vs 87%). Noteworthy, in the EORTC trials the rate of isolated CNS relapses was quite high in NOTCH1+ patients (7.8%=6/77) as compared to NOTCH- patients (1.9%=1/53). Recently it was shown that NOTCH1 positively controls the expression of the chemokine receptor CCR7, an adhesion signal required for targeting T-ALL cells into the CNS (Buonamici et al. 2009). This may explain the higher propensity of NOTCH+ ALL to relapse in CNS. Although this is not the only difference in treatment between EORTC and BFM, the use of high dose methotrexate and intrathecal chemotherapy only, with omission of cranial irradiation prophylaxis in EORTC protocols, might have led to a suboptimal prevention of CNS relapses in NOTCH+ T-ALL, resulting in a lower EFS in EORTC trials as compared with German BFM in this group of patients.
No relevant conflicts of interest to declare.
The properties of saliva led us to hypothesize that the salivary flow increase induced by gum chewing might protect the oral mucosa from lesions due to cancer chemotherapy. We conducted a multicenter ...randomized trial to evaluate the efficacy of chewing gum in preventing oral mucositis in 145 children receiving chemotherapy regimens expected to induce WHO grade 3-4 oral mucositis in at least 30% of patients. Patients were allocated at random to standard oral care with or without 5 gum pieces per day. No overall reduction in severe oral mucositis occurred in the gum arm (51%) compared with the standard arm (44%). VIDE, COPADM, and multidrug intensive chemotherapy caused severe oral mucositis in 75% of patients in both arms. In patients receiving less toxic regimens, a decrease in WHO grade 1-4 oral mucositis was noted in the gum arm compared with the standard arm (49% vs. 72%, P=0.03). In the multivariate analysis, the risk of oral mucositis was related only to the type of chemotherapy regimen, suggesting that further strategies for preventing oral mucositis could be mainly based on these criteria.
