Pediatric Transplants

Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children's Oncology Group


Mucositis can be a serious complication of hematopoietic SCT (HSCT). A previous phase II trial in 32 children undergoing HSCT reported a beneficial effect of the homeopathic remedy Traumeel S. The Children's Oncology Group sought to replicate the results in a multi-institutional trial. The study was an international multi-center, double-blind, randomized trial comparing Traumeel with placebo in patients aged 3–25 years undergoing myeloablative HSCT. Traumeel/placebo was started on Day −1 as a five-time daily mouth rinse. Efficacy of the treatment was assessed using the modified Walsh scale for mucositis, scored daily from Day −1 to 20 days after HCST. The main outcome was the sum of Walsh scale scores (area-under-the-curve (AUC)) over this period. Other outcomes included narcotic use, days of total parenteral feeding, days of nasogastric feeding and adverse events. In 181 evaluable patients, there was no statistical difference in mucositis (AUC) in the Traumeel group (76.7) compared with placebo (67.3) (P=0.13). There was a trend towards less narcotic usage in the Traumeel patients. No statistically beneficial effect from Traumeel was demonstrated for mucositis. We could not confirm that Traumeel is an effective treatment for mucositis in children undergoing HSCT.


Oral mucositis is a common and debilitating complication of chemotherapy, occurring in 52–80% of children treated with chemotherapy and 95% of patients undergoing SCT.1, 2, 3, 4 Mucositis evolves through a complex series of events involving the epithelium, extracellular matrix, connective tissue and a submucosal cellular infiltrate.1, 5, 6, 7 It is associated with pain and trouble swallowing, which can lead to dehydration and malnutrition. Narcotic analgesics and parenteral nutrition are frequent necessary supportive care measures. Systemic infection, extended hospital stay, decreased quality of life and increased risk of mortality are associated with severe mucositis.1, 2, 8, 9, 10 No available treatment has proven to reliably ameliorate mucositis.11 Thus, there is a need for alternative therapeutic approaches.

Up to one-half of the adult population in developed countries use some form of complementary and alternative medicine (CAM).12, 13, 14, 15This increasing trend is also apparent among cancer patients, ranging from 40–91%,16, 17, 18, 19 and from 31–91%20, 21, 22, 23, 24, 25 in pediatric cancer patients. In the latter, CAM is usually used as a supportive therapy.26 The few studies of pediatric hematopoietic SCT (HSCT) patients and CAM therapies published have been primarily examining mind/body or health promotion techniques27, 28, 29 rather than ingestible or parenteral agents.

Homeopathy is a popular system of CAM, founded by the German physician Samuel Hahneman in the early 1800s. It is based on treating disease using minute doses of a drug (called a ‘remedy’) that produces symptoms in healthy persons similar to those of the disease.30 ‘Classical’ homeopathy employs highly diluted individualized remedies, whereas ‘complex’ homeopathy uses combinations of dilute agents for specific clinical conditions. Traumeel is a complex homeopathic remedy sold over-the-counter for over 50 years primarily as an anti-inflammatory medication. It is traditionally used to treat a variety of conditions related to trauma and inflammation. It contains 14 medicinal plants and minerals in very low concentrations (Table 1).

Table 1 Composition of the homeopathic complex Traumeel S

In 2001, Oberbaum et al.31 published the results of a small, randomized, double-blind pilot study using Traumeel to treat mucositis in 32 children undergoing HSCT, showing Traumeel to be substantially superior to placebo in preventing or ameliorating mucositis. This was one of the first reported randomized controlled trials of a CAM intervention in children with cancer.

In 2005, the Committee of the American Institute of Medicine on the use of CAM recommended that the same principles and standards of evidence of treatment effectiveness apply to all treatments, whether currently labeled as conventional medicine or CAM.32 Following this recommendation, the CAM subcommittee of the Children's Oncology Group (COG) sought to replicate the Oberbaum study in a larger, multi-center, double-blind, randomized controlled trial. We report here on that trial.

Materials and methods


Eligible patients were 3–25 years old, undergoing myeloablative HSCT, allogeneic or autologous, for malignant and nonmalignant conditions. Patients entered the trial between April 2004 and December 2006 at 1 out of 28 COG member institutions and at 2 Israeli institutions. Each institution obtained institutional review board approval. Patients receiving a non-myeloablative HSCT, those taking glutamine or vancomycin oral paste, and any individuals allergic or sensitive to Echinacea (a component of Traumeel) were excluded. All the patients or their guardians gave signed informed consent. In all, 195 patients were enrolled.

Study medication

Traumeel S and a placebo identical in appearance and taste were provided free of charge by Heel (Baden-Baden, Germany) in sterile 2.2 mL glass ampoules. Traumeel S is manufactured in accordance with the European Union Guidelines on good manufacturing practice for medicinal products. It was prepared by serial dilution and agitation in saline according to the German Homeopathic Pharmacopoeia. Normal saline was used as placebo.

Study design

The study was an international multi-center, double-blind, placebo-controlled randomized trial conducted under the auspices of COG. Patients were assigned by block randomization to receive Traumeel or placebo in a 1:1 ratio, stratified by TBI (yes/no), allogeneic vs autologous transplant and COG vs Israeli institution.

Patients were registered in the COG Cancer Registry and identified throughout the study by the COG patient-identification number. Patients were enrolled in the study once all eligibility requirements had been met and not later than 4 days before transplant. The study medications were prepared by Heel and were identified by serial number only. The code was kept by the company and the COG statistician only and was not broken until completion of the trial. Patient assignment was communicated to McKesson Bioservices Corporation (Rockville, MD, USA) who dispensed the study drug or placebo in blinded fashion. Treatment began on the day before transplant, so that in all the cases, treatment began before the first symptoms of regimen-induced mucositis appeared. Treatment ended when patients met the completion criteria (see below) and not later than the twentieth day after transplant.

A pharmacist drew the contents of the blinded ampoules into an oral syringe. Patients were instructed to rinse the mouth vigorously with the study medication, retain it for thirty seconds and then swallow. This was repeated five times daily. Patients were instructed not to eat or drink for 30 min after each dose. Patients were permitted any type of analgesic for pain control. Narcotics could be taken orally, i.v. or by patch. The type and amount of narcotics were subsequently normalized to morphine equivalents according to a conversion table.33

Efficacy of the treatment was assessed using the three-grade modified Walsh scale for mucositis34 recorded daily from the day before transplant to the twentieth day thereafter. The simpler five-grade World Health Organization oral-toxicity scale35 was also recorded over the same period. Additionally recorded were: amount of narcotic equivalents used per day, number of days of total parenteral nutrition, number of days of nasogastric feeding, occurrences of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events v. 3.0 (CTCAE),36 mortality up to 30 days after termination of protocol therapy, veno-occlusive disease of the liver, acute GVHD and invasive infection within 100 days post transplant.

Study therapy was terminated when: (i) a Walsh score of 1 was recorded for two consecutive days following an episode of mucositis or (ii) a Walsh score of 1 from the day before transplant until the twelfth day after transplant or (iii) 20 days post transplant (22 days of drug) was reached with no occurrence of criteria (i) and (ii). Patients were removed from study therapy if the patient, parent or guardian refused further therapy, or if the physician determined that it was in the patient's interest to discontinue.

Statistical methods

The primary outcome for this trial was area-under-the-curve (AUC) of the Walsh score from the day before transplant to 20 days post transplant. For patients with complete follow-up data, this outcome was simply the sum of the total scores over the 22 days. The mean AUCs in the Traumeel and placebo groups were compared, and the probability of a patient on Traumeel having a lower AUC than a patient on placebo was estimated. Differences between the groups were tested using the Mann–Whitney test.37

The target sample size of 180 was based on a power of 90% to detect an effect significant at the 5% level, assuming a 0.65 probability that a Traumeel patient had a lower AUC than a placebo patient, and a 14% loss to follow-up.

Missing follow-up data were imputed by linear interpolation when 3 consecutive days or less were missing. Other missing scores were imputed randomly 10 times from scores of similar patients with complete data, and the method of multiple imputation38 was applied to the 10 full data sets so created.

The treatment groups were compared for balance on potential prognostic factors. Where substantial imbalance was seen, the comparison between the treatment groups was adjusted for the imbalance using a stratified Mann–Whitney test.

Maximum treatment duration was 22 days. For any day of treatment, a patient was defined as compliant if he/she took three or more of the five doses of study drug and noncompliant otherwise. A ‘noncompliant center’ was defined as one in which more than half of their patients were noncompliant on 70% of the treatment days. A secondary analysis compared AUCs in the Traumeel and placebo groups excluding the ‘noncompliant centers’. Another analysis was conducted according to individual patient compliance. Patients were classified as compliant on 100%, 65–99%, 30–65% or <30% of treatment days. The AUCs for Traumeel and placebo were then compared within each of these subgroups and also as a combined group excluding the fourth (least compliant) subgroup.

The Traumeel and placebo groups were also compared with respect to the World Health Organization score for oral mucositis, using the same approach as for the Walsh score, the amount of narcotics used and days of total parenteral nutrition, using Mann–Whitney tests, the proportions of patients requiring nasogastric feeding, of patients with serious adverse events (including veno-occlusive disease and GVHD), and of deaths up to 31 days after termination of protocol therapy, using the Chi-squared test.

Study monitoring was performed after 40, 80 and 120 evaluable patients were entered. Group differences in AUCs for the Walsh score were tested at two-sided significance levels 0.003, 0.004 and 0.0049, respectively. No significant differences were found on monitoring. The final analysis critical significance level was 0.047 to yield an overall 5% level. All the other outcomes were tested at the 5% level. Statistical analysis was conducted by COG statisticians (TZ and ZC).


A total of 195 patients entered the trial, of whom 190 met study eligibility. A flow diagram is presented in Figure 1. Five patients were ineligible to participate, one allocated to Traumeel and four allocated to placebo. Treatment groups were well balanced on all baseline variables except gender (Table 2).

Figure 1

Flow diagram.

Table 2 Baseline characteristics of the 190 eligible patients

The protocol required recording of the Walsh score on each of the 22 study days. Full data were obtained on 106 (56%) of the eligible patients. A further 35 (18%) had 4 missing scores, 24 (13%) between 5 and 10 missing scores and 25 (13%) had more than 11 scores missing, including 9 patients with no follow-up data. Among patients with full data, AUCs ranged from 0 to 238.5. The mean Walsh AUCs were similar in the two groups: 71.7 (s.e.=7.2) in the Traumeel group (56 patients) and 69.8 (s.e.=8.2) in the placebo group (50 patients). After imputation of missing values for the 181 patients with follow-up data, the mean AUCs were 76.7 (s.e.=5.5) for Traumeel and 67.3 (s.e.=6.3) for placebo, with an estimated probability of 0.43 (95% confidence interval: 0.34, 0.52) that a Traumeel patient would have a lower AUC than a placebo patient (z=−1.56, P=0.13) (Table 3).

Table 3 Area-under-curve (AUC) analysis of Walsh score by treatment group

Each patient was classified as being compliant with study medication on 100%, 65–99%, 30–65% or <30% of treatment days. There was no clear evidence of a beneficial effect of Traumeel in any category of compliance (Table 3). Stratification by gender strengthened the evidence against Traumeel having a beneficial effect (z=−2.23, P=0.026).

In all, 4 out of the 28 participating centers had >50% of their patients compliant on <than 30% of days. Excluding these four centers from the analysis, the estimated probability that a Traumeel patient would have a lower AUC than a placebo patient was 0.48 (z=−0.34, P=0.73).

The analysis of World Health Organization oral mucositis score was based on 171 patients (91 Traumeel and 80 placebo) with at least some follow-up data. After performing multiple imputation for missing values, the mean AUC scores were 21.6 (s.e.=2.07) for the placebo group and 24.4 (s.e.=1.80) for the Traumeel group, with an estimated probability of 0.45 that a Traumeel patient would have a lower AUC than a placebo patient (z=−1.18, P=0.24).

The average total doses (in equivalent mg/kg) of morphine were 17.7 (s.e.=3.1) for Traumeel and 28.5 (s.e.=10.9) for placebo (P=0.2). Although not statistically significant, there is clearly a trend towards less narcotic usage in the Traumeel-treated group. The average number of days of total parenteral nutrition were 15.3 (s.e.=0.56) for Traumeel and 15.2 (s.e.=0.65) for placebo (P=0.9). The number of patients with nasogastric feeding was 11 in the Traumeel group and 9 in the placebo group (P=0.75).

The mortality proportion to 31 days after termination of protocol therapy was 17% (17/98) for Traumeel vs 14% (13/92) for placebo (P=0.54). The proportion of patients with veno-occlusive disease of the liver was 6% (5/86) for Traumeel vs 5% (4/76) for placebo (P=0.88). The proportion with GVHD was 21% (18/86) for Traumeel vs 18% (14/76) for placebo (P=0.69). Finally, there was no statistically significant difference in the numbers of adverse events between the groups (Table 4).

Table 4 Adverse events by treatment group


Our multicenter trial did not confirm the results of the previous small single-center trial, which reported a beneficial effect of Traumeel on chemotherapy-induced mucositis compared with placebo. We did not observe any statistically significant advantage of the Traumeel group over the placebo group in mucositis scores, narcotic use, days of total parenteral nutrition or days of nasogastric feeding feeding. However, there was a trend towards less narcotic usage in the Traumeel-treated group of patients.

We cannot fully explain the negative results obtained in the current study compared with the study of Oberbaum et al.31 One possible difference in practice was that in the pilot study, a standardized oral care protocol was used (twice daily mouth washes with chloroheximide, oral amphoterin B and gentle tooth brushing), whereas in the current study, each center used its own oral care protocol. However, such a standard oral care protocol is quite thorough, as well as similar, and we would not expect this difference to influence the outcome of the trial. A second difference relates to administration of the study drug. Oral administration of Traumeel is not simple. The medicine is supplied in glass ampoules. Some skill is required to extract the full amount of liquid and deliver it entirely to the patient's mouth. Patients must also be encouraged to retain the liquid in their mouths for at least 30 s. In Oberbaum's trial, a single trained study nurse administered the study drug to all patients. In the current study, each center employed separate staff. As mentioned elsewhere, more than half of the centers entered five or fewer patients, limiting the experience that staff members could gain in this rather complex process. One further potential difference in practice should also be noted. The standard practice in most, but not all, North American hospitals is to use a 5-μm filtered straw needle to draw liquid medication from glass ampoules to reduce the number of glass particle contaminants. This was not the practice in the Israeli hospitals at the time of the pilot and is a potential confounding factor. We were initially concerned that the filtering process might change the bioactivity of the Traumeel formulation. In one of our labs, the filtered Traumeel was studied (JAI) and found to have higher silica content than unfiltered drug. The higher silica content, interestingly, was found to positively correlate with increased enzyme activity (39), in which case we might expect to have found the Traumeel group to show less mucositis, which was not the case.

During the study, we encountered a lack of compliance, both in patients taking the study drug or placebo and in obtaining the necessary daily mucositis scoring. Patients were required to take the drug five times daily, to swish for 30 s and swallow, and neither eat nor drink for the following 30 min. Administering five daily oral doses in the pediatric transplant setting was itself difficult. Patients with mucositis often have thickened oral secretions that are expectorated frequently; swallowing these secretions with the medication was difficult. In addition, the 30-min fasting after each dose proved especially challenging, causing a high rate of drug refusal. Pediatric SCT patients frequently feel too nauseated or uncomfortable to take an oral substance, but patients nevertheless found it difficult to be denied food and drink for 2.5 h/day. Refusal was similar in both treatment groups, suggesting that Traumeel per se was not the cause of the noncompliance.

Compliance problems may have been related to recruitment of small numbers of patients at some centers. In all, 16 out of the 28 institutions entered five or fewer patients. Perhaps researchers/health care providers at these centers were less experienced or successful in encouraging patients to persevere with the study protocol and perform the study-required oral evaluations. There was variation between institutions in who was completing the daily forms, ranging from the bedside nurses, research nurses, transplant coordinators or other health care providers. Those institutions that assigned one nurse to evaluation and reporting were generally the most successful. Weekend observations, in particular, were often missing. Future mucositis trials should encourage centers to assign a small number of trained observers to assess the patient's oral cavity. This will increase reliability and accuracy. In addition, contingencies need to be made for weekend evaluations.

It should be noted that this international and multicenter trial accrued patients over a short period of time, suggesting that parents or caretakers are interested in CAM and are willing for their children to participate in a CAM study that may improve treatment of a significant complication such as mucositis.

In view of the considerable level of missing data, we used the method of multiple imputation in our analysis, different from the usual ‘last observation carried forward’ approach.40 The latter method has been shown to introduce bias into the comparison and is no longer recommended.41 Multiple imputation both avoids bias in the treatment comparison and adjusts the confidence limits for the extra uncertainty due to the missing data. It should be noted that using this method, the 95% confidence limits for the Traumeel–placebo difference were still narrow enough to exclude a clinically useful benefit of Traumeel.

The result of this trial reinforces for CAM research, a common observation in conventional medicine, namely the importance of confirming observations in the multicenter randomized setting. We were not able to reproduce the earlier positive result, and Traumeel cannot be recommended for mucositis prevention.

Despite the results of this study, Traumeel may yet prove to be an interesting therapeutic agent for other conditions. Research has found anti-inflammatory biological activity, both in cell culture42 and in animal models,43 and we believe that further research on Traumeel may be warranted for other conditions in which an inflammatory process is involved. In addition, the high degree of acceptance of trialing a biological yet complementary agent by both the pediatric HSCT medical community and the patients/families is testimony to the recognition of the need to study those therapies that show promise in reducing the pain and suffering of transplant, whether ‘conventional’ or ‘complementary.’ Currently, the COG cancer control and HSCT disciplines are collaborating on several supportive care protocols. The transplant community is actively engaged in studying ways to reduce transplant morbidity and mortality. As we develop new trials, however, we must carefully consider how patient and caregiver compliance will affect the outcome of the intervention.


  1. 1

    Wilkes RW . Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol 1998; 25: 538–551.

    CAS  PubMed  Google Scholar 

  2. 2

    Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB et al. The burdens of cancer therapy: clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 2003; 98: 1531–1539.

    Article  Google Scholar 

  3. 3

    Bonnaure-Mallet M, Bunetel L, Tricot-Doleux S, Guérin J, Bergeron C, LeGall E . Oral complications during treatment of malignant diseases in childhood: effects of tooth brushing. Eur J Cancer 1998; 34: 1588–1591.

    CAS  Article  Google Scholar 

  4. 4

    Childers NK, Stinnett AE, Wheeler P, Wright JT, Castleberry RP, Dasanayake AP . Oral complications in children with cancer. Oral Surg Oral Med Oral Pathol 1993; 75: 41–47.

    CAS  Article  Google Scholar 

  5. 5

    Sonis ST . Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 1998; 34: 39–43.

    CAS  Article  Google Scholar 

  6. 6

    Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M et al. Perspectives on cancer therapy-induced mucosal injury. Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004; 100(Suppl 9): 1995–2025.

    Article  Google Scholar 

  7. 7

    Treister N, Sonis S . Mucositis: biology and management. Curr Opin Otolaryngol Head Neck Surg 2007; 15: 123–129.

    Article  Google Scholar 

  8. 8

    Sonis ST, Oster G, Fuchs H . Oral mucositis and the clinical economic outcomes of hematopoietic stem-cell transplantation. J Clin Oncol 2001; 19: 2201–2205.

    CAS  Article  Google Scholar 

  9. 9

    Ruescher TJ, Sodeifi A, Scrivani SJ, Kaban LB, Sonis ST . The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies. Cancer 1998; 82: 2275–2281.

    CAS  Article  Google Scholar 

  10. 10

    Rapoport AP, Miller Watelet LF, Linder T, Eberly S, Raubertas RF, Lipp J et al. Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants. J Clin Oncol 1999; 17: 2446–2453.

    CAS  Article  Google Scholar 

  11. 11

    Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 2004; 100 (Suppl 9): 2026–2046.

    Article  Google Scholar 

  12. 12

    Barnes PM, Bloom B, Nahin R . CDC National Health Statistics Report no. 12, Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. December 10, 2008..

  13. 13

    Harris P, Rees R . The prevalence of complementary and alternative medicine use among the general population: a systematic review of the literature. Complement Ther Med 2000; 8: 88–96.

    CAS  Article  Google Scholar 

  14. 14

    Thomas KJ, Nicholl JP, Coleman P . Use and expenditure on complementary medicine in England: a population based survey. Complement Ther Med 2001; 9: 2–11.

    CAS  Article  Google Scholar 

  15. 15

    Cheung CK, Wyman JF, Halcon LL . Use of complementary and alternative therapies in community-dwelling older adults. J Altern Complement Med 2007; 13: 997–1006.

    Article  Google Scholar 

  16. 16

    Molassiotis A, Browall M, Milovics L, Panteli V, Patiraki E, Fernandez-Ortega P . Complementary and alternative medicine use in patients with gynecological cancers in Europe. Int J Gynecol Cancer 2006; 16 (Suppl 1): 219–224.

    Article  Google Scholar 

  17. 17

    Hyodo I, Amano N, Eguchi K, Narabayashi M, Imanishi J, Hirai M et al. Nationwide survey on complementary and alternative medicine in cancer patients in Japan. J Clin Oncol 2005; 23: 2645–2654.

    Article  Google Scholar 

  18. 18

    Chrystal K, Allan S, Forgeson G, Isaacs R . The use of complementary/alternative medicine by cancer patients in a New Zealand regional cancer treatment centre. NZ Med J 2003; 116: U296.

    Google Scholar 

  19. 19

    Yates J, Mustian M, Morrow GR, Gillies LJ, Padmanaban D, Atkins JN et al. Prevalence of complementary and alternative medicine user in cancer patients during treatment. Support Care Cancer 2005; 13: 806–811.

    Article  Google Scholar 

  20. 20

    Kelly KM, Jacobson JS, Kennedy DD, Braudt SM, Mallick M, Weiner MA . Use of unconventional therapies by children with cancer at an urban medical center. J Pediatr Hematol Oncol 2000; 22: 412–416.

    CAS  Article  Google Scholar 

  21. 21

    Bold J, Leis A . Unconventional therapy use among children with cancer in Saskatchewan. J Pediatr Oncol Nurs 2001; 18: 16–25.

    CAS  Article  Google Scholar 

  22. 22

    Bishop F, Prescott P, Chan YK, Saville J, von Elm E, Lewith GT . Prevalence of complementary medicine use in pediatric cancer: a systematic review. Pediatrics 2010; 125: 768–776.

    Article  Google Scholar 

  23. 23

    Martel D, Bussières JF, Théorêt Y, Lebel D, Kish S, Moghrabi A et al. Use of alternative and complementary therapies in children with cancer. Pediatric Blood & Cancer 2005; 44: 660–668.

    Article  Google Scholar 

  24. 24

    Neuhouser ML, Patterson RE, Schwartz SM, Hedderson MM, Bowen DJ, Standish LJ . Use of alternative medicine by children with cancer in Washington State. Prev Med 2001; 33: 347–354.

    CAS  Article  Google Scholar 

  25. 25

    Gagnon EM, Recklitis CJ . Parents’ decision-making preferences in pediatric oncology: the relationship to health care involvement and complementary therapy use. Psycho-oncology 2003; 12: 442–452.

    Article  Google Scholar 

  26. 26

    Sencer SF, Kelly KM . Complementary and alternative therapies in pediatric oncology. Pediatr Clin North Am 2007; 54: 1043–1060.

    Article  Google Scholar 

  27. 27

    Phipps S, Barrera M, Vannatta K, Xiong X, Doyle JJ, Alderfer MA . Complementary therapies for children undergoing stem cell transplantation: report of a multisite trial. Cancer 2010; 116: 3924–3933.

    Article  Google Scholar 

  28. 28

    Phipps S . Reduction of distress associated with paediatric bone marrow transplant: complementary health promotion interventions. Pediatr Rehabil 2002; 5: 223–234.

    Article  Google Scholar 

  29. 29

    Sahler OHJ, Hunter BC, Liesveld JL . The effect of using music therapy with relaxation imagery in the management of patients undergoing bone marrow transplantation: a pilot feasibility study. Altern Ther Health Med 2003; 9: 70–74.

    PubMed  Google Scholar 

  30. 30 (accessed in November 2008).

  31. 31

    Oberbaum M, Yaniv I, Ben-Gal Y, Stein J, Ben-Zvi N, Freedman LS et al. A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced mucositis in children undergoing stem cell transplantation. Cancer 2001; 92: 684–690.

    CAS  Article  Google Scholar 

  32. 32

    Institute of Medicine. Complementary and Alternative Medicine in the United States. National Academy Press: Washington, DC, ISBN 0-309-09270-1 2005.

  33. 33

    Foley KM . The treatment of cancer pain. N Engl J Med 1985; 313: 84–95.

    CAS  Article  Google Scholar 

  34. 34

    Walsh LJ, Hill G, Seymour G, Roberts A . A scoring system for the quantitative evaluation of oral mucositis during bone marrow transplantation. Spec Care Dentist 1990; 10: 190–195.

    CAS  Article  Google Scholar 

  35. 35

    World Health Organization Handbook for reporting results of cancer treatment (offset publication 48) World Health Organization: Geneva, 1979: 15–22.

  36. 36 (accessed on 3 December 2008).

  37. 37

    Wilcoxon F . Individual comparisons by ranking methods. Biometrics 1945; 1: 80–83.

    Article  Google Scholar 

  38. 38

    Little RJA, Rubin DB . Statistical Analysis with Missing Data, 2nd edn. Wiley: Hoboken NJ, 2002.

    Google Scholar 

  39. 39

    Ives JA, Moffett JR, Arun P, Lam D, Todorov TI, Brothers AB, et al. Enzyme Stabilization by Glass-Derived Silicates in Glass-Exposed Aqueous Solutions. Homeopathy 2010; 99: 15–24.

    Article  Google Scholar 

  40. 40

    Shao J, Zhong B . Last observation carry-forward and last observation analysis. Stat Med 2003; 22: 2429–2441.

    Article  Google Scholar 

  41. 41

    Leon AC, Mallinckrodt CH, Chuang-Stein C, Archibald DG, Archer GE, Chartier K . Attrition in randomized clinical trials: methodological issues in psychopharmacology. Biol Psychiatry 2006; 59: 1001–1005.

    Article  Google Scholar 

  42. 42

    Porozov S, Cahalon L, Weiser M, Branski D, Lider O, Oberbaum M . Inhibition of IL-1beta and TNF-alpha secretion from resting and activated human immunocytes by the homeopathic medication Traumeel S. Clin Dev Immunol 2004; 11: 143–149.

    CAS  Article  Google Scholar 

  43. 43

    Lussignoli S, Bertani S, Metelmann H, Bellavite P, Conforti A . Effect of Traumeel S, a homeopathic formulation, on blood-induced inflammation in rats. Complement Ther Med 1999; 7: 225–230.

    CAS  Article  Google Scholar 

  44. 44

    Biologische Heilmittel Heel GmbH. Traumeel Product Monograph, 2nd ed. Baden-Baden: Germany, 2009.

Download references


This research is supported by the CCOP Grant U10 CA95861, Chair's Grant U10 CA98543 and the Statistics and Data Center Grant U10 CA98413 of the Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. The authors would also like to thank the CRA's and nurses of the participating COG institutions; they are the backbone of clinical research.

Author information



Corresponding author

Correspondence to S F Sencer.

Ethics declarations

Competing interests

Drs. Ives and Oberbaum previously had consulting relationships with Heel Incorporated, but currently none of the authors have any financial relationships with HEEL or any other conflicts.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sencer, S., Zhou, T., Freedman, L. et al. Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children's Oncology Group. Bone Marrow Transplant 47, 1409–1414 (2012).

Download citation


  • Traumeel S
  • mucositis
  • SCT

Further reading