Med Pediatr Oncol 2003;41:592–593

CORRESPONDENCETumor Lysis Syndrome and Neuroblastoma

To the Editor: Recently, Kushner et al. [1] published inMedical and Pediatric Oncology a Brief Report ‘‘Tumor lysissyndrome (TLS), neuroblastoma (NB), and correlation betweenserum lactate dehydrogenase (LDH) levels and MYCN-amplification,’’ reporting on a fatal case of fulminant TLSduring induction therapy in a child with high-risk stage 4 NB.

We completely agree with the opinion of these authors, onthe need for prophylaxis, with hyperhydration, urine alkalini-zation, and allopurinol administration. These are needed inorder to avoid severe complications due to metabolic alterationssecondary to induction chemotherapy (i.e., hyperuricemia,hyperphosphatemia, hypocalcemia, hyperkalemia, and acuterenal failure).

We wish to point out that in our experience with more than100 cases of NB observed in the last 15 years, we have neverhad a case of fatal tumor lysis syndrome in these patients.Perhaps this is because we have used uricase, a major uricolyticagent currently employed in Italy and many other Europeancountries [2,3]. We therefore suggest that uricase be adminis-tered when serum uric acid increases over 6.5 mg/dl in NBpatients with very high serum LDH levels, extensive diseaseand especially liver deposits. Uricase would be added tostandard urine alkalinization and allopurinol dosage.

Finally, the recent introduction of the novel drug rasburi-case, a promising recombinant form of uricase, promises to

be of major clinical benefit in most cases of severe TLS[4,5].

Giuseppe Maria Milano, MD, Luigi De Sio, MD,Raffaele Cozza, MD, and Alberto Donfrancesco, MD*

Department of Pediatric Onco-HematologyDivision of Oncology

IRCCS Bambino Gesu HospitalRome, Italy

REFERENCES

1. Kushner BH, LaQuaglia MP, Modak S, et al. Tumor lysis syndrome,

neuroblastoma, and correlation between serum lactate dehydrogenase levels

and MYCN-amplification. Med Pediatr Oncol 2003;41:80–82.

2. Drakos P, Bar-Ziv J, Catane R. Tumor lysis syndrome in non haematologic

malignancies. Report of a case and review of the literature. Am J Clin Oncol

1994;17:502–505.

3. Patte C, Sakiroglu O, Sommelet D. European experience in the treatment of

hyperuricemia. Semin Hematol 2001;38(4 Suppl 10): 9–12.

4. Pui CH, Jeha S, Irwin D, et al. Recombinant urate oxidase (rasburicase) in the

prevention and treatment of malignancy-associated hyperuricemia in

pediatric and adult patients: Results of a compassionate-use trial. Leukemia

2001;15:1505–1509.

5. Annemans L, Moeremans K, Lamotte M, et al. Pan-European multicentre

economic evaluation of recombinant urate oxidase (rasburicase) in prevention

and treatment of hyperuricaemia and tumour lysis syndrome in haematolo-

gical cancer patients. Support Care Cancer 2003;11:249–257.

Importance of Informed Consent in Offering to Return Research Resultsto Research Participants

To the Editor: We applaud the efforts by Schultz et al. [1] toexamine the impact of returning research results to researchparticipants as a means of acknowledging the responsibility ofresearchers to demonstrate respect for persons[2]. As theauthors point out, one of the limitations of their study was theunder-representation of participants who had received radio-therapy as part of their treatment. It is these participants whohave the greatest potential for adverse outcomes as aconsequence of receiving the findings of their study, whichexamined the risk for second malignancies in retinoblastomasurvivors. Neither this study nor a similar study of return of

research results following a clinical trial published by Partridgeet al. [3] examined the wants of individual participants beforeproviding or offering to provide them with results.

——————*Correspondence to: Alberto Donfrancesco, MD, IRCCS Bambino Gesu

Hospital, p.za S. Onofrio 4, 00165 Rome, Italy.

E-mail: donfranc@opbg.net

Received 24 June 2003; Accepted 26 June 2003DOI 10.1002/mpo.10428

——————Re: Schulz CJ et al. Impact on survivors of retinoblastoma when informed of

study results on risk of second cancers. Med Pediatr Oncol 2003;41(1):36–43.

*Correspondence to: Conrad V. Fernandez, IWK Health Centre, Box 3070, 5850

University Avenue, Halifax, Nova Scotia, Canada B3J 3G9.

E-mail: conrad.fernandez@iwk.nshealth.ca

Received 22 July 2003; Accepted 22 July 2003

� 2003 Wiley-Liss, Inc.DOI 10.1002/mpo.10435

We believe that the principle of respect for persons shouldinclude a process of informed consent before providing resultsback to participants [4]. As the receipt of results have potentialsignificant consequences for the individual in long-term followup, such as impact upon insurability and long-term distress andworry about the risk of second malignancy, we as researchershave a duty to inform participants of the risks and benefits ofreceiving research results.

We also believe that results should not be offered without aneffective mechanism to provide immediate support. While themajority of participants indicated that they were satisfied withthe letter, a substantial minority suffered fear, anxiety, anger, andguilt. It would seem more appropriate to offer results withanticipated adverse effects in a form of oral communication,rather than by written note that may arrive to a setting wherelittle support exists. Oral communication is certainly morelabor intensive and costly. We nonetheless believe that thisshould be at least offered to participants before dissemination ofresults to help avoid some of the serious consequences describedabove and to provide a more immediate response to those indistress.

We agree that much work needs to be done in this area toexplore appropriate means of returning results. This study is anexcellent starting point but it will be important to address theneeds of participants who are at highest risk of adverseoutcomes. In the interim, we have published detailed recom-mendations for the return of research data including discussionof issues of timing, detail and dissemination of results [4].

Conrad V. Fernandez, MD, FRCPC*Division of Pediatric Hematology/Oncology

Department of PediatricsIWK Health Centre

Dalhousie UniversityHalifax, Nova Scotia, Canada

Eric Kodish, MD

Department of Pediatric Hematology/OncologyRainbow Babies and Children’s Hospital

Cleveland, Ohio

Charles Weijer, MD, PhD

Department of BioethicsDalhousie University

Halifax, Nova Scotia, Canada

REFERENCES

1. Schulz CJ, Riddle MP, Valdimirsdottir HB, et al. Impact on survivors of

retinoblastoma when informed of study results on risk of second cancers. Med

Pediatr Oncol 2003;41:36–43.

2. Partridge AH, Winer EP. Informing clinical trial participants about study

results. JAMA 2002;288:363–365.

3. Partridge AH, Burstein HJ, Gelman RS, et al. Do patients participating in

clinical trials want to know study results? J Natl Cancer Inst 2003;95:491–

492.

4. Fernandez C, Kodish E, Weijer C. Informing study participants of research

results: An ethical imperative. IRB: Ethics & Hum Res 2003;25:12–19.

Kaposiform Hemangioendothelioma and Therapy With Interferon-a

To the Editor: We read with interest the article recentlypublished by Walker et al. [1], but a few points deserve furtherelaboration:

� In the article, Walker et al. described an infant sufferingfrom a large hemangiomatous lesion of the right lower limb,but biopsy was apparently not performed prior to startingtreatment to confirm the diagnosis of kaposiform heman-gioendothelioma (HE).

� Pretreatment bFGF and VEGF levels, which are highlycorrelated with outcome, were not assessed at diagnosis.

� Medical therapy with high dose oral steroids was admini-stered for only 1 week at full doses, which is usually con-sidered inadequate to obtain a response.

� Interferon alpha (IFNa) therapy was also administered forless than 10 days, which is unlikely to elicit any measurableclinical response.

� Oral steroids and subcutaneous IFN were used simul-taneously with the possibility of severe antagonistic effects.

� In our experience with hemangiomatous disease and kaposi-form HE, we successfully treated children and infantsaffected with the diseases employing IFNa alone [2]. We

think that amputation and/or mutilating surgery should bereserved as a last resort only after having exploited allavailable medical or conservative therapeutic options.

Giovanni Deb, MD*Division of Pediatric Oncology

Ospedale Bambino GesuIRCCS, Piazza S. Onofrio

4, 00165 Rome, Italy

REFERENCES

1. Walker GM, Abu-Rajab R, MacLennan A, et al. Kasabach-Merritt syndrome

in a neonate caused by a kaposiform haemangioendothelioma. Med Pediatr

Oncol 2002;38:424–427.

2. Deb G, Donfrancesco A, Ilari I, et al. Hemangioendothelioma: Successful

therapy with Interferon-a. A Study in Association With the Italian Pediatric

Haematology/Oncology Society (AIEOP). Med Pediatr Oncol 2002;38:118–

119.

*Correspondence to: Giovanni Deb, MD, Division of Pediatric Oncology,

Ospedale Bambino Gesu, IRCCS, Piazza S.Onofrio, 4, 00165 Rome, Italy.

E-mail: deb@opbg.net

Received 13 January 2003; Accepted 23 April 2003

� 2003 Wiley-Liss, Inc.DOI 10.1002/mpo.10399

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