Pediatr Blood Cancer 2009;53:1130–1131

BRIEF REPORTSuccessful Treatment With Daclizumab of Refractory

Anaplastic Lymphoma

Vıtor Costa, MD,* Teresa Oliva, MD, and Lucılia Norton, MD

INTRODUCTION

Anaplastic large cell lymphoma (ALCL) is a relatively rare and

highly malignant form of non-Hodgkin lymphoma (NHL) which

accounts for 10–15% of these childhood lymphomas [1]. In contrast

to patients with other highly malignant NHL, ALCL often presents

with skin, bone, and lung involvement, as well as general symptoms;

central nervous system (CNS) and bone marrow are rarely involved

[2,3]. Current treatment protocols for ALCL in children consist of

a short course of high intensity polychemotherapy [4]. In our

department patients are currently treated according to ALCL 99

protocol. Depending on disease stage, cure rates ranging from 75%

to almost 100% have been achieved with this protocol [5]. However,

patients who do not achieve remission, or develop an early relapse

even after intensive therapy, carry a dismal prognosis [5]. Even with

high dose chemotherapy, followed by autologous hematopoietic

stem-cell transplantation (HSCT), second continuous complete

remissions (CCR) are achieved in only 55% of patients [5].

The monoclonal antibody daclizumab (anti-CD25) targets the

interleukin 2 (IL-2) receptor subunit alpha, and blocks the inter-

action of this cytokine with its growth factor. The rationale under-

lying this therapy in lymphoid malignancies is the higher expression

rate of IL-2R in abnormal leukemia/lymphoma T cells, as opposed

to normal T cells. These insights concerning the IL-2/IL-2R system

encouraged the utilization of daclizumab antibody therapy in

selected patients with leukemia/lymphoma [6].

Here, we report a successful treatment of a child with refractory

ALCL using daclizumab.

CASE REPORT

An 8-year-old female presented with high fever and cervical

lymph node enlargement. The biopsy disclosed ALCL of T-cell

type: CD3þ, CD30þ, and ALK negative. The tumor involved the

cervical and supraclavicular nodes and was classified as stage II

ALCL (Murphy classification) [7]. The patient was treated

according to the ALCL 99 protocol-standard risk group [8]. Partial

response was observed, which lead to therapy intensification, as

indicated for the high-risk group and a complete remission (CR) was

obtained. Four weeks later she developed a first relapse with high

fever, cervical lymphadenopathy and abdominal skin lesions. A new

biopsy confirmed ALCL relapse, with similar immunophenotype

and clinical features. Treatment was initiated according to the

ALCL-Relapse 2004 protocol, but disease progression was noted

2 months later. A second remission was achieved following

two cycles of: vincristine, prednisolone, high-dose methotrexate,

cyclophosphamide, daunorubicin, and intrathecal therapy with

prednisolone and methotrexate (COPADM). She received high-

dose chemotherapy with carmustine, etoposide, cytarabine, and

melphalan, followed by autologous HSCT. Three weeks later, high

fever and fatigue recurred. Chest-abdominal computed tomography

(CT) and fluorodeoxiglucose positron emission tomography (FDG-

PET) revealed supraclavicular, mediastinal, axillary, and abdominal

lymphadenopathies. Mediastinal fine needle aspiration confirmed

a third relapse of her T-type ALCL. At this point, a curative

therapeutic option was not devised. The patient was then offered

treatment with the anti-CD25 monoclonal antibody daclizumab.

She received 4 weekly infusions at a dose of 30 mg (1 mg/kg of body

weight). CR was rapidly achieved after the first two infusions.

Chest-CT and FDG-PET scans were normal. Treatment was

extremely well tolerated, and no adverse events were noted.

In addition, she also received 80 courses of weekly vimblastine

(6 mg/m2), as maintenance therapy. The patient remains in clinical

remission 45 months after starting daclizumab infusions.

DISCUSSION

We present a case of a refractory ALCL good response after

treatment with daclizumab, and the first reported in childhood. The

therapeutic success of daclizumab in this chemorefractory disease

was outstanding. It must be noted that this patient’s tumor was

ALK negative what is unusual in children. The previous report of

refractory ALCL remission in a 37-year-old woman treated with this

drug [9] prompted its use in this case. Unlike very intensive salvage

chemotherapy regimens [10], daclizumab therapy has demonstrated

excellent efficacy in this case, within a very short period of time and,

without any apparent immediate or long-term adverse effects. We

Anaplastic large cell lymphoma (ALCL) is a relatively rare andhighly malignant form of non-Hodgkin lymphoma (NHL) whichaccounts for 10–15% of these childhood lymphomas. Currenttreatment protocols for ALCL in children consist of a short course ofhigh intensity polychemotherapy. Here we describe an 8-year-oldfemale with relapsed ALCL who achieved good response with anti-

CD25 monoclonal antibody daclizumab. Daclizumab appears tooffer a safe treatment option, but further research needs to beconducted in order to define its role in children with ALCL who donot respond to intensive chemotherapy. Pediatr Blood Cancer2009;53:1130–1131. � 2009 Wiley-Liss, Inc.

Key words: ALCL; daclizumab; relapse

� 2009 Wiley-Liss, Inc.DOI 10.1002/pbc.22177Published online 13 July 2009 in Wiley InterScience(www.interscience.wiley.com)

——————Departamento de Pediatria, Instituto Portugues de Oncologia Francisco

Gentil, Porto, Portugal

*Correspondence to: Vıtor Costa, Rua Dr. Antonio Bernardino de

Almeida, Instituto Portugues de Oncologia Francisco Gentil, 4200-072

Porto, Portugal. E-mail: vitormendescosta@hotmail.com

Received 12 February 2009; Accepted 1 June 2009

conclude that daclizumab may represent a valid and promising new

therapeutic option in childhood relapsed/refractory ALCL.

REFERENCES

1. Alessandri AJ, Pritchard SL, Shultz KR, et al. A population-based

study of pediatric anaplastic large cell lymphoma. Cancer 2002;94:

1830–1835.

2. Stein H, Foss HD, Durkop H, et al. CD30þ anaplastic large cell

lymphoma: A review of its histopathologic, genetic, and clinical

features. Blood 2000;96:3681–3695.

3. Sandlund JT, Downing JR, Crist WM. Non-hodgkin’s lymphomain

childhood. N Engl J Med 1996;334:1238–1248.

4. Reiter A, Scharappe M, Parwaresch R, et al. Non-hodgkin’s

lymphomas of childhood and adolescence: Results of a treatment

stratified for biologic subtypes and stage—A report of the berlin-

frankfurt-munster group. J Clin Oncol 1995;13:359–372.

5. Seidmann K, Tiemann M, Schrappe M, et al. Short-pulse b-non-

hodgkin lymphoma-type chemotherapy is efficacious treatment for

pediatric anaplastic large cell: A report of the berlin-frankfurt-

munster group trial nhl-bfm 90. Blood 2001;97:3699–3706.

6. Waldmann TA. Daclizumab (anti-Tac, Zenapax) in the treatment of

leukemia/lymphoma. Oncogene 2007;26:3699–3703.

7. Murphy SB. Classification, staging and results of treatment of

childhood non-hodgkin’s lymphoma: Dissimilarities in adults.

Semin Oncol 1980;7:332–339.

8. Brugieres L, Le Deley MC, Pacquement H, et al. CD30 positive

anaplastic large cell lymphoma in children: Analysis of 82 patients

enrolled in two consecutive studies of the French Society of

Pediatric Oncology. Blood 1998;92:3591.

9. Linden O. Remission of a refractory, anaplastic lerge cell

lymphoma after treatment with daclizumab. N Engl J Med 2004;

351:1466–1467.

10. Stockklausner C, Behnisch W, Mechtersheimer G, et al. Long-term

remission of children with relapsed and secondary anaplastic large

cell non-hodgkin lymphoma (ALCL) following treatment with

pulsed dexamethasone and low dose etopside. Pediatr Blood

Cancer 2008;50:126–129.

Pediatr Blood Cancer DOI 10.1002/pbc

Refractory Anaplastic Lymphoma 1131