Treatment Option Overview
Many of the improvements in childhood cancer survival have been made using
combinations of known and/or new agents that have attempted to improve the
best available, accepted therapy. Clinical trials in pediatrics are designed
to compare potentially better therapy with therapy that is currently accepted
as standard. This comparison may be done in a randomized study of two treatment
arms or by evaluating a single new treatment and comparing the results with
those previously obtained with standard therapy.
All children with non-Hodgkin lymphoma (NHL) should be considered for entry
into a clinical trial. Treatment planning by a multidisciplinary team of
cancer specialists with experience treating tumors of childhood is strongly
recommended to determine, coordinate, and implement treatment to achieve
optimal survival. Children with NHL should be referred for treatment by a
multidisciplinary team of pediatric oncologists at an institution with
experience in treating pediatric cancers. Information about ongoing clinical
trials is available from the NCI Web site.
NHL in children is generally considered to be widely disseminated from the
outset, even when apparently localized; as a result, combination chemotherapy
is recommended for most patients.[1] There are two potentially life-threatening
clinical situations that are often seen in children with NHL: (1) superior vena
cava syndrome (or mediastinal tumor with airway obstruction), most often seen
in lymphoblastic lymphoma; and (2) tumor lysis syndrome, most often seen in lymphoblastic and Burkitt or Burkitt-like NHL. These emergent situations should be anticipated in
children with NHL and addressed immediately.
Patients with large mediastinal masses are at risk of cardiac or respiratory
arrest during general anesthesia or heavy sedation.[2] Due to the risks of
general anesthesia or heavy sedation, a careful physiologic and radiographic
evaluation of the patient should be carried out and the least invasive
procedure should be used to establish the diagnosis of lymphoma.[3,4] Bone
marrow aspirate and biopsy should always be performed early in the work up of
these patients. If a pleural effusion is present, a cytologic diagnosis is
frequently possible using thoracentesis. In those children who present with
peripheral adenopathy, a lymph node biopsy under local anesthesia and in an
upright position may be possible.[5] In situations in which the above
diagnostic procedures are not fruitful, consideration of a computed tomography–guided core
needle biopsy should be contemplated. This procedure can frequently be carried
out using light sedation and local anesthesia before proceeding to more
invasive procedures. Mediastinoscopy, anterior mediastinotomy, or thoracoscopy
are the procedures of choice when other diagnostic modalities fail to establish
the diagnosis. A formal thoracotomy is rarely if ever indicated for the
diagnosis or treatment of childhood lymphoma. Occasionally it will not be
possible to perform a diagnostic operative procedure because of the risk of
general anesthesia or heavy sedation. In these situations, preoperative
treatment with steroids or localized radiation therapy should be considered.
Since preoperative treatment may affect the ability to obtain an accurate
tissue diagnosis, a diagnostic biopsy should be obtained as soon as the risk of
general anesthesia or heavy sedation is thought to be alleviated.
Tumor lysis syndrome results from rapid breakdown of malignant cells resulting
in a number of metabolic abnormalities, most notably hyperuricemia,
hyperkalemia, and hyperphosphatemia. Hyperhydration and allopurinol or
rasburicase (urate oxidase) are essential components of therapy in all but
patients with the most limited disease.[6-8] An initial prephase consisting of low-dose
cyclophosphamide and vincristine does not obviate the need for
allopurinol or rasburicase and hydration. Gastrointestinal bleeding, obstruction, and
(rarely) perforation may occur. Hyperuricemia and tumor lysis syndrome,
particularly when associated with ureteral obstruction, frequently result in
life-threatening complications. Patients with NHL should be managed only in
institutions having pediatric tertiary care facilities.
Certain pediatric NHL clinical trials are based on immunophenotype and/or histopathology. Children with limited disease have an excellent
prognosis when treated with chemotherapy.
As opposed to the treatment of adults with NHL, the use of radiation therapy is limited in children with NHL. Early studies demonstrated that the routine use of radiation had no benefit for localized NHL.[9] It has been demonstrated that prophylactic central nervous system (CNS) radiation can be omitted in lymphoblastic lymphoma.[10] It has also been demonstrated that CNS radiation can be eliminated for patients with anaplastic large cell lymphoma and B-cell NHL, even for patients who present with CNS disease.[11,12] Further data to support the limited use of radiation in pediatric NHL comes from the Childhood Cancer Survivor Study.[13] This analysis demonstrated that radiation was a significant risk factor for secondary malignancy and death in long-term survivors.
(Refer to the PDQ summary on Primary CNS Lymphoma Treatment for more information on
treatment options for nonacquired immunodeficiency syndrome–related primary central nervous system lymphoma.)
References
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Sandlund JT, Downing JR, Crist WM: Non-Hodgkin's lymphoma in childhood. N Engl J Med 334 (19): 1238-48, 1996.
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Azizkhan RG, Dudgeon DL, Buck JR, et al.: Life-threatening airway obstruction as a complication to the management of mediastinal masses in children. J Pediatr Surg 20 (6): 816-22, 1985.
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King DR, Patrick LE, Ginn-Pease ME, et al.: Pulmonary function is compromised in children with mediastinal lymphoma. J Pediatr Surg 32 (2): 294-9; discussion 299-300, 1997.
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Shamberger RC, Holzman RS, Griscom NT, et al.: Prospective evaluation by computed tomography and pulmonary function tests of children with mediastinal masses. Surgery 118 (3): 468-71, 1995.
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Prakash UB, Abel MD, Hubmayr RD: Mediastinal mass and tracheal obstruction during general anesthesia. Mayo Clin Proc 63 (10): 1004-11, 1988.
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Pui CH, Mahmoud HH, Wiley JM, et al.: Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients With leukemia or lymphoma. J Clin Oncol 19 (3): 697-704, 2001.
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Goldman SC, Holcenberg JS, Finklestein JZ, et al.: A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis. Blood 97 (10): 2998-3003, 2001.
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Link MP, Shuster JJ, Donaldson SS, et al.: Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med 337 (18): 1259-66, 1997.
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Burkhardt B, Woessmann W, Zimmermann M, et al.: Impact of cranial radiotherapy on central nervous system prophylaxis in children and adolescents with central nervous system-negative stage III or IV lymphoblastic lymphoma. J Clin Oncol 24 (3): 491-9, 2006.
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Seidemann K, Tiemann M, Schrappe M, et al.: Short-pulse B-non-Hodgkin lymphoma-type chemotherapy is efficacious treatment for pediatric anaplastic large cell lymphoma: a report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 97 (12): 3699-706, 2001.
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Cairo MS, Gerrard M, Sposto R, et al.: Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents. Blood 109 (7): 2736-43, 2007.
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Bluhm EC, Ronckers C, Hayashi RJ, et al.: Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood 111 (8): 4014-21, 2008.
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