Childhood Non-Hodgkin Lymphoma Treatment (PDQ®) 1/8 –Health Professional Version - National Cancer Institute

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version - National Cancer Institute

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version

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ON THIS PAGE

• General Information About Childhood Non-Hodgkin Lymphoma (NHL)
• Histopathologic and Molecular Classification of Childhood NHL
• Stage Information for Childhood NHL
• Treatment Option Overview for Childhood NHL
• Aggressive Mature B-cell NHL
• Lymphoblastic Lymphoma
• Anaplastic Large Cell Lymphoma
• Lymphoproliferative Disease Associated With Immunodeficiency in Children
• Rare NHL Occurring in Children
• Changes to This Summary (08/06/2019)
• About This PDQ Summary

General Information About Childhood Non-Hodgkin Lymphoma (NHL)

In This Section

• Incidence
• Risk Factors
• Anatomy
• Diagnostic Evaluation
• Prognosis and Prognostic Factors for Childhood NHL
  • Response to therapy
  • Stage at diagnosis/minimal disseminated disease (MDD)
  • Sites of disease at diagnosis
  • Age
  • Immune response to tumor

Dramatic improvements in survival have been achieved for children and adolescents with cancer.[1] Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[1] For NHL, the 5-year survival rate increased over the same time period, from 45% to 87% in children younger than 15 years and from 48% to 82% for adolescents aged 15 to 19 years.[1] Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

On the basis of immunophenotype, molecular biology, and clinical response to treatment, the vast majority of NHL cases occurring in childhood and adolescence fall into three categories:

1. Aggressive mature B-cell NHL (Burkitt and Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and primary mediastinal B-cell lymphoma).
2. Lymphoblastic lymphoma.
3. Anaplastic large cell lymphoma.

Other rare types of pediatric NHL include the following:

• Pediatric-type follicular lymphoma.
• Marginal zone lymphoma (including mucosa-associated lymphoid tissue [MALT] lymphoma).
• Primary central nervous system (CNS) lymphoma.
• Peripheral T-cell lymphoma.
• Cutaneous T-cell lymphoma.

Incidence

Lymphoma (Hodgkin lymphoma and NHL) is the third most common childhood malignancy, and NHL accounts for approximately 7% of cancers in children younger than 20 years in high-income countries.[2,3]

The following factors affect the incidence of NHL in children and adolescents:[2]

• Geographic location: In the United States, about 800 new cases of NHL are diagnosed each year. The incidence is approximately ten cases per 1 million people per year.
  In sub-Saharan Africa, the incidence of Epstein-Barr virus (EBV)–induced Burkitt lymphoma/leukemia is tenfold to twentyfold higher than the incidence in the United States, resulting in a much higher incidence of NHL.[4]
• Race: The incidence of NHL is higher in whites than in African Americans, and Burkitt lymphoma/leukemia is more common in non-Hispanic whites (3.2 cases/million person-years) than in Hispanic whites (2.0 cases/million person-years).[5]
• Age: Although there is no sharp age peak, childhood NHL occurs most commonly in the second decade of life, and occurs infrequently in children younger than 3 years.[2] NHL in infants is very rare (1% in Berlin-Frankfurt-Münster [BFM] trials from 1986 to 2002).[6] The incidence of NHL is increasing overall because of a slight increase in the incidence for those aged 15 to 19 years; however, the incidence of NHL in children younger than 15 years has remained constant over the past several decades.[2]
• Sex: Childhood NHL is more common in males than in females, with the exception of primary mediastinal B-cell lymphoma, in which the incidence is almost the same in males and females.[2,7] A review of Surveillance, Epidemiology, and End Results (SEER) data revealed that 2.5 cases per 1 million person-years of Burkitt lymphoma/leukemia were diagnosed in the United States between 1992 and 2008, with more cases in males than in females (3.9:1.1).[2] The incidence of diffuse large B-cell lymphoma increases with age in both males and females. The incidence of lymphoblastic lymphoma remains relatively constant across ages for both males and females.[2]

The incidence and age distribution of histologic types of NHL according to sex is described in Table 1.

Table 1. Incidence and Age Distribution of Specific Types of NHLa

	Incidence of NHL per Million Person-Years
	Males				Females
ALCL = anaplastic large cell lymphoma; DLBCL = diffuse large B-cell lymphoma; NHL = non-Hodgkin lymphoma.
aAdapted from Percy et al.[2]
bIndolent and aggressive histologies (more commonly seen in adult patients) are mostly found in older adolescents.
Age (y)	<5	5–9	10–14	15–19	<5	5–9	10–14	15–19
Burkitt	3.2	6	6.1	2.8	0.8	1.1	0.8	1.2
Lymphoblastic	1.6	2.2	2.8	2.2	0.9	1.0	0.7	0.9
DLBCL	0.5	1.2	2.5	6.1	0.6	0.7	1.4	4.9
Other (mostly ALCL)	2.3	3.3	4.3	7.8b	1.5	1.6	2.8	3.4b

Risk Factors

Relatively little data on the epidemiology of childhood NHL have been published. However, known risk factors include the following:

• EBV: EBV is associated with most cases of NHL seen in the immunodeficient population.[2] Almost all Burkitt lymphoma/leukemia is associated with EBV in endemic Africa; however, approximately 15% of cases in Europe and the United States will have EBV detectable in the tumor tissue.[8]
• Immunodeficiency: Immunodeficiency, both congenital and acquired (HIV or posttransplant immunodeficiency), increases the risk of NHL.[2,3] U.S. transplant and cancer registries show that posttransplant lymphoproliferative disease (PTLD) accounts for about 3% of all pediatric NHL diagnoses; and that 65% of PTLDs are diffuse large B-cell lymphoma histology, and 9% are Burkitt histology.[9]
• DNA repair syndromes: The incidence of NHL is increased in patients with DNA repair syndromes, including ataxia-telangiectasia, Nijmegen breakage syndrome, and constitutional mismatch repair deficiency.[10]
• Previous neoplasm: NHL presenting as a subsequent neoplasm is rare in pediatrics. A retrospective review of the German Childhood Cancer Registry identified 2,968 children who were newly diagnosed with cancer, 11 of whom (0.3%) were later diagnosed with NHL as a subsequent neoplasm before age 19 years.[11] In this small cohort, outcomes were similar to those for patients with de novo NHL who were treated with standard therapy.[11]

Anatomy

Unlike adults with NHL who present most often with nodal disease, children typically have extranodal disease involving the mediastinum, abdomen, and/or head and neck, as well as the bone marrow or CNS.[3] For example, in developed countries, Burkitt lymphoma/leukemia occurs in the abdomen in approximately 60% of cases, with 15% to 20% of cases arising in the head and neck.[12,13] This high incidence of extranodal disease substantiates the use of the Murphy staging system for pediatric NHL, instead of the Ann Arbor staging system.

Diagnostic Evaluation

The following tests and procedures are used to diagnose childhood NHL:

• History and physical exam.
• Pathologic examination of tumor cells.
  • Immunophenotyping by immunohistochemistry and/or flow cytometry.
  • Cytogenetics and/or fluorescence in situ hybridization (FISH).
• Bone marrow biopsy and aspiration.
• Lumbar puncture.
• Total-body imaging (e.g., computed tomography scan, positron emission tomography, and magnetic resonance imaging).
• Measurement of serum electrolytes, lactate dehydrogenase (LDH), uric acid, blood urea nitrogen (BUN), and creatinine.
• Liver function tests.

Prognosis and Prognostic Factors for Childhood NHL

In high-income countries and with current treatments, more than 80% of children and adolescents with NHL will survive at least 5 years, although outcome depends on a number of factors, including clinical stage and histology.[14]

Prognostic factors for childhood NHL include the following:

• Response to therapy.
• Stage at diagnosis/presence of minimal disseminated disease (MDD).
• Sites of disease at diagnosis.
• Age.
• Immune response to tumor.

Response to therapy

Response to therapy in pediatric lymphoma is one of the most important prognostic markers. Regardless of histology, pediatric NHL that is refractory to first-line therapy has a very poor prognosis.[15-17]

• Burkitt lymphoma/leukemia: One of the most important predictive factors is response to the initial prophase treatment; poor responders (i.e., <20% resolution of disease) have an event-free survival (EFS) of 30%.[18,19]
• Lymphoblastic lymphoma: The presence of a residual mediastinal mass at day 33 or at the end of induction was not found to be associated with a decreased survival in the BFM 90-95 studies, but all patients with less than 70% reduction at the end of induction had therapy intensified.[20]

International pediatric NHL response criteria have been proposed but require prospective evaluation. The clinical utility of these new criteria are under investigation.[21]

Unlike in acute leukemia, in pediatric NHL, the prognostic value of minimal residual disease (MRD) after therapy is initiated remains uncertain and requires further investigation.

• Burkitt lymphoma/leukemia: One study suggests an inferior outcome for patients with Burkitt lymphoma/leukemia who had detectable MRD after induction chemotherapy.[22] However, other studies found that detectable MRD at the end of induction was not prognostic, possibly because of the low number of relapses in patients with disease detected in blood or bone marrow at diagnosis.[23,24]
• T-cell lymphoblastic lymphoma: In a small study, one of ten patients had measurable MRD at the end of induction, and this was the only patient who relapsed.[25]
• Anaplastic large cell lymphoma: A retrospective analysis of a collaborative European study showed that after induction, MRD-negative patients had a relapse risk of approximately 20% and an overall survival (OS) rate of approximately 90%. By contrast, MRD-positive patients had a relapse risk of 81% and an OS rate of 65% (P < .001). The presence of MRD is significantly associated with uncommon histologic subtypes containing small cell and/or lymphohistiocytic components.[26][Level of evidence: 2A]

Stage at diagnosis/minimal disseminated disease (MDD)

In general, patients with low-stage disease (i.e., single extra-abdominal/extrathoracic tumor or totally resected intra-abdominal tumor) have an excellent prognosis (a 5-year survival rate of approximately 90%), regardless of histology.[18,20,27-30] Apart from this finding, the outcome by clinical stage, if the correct therapy is given, does not differ significantly.

A surrogate for tumor burden (i.e., elevated levels of LDH) has been shown to be prognostic in many studies.[18,28,31,32]

MDD is generally defined as submicroscopic bone marrow involvement that is present at diagnosis. MDD is generally detected by sensitive methods such as flow cytometry or reverse transcription–polymerase chain reaction (RT-PCR). Patients with morphologically involved bone marrow with more than 5% lymphoma cells are considered to have stage IV disease.

• Burkitt lymphoma/leukemia: The role of MDD remains to be defined. One study suggests MDD is predictive of outcome,[33,34] while another study does not.[23]
• T-cell lymphoblastic lymphoma: A Children's Oncology Group (COG) study demonstrated a 2-year EFS of 91% for patients who had an MDD level by flow cytometry lower than 1%, compared with 68% if the MDD level exceeded 1%, and 52% if the MDD was 5% and higher.[35] This has been confirmed by others.[36]
• Anaplastic large cell lymphoma: In a retrospective subset analysis of children with anaplastic large cell lymphoma, MDD detected by RT-PCR for the NPM-ALK gene transcript could be found in 57% of patients at diagnosis and correlated with clinical stage.[37] The presence of MDD was associated with a 46% cumulative incidence of relapse, compared with a 15% cumulative incidence of relapse in patients with no bone marrow involvement.[37] Patients with MDD who achieved MRD-negative status before their second course of therapy had an intermediate EFS (69%) compared with MDD-negative patients (82%) and patients with both MDD and MRD-positive status (19%).[37]
  The presence of MDD is significantly associated with uncommon histologic subtypes containing small cell and/or lymphohistiocytic components.[37]

Sites of disease at diagnosis

In pediatric NHL, some sites of disease appear to have prognostic value, including the following:

• Bone marrow and CNS: Bone marrow and CNS involvement at diagnosis usually requires more intensive therapy.[19,20,38] Although these intensive therapies produce improved outcomes, patients who present with CNS disease continue to have the worst outcomes.[19,20,38,39] Patients with mature B-cell lymphoma/leukemia with CNS disease at presentation have a 3-year EFS of around 70%, while those with bone marrow involvement alone have a 3-year EFS of 90%.[19,28,32] The combination of CNS involvement and bone marrow disease appears to impact outcome the most.[19]
• Mediastinum: Mediastinal involvement in children and adolescents with nonlymphoblastic NHL results in an inferior outcome.[14,18,28,32] In children and young adults with primary mediastinal B-cell lymphoma, series have reported a 3-year EFS of 50% to 70%.[28,31,32,40] However, studies using the dose-adjusted (DA)–EPOCH protocol (etoposide, prednisone, vincristine, and doxorubicin) with rituximab have reported an EFS higher than 80%.[41,42]
• Viscera: For anaplastic large cell lymphoma, a retrospective study by the European Intergroup for Childhood NHL (EICNHL) found a high-risk group of patients defined by involvement of mediastinum, skin, or viscera.[43] In a subsequent study analysis from EICNHL utilizing biologic risk factors, the clinical risk features were not found to be significant.[44] In the CCG-5941 (NCT00002590) study for anaplastic large cell lymphoma patients, these clinical risk factors could not be confirmed; only bone marrow involvement predicted inferior progression-free survival (PFS).[45][Level of evidence: 2A]
• Bone: Although previously thought to be a poor prognostic site, patients with NHL arising in bone have an excellent prognosis, regardless of histology.[46,47]
• Testicle: Testicular involvement does not affect prognosis.[20,27,48]
• Head and Neck: For mature B-cell NHL, OS is comparable to that observed for patients with primary tumors at other sites. Head and neck primary tumors are associated with higher rates of disseminated and CNS disease and lower rates of LDH levels that were more than twofold higher than the upper limit of normal. Childhood NHL of the head and neck site was not associated with inferior OS.[13]
• Skin: The prognostic implication of skin involvement is limited to anaplastic large cell lymphoma and depends on whether the disease is localized to skin. ALK-negative, skin-limited anaplastic large cell lymphoma appears to have an excellent prognosis. However, studies from EICNHL and the COG have demonstrated that skin involvement in systemic anaplastic large cell lymphoma does not appear to have positive prognostic value.[44,45]

Age

NHL in infants is rare (1% in BFM trials from 1986 to 2002).[6] In this retrospective review, the outcome for infants was inferior compared with the outcome for older patients with NHL.[6]

Adolescents have been reported to have outcomes inferior to those of younger children.[12,14,49,50] This adverse effect of age appears to be most pronounced for adolescents with diffuse large B-cell lymphoma, and to a lesser degree T-cell lymphoblastic lymphoma, compared with younger children with these diagnoses.[14,50] On the other hand, for patients with Burkitt and Burkitt-like lymphoma/leukemia who were treated on the FAB/LMB-96 (COG-C5961) clinical trial, adolescent age (≥15 years) was not an independent risk factor for inferior outcome.[32]

Immune response to tumor

An immune response against the ALK protein (i.e., anti-ALK antibody titer) appeared to correlate with lower clinical stage and predicted relapse risk but not OS.[51] A study by the EICNHL, which combined the level of anti-ALK antibody with MDD, demonstrated that patients with newly diagnosed anaplastic large cell lymphoma could be stratified into three risk groups, with a PFS of 28% (low risk), 68% (intermediate risk), and 93% (all remaining patients) (P < .0001).[44]

References

1. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014. [PUBMED Abstract]
2. Percy CL, Smith MA, Linet M, et al.: Lymphomas and reticuloendothelial neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649, pp 35-50. Also available online. Last accessed April 12, 2019.
3. Sandlund JT, Downing JR, Crist WM: Non-Hodgkin's lymphoma in childhood. N Engl J Med 334 (19): 1238-48, 1996. [PUBMED Abstract]
4. Aka P, Kawira E, Masalu N, et al.: Incidence and trends in Burkitt lymphoma in northern Tanzania from 2000 to 2009. Pediatr Blood Cancer 59 (7): 1234-8, 2012. [PUBMED Abstract]
5. Mbulaiteye SM, Biggar RJ, Bhatia K, et al.: Sporadic childhood Burkitt lymphoma incidence in the United States during 1992-2005. Pediatr Blood Cancer 53 (3): 366-70, 2009. [PUBMED Abstract]
6. Mann G, Attarbaschi A, Burkhardt B, et al.: Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma. Br J Haematol 139 (3): 443-9, 2007. [PUBMED Abstract]
7. Swerdlow SH, Campo E, Pileri SA, et al.: The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127 (20): 2375-90, 2016. [PUBMED Abstract]
8. Gutiérrez MI, Bhatia K, Barriga F, et al.: Molecular epidemiology of Burkitt's lymphoma from South America: differences in breakpoint location and Epstein-Barr virus association from tumors in other world regions. Blood 79 (12): 3261-6, 1992. [PUBMED Abstract]
9. Yanik EL, Shiels MS, Smith JM, et al.: Contribution of solid organ transplant recipients to the pediatric non-hodgkin lymphoma burden in the United States. Cancer 123 (23): 4663-4671, 2017. [PUBMED Abstract]
10. Attarbaschi A, Carraro E, Abla O, et al.: Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents. Haematologica 101 (12): 1581-1591, 2016. [PUBMED Abstract]
11. Landmann E, Oschlies I, Zimmermann M, et al.: Secondary non-Hodgkin lymphoma (NHL) in children and adolescents after childhood cancer other than NHL. Br J Haematol 143 (3): 387-94, 2008. [PUBMED Abstract]
12. Patte C, Auperin A, Michon J, et al.: The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 97 (11): 3370-9, 2001. [PUBMED Abstract]
13. Lervat C, Auperin A, Patte C, et al.: Head and neck presentations of B-NHL and B-AL in children/adolescents: experience of the LMB89 study. Pediatr Blood Cancer 61 (3): 473-8, 2014. [PUBMED Abstract]
14. Burkhardt B, Zimmermann M, Oschlies I, et al.: The impact of age and gender on biology, clinical features and treatment outcome of non-Hodgkin lymphoma in childhood and adolescence. Br J Haematol 131 (1): 39-49, 2005. [PUBMED Abstract]
15. Attarbaschi A, Dworzak M, Steiner M, et al.: Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group. Pediatr Blood Cancer 44 (1): 70-6, 2005. [PUBMED Abstract]
16. Kobrinsky NL, Sposto R, Shah NR, et al.: Outcomes of treatment of children and adolescents with recurrent non-Hodgkin's lymphoma and Hodgkin's disease with dexamethasone, etoposide, cisplatin, cytarabine, and l-asparaginase, maintenance chemotherapy, and transplantation: Children's Cancer Group Study CCG-5912. J Clin Oncol 19 (9): 2390-6, 2001. [PUBMED Abstract]
17. Harris RE, Termuhlen AM, Smith LM, et al.: Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Children's Oncology Group study A5962. Biol Blood Marrow Transplant 17 (2): 249-58, 2011. [PUBMED Abstract]
18. Patte C, Auperin A, Gerrard M, et al.: Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell non-Hodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients. Blood 109 (7): 2773-80, 2007. [PUBMED Abstract]
19. 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. [PUBMED Abstract]
20. Reiter A, Schrappe M, Ludwig WD, et al.: Intensive ALL-type therapy without local radiotherapy provides a 90% event-free survival for children with T-cell lymphoblastic lymphoma: a BFM group report. Blood 95 (2): 416-21, 2000. [PUBMED Abstract]
21. Sandlund JT, Guillerman RP, Perkins SL, et al.: International Pediatric Non-Hodgkin Lymphoma Response Criteria. J Clin Oncol 33 (18): 2106-11, 2015. [PUBMED Abstract]
22. Mussolin L, Pillon M, Conter V, et al.: Prognostic role of minimal residual disease in mature B-cell acute lymphoblastic leukemia of childhood. J Clin Oncol 25 (33): 5254-61, 2007. [PUBMED Abstract]
23. Shiramizu B, Goldman S, Kusao I, et al.: Minimal disease assessment in the treatment of children and adolescents with intermediate-risk (Stage III/IV) B-cell non-Hodgkin lymphoma: a children's oncology group report. Br J Haematol 153 (6): 758-63, 2011. [PUBMED Abstract]
24. Shiramizu B, Goldman S, Smith L, et al.: Impact of persistent minimal residual disease post-consolidation therapy in children and adolescents with advanced Burkitt leukaemia: a Children's Oncology Group Pilot Study Report. Br J Haematol 170 (3): 367-71, 2015. [PUBMED Abstract]
25. Stark B, Avigad S, Luria D, et al.: Bone marrow minimal disseminated disease (MDD) and minimal residual disease (MRD) in childhood T-cell lymphoblastic lymphoma stage III, detected by flow cytometry (FC) and real-time quantitative polymerase chain reaction (RQ-PCR). Pediatr Blood Cancer 52 (1): 20-5, 2009. [PUBMED Abstract]
26. Damm-Welk C, Mussolin L, Zimmermann M, et al.: Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. Blood 123 (3): 334-7, 2014. [PUBMED Abstract]
27. 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. [PUBMED Abstract]
28. Woessmann W, Seidemann K, Mann G, et al.: The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95. Blood 105 (3): 948-58, 2005. [PUBMED Abstract]
29. Gerrard M, Cairo MS, Weston C, et al.: Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Br J Haematol 141 (6): 840-7, 2008. [PUBMED Abstract]
30. 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. [PUBMED Abstract]
31. Reiter A, Schrappe M, Tiemann M, et al.: Improved treatment results in childhood B-cell neoplasms with tailored intensification of therapy: A report of the Berlin-Frankfurt-Münster Group Trial NHL-BFM 90. Blood 94 (10): 3294-306, 1999. [PUBMED Abstract]
32. Cairo MS, Sposto R, Gerrard M, et al.: Advanced stage, increased lactate dehydrogenase, and primary site, but not adolescent age (≥ 15 years), are associated with an increased risk of treatment failure in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB LMB 96 study. J Clin Oncol 30 (4): 387-93, 2012. [PUBMED Abstract]
33. Mussolin L, Pillon M, d'Amore ES, et al.: Minimal disseminated disease in high-risk Burkitt's lymphoma identifies patients with different prognosis. J Clin Oncol 29 (13): 1779-84, 2011. [PUBMED Abstract]
34. Pillon M, Mussolin L, Carraro E, et al.: Detection of prognostic factors in children and adolescents with Burkitt and Diffuse Large B-Cell Lymphoma treated with the AIEOP LNH-97 protocol. Br J Haematol 175 (3): 467-475, 2016. [PUBMED Abstract]
35. Coustan-Smith E, Sandlund JT, Perkins SL, et al.: Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the children's oncology group. J Clin Oncol 27 (21): 3533-9, 2009. [PUBMED Abstract]
36. Mussolin L, Buldini B, Lovisa F, et al.: Detection and role of minimal disseminated disease in children with lymphoblastic lymphoma: The AIEOP experience. Pediatr Blood Cancer 62 (11): 1906-13, 2015. [PUBMED Abstract]
37. Damm-Welk C, Busch K, Burkhardt B, et al.: Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma. Blood 110 (2): 670-7, 2007. [PUBMED Abstract]
38. Salzburg J, Burkhardt B, Zimmermann M, et al.: Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin-Frankfurt-Munster Group Report. J Clin Oncol 25 (25): 3915-22, 2007. [PUBMED Abstract]
39. Williams D, Mori T, Reiter A, et al.: Central nervous system involvement in anaplastic large cell lymphoma in childhood: results from a multicentre European and Japanese study. Pediatr Blood Cancer 60 (10): E118-21, 2013. [PUBMED Abstract]
40. Gerrard M, Waxman IM, Sposto R, et al.: Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy. Blood 121 (2): 278-85, 2013. [PUBMED Abstract]
41. Dunleavy K, Pittaluga S, Maeda LS, et al.: Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med 368 (15): 1408-16, 2013. [PUBMED Abstract]
42. Giulino-Roth L, O'Donohue T, Chen Z, et al.: Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R. Br J Haematol 179 (5): 739-747, 2017. [PUBMED Abstract]
43. Le Deley MC, Reiter A, Williams D, et al.: Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. Blood 111 (3): 1560-6, 2008. [PUBMED Abstract]
44. Mussolin L, Damm-Welk C, Pillon M, et al.: Use of minimal disseminated disease and immunity to NPM-ALK antigen to stratify ALK-positive ALCL patients with different prognosis. Leukemia 27 (2): 416-22, 2013. [PUBMED Abstract]
45. Lowe EJ, Sposto R, Perkins SL, et al.: Intensive chemotherapy for systemic anaplastic large cell lymphoma in children and adolescents: final results of Children's Cancer Group Study 5941. Pediatr Blood Cancer 52 (3): 335-9, 2009. [PUBMED Abstract]
46. Lones MA, Perkins SL, Sposto R, et al.: Non-Hodgkin's lymphoma arising in bone in children and adolescents is associated with an excellent outcome: a Children's Cancer Group report. J Clin Oncol 20 (9): 2293-301, 2002. [PUBMED Abstract]
47. Zhao XF, Young KH, Frank D, et al.: Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases. Am J Clin Pathol 127 (1): 47-54, 2007. [PUBMED Abstract]
48. Dalle JH, Mechinaud F, Michon J, et al.: Testicular disease in childhood B-cell non-Hodgkin's lymphoma: the French Society of Pediatric Oncology experience. J Clin Oncol 19 (9): 2397-403, 2001. [PUBMED Abstract]
49. Cairo MS, Sposto R, Perkins SL, et al.: Burkitt's and Burkitt-like lymphoma in children and adolescents: a review of the Children's Cancer Group experience. Br J Haematol 120 (4): 660-70, 2003. [PUBMED Abstract]
50. Burkhardt B, Oschlies I, Klapper W, et al.: Non-Hodgkin's lymphoma in adolescents: experiences in 378 adolescent NHL patients treated according to pediatric NHL-BFM protocols. Leukemia 25 (1): 153-60, 2011. [PUBMED Abstract]
51. Ait-Tahar K, Damm-Welk C, Burkhardt B, et al.: Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk. Blood 115 (16): 3314-9, 2010. [PUBMED Abstract]