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. Author manuscript; available in PMC: 2013 Mar 1.
Published in final edited form as: Pediatr Blood Cancer. 2011 Oct 28;58(3):334–343. doi: 10.1002/pbc.23385

Table IV.

Evolution of Therapy for Non-Hodgkin Lymphoma

Treatment
Modality		 Decade Historic Treatment
Modalities Used in
Contemporary Therapy
1960 1970 1980 1990 Post-2000
Chemotherapy/Agents

  • Non-protocol or as per ALL regimens

  • Antimetabolites (methotrexate, mercaptopurine)

  • corticosteroids

  • Vincristine

  • Cyclophosphamide

  • Anthracyclines

  • Asparaginase

  • NHL specific protocols/regimens

    • LSA2L2 (ALL)

    • COMP

    • CHOP + 6MP + MTX(NHL 75)

 Histology-and immunophenotype-directed therapy Agents below are all still commonly used for NHL, but specific combinations vary based on histology.

  • Cyclophosphamide

  • Doxorubicin

  • Vincristine

  • Prednisone

  • 6MP

  • Methotrexate

  • Ara-C

  • Asparaginase

  • Etoposide

  • Ifosfamide
Burkitt:
CHOP
HDMTX
Ara-C
Etoposide

  • Introduction of ifosfamide in to BFM regimens

 Burkitt:

  • Intensification of CTX and MTX (LMB-89)

  • Decreased intensity for Group B(LMB-89)

 Burkitt:

  • Intensive CTX-based with HDMTX/Ara-C
Lymphoblastic:

  • ALL-based treatment

 Lymphoblastic:

  • Intensified ALL regimen with prophylactic cranial RT (BFM90)

 Lymphoblastic:

  • Intensive ALL based therapy
Large cell:

  • CHOP/APO in U.S.

  • Immunophenotype-based (B-vs T-cell)in Europe

 Large cell:

  • B-cell (as per Burkitt)

  • ALCL (as per Burkitt or CHOP/APO)

 Large cell:

  • Immunophenotype-directed therapy (B-vs T-cell)

  • Duration of therapy varies by histological subtype:

    Burkitt/DLBCL: 3 to 8 months

    Lymphoblastic: 2 to 3 years

    ALCL: 4 to 12 months
Radiation Therapy Varied Varied; NHL75 randomized RT for advanced stage patients

  • CNS prophylaxis with cranial RT for lymphoblastic

  • Elimination of IFRT in limited stage NHL

  • Elimination of cranial RT for CNS+ Burkitt/B-ALL (LMB-96)

  • Elimination of prophylactic cranial RT (BFM 95)

  • Radiation therapy limited to cases with relapsed/refractory disease

  • Irradiation limited to cases with relapsed/refractory disease

ALCL – anaplastic large cell; ALL – acute lymphoblastic leukemia; APO - doxorubicin, vincristine, mercaptopurine, and prednisone; Ara-C – cytosine arabinoside; BFM – Berlin-Frankfurt-Münster; CHOP - cyclophosphamide, doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone; COMP - cyclophosphamide, vincristine, methotrexate, prednisone; CTX – cyclophosphamide; DLBCL – diffuse large B-cell lymphoma (including mediastinal large B-cell lymphoma); HDMTX – high-dose methotrexate; IFRT – involved-field radiation; RT - radiation