TREATMENT GROUPS

Treatment groups can be divided into the following categories:

• Localized NHL
  
  
• Stage III small noncleaved NHL
  
  
• Stage IV small noncleaved NHL, including B-cell acute lymphoblastic leukemia
  
  
• Stage III and IV lymphoblastic NHL
  
  
• Stage III and IV Ki-1+ Anaplastic large cell lymphoma
  
  

Localized Non-Hodgkin's Lymphoma

Patient eligibility criteria include:

• Less than or equal to 21 years of age at the time of diagnosis.
  
  
• Histology-proven diagnosis of diffuse, non-Hodgkin's lymphoma:
  
  
  • In the working formulations - lymphoblastic, diffuse small noncleaved cell (Burkitt's and non-Burkitt's types), diffuse large cell (cleaved, non-cleaved, and immunoblastic subtypes), and large cell anaplastic lymphoma Ki-1+ subtype. In the Rapport classification - lymphoblastic (convoluted or nonconvoluted) diffuse, histiocytic, or diffuse undifferentiated (Burkitt's and non-Burkitt's types).
    
    
• Stage I or II by the Murphy staging system. In this staging system, the following patients are eligible :-
  
  
  • One or more nodal areas on same side of diaphragm
    
    
  • One or more extranodal tumors with or without regional nodes on same side of diaphragm
    
    
  • Primary gastrointestinal tumor (usually ileocecal) with or without mesenteric nodules
    
    
  • Primary NHL of skin localized to a single site with or without regional nodes
    
    
  • Involvement of single bone
    
    
  • Primary head and neck
    
    
  • Base of skull involvement without cranial nerve involvement, negative brain CT or MRI, and negative cerebrospinal fluid cytology.
    
    

Treatment : see Table 5

Table 5 : Treatment Regimens for Patients with Localized Non-Hodgkin's Lymphoma

Therapy	Route of Administration	Schedule
Induction and consolidation therapy (9 weeks)
Vincristine	Intravenous	1.5 mg/m2 of body surface area weekly for 7 weeks on days 1, 8, 15,22, 29, 36 and 43.
Doxorubicin	Intravenous	40 mg/m2 on days 1, 22, and 43
Cyclophosphamide	Intravenous	750 mg/m2 on days 1, 22, and 43
Prednisone	Oral	40 mg/m2 daily on days 1-28, 43-47
Continuous therapy (24 weeks)
Mercaptopurine	Oral	50 mg/m2 daily
Methotrexate	Ora	l 25 mg/m2 weekly
Central nervous system		Age-adjusted doses given on days 1,8,22,43 and 64 of Therapy induction-consolidation therapy and every six weeks during continuous therapy
		1 yr	2 yrs	3-8 yrs	> 9 yrs.(Age group)
Methotrexate	Intrathecal	8 mg	10 mg	12 mg	15mg
Cytarabine	Intrathecal	16 mg	20 mg	24 mg	30 mg
Hydrocortisone	Intrathecal	8 mg	10 mg	12 mg	15mg

Consolidation begins on day 43

Optional; give Mesna 400 mg/m2 i.v. push 15 minutes prior to and 3 hours after cyclophosphamide administration

Continuation therapy (i.e. maintenance therapy) starts on day 64,; only for patients with lymphoblastic lymphoma

Central nervous system therapy; triple intrathecal chemotherapy only for patients with head and neck primaries.

Note: Diagnostic lumbar puncture is performed on days 1 and 64. Remission status is assessed on day 64 with physical examination, radio imaging studies, bone marrow, and lumbar puncture.

Results :

• Localized nonlymphoblastic lymphoma : 5-year rate of continuous complete remission 90%
  
  
• Localized lymphoblastic lymphoma: 5-year rate of continuous remission 65%
  
  

Stage III Small noncleaved Non-Hodgkin's Lymphoma

Results : 80% event-free 5-year survival.

Stage IV Small noncleaved Non-Hodgkin's Lymphoma including B-cell Acute Lymphoblastic Leukemia

Results : 80% event-free 5 year survival.

Stage III and IV Lymphoblastic Non-Hodgkin's Lymphoma

Results : Stage III and stage IV event-free survival at 6 years is 79+6% and 79+9%, respectively.