Combination Chemotx in Treating Children or Adolescents With Newly Diagnosed Stg III or Stg IV Lymphoblastic Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of combination chemotherapy is most effective for lymphoblastic lymphoma. PURPOSE: This randomized phase III trial is studying different regimens of combination chemotherapy to compare how well they work in treating children or adolescents with newly diagnosed stage III or stage IV lymphoblastic lymphoma.

Detailed Description
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OBJECTIVES: Compare the event-free survival and overall survival of children or adolescents with newly diagnosed disseminated stage III or IV lymphoblastic lymphoma treated with 4 chemotherapy regimens*. Determine whether treatment with a regimen without methotrexate maintains the same disease-free survival as NHL/BFM 90 in these patients. Determine whether intensification with anthracycline and cyclophosphamide improves disease-free survival in these patients. Collect outcome data on uniformly treated patients with localized disease or CNS-positive disease. Determine whether rapid reduction in tumor volume by chest radiography and CT scan is predictive of improved outcome in patients treated with these regimens. Determine the prevalence of bone marrow involvement at presentation in these patients. Determine whether peripheral blood can replace bone marrow in the initial staging of these patients. Determine the clinical significance of bone marrow and peripheral blood involvement in these patients. NOTE: *All patients as of 4/2006 receive treatment on Arm III regimen only OUTLINE: Patients are stratified by disease characteristics (disseminated lymphoblastic lymphoma vs localized lymphoblastic lymphoma [localized lymphoblastic lymphoma is closed to accrual as of 10/2005]) and age. Patients with CNS negative disseminated lymphoblastic lymphoma are randomized to 1 of 4 treatment arms*. Patients with testicular involvement at diagnosis are nonrandomly assigned to arm IV and do not receive testicular radiotherapy. Patients with localized lymphoblastic lymphoma (closed to accrual as of 10/2005) are not randomized. NOTE: *All patients as of 4/2006 receive treatment on Arm III only Localized lymphoblastic lymphoma (closed to accrual as of 10/2005): Induction (5 weeks): Patients receive vincristine IV and daunorubicin IV over 15 minutes to 2 hours on days 0, 7, 14, and 21; oral prednisone on days 0-27; and asparaginase intramuscularly (IM) on days 3, 5, and 7 and then 3 times a week for 9 doses (during days 8-21). Patients also receive methotrexate intrathecally (IT) on days 7 and 28 and cytarabine IT on day 0. Consolidation (5 weeks): Patients receive methotrexate IT on days 0, 7, 14, and 21 followed by cyclophosphamide IV over 1 hour on days 0 and 14; cytarabine IV on days 0-3, 7-10, 14-17, and 21-24; oral mercaptopurine on days 0-27; and oral prednisone over 10 days. Interim maintenance (8 weeks): Patients receive methotrexate IT on days 0 and 28; oral mercaptopurine on days 0-41; and oral methotrexate on days 7, 14, 21, and 35. Delayed intensification (7 weeks): Patients receive vincristine IV and doxorubicin IV over 15 minutes to 2 hours on days 0, 7, and 14; asparaginase IM on day 3 and then 3 times a week for 6 doses; oral dexamethasone on days 0-30; cyclophosphamide IV over 1 hour on day 28; and cytarabine IV or SC on days 28-31 and 35-38. Patients also receive oral thioguanine on days 28-41 and methotrexate IT on days 28 and 35. Maintenance (84 day course): Patients receive vincristine IV on days 0, 28, and 56; oral prednisone on days 0-4, 28-32, and 56-60; oral methotrexate on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; oral mercaptopurine on days 0-83; and methotrexate IT on day 0. Disseminated lymphoblastic lymphoma: Arm I (closed to accrual as of 4/2006): Patients receive same induction, consolidation, and interim maintenance therapy schedule as localized lymphoblastic lymphoma patients. Delayed intensification (7 weeks): Patients receive vincristine IV and doxorubicin IV over 15 minutes to 2 hours on days 0, 7, 14, and 21; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-28. Patients also receive cyclophosphamide IV over 1 hour on day 35; cytarabine IV or SC on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. Maintenance (84 day course): Patients receive same therapy as localized lymphoblastic lymphoma patients, except methotrexate IT is administered on day 0 and 28 (for first 4 courses). Arm II (closed to accrual as of 4/2006): Patients receive consolidation, interim maintenance, and maintenance therapy as in arm I. Induction (5 weeks): Patients receive vincristine IV on days 0, 7, 14, and 21; daunorubicin IV over 48 hours on days 0-2; oral prednisone on days 0-27; and asparaginase IM on days 3, 5, and 7 and then 3 times a week for 9 doses (during days 8-21). Patients also receive methotrexate IT on days 7 and 28; cyclophosphamide IV over 1 hour on day 2; and cytarabine IT on day 0. Delayed intensification (7 weeks): Patients receive vincristine IV on days 0, 7, 14, 21; daunorubicin IV over 48 hours on days 0-2; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-28. Patients also receive cyclophosphamide IV over 1 hour on days 2 and 35; cytarabine IV or SC on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. Arm III: Induction (5 weeks): Patients receive vincristine IV and daunorubicin IV over 1 hour on days 0, 7, 14, and 21 and oral prednisone on days 0-37. Patients also receive asparaginase IM on day 11 and then 3 times a week for 9 doses; methotrexate IT on days 7 and 28; and cytarabine IT on day 0. Consolidation (5 weeks): Patients receive methotrexate IT and cyclophosphamide IV over 1 hour on days 0 and 14; cytarabine IV or SC on days 0-3, 7-10, 14-17, and 21-24; oral mercaptopurine on days 0-27; and oral prednisone over 10 days. Interim maintenance (9 weeks): Patients receive methotrexate IT and IV on days 7, 21, 35, and 49; oral mercaptopurine on days 0-55; and leucovorin calcium IV at 42, 48, and 54 hours after methotrexate IV. Delayed intensification (10 weeks): Patients receive vincristine IV and doxorubicin IV over 1 hour on days 0, 7, 14, and 21; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-29. Patients also receive cyclophosphamide IV over 1 hour on day 35; cytarabine IV on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. Maintenance (84 day courses): Patients receive vincristine IV on days 0, 28, and 56; oral prednisone on days 0-4, 28-32, and 56-60; oral methotrexate on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and oral mercaptopurine on days 0-83. Arm IV (closed to accrual as of 4/2006): Patients receive consolidation and interim maintenance therapy as in arm III. Induction: Patients receive vincristine IV on days 0, 7, 14, and 21; daunorubicin IV over 48 hours on days 0-2; oral prednisone on days 0-37; asparaginase IM on day 11 and then 3 times a week for 9 doses; methotrexate IT on days 7, 14, 21, and 28; cyclophosphamide IV on day 2; and cytarabine IT on day 0. Delayed intensification (10 weeks): Patients receive vincristine IV on days 7, 14, 21, and 28; daunorubicin IV over 48 hours on days 0-2; asparaginase IM on day 3 and then 3 times a week for 6 doses; and oral dexamethasone on days 0-29. Patients also receive cyclophosphamide IV over 1 hour on days 2 and 35; cytarabine IV on days 35-38 and 42-45; oral thioguanine on days 35-48; and methotrexate IT on days 35 and 42. Maintenance (84 day courses): Patients receive therapy as in arm III. Patients who are over 1 year of age and have CNS disease at diagnosis undergo cranial radiotherapy once daily 5 days a week beginning on day 0. Patients over 2 years of age undergo radiotherapy over 11-14 days (6-9 days for 1-2 years of age). Patients are followed monthly for one year, every 3 months for 1 year, every 6 months for 1.5 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 250-400 patients will be accrued for this study within 5 years.

Official Title
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Randomized Phase III Study for the Treatment of Newly Diagnosed Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: asparaginase
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: daunorubicin hydrochloride
* Drug: dexamethasone
* Drug: doxorubicin hydrochloride
* Drug: leucovorin calcium
* Drug: mercaptopurine
* Drug: methotrexate
* Drug: prednisone
* Drug: thioguanine
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Newly diagnosed disseminated lymphoblastic lymphoma or localized lymphoblastic lymphoma* Less than 25% tumor cells in the bone marrow Previously untreated (prior intrathecal cytarabine allowed if protocol therapy begins within 72 hours) Stage III or IV disease NOTE: *Localized lymphoblastic lymphoma is closed to accrual as of 10/2005 PATIENT CHARACTERISTICS: Age: 1 to 30 Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Cardiovascular: Adequate cardiac function PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Endocrine therapy: Emergency steroid therapy (if required) must be started within 72 hours prior to protocol therapy Radiotherapy: Emergency radiotherapy (if required) must be started within 72 hours prior to protocol therapy Surgery: Not specified Other: No other prior therapy except for emergency treatment of airway obstruction and/or superior vena cava syndrome

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A0 (localized disease Stg I/II) Modified CCG BFM<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Doxorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|
| Experimental: A1 (Disseminated, No CNS - CCG mod BFM w/out intens<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, prednisone, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|
| Experimental: A2 (Disseminated, No CNS - CCG mod BFM w/ intens<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|
| Experimental: B2 (CNS+) NHL/BFM-95 w/intens delayed radiation therapy<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #003590;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;Radiation: radiation therapy<br> <br> |
| Experimental: B1 (Disseminated CNS- <Amend 7B) NHL/BFM-95 w/out intens<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #003590;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|
| Experimental: B2 (Disseminated,CNS- (< Amend 7B)) NHL/BFM-95 w/intens<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, daunorubicin, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #003590;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|
| Experimental: B1 (Disseminated CNS-) NHL/BFM-95 w/out intens<br>Phase I - 5 week induction (Vincristine Sulfate, daunorubicin hydrochloride, Cyclophosphamide, L-Asparaginase, Intrathecal Cytarabine, Intrathecal Methotrexate, Prednisone). Phase II - 5 week consolidation (Mercaptopurine, Cyclophosphamide, Cytarabine, Intrathecal Methotrexate, Prednisone). Phase III - 8 week Interim Maintenance (Mercaptopurine, Methotrexate, Intrathecal Methotrexate, Leucovorin Calcium). Phase IV - 7 week Delayed Intensification (Vincristine Sulfate, Cyclophosphamide, doxorubicin hydrochloride, L-Asparaginase, Dexamethasone, Cyclophosphamide, Thioguanine, Cytarabine, Intrathecal Methotrexate). Phase V - 12 week courses (Vincristine Sulfate, Prednisone, Mercaptopurine, Methotrexate, Intrathecal Methotrexate) | Drug: asparaginase<br>* Given IV<br>* Other names: NSC#109229;Drug: cyclophosphamide<br>* Given IV<br>* Other names: NSC #26271;Drug: cytarabine<br>* Given IV<br>* Other names: NSC #63878;Drug: daunorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #82151;Drug: dexamethasone<br>* Given IV<br>* Other names: NSC #34521;Drug: doxorubicin hydrochloride<br>* Given IV<br>* Other names: NSC #123127;Drug: leucovorin calcium<br>* Given IV<br>* Other names: NSC #003590;Drug: mercaptopurine<br>* Given IV<br>* Other names: NSC #000755;Drug: methotrexate<br>* Given IV<br>* Other names: NSC #000740;Drug: prednisone<br>* Given IV<br>* Other names: NSC #010023;Drug: thioguanine<br>* Given PO<br>* Other names: NSC # 751;Drug: vincristine sulfate<br>* Given IV<br>* Other names: NSC #67574;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | Assessed by time to treatment failure, occurrence of second malignant neoplasm, or death from any cause. Statistical analysis will be to estimate the difference in the proportion of patients treated with each therapy who are long-term event-free survivors due either to the difference between the backbone therapy regimens (CCG BFM vs NHL/BFM-95), or due to the intensification. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Overall Survival as Assessed by Time to Death | Overall survival will be computed by measuring the rate of deaths during induction due primarily to treatment toxicity and cumulative incidence of toxic deaths in induction or deaths in remission overall and separately for treatment groups defined by the two design factors. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma