Standard Treatment Options for Lymphoblastic Lymphoma

COG-A5971 (NCT00004228): Stage I or stage II patients (arm A0; localized disease) received a modified Children's Cancer Group (CCG) BFM regimen and a reduced number of intrathecal treatments during the maintenance phase.[6]

COG-A5971 (NCT00004228): Stage I or stage II patients (arm A0; localized disease) received a modified Children's Cancer Group (CCG) BFM regimen and a reduced number of intrathecal treatments during the maintenance phase.[6]

In 56 patients, the 5-year EFS rate was 90%, and the OS rate was 96%.

GER-GPOH-NHL-BFM-95: Only CNS-positive patients received CNS radiation therapy. The treatment duration for patients with T-cell and B-cell precursor lymphoblastic lymphoma was 24 months.[18,19]

GER-GPOH-NHL-BFM-95: Only CNS-positive patients received CNS radiation therapy. The treatment duration for patients with T-cell and B-cell precursor lymphoblastic lymphoma was 24 months.[18,19]

The 5-year DFS rate was 88%, and the OS rate was 85%.

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%.

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%.

First randomization:

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%. › First randomization:

Arm A1 (disseminated disease, no CNS disease): Modified CCG-BFM regimen without intensification. No high-dose methotrexate was administered during the interim maintenance phase, but intrathecal therapy was administered throughout the maintenance phase.

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%. › First randomization:

Arm B1 (disseminated disease, no CNS disease): GER-GPOH-NHL-BFM-95 regimen without intensification and without intrathecal therapy during the maintenance phase.

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%.

Second randomization:

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%. › Second randomization:

Arm A2 (disseminated disease, no CNS disease): Modified CCG-BFM regimen (arm A1) with intensified induction and delayed intensification.

COG-A5971 (NCT00004228): This trial evaluated two strategies for CNS prophylaxis, without the use of CNS irradiation, for patients with stage III and stage IV lymphoblastic lymphoma. Patients were randomly assigned to receive either high-dose methotrexate during the interim maintenance phase (BFM-95) or intrathecal chemotherapy throughout the maintenance phase (CCG-BFM).[20][Level of evidence A1]Equivalent outcomes were observed for patients treated on arms A1, B1, A2, and B2. The 5-year EFS rates were 81%, 80%, 84%, and 80%, respectively. The OS rates were 84%, 88%, 85%, and 85%, respectively. Patients with CNS disease at diagnosis had a 5-year EFS rate of 63% and an OS rate of 81%. › Second randomization:

Arm B2 (disseminated disease, no CNS disease): GER-GPOH-NHL-BFM-95 regimen (arm B1) with intensified induction and delayed intensification. Patients with CNS disease were nonrandomly treated on arm B2 with the addition of radiation therapy.

COG AALL0434 (NCT00408005): In this trial, patients with stages II to IV T-cell lymphoblastic lymphoma received COG-augmented, BFM-backbone therapy with Capizzi methotrexate and intrathecal chemotherapy through the maintenance phase. No patients with CNS disease received cranial radiation therapy because patients with CNS3 disease were not eligible. Patients with less than 1% minimal disseminated disease (MDD) in their bone marrow at diagnosis, assessed by flow cytometry, were nonrandomly assigned to treatment without nelarabine. Patients with greater than 1% MDD were randomly assigned to receive treatment with or without nelarabine.[26]

COG AALL0434 (NCT00408005): In this trial, patients with stages II to IV T-cell lymphoblastic lymphoma received COG-augmented, BFM-backbone therapy with Capizzi methotrexate and intrathecal chemotherapy through the maintenance phase. No patients with CNS disease received cranial radiation therapy because patients with CNS3 disease were not eligible. Patients with less than 1% minimal disseminated disease (MDD) in their bone marrow at diagnosis, assessed by flow cytometry, were nonrandomly assigned to treatment without nelarabine. Patients with greater than 1% MDD were randomly assigned to receive treatment with or without nelarabine.[26]

The overall 4-year DFS rate was 85%, and the OS rate was 89%.

COG AALL0434 (NCT00408005): In this trial, patients with stages II to IV T-cell lymphoblastic lymphoma received COG-augmented, BFM-backbone therapy with Capizzi methotrexate and intrathecal chemotherapy through the maintenance phase. No patients with CNS disease received cranial radiation therapy because patients with CNS3 disease were not eligible. Patients with less than 1% minimal disseminated disease (MDD) in their bone marrow at diagnosis, assessed by flow cytometry, were nonrandomly assigned to treatment without nelarabine. Patients with greater than 1% MDD were randomly assigned to receive treatment with or without nelarabine.[26]

There was no difference in DFS observed between standard-risk and high-risk patients. Disease stage and MDD status at diagnosis also did not demonstrate differences in EFS.

COG AALL0434 (NCT00408005): In this trial, patients with stages II to IV T-cell lymphoblastic lymphoma received COG-augmented, BFM-backbone therapy with Capizzi methotrexate and intrathecal chemotherapy through the maintenance phase. No patients with CNS disease received cranial radiation therapy because patients with CNS3 disease were not eligible. Patients with less than 1% minimal disseminated disease (MDD) in their bone marrow at diagnosis, assessed by flow cytometry, were nonrandomly assigned to treatment without nelarabine. Patients with greater than 1% MDD were randomly assigned to receive treatment with or without nelarabine.[26]

Although nelarabine was beneficial in patients with T-ALL, there was no statistical difference in outcome for patients with NHL who did or did not receive nelarabine. This result may be explained by small numbers of randomized NHL patients or lower CNS relapse rates in NHL patients (i.e., 1.4%).

COG AALL1231 (NCT02112916): Patients who were newly diagnosed with T-cell lymphoblastic lymphoma were treated with the AALL0434 backbone, with some treatment modifications. Dexamethasone was given instead of prednisone in the induction and maintenance phases, and two additional pegaspargase doses were given during the induction and delayed intensification phases. Patients were randomly assigned to receive treatment with or without bortezomib (four doses in induction and four doses in delayed intensification).[27]

COG AALL1231 (NCT02112916): Patients who were newly diagnosed with T-cell lymphoblastic lymphoma were treated with the AALL0434 backbone, with some treatment modifications. Dexamethasone was given instead of prednisone in the induction and maintenance phases, and two additional pegaspargase doses were given during the induction and delayed intensification phases. Patients were randomly assigned to receive treatment with or without bortezomib (four doses in induction and four doses in delayed intensification).[27]

There was an increased rate of toxic deaths in the AALL1231 trial (4%), compared with the AALL0434 trial (2%).

COG AALL1231 (NCT02112916): Patients who were newly diagnosed with T-cell lymphoblastic lymphoma were treated with the AALL0434 backbone, with some treatment modifications. Dexamethasone was given instead of prednisone in the induction and maintenance phases, and two additional pegaspargase doses were given during the induction and delayed intensification phases. Patients were randomly assigned to receive treatment with or without bortezomib (four doses in induction and four doses in delayed intensification).[27]

Patients who received bortezomib had statistically significantly better 4-year EFS rates than those who did not receive bortezomib (EFS rates, 86% vs. 76%; P = .04). However, patients in the bortezomib arm had EFS and OS rates similar to patients in both arms of the AALL0434 trial, who were treated with and without nelarabine.

COG AALL1231 (NCT02112916): Patients who were newly diagnosed with T-cell lymphoblastic lymphoma were treated with the AALL0434 backbone, with some treatment modifications. Dexamethasone was given instead of prednisone in the induction and maintenance phases, and two additional pegaspargase doses were given during the induction and delayed intensification phases. Patients were randomly assigned to receive treatment with or without bortezomib (four doses in induction and four doses in delayed intensification).[27]

The poorer-than-expected outcome for patients treated without bortezomib cannot be explained solely by an increased toxic death rate. Despite more intensive therapy in the AALL1231 trial than in the AALL0434 trial, more relapses were observed in AALL1231.