Consolidation therapy

Longer-term therapy at lower doses (maintenance therapy).

Allogeneic BMT.

Several trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (ECOG-2993 [NCT00002514]), of aggressive consolidation chemotherapy for ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40%.[1-7]

Several trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (ECOG-2993 [NCT00002514]), of aggressive consolidation chemotherapy for ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40%.[1-7]

In two series,[4,5] especially good prognoses were found for patients with T-cell lineage ALL, with DFS rates of 50% to 70% for patients receiving consolidation therapy.

Several trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (ECOG-2993 [NCT00002514]), of aggressive consolidation chemotherapy for ALL have confirmed a long-term disease-free survival (DFS) rate of approximately 40%.[1-7]

These series represent a significant improvement in DFS rates over previous, less intensive chemotherapeutic approaches.

In contrast, poor cure rates were demonstrated in patients with Philadelphia chromosome (Ph)–positive ALL, B-cell lineage ALL with an L3 phenotype (surface immunoglobulin positive), and B-cell lineage ALL characterized by t(4;11).

The results of a series of retrospective and prospective studies published between 1987 and 1994 suggest that allogeneic BMT or autologous BMT as consolidation therapy offer no survival advantage over intensive chemotherapy, except perhaps for patients with high-risk or Ph-positive ALL.[14-17] This was confirmed in the ECOG-2993 study (NCT01505699).[7]

The results of a series of retrospective and prospective studies published between 1987 and 1994 suggest that allogeneic BMT or autologous BMT as consolidation therapy offer no survival advantage over intensive chemotherapy, except perhaps for patients with high-risk or Ph-positive ALL.[14-17] This was confirmed in the ECOG-2993 study (NCT01505699).[7]

The use of allogeneic BMT as primary consolidation therapy is limited by both the need for an HLA-matched sibling donor and the increased mortality from allogeneic BMT in patients in their fifth or sixth decade.

The results of a series of retrospective and prospective studies published between 1987 and 1994 suggest that allogeneic BMT or autologous BMT as consolidation therapy offer no survival advantage over intensive chemotherapy, except perhaps for patients with high-risk or Ph-positive ALL.[14-17] This was confirmed in the ECOG-2993 study (NCT01505699).[7]

The mortality from allogeneic BMT using an HLA-matched sibling donor in these studies ranged from 20% to 40%.

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

Ninety percent of patients in this study achieved remission after induction therapy. Of these patients, 443 had an HLA-identical sibling, 310 of whom underwent an allogeneic BMT. For the 456 patients in remission who were eligible for transplant but lacked a donor, 227 received chemotherapy alone, while 229 underwent an autologous BMT.

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

By donor-to-no-donor analysis, standard-risk ALL patients with an HLA-identical sibling had a 5-year OS rate of 53%, compared with 45% for patients lacking a donor (P = .01).

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

In a subgroup analysis, the advantage for patients with standard-risk ALL who had donors remained significant (OS rate, 62% vs. 52%; P = .02).

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years. › In a subgroup analysis, the advantage for patients with standard-risk ALL who had donors remained significant (OS rate, 62% vs. 52%; P = .02).

For patients with high-risk disease (older than 35 years or high WBC count), the difference in OS was 41% versus 35% (donor vs. no donor) but was not significant (P = .2).

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years. › In a subgroup analysis, the advantage for patients with standard-risk ALL who had donors remained significant (OS rate, 62% vs. 52%; P = .02).

Relapse rates were significantly lower (P < .00005) for both standard- and high-risk patients with HLA-matched donors.

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

In contrast to allogeneic BMT, autologous BMT was less effective than maintenance chemotherapy as consolidation treatment (5-year OS rate, 46% for chemotherapy vs. 37% for autologous BMT; P = .03).

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

The results of this trial suggest the existence of a graft-versus-leukemia effect for adult Ph-negative ALL and support the use of sibling donor allogeneic BMT as the consolidation therapy providing the greatest chance for long-term survival for patients with standard-risk adult ALL in first remission.[7][Level of evidence B4]

Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched to examine the role of transplant as consolidation therapy for ALL more definitively. Patients were accrued from 1993 to 2006.[7] Patients with Ph-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[1-3] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent allogeneic BMT as consolidation therapy. Patients without a donor were randomly assigned to receive either an autologous BMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS). Event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.

The results also suggest that in the absence of a sibling donor, maintenance chemotherapy is preferable to autologous BMT as consolidation therapy.[7][Level of evidence B4]

One group of investigators retrospectively reviewed three sequential cooperative group trials from Germany and found the following results:[19]

One group of investigators retrospectively reviewed three sequential cooperative group trials from Germany and found the following results:[19]

A marked improvement in survival, from zero survivors in a 1981 study that used standard pediatric therapy and lasted 2.5 years, to a 50% survival rate in two subsequent trials that used rapidly alternating lymphoma-like chemotherapy and were completed within 6 months.