Serviço de Hematologia Clínica
Contributions
Type: Publication Only
Background
The optimal post-remission therapy for adult acute lymphoblastic leukemia (ALL) patients is not well established. Although allogeneic stem cell transplantation (allo-SCT) has been used in adult ALL for more than 20 years, its role remains controversial as demonstrated by conflicting results in many studies.
Aims
Compare allo-SCT vs maintenance chemotherapy as post-remission therapy in adult B-ALL patients.
Methods
We retrospectively analyzed 64 patients with de novo B-ALL in a single centre from 2006 to 2014.
Results
The median age at diagnosis was 47 years [17-70], 25(39.1%) patients with ≤ 40 years. The median white blood count (WBC) was 9x10^9/L [1.0-254] and 17(26.6%) patients had hyperleucocytosis (>30x10^9/L). Forty (62.5%) cases corresponded to common-B ALL, 20 (31.3%) to a pre-B ALL and 4 (6.2%) were pro-B ALL. Thirty-three (51.6%) patients had an unfavorable karyotype: t(9,22) in 31 (48.4%) patients, t(4,11) in 1 (1.6%) and hypodiploidy in 1 (1.6%) patient. Thirty-four (53.1%) patients received remission induction therapy with the HOVON 100 ALL/EORTC 06083 protocol (nonexperimental arm), 24 (37.5%) with the Hyper-CVAD protocol and 6 (9.4%) with CLG/EORTC 58951 protocol. In cases of Philadelphia chromosome–positive (Ph+) ALL, all patients received tyrosine kinase inhibitors (TKI) (in addition to multiagent chemotherapy). Sixty-two (96.9%) patients achieved complete remission (CR) after either one (90.6%, n=58) or two (6.3%, n=4) courses of induction therapy. Four patients (6.25%) died during consolidation treatment (2 related to toxicity of chemotherapy and 2 due to early relapse).
Among 58 (90.6%) patients who completed consolidation therapy, 30 (51.7%, n=30/58) received allo-SCT (matched related donor, n= 23 and unrelated donor, n=7) and 28 (48.3%, n=28/58) were treated with maintenance chemotherapy. In patients receiving allo-SCT, 12 (40%, n=12/30) had ≤ 40 years and 19 (63.3%, n=19/30) were Ph+ ALL. The mortality rate in patients submitted to allo-SCT was 56.7% (n=17/30) and the majority (52.9%, n=9/17) of patients died in CR. In patients treated with maintenance chemotherapy, the mortality rate was 42.9% (n=12/28) and the main (75% n=9/12) cause of death was disease relapse.
The median follow-up was 27 months [1-108]. The disease-free survival (DFS) and overall survival (OS) rates at 3 years of the all cohort were 41.1% (+/-6.7%) and 48.4% (+/-6.7%), respectively. Comparing Hyper-CVAD protocol with HOVON 100 ALL/EORTC 06083 protocol, no differences statistically significant were found for RC vs NR (p=0.270), DFS (p=0.741) or OS (p=0.411).
According to allo-SCT vs maintenance chemotherapy comparisons, no significant differences were observed for DFS (p=0.167) and OS (p=0.259) even including only Ph+ ALL patients in the analysis (DFS for Ph+ ALL allo-SCT vs Ph+ ALL chemotherapy - p=0.539; OS for Ph+ ALL allo-SCT vs Ph+ ALL chemotherapy - p=0.857). Additionally, when patients with ≤ 40 years were analyzed as a separate group, we failed to observe any statistical difference between the two post-remission therapies in terms of DFS (p=0.575) and OS (p=0.780).
Summary
Our study does not demonstrate any advantage for allo-SCT compared with maintenance chemotherapy as post-remission therapy in adult B-ALL even in those patients with Ph+ or ≤ 40 years. In our analysis the non-relapse treatment-related mortality in patients submitted to allo-SCT was very significant. Although our series was small, it represents the results of daily clinical practice, where graft-versus-host-disease and serious infections are major challenges.
Keyword(s): Acute lymphoblastic leukemia, Allogeneic stem cell transplant, Chemotherapy
Session topic: Publication Only
Type: Publication Only
Background
The optimal post-remission therapy for adult acute lymphoblastic leukemia (ALL) patients is not well established. Although allogeneic stem cell transplantation (allo-SCT) has been used in adult ALL for more than 20 years, its role remains controversial as demonstrated by conflicting results in many studies.
Aims
Compare allo-SCT vs maintenance chemotherapy as post-remission therapy in adult B-ALL patients.
Methods
We retrospectively analyzed 64 patients with de novo B-ALL in a single centre from 2006 to 2014.
Results
The median age at diagnosis was 47 years [17-70], 25(39.1%) patients with ≤ 40 years. The median white blood count (WBC) was 9x10^9/L [1.0-254] and 17(26.6%) patients had hyperleucocytosis (>30x10^9/L). Forty (62.5%) cases corresponded to common-B ALL, 20 (31.3%) to a pre-B ALL and 4 (6.2%) were pro-B ALL. Thirty-three (51.6%) patients had an unfavorable karyotype: t(9,22) in 31 (48.4%) patients, t(4,11) in 1 (1.6%) and hypodiploidy in 1 (1.6%) patient. Thirty-four (53.1%) patients received remission induction therapy with the HOVON 100 ALL/EORTC 06083 protocol (nonexperimental arm), 24 (37.5%) with the Hyper-CVAD protocol and 6 (9.4%) with CLG/EORTC 58951 protocol. In cases of Philadelphia chromosome–positive (Ph+) ALL, all patients received tyrosine kinase inhibitors (TKI) (in addition to multiagent chemotherapy). Sixty-two (96.9%) patients achieved complete remission (CR) after either one (90.6%, n=58) or two (6.3%, n=4) courses of induction therapy. Four patients (6.25%) died during consolidation treatment (2 related to toxicity of chemotherapy and 2 due to early relapse).
Among 58 (90.6%) patients who completed consolidation therapy, 30 (51.7%, n=30/58) received allo-SCT (matched related donor, n= 23 and unrelated donor, n=7) and 28 (48.3%, n=28/58) were treated with maintenance chemotherapy. In patients receiving allo-SCT, 12 (40%, n=12/30) had ≤ 40 years and 19 (63.3%, n=19/30) were Ph+ ALL. The mortality rate in patients submitted to allo-SCT was 56.7% (n=17/30) and the majority (52.9%, n=9/17) of patients died in CR. In patients treated with maintenance chemotherapy, the mortality rate was 42.9% (n=12/28) and the main (75% n=9/12) cause of death was disease relapse.
The median follow-up was 27 months [1-108]. The disease-free survival (DFS) and overall survival (OS) rates at 3 years of the all cohort were 41.1% (+/-6.7%) and 48.4% (+/-6.7%), respectively. Comparing Hyper-CVAD protocol with HOVON 100 ALL/EORTC 06083 protocol, no differences statistically significant were found for RC vs NR (p=0.270), DFS (p=0.741) or OS (p=0.411).
According to allo-SCT vs maintenance chemotherapy comparisons, no significant differences were observed for DFS (p=0.167) and OS (p=0.259) even including only Ph+ ALL patients in the analysis (DFS for Ph+ ALL allo-SCT vs Ph+ ALL chemotherapy - p=0.539; OS for Ph+ ALL allo-SCT vs Ph+ ALL chemotherapy - p=0.857). Additionally, when patients with ≤ 40 years were analyzed as a separate group, we failed to observe any statistical difference between the two post-remission therapies in terms of DFS (p=0.575) and OS (p=0.780).
Summary
Our study does not demonstrate any advantage for allo-SCT compared with maintenance chemotherapy as post-remission therapy in adult B-ALL even in those patients with Ph+ or ≤ 40 years. In our analysis the non-relapse treatment-related mortality in patients submitted to allo-SCT was very significant. Although our series was small, it represents the results of daily clinical practice, where graft-versus-host-disease and serious infections are major challenges.
Keyword(s): Acute lymphoblastic leukemia, Allogeneic stem cell transplant, Chemotherapy
Session topic: Publication Only