Summary Although the incidence rate of acute lymphoblastic leukaemia ( ALL ) is slightly higher in older than in younger adults, response rates to induction chemotherapy and survival rates are poorer. The contribution of disease‐related versus treatment‐related factors remains unclear. We analysed 100 older patients (aged 55–65 years) treated on the UKALLXII / ECOG 2993 trial compared with 1814 younger patients (aged 14–54 years). Baseline characteristics, induction chemotherapy course, infections, drug reductions and survival outcomes were compared. There were more Philadelphia‐positive ( P h+) patients in the older group (28% vs. 17%, P = 0·02), and a trend towards higher combined cytogenetic risk score (46% vs. 35%, P = 0·07). The complete remission rate in older patients was worse (73% vs. 93%, P < 0·0001) as was 5‐year overall survival (21% vs. 41%, P < 0·0001) and event‐free survival ( EFS ) (19% vs. 37%, P < 0·0001). Older patients had more infections during induction (81% vs. 70%, P = 0·05), and drug reductions (46% vs. 28%, P = 0·0009). Among older patients, P h+ and cytogenetic risk category as well as infection during induction predicted for worse EFS . Poorer outcomes in these patients are partly due to cytogenetic risk, but there is significant morbidity and mortality during induction chemotherapy with frequent delays and drug reductions. New approaches, including better risk stratification and use of targeted therapies, could improve treatment for these patients.
PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P = .065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P = .71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.
Purpose The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma (FL). Patients and Methods Patients with relapsed FL who achieved either complete or very good partial remission with salvage chemotherapy were randomly assigned using a factorial design to rituximab purging (P+; 375 mg/m 2 once per week for 4 weeks) or observation (NP) before HDC-ASCT and to maintenance rituximab (M+; 375 mg/m 2 once every 2 months for four infusions) or observation (NM). Results From October 1999 to April 2006, 280 patients were enrolled. The median age was 51 years (range, 26 to 70 years), and baseline characteristics were well balanced between groups. On average, patients were 44 months (range, 3 to 464 months) from diagnosis, with 79% having received two lines and 15% three lines of prior therapy. Median follow-up was 8.3 years. In contrast to purging, 10-year progression-free survival (PFS) was 48% for P+ and 42% for NP groups (hazard ratio [HR], 0.80; 95% CI, 0.58 to 1.11; P = .18); maintenance had a significant effect on PFS (10-year PFS, 54% for M+ and 37% for NM; HR, 0.66; 95% CI, 0.47 to 0.91; P = .012). Overall survival (OS) was not improved by either rituximab purging or maintenance. Conclusion Rituximab maintenance after HDC-ASCT is safe and significantly prolongs PFS but not OS in patients undergoing transplantation for relapsed FL. Pretransplantation rituximab in vivo purging, even in rituximab-naive patients, failed to improve PFS or OS.
A significant proportion of previously treated patients fail to mobilize sufficient stem/progenitor cells to enable high‐dose therapy and peripheral blood stem cell transplantation to be performed. In this study, the value of remobilizing such patients has been evaluated in 20 patients who all failed to achieve progenitor yields of 1 × 10 6 /kg CD34 + cells and 1 × 10 5 /kg granulocyte–monocyte colony‐forming units (GM‐CFCs) at the first attempt. Most patients remained relatively poor mobilizers at the second mobilization, but the yield of CD34 + cells and GM‐CFCs on the first apheresis was significantly greater with the second mobilization than the first. A total yield (all aphereses from both mobilizations) of > 1 × 10 6 /kg CD34 + cells and > 1 × 10 5 /kg GM‐CFCs was achieved in 14 out of 20 patients. Seven patients have received high‐dose therapy with stem cell infusion; neutrophil recovery was rapid in all patients and platelet independence occurred in < 21 d in five out of seven patients. We conclude that remobilization is worth considering in those patients in whom a chemotherapy‐free interval of several months is possible.
We commenced a study in September 1981 to investigate the role of high-dose combination chemotherapy in the management of patients with non-Hodgkin's lymphomas who had failed conventional therapy. Fifty patients with diffuse intermediate- and high-grade non-Hodgkin's lymphomas were treated with high-dose combination chemotherapy with autologous bone marrow rescue (ABMT) and have a minimum follow-up of 1 year. Twenty patients had disease that was still responsive to conventional-dose chemotherapy, 15 had achieved a partial response (PR) to first-line therapy, and five were showing PR to salvage therapy after relapse. Twelve of these patients (60%) achieved complete remission (CR) (two following boost radiotherapy) and three patients have nonprogressive masses on computed tomographic (CT) scan as the only abnormality. None of these patients died during the procedure. Twenty-nine patients had disease not responsive to chemotherapy at conventional dosages: 19 had no response to first-line therapy and 10 showed no response to salvage therapy given after relapse. Only three of these patients achieved CR, all of short duration only. Only two patients in this group remain alive more than 2 years after the procedure and both have nonprogressive abnormalities on CT scan. Nine patients (31%) died of sepsis during the procedure. In those patients with disease not responsive to conventional-dose therapy, dose escalation is associated with a high procedure-related mortality and a low response rate. In those patients who still have chemotherapy-responsive disease the response rate is high and mortality is low.(ABSTRACT TRUNCATED AT 250 WORDS)
24 adult patients with acute myeloid leukaemia (AML) were treated with intensive chemotherapy followed by autologous marrow rescue. The procedure was repeated twice in eight patients. 11 of 16 patients treated in first remission continue in first unmaintained remission (9-54 months, median 17 months). Eight patients treated at relapse or second remission have relapsed again and died within 14 months of their first autologous bone marrow transplant (ABMT). This form of intensification therapy would appear valuable for adult AML patients in first remission.
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