Death In CR Research Articles

Hematopoietic Stem Cell Transplantation in Adult Acute Lymphoblastic Leukemia: a Single-Centre Analysis

The role of autologous or allogeneic hematopoietic stem cell transplantation (HSCT) in ALL is controversial because of its adverse risk/benefit ratio, and the main policy is to reserve it for high-risk patients. In our Institution, between 1984 and 2002, 40 patients received an allogeneic HSCT and 39 underwent autografting. The conditioning regimen included HD-Ara-C, HD-CTX and 10 Gy fractionated TBI. After allogeneic SCT in first CR, four patients relapsed, leading to a 10-year EFS chance of 78.3%; of the other patients, 5 are still in CR. After autografting in first CR, there was an early death, one secondary AML, one death in CR and six relapses, leading to a 10-year EFS chance of 44.4%; of the other patients, 6 are still in CR. Even considering the limited number of patients and the slow accrual rate, selection bias cannot be considered a sufficient explanation for the favorable outcome of allografting in first CR as the majority of the patients had adverse prognostic factors. It cannot be claimed that allogeneic SCT was performed in patients already cured, as the autografted patients had a notably worse outcome, and a 10-year EFS chance of about 80% is an uncommon finding even in standard-risk ALL patients. It might be inferred that the timing of SCT as late intensification, in addition to a rather aggressive conditioning regimen, helped to minimize the leukemic burden, thus favoring the expression of a GVL effect. Conversely, the results in more advanced disease phases are discouraging, due to poor quality CRs and inefficacy of GVL in managing large residual disease.

773 Total therapy of acute myeloid leukaemia

Our total therapy programme for AML comprises chemotherapy followed by BMT in CR1. From 4/90 to 12/94, 54 pts (13–53 y, med 33.5) received BF12 induction: high-dose ARA-C and VP-16 with idarubicin or mitoxantrone followed by two consolidation cycles. 42 pts attained CR (78%). 32 underwent BMT in CR1; one is awaiting BMT. Of the nine not transplanted in CR1 (early relapse, n = 7; refusal, n = 1; death in CR, n =1), one was transplanted in rell and five in CR2. Subgroup No Cant. CR Relapse Toxic deaths Total deaths Total alive Whole group 54 25 29 (54%) Overall CR 42 23 12 7 13 29 (69%) ABMT in CR1 19 14 3 2 5 14 (71%) Allo in CRl 12 7 1 4 5 7 (58%) Twin in CRl 1 1 − − − 1 No BMT in CR1 10 1 8 1 3 7 (70%) With 54% survival at 3–59 months (median 31) after diagnosis, we believe that this total therapy programme represents state-of-the-art management of AML.

Effect of All Transretinoic Acid in Newly Diagnosed Acute Promyelocytic Leukemia. Results of a Multicenter Randomized Trial

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) ("events" being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.

Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia. Results of a multicenter randomized trial. European APL 91 Group

We designed a multicenter randomized trial comparing chemotherapy with daunorubicin-Ara C (chemotherapy group) and all transretinoic acid (ATRA) combined to the same chemotherapy (ATRA group) in newly diagnosed APL patients aged 65 years or less. The major endpoint of the study was event-free survival (EFS) (“events” being defined as failure to achieve complete remission [CR], occurrence of relapse, or death in CR). Early termination of the trial was decided after the first interim analysis, as EFS was significantly higher in the ATRA group. At the time, 101 patients had been randomized (54 in the ATRA group and 47 in the chemotherapy group). In the ATRA group, 49 (91%) patients achieved CR, 5 (9%) had early death, and 0 had resistant leukemia, compared with 38 (81%), 4 (8%), and 5 (10%) patients, respectively, in the chemotherapy group. The difference in CR rate between the two groups was not significant. The duration of coagulopathy was significantly reduced in the ATRA group, compared with the chemotherapy group. In the ATRA group, six patients relapsed after 7 to 15.5 months. In the chemotherapy group, 12 patients relapsed after 1 to 16 months, and 2 died in CR. Kaplan-Meier EFS was estimated at 79% +/- 7% and 50% +/- 9% at 12 months, respectively, in the ATRA and the chemotherapy group (P = .001). Kaplan-Meier estimate of relapse was 19% +/- 8% and 40% +/- 12% at 12 months (P = .005). In conclusion, ATRA followed by chemotherapy increases EFS in newly diagnosed APL. These results strongly suggest that ATRA should be incorporated in the front line therapy of newly diagnosed APL.

The value of BMT in AML patients in first remission A statistician's view-point

For several years there has been extensive debate concerning the value of bone marrow transplantation (BMT), allogeneic (allo-BMT) or autologous (A-BMT), in acute myelogenous leukemia (AML) patients in first remission (CR). Before starting a proper randomized phase III trial in order to reach a conclusion on the value of BMT in terms of disease-free survival (DFS), i.e., the time from the first CR until relapse or death in CR, and duration of survival (S), several authors have tried to compare the DFS of the patients who underwent BMT with those who received chemotherapy as post-remission treatment (non-BMT group)