No abstract

In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.

The leukemic B lymphocytes from chronic lymphocytic leukemic (CLL) patients have a long survival in vivo, although ex vivo they rapidly die by apoptosis. To further investigate the mechanism of this, we have studied the influence of bone marrow stromal cells from normal subjects on apoptosis of B-CLL cells and normal umbilical cord blood (UCB) B lymphocytes. After 48 hours of incubation in medium alone, leukemic and normal B cells showed, respectively, 22 ± 3% and 31 ± 5% of apoptosis. Cocultures with stromal cells reduced the percentage of leukemic cells undergoing apoptosis (8 ± 2%, P< .0005) and prevented the loss of bcl-2 protein expression. In contrast, stromal cells slightly increased normal B-cell apoptosis (37 ± 6%). Direct contact between leukemic cells and stromal cells was found to be essential for inhibition of leukemic cell apoptosis; indeed, separation of leukemic cells from stromal cells by microporous membrane increased spontaneous apoptosis, and comparable results were obtained with stromal cell conditioned medium. The difference in behavior observed between normal and leukemic B cells plated on stromal cells can be explained by the fact that only a few normal B cells adhere to stromal cells in comparison with B-CLL cells. B-CLL cell adhesion to stromal cells is mediated by β1 and β2 integrins acting simultaneously. Contact between B-CLL cells and bone marrow stromal cells seems to play a major role in the accumulation and survival of B-CLL cells in the bone marrow.

Summary:vary from one study to another, they show generally a lower risk of relapse, and a longer disease-free survival (DFS) after AlloBMT and ABMT than after ICC. A cross-sectional study of quality of life (QOL) was performed in 98 patients in continued first complete From 1986 to 1992, the EORTC and GIMEMA Leukemia Cooperative Groups prospectively compared these remission (CR) for 1-7.4 years, after inclusion in the AML 8A trial which prospectively compared allogeneic three therapeutic options: patients with newly diagnosed AML were entered in the AML 8A trial, and, after the same bone marrow transplantation (AlloBMT), autologous BMT (ABMT) and intensive consolidation chemoinduction and intensive consolidation course, were assigned, according to availability of a family HLAtherapy. Several significant differences between the three treatment groups were observed, on the basis of matched donor or randomization, to AlloBMT, ABMT or a second ICC course. At a median follow-up time of 3.3 patient self-reports, with regard to somatic symptoms (mouth sores, cough, hair loss, headache), repeated years, there was a significantly longer DFS in the AlloBMT (55%) and ABMT (48%) arms than in the ICC arm (30%). 5 acute medical problems, physical functioning, role functioning, leisure activities and, above all, sexual funcHowever, the overall survival after CR was similar in the three arms, patients relapsing after ICC being more easily tioning. There were also significant differences for overall physical condition, and overall quality of life. For all salvaged and frequently receiving an ABMT during second CR. these parameters, the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy. These dif-The conclusions of this study were based on analyses made according to the intention-to-treat principle. In ferences remain significant after adjustment for time interval between CR and QOL evaluation, sex or age.addition, we have observed a significant difference with regard to the short-term toxicity of the treatment actually These results, confirming a higher risk of permanent impairment of QOL after BMT, may have an impact administered, the treatment-related mortality being 20, 10 and 6% after AlloBMT, ABMT and second ICC, respecton medical decisions and warrant further studies. Keywords: quality of life; acute myeloid leukemia; bone ively. Furthermore, the final results may also be hampered by long-term toxicity, especially due to the conditioning marrow transplantation regimens, with or without total body irradiation (TBI), for both BMT procedures, and to chronic graft-versus-host disease (GVHD) after AlloBMT. Such long-term somatic toxiAllogeneic bone marrow transplantation (AlloBMT), autocity is also likely to induce psychosocial sequelae. Indeed, logous bone marrow transplantation (ABMT), or intensive some previous studies have shown that quality of life consolidation chemotherapy (ICC) are currently proposed (QOL) might be more or less markedly impaired after for patients with acute myelogenous leukemia (AM...

Purpose:To assess the v a lu e o f granulocyte-m acro phage co lo n y-stim u la tin g fa c to r (GM-CSF) fo r induction tre a tm e n t o f acute m ye lo id le u ke m ia (AML)/ both fo r prim ing o f leukem ic cells a n d

The leukemic B lymphocytes from chronic lymphocytic leukemic (CLL) patients have a long survival in vivo, although ex vivo they rapidly die by apoptosis. To further investigate the mechanism of this, we have studied the influence of bone marrow stromal cells from normal subjects on apoptosis of B-CLL cells and normal umbilical cord blood (UCB) B lymphocytes. After 48 hours of incubation in medium alone, leukemic and normal B cells showed, respectively, 22 ± 3% and 31 ± 5% of apoptosis. Cocultures with stromal cells reduced the percentage of leukemic cells undergoing apoptosis (8 ± 2%, P< .0005) and prevented the loss of bcl-2 protein expression. In contrast, stromal cells slightly increased normal B-cell apoptosis (37 ± 6%). Direct contact between leukemic cells and stromal cells was found to be essential for inhibition of leukemic cell apoptosis; indeed, separation of leukemic cells from stromal cells by microporous membrane increased spontaneous apoptosis, and comparable results were obtained with stromal cell conditioned medium. The difference in behavior observed between normal and leukemic B cells plated on stromal cells can be explained by the fact that only a few normal B cells adhere to stromal cells in comparison with B-CLL cells. B-CLL cell adhesion to stromal cells is mediated by β1 and β2 integrins acting simultaneously. Contact between B-CLL cells and bone marrow stromal cells seems to play a major role in the accumulation and survival of B-CLL cells in the bone marrow.

During the last ten years a substantial reduction in mortality has been obtained for Hodgkin's and non-Hodgkin's lymphoma. Since lymphoma treatment is often accompanied by side effects and long-term sequelae, however, patients often have problems with rehabilitation. It is thus very important that these problems and needs be identified. Going back to work is one of the main objectives of rehabilitation and can be taken as a valuable indicator of the problems and needs of such patients. We therefore conducted a study at the Jules Bordet Institute between December 1989 and December 1990. Of the patients in remission and able to go back to work, only 54% of them have done so. Anxiety, depression, and treatment toxicity interfere with return to work, and the likelihood of job reentry increases with the time lapse since the end of treatment. Rehabilitation programs must focus on alleviating illness and treatment sequelae as soon as treatment ends.

Prognosis of B-cell chronic lymphocytic leukemia (CLL) is based on clinical staging whose limitation is the failure to assess whether the disease will progress or remain stable in early stage (Binet A, or Rai 0, I, II) patients. We previously reported that soluble CD23 (sCD23), a protein derived from the B-cell membrane CD23 Ag, is selectively elevated in the serum of CLL patients. This prospective study assessed the predictive value of serum sCD23 level measured at study entry on the overall survival of all CLL patients and on disease progression of stage Binet A patients. Prognostic value of repeated measurements of sCD23 over time in stage A patients was also analyzed. One hundred fifty-three CLL patients were prospectively followed with a median follow-up of 78 months. Eight clinical or biological parameters were collected from the date of the first sCD23 measurement. At study entry, by Cox model, Binet staging (P = .0001) and serum sCD23 level (P = .03) appeared as prognostic factors for survival. Patients with sCD23 level above median value (> 574 U/mL) had a significantly worse prognosis than those with lower values (median survival of 53 v 100+ months, P = .0001). During follow-up, sCD23 doubling time increased by 3.2 the risk of death (P = .001). Among stage A patients (n = 100), sCD23 determination at study entry was the sole variable predictive of disease progression, patients with sCD23 level above 574 U/mL had a median time progression of 42 months versus 88 months for those with lower levels (P = .0001). Stage A patients who doubled their sCD23 level exhibited a 15-fold increased risk of progression (P = .0001) and, in addition, the sCD23 increase preceded by 48 months disease progression. We conclude that in CLL patients, serum sCD23 level provides significant additional prognostic information in terms of overall survival. Most interestingly, among early stage patients, sCD23 determination at diagnosis and during the course of the disease may help to the early identification of patients who will rapidly progress to upper stages.