Identification of a rare e6a2 BCR-ABL fusion gene during the disease progression of chronic myelomonocytic leukemia: a case report.
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Disease Progression↗
Biomedical subjects
X Thomas
Publications and source records attributed to X Thomas.
Implementation of subcellular water mapping by electron energy loss spectroscopy in a medium-voltage scanning transmission electron microscope.
The water concentration in biological cells plays a predominant role in cellular life. Using electron energy loss spectroscopy, the feasibility to measure the water content in cells has already been demonstrated. In this paper, we present an upgrade of water measurement in hydrated cryosections by spectrum imaging mode in a medium-voltage scanning transmission electron microscope. The electron energy loss spectra are recorded in spectrum imaging mode in a 2(n)x2(n) pixels array. Each spectrum is processed in order to determine the water mass content in the corresponding pixel. Then a parametric image is obtained in which grey levels are related to water concentration. In this image, it is possible to recognize the different subcellular compartments. By averaging the water concentration over the relevant pixels, we can determine the water mass content in the concerned subcellular compartment. As an example, we present water mass content measurement at subcellular level in rat hepatocytes.
Animals↗
Salvage by timed sequential chemotherapy in primary resistant acute myeloid leukemia: analysis of prognostic factors.
Primary resistant acute myeloid leukemia (AML) has a very poor prognosis. Etoposide-mitoxantrone-cytarabine (EMA) timed sequential chemotherapy including a first sequence combining mitoxantrone (12 mg/m(2) per day over 3 days) with cytarabine (500 mg/m(2) per day over the same period), and a second sequence consisting in etoposide (200 mg/m(2) per day for 3 days) and cytarabine as in the first sequence, has been proposed as a salvage regimen. Over a 10-year period, 66 primary resistant AML patients have been treated by EMA salvage chemotherapy. All patients displayed intermediate- or high-risk karyotypic abnormalities. Of the 66 patients, 24 [36%, 95% confidence interval (CI): 25-49%] achieved complete remission (CR). Thirty-eight patients were resistant to EMA chemotherapy and four patients died from toxicity during aplasia. After CR achievement, 18 patients received consolidation therapy. Five patients with an HLA-identical sibling donor underwent allogeneic stem cell transplantation (SCT), one patient received autologous SCT, two patients received a second course of EMA chemotherapy, and ten were scheduled for 6-monthly maintenance courses (mini-EMA). Median follow-up was 7.3 years. At the time of analysis, 21 of the 24 patients (87%) who achieved CR have relapsed. Median disease-free survival (DFS) was 5 months (95% CI: 4.3-7.7 months). Median overall survival (OS) was 5 months (95% CI: 3.8-6.7 months). There were only two long-term remitters (3%). In the univariate analysis, CR achievement was mainly related to white blood cell (WBC) count at the time of starting salvage therapy with poorer outcome for patients with more aggressive leukemia (WBC count > or =10 x 10(9)/l) (CR rates: 50% vs 10%, p<0.001). Overall survival was also influence by WBC count (median OS: 7.2 months vs 2.8 months, respectively, for WBC or =10 x 10(9)/l, p<0.0001). Initial karyotype was not a significant prognostic factor either for CR achievement or for DFS or OS when comparing patients with normal karyotype and those with chromosomal abnormality. In multivariate analysis, WBC count less than 10 x 10(9)/l with the absence of circulating blasts at the time of starting salvage therapy appeared to be of favorable prognostic value for CR achievement ( p=0.002), while WBC count less than 10 x 10(9)/l appeared to be of favorable prognostic value for survival ( p<0.0001). Using these two objective parameters of proven significance, we devised a prognostic system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices. Patients with both factors (WBC count <10 x 10(9)/l and no circulating blasts) or with at least one at the time of starting salvage therapy had a CR rate of 50% and were therefore candidates for intensified post-remission therapy. All other patients displayed a very poor outcome and must be oriented after failure of first-line therapy to alternate therapeutic programs based on investigational drugs.
Adolescent↗
Therapy-related acute promyelocytic leukemia.
PURPOSE: To analyze patient cases of therapy-related acute promyelocytic leukemia (tAPL), occurring after chemotherapy (CT), radiotherapy (RT) or both for a prior disorder, diagnosed during the last 20 years in three European countries. PATIENTS AND METHODS: The primary disorder and its treatment, interval from primary disorder to tAPL, characteristics of tAPL, and its outcome were analyzed in 106 patients. RESULTS: Eighty of the 106 cases of tAPL were diagnosed during the last 10 years, indicating an increasing incidence of tAPL. Primary disorders were predominantly breast carcinoma (60 patients), non-Hodgkin's lymphoma (15 patients), and other solid tumors (25 patients). Thirty patients had received CT alone, 27 patients had received RT alone, and 49 patients had received both. CT included at least one alkylating agent in 68 patients and at least one topoisomerase II inhibitor in 61 patients, including anthracyclines (30 patients), mitoxantrone (28 patients), and epipodophyllotoxins (19 patients). Median interval from primary disorder to tAPL diagnosis was 25 months (range, 4 to 276 months). Characteristics of tAPL were generally similar to those of de novo APL. With treatment using anthracycline-cytarabine-based CT or all-trans-retinoic acid combined with CT, actuarial survival was 59% at 8 years. CONCLUSION: tAPL is not exceptional, and develops usually less than 3 years after a primary neoplasm (especially breast carcinoma) treated in particular with topoisomerase II-targeted drugs (anthracyclines or mitoxantrone and less often etoposide). Characteristics and outcome of tAPL seem similar to those of de novo APL.
Adult↗
Adult T-biphenotypic acute leukaemia: clinical and biological features and outcome.
Biphenotypic acute leukaemia with T-lymphoid and myeloid markers is rare and poorly documented. In the Leucemie Aigue Lymphoblastique de l'Adulte (LALA) prospective trial (LALA 94) of treatment for adult acute lymphoblastic leukaemia (ALL), seven patients (0.86%) had T-biphenotypic forms. The clinical and biological characteristics and outcome of these seven patients are reported here. The patients' median age was 35 years. At diagnosis, all had a tumoural syndrome and five had a mediastinal mass. In all the cases, leukaemic cells expressed myeloid and lymphoid markers. Two patients (28%) entered complete remission (CR) after induction chemotherapy. Four of the five remaining and assessable patients entered CR after designed salvage chemotherapy with mitoxantrone and high-dose cytosine arabinoside. Three patients are currently in CR. Three patients died, from treatment toxicity in two cases and progressive disease in one case. One patient relapsed 6 months after allogeneic bone marrow transplantation and is still alive. Thus, biphenotypic T-acute leukaemia is clinically frequently associated with mediastinal involvement and the response to conventional chemotherapy used in ALL is poor. However, sustained CR can be achieved by salvage chemotherapy combining an intercalating agent with high-dose cytosine arabinoside, as used in acute myeloid leukaemia.
Acute Disease↗
Anthracycline-related toxicity requiring cardiac transplantation in long-term disease-free survivors with acute promyelocytic leukemia.
We describe three cases of acute promyelocytic leukemia (APL) with long-term disease-free survival who developed congestive heart failure (CHF) requiring cardiac transplantation. All three patients presented late-onset cardiotoxicity. Cardiac failure occurred progressively after 31-month, 32-month, and 14-month intervals, respectively, following completion of first anthracycline therapy. Cumulative anthracycline doses were 585 mg of daunorubicin and 64 mg of mitoxantrone in case 1, 1779 mg of daunorubicin in case 2, and 825 mg of daunorubicin in case 3. The questions relating to the pathogenesis of cardiac failure are discussed. We also discuss the prophylactic measures required for such treatment-related side effects.
Adult↗
Prognostic significance of FLT3 internal tandem repeat in patients with de novo acute myeloid leukemia treated with reinforced courses of chemotherapy.
FLT3 internal tandem duplications (FLT3-ITDs) are present in nearly 25% of patients with AML and have been associated with poor response to conventional therapy and poor outcome. We retrospectively evaluated the effect of reinforced courses of chemotherapy on the prognostic value of FLT3-ITDs in 159 AML patients prospectively enrolled in the ALFA-9000 trial, which randomly compared three reinforced induction regimens (standard 3+7 including high-dose daunorubicin, double induction, and timed-sequential therapy). FLT3-ITD was present in 40/159 (25%) blast samples and associated with high WBC (P = 0.002) and cytogenetics (P < 0.001) with a higher incidence (35%) in patients with a normal karyotype. There was no difference in CR rate between FLT3-wt and FLT3-ITD patients (80% vs 78%). Relapse-free survival (RFS) was similar in both groups (5-year RFS, 33% vs 32%; P = 0.41), even after adjustment for age, sex, WBC, cytogenetics, and treatment arm. A trend to a worse survival was observed in the FLT3-ITD group (estimated 5-year OS, 23% vs 37%; P = 0.09), mainly in patients with a normal karyotype. This was associated with a dramatic outcome in relapsing FLT3-ITD patients (estimated 3-year post-relapse survival, 0% vs 27%; P = 0.04). These results suggest that the bad prognosis associated with FLT3-ITDs in AML might be partly overcome using reinforced chemotherapy. Early detection of FLT3 mutations might thus be useful to intensify induction as well as post-remission therapy in FLT3-ITD patients.
Acute Disease↗
Treatment of acute lymphoblastic leukemia in the elderly: an evaluation of interferon alpha given as a single agent after complete remission.
Although interferon (IFN) has been used in elderly patients with acute lymphoblastic leukemia (ALL), the benefits from IFN therapy have not been properly assessed, especially as it was given combined with other cytotoxic drugs, which obscured the role of IFN if any. In 1997, we started a study aimed at improving our previous results in elderly patients with ALL and at assessing the therapeutic role of IFN in this disease. Fifty-eight patients with ALL, aged 55-81 years (median: 64.9 years), were randomly allocated to treatment with vindesine or vincristine during induction. After a first consolidation course, IFN was administered as a single agent for three months together with cranial radiotherapy. Chemotherapy was then resumed with a second consolidation course and maintenance. A complete remission (CR) was obtained in 58% of patients (CI: 45-71%), significantly less than in our previous study which included IFN combined with chemotherapy during maintenance (CR: 85%, CI:70-94%, p = 0.007). Overall survival (median: 289 vs 434 days in the previous study, p = 0.01) and disease-free survival (median: 146 vs 427 days, p = 0.009) were also inferior in the present study. In particular, the pattern of relapses over time suggested that the 3 month IFN treatment phase with no additional chemotherapy might have contributed to the comparatively poor outcome of this cohort. In addition, vindesine given during induction did not prove less neurotoxic than vincristine, did not improve the CR rate, and had no impact on survival. In conclusion, although similar to published studies in elderly patients with ALL, this study is inferior to our previous one. INF, given as a single drug, has a modest role if any in the treatment of older persons with ALL.
Aged↗
Influence of cigarette smoking on the presentation and course of acute myeloid leukemia.
BACKGROUND: It is known that cigarette smoking is associated with an approximately 50% increase in leukemia risk. In order to detect a possible influence of cigarette smoking on initial characteristics at the time of presentation and on the course of the disease, we conducted a retrospective study in 643 patients with newly diagnosed acute myeloid leukemia. PATIENTS AND METHODS: The study comprised 339 males and 304 females (median age 59 years, range 18-84 years). Two hundred and ninety-six patients (46%), smoking at least one cigarette per day for 6 months, were considered as smokers, while 347 patients (54%) were non-smokers. RESULTS: Cigarette smoking was significantly related to male gender (P <0.0001), professional occupancy (P = 0.002), presence of organomegaly (P = 0.01), and lower peripheral blood and bone marrow leukemic cell involvement (P = 0.007 and P = 0.0001, respectively). Leukemia of French-American-British (FAB) M1 subtype was more frequent in non-smokers (P = 0.005). Although not statistically significant, smokers tended to have lower leukocyte counts than non-smokers. No difference was noted in terms of complete remission rates between smokers and non-smokers (67% compared to 64%). However, a higher rate of severe pulmonary infection was observed in smokers during induction chemotherapy (P = 0.02). Cigarette smoking (>or=20 pack-years or smoking duration >or=30 years) was significantly associated with shorter disease-free survival (P = 0.03) and overall survival (OS; P = 0.02 and P = 0.004, respectively). Other characteristics associated with poor prognosis included mainly older age, unfavorable karyotype, secondary acute myeloid leukemia (AML) and elevated World Health Organization (WHO) performance status. Cigarette smoking was associated with shorter OS in younger adults, but did not significantly influence survival in patients >60 years old. Cigarette smoking worsened the poor OS in patients with unfavorable karyotype, but did not significantly influence the prognosis of other karyotypic risk groups. In a multivariate analysis, only karyotypic grouping and age remained of prognostic value for the occurrence of disease-free and overall survival. CONCLUSIONS: Cigarette smoking has a deleterious effect on survival in AML by shortening complete remission duration and subsequent survival. It was associated with severe infections during aplasia. Leukemogenic compounds favoring complex karyotypic abnormalities could also be involved.
Acute Disease↗
Expression of high Km 5'-nucleotidase in leukemic blasts is an independent prognostic factor in adults with acute myeloid leukemia.
Cytarabine (ara-C) requires activation into its triphosphorylated form, ara-CTP, to exert cytotoxic activity. Cytoplasmic 5'-nucleotidase (5NT) dephosphorylates ara-CMP, a key intermediate, preventing accumulation of ara-CTP and may reduce cellular sensitivity to the cytotoxic activity of ara-C. To determine whether the level of expression of 5NT is correlated with clinical outcome in patients with acute myeloid leukemia (AML) treated with ara-C, this study analyzed the levels of messenger RNA expression of high Km 5NT by real-time polymerase chain reaction at diagnosis in blast cells of 108 patients with AML. High Km 5NT was expressed at diagnosis in the blast cells of 54% of patients. In univariate analysis, (1) patients whose blast cells contained high levels (values greater than the median value for total population) of high Km 5NT at diagnosis had significantly shorter disease-free survival (DFS) than patients with low levels of high Km 5NT (11 months versus 17.5 months, P =.02) and (2) high levels of high Km 5NT also predicted significantly shorter overall survival (15.7 months versus 39 months, P = .01) in young patients (< or = 57 years; median value for the entire population). In a multivariate analysis taking into account age, karyotype risk, and other factors found to have prognostic significance in univariate analysis, (1) high Km 5NT expression was an independent prognostic factor for DFS and (2) high levels of high Km 5NT also predicted significantly shorter overall survival in young patients. These results demonstrate that the expression of high levels of high Km 5NT in blast cells is correlated with outcome in patients with AML.
5'-Nucleotidase↗
Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome.
PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12% and 38% +/- 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.
Adolescent↗
Acute lymphoblastic leukemia in the elderly: The Edouard Herriot Hospital experience.
Data on all patients with acute lymphoblastic leukemia (ALL) aged 60 or older, referred to our institution over a 18-year period, were studied to determine the incidence and range of clinical and biological subtypes, and the outcome of different therapeutic approaches. Sixty-nine ALL cases (median age: 68 years) were diagnosed between 1980 and 1998 (18% of all adult ALL seen during this period). Ten of them (14%) had a past history of previous malignancy. Karyotypic analysis was performed successfully in 42 cases. Ten patients were diagnosed as Philadelphia chromosome positive (Ph(+)) ALL. Immunophenotyping was performed in 63 cases. Fifty-six patients had B-cell lineage ALL. T lymphoid markers were observed only in 5 cases. Co-expression of myeloid markers was observed in 19% of tested cases. Five patients died before any chemotherapy could be given. All other patients received "curative" treatment according to different protocols used during the period of study. Overall complete remission (CR) rate of these patients was 62% (95% confidence interval (CI): 50-74%). Thirty-nine patients achieved CR after one course of chemotherapy and 4 patients after salvage therapy. Median disease-free survival (DFS) of the entire cohort was 8.3 months (95% CI: 5-12.8 months) and median overall survival was 7 months (95% CI: 6-10 months). In multivariate analysis, the presence of hemorrhage (P = 0.02) was a poor prognostic for CR achievement. Higher WHO performance status (P = 0.003) and the presence of hemorrhage (P = 0.01) at diagnosis were poor prognostics for overall survival. When patients were stratified into three groups according to the time of admission, survival appeared significantly longer for patients admitted between July 1992 and December 1998 (median overall survival at 10 months) than for patients admitted before July 1992 (P = 0.04). "Age-adapted" therapy appeared superior to "young adult-like" therapy in terms of CR rate (96% versus 60%; P = 0.007). However, "age-adapted" therapy did not show any advantage in terms of DFS or overall survival, making the difference in CR rates questionable. We conclude that the pejorative overall outcome in elderly ALL points to the need for new therapeutic trials taking into account the specific characteristics of ALL in this age group.
Age Factors↗
Autologous transplantation in acute myeloid leukemia: peripheral blood stem cell harvest after mobilization in steady state by granulocyte colony-stimulating factor alone.
In order to determine whether granulocyte colony-stimulating factor (G-CSF) alone initiated during steady state was able to mobilize peripheral blood stem cells (PBSC) in acute myeloid leukemia (AML) and to assess predictive factors for engraftment after autologous PBSC transplantation, we studied 49 successive adult AML patients for whom autologous transplantation was planned between July 1994 and November 1998. G-CSF was used as priming agent and was initiated at least 4 weeks after the last day of chemotherapy, while neutrophil count was >0.5 x 10(9)/l and platelet count was >30 x 10(9)/l. A median of three aphereses was performed resulting in a median collection of 14.8 x 10(8) nucleated cells/kg containing 7.7 x 10(8) mononuclear cells/kg, 47.1 x 10(4) CFU-GM/kg, and 3.8 x 10(6) CD34+ cells/kg. A significant correlation was observed between nucleated cell, mononuclear cell, and CFU-GM yields, while no correlation was found with CD34+ cell yield. Recruitment was not significantly different in patients with CD34+ leukemic cells at the time of initial diagnosis when compared to that of those presenting with CD34- blastic cells. Thirty-three patients actually underwent transplantation. Reasons for not autografting were inadequate stem cell harvest (ten patients), early relapse (two patients), prolonged neutropenia (one patient), organ failure (two patients), or patient refusal (one patient). Median time to achieve a neutrophil count greater than 0.5 x 10(9)/l and platelet count >50 x 10(9)/l untransfused was 13 and 36 days, respectively. A predictive factor for a shorter period neutropenia and a shorter thrombopenia was a higher count of harvested nucleated cells (p < 0.01 and p = 0.02, respectively). A higher count of harvested cells was also a predictive factor for less red cell and platelet transfusions (p=0.03 and p=0.02, respectively). The number of CD34+ harvested PBSC was not predictive for engraftment. We conclude that PBSC mobilization with G-CSF alone initiated in steady state is a feasible, safe, and suitable procedure for harvesting cells in sight of autologous transplantation in adult acute myeloid leukemia.
Aged↗
Prognostic factors and treatment effects on survival in acute myeloid leukemia of M6 subtype: a retrospective study of 54 cases.
UNLABELLED: classification system of acute myeloid leukemia (AML) which designates it as M6 AML. This report describes the data of 54 patients with newly diagnosed M6 AML, consecutively seen in our hospital between May 1976 and May 1999. PATIENTS AND METHODS: There were 40 males and 14 females. Median age was 59 years. Pancytopenia was the most common feature at diagnosis. Twenty-six percent of cases presented with secondary AML. Karyotype was successfully performed in 35 cases. Eleven patients presented with normal karyotype, nine with simple karyotypic abnormalities, and fifteen with major karyotypic abnormalities. Fifty of the fifty-four patients received one or two courses of induction chemotherapy combining anthracyclines with cytarabine according to different successive protocols. One elderly patient only received low-dose cytarabine, and three patients died before any chemotherapy could be given. RESULTS: Complete remission (CR) was achieved in 29 cases (54%, 95% confidence interval (CI): 40%-67%). As post-remission therapy, four patients could be allografted, and two underwent autologous transplantation. All other treated patients received continuation chemotherapy. Twenty-one patients have relapsed (72%). Median time to relapse was six months. Among those patients, only eight achieved a second CR (38%). The median disease-free survival (DFS) was eight months (95% CI: 4-10 months) with a five-year survival rate of 17%. Median overall survival (OS) was nine months (95% CI: 5-12 months) with a five-year survival rate of 13%. In univariate analysis, poor prognostic factors for DFS were secondary AML (P = 0.05) and initial platelet count <50 x 109/l (P = 0.02). Poor prognostic factors for OS were age > or = 60 years (P = 0.005), secondary AML (P = 0.05), initial 'blastic' fever (P = 0.0004), and initial haemoglobin level < 90 g/l (P = 0.03). All factors, but haemoglobin level, remained significant in the multivariate analysis. Although it was not statistically significant, there was a trent for a better prognosis of M6 patients presenting with normal karyotype as compared to those displaying chromosomal abnormality. CONCLUSIONS: This retrospective analysis points to a somewhat heterogenous group of AML in terms of clinical and biological features, and outcome. Distinctive subgroups can be identified according to prognostic factors related to survival. A larger multicenter study with well-defined diagnostic criteria is warranted to further clarify treatment effects.
Adult↗
Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period.
Although the prospect of long-term leukemia-free survival (LFS) after treatment for adult acute lymphoblastic leukemia (ALL) is widely accepted, few studies have reported long-term survival data. Three hundred and seventy-eight ALL patients, referred to our hospital from 1978 to 1999, were reviewed for long-term follow-up data. The analysis included data on 351 patients treated by standard chemotherapy according to 11 different successive and/or concomitant regimens. Complete remission (CR) was achieved in 299 patients (79%). Initial performance status, LDH level, immunophenotype, age, and risk group (defined according to Hoelzer's criteria) at diagnosis were of significant prognostic value for CR achievement. Median leukemia-free survival (LFS) was 14 months with a 3-year, a 5-year, and an 8-year LFS at 30%, 26%, and 24%, respectively. LFS was better in T cell lineage ALL than in B cell lineage ALL (P = 0.05). Younger age was also a favorable prognostic factor for LFS (P = 0.001). Philadelphia-positive (Ph+) ALL displayed a poor outcome since median LFS was 7 months with only 13% of survival at 3 years. Median overall survival (OS) of the entire cohort was 18 months with a 3-year, a 5-year, and an 8-year OS at 32%, 24%, and 22% respectively. Favorable prognostic factors for OS were younger age (P < 0.0001), and T cell lineage ALL (P = 0.001). Among non-T cell lineage ALL, standard-risk ALL confirmed a significant better outcome than high-risk ALL (P = 0.0003). It was apparent from this analysis that hazard rates for death and relapse were greatest in the first year, decreased substantially between years 1 and 2, then decrease further between years 2 and 3. Rates of death and relapse were quite low after 3-4 years. All patients relapsing after 3 years of CR were B or non-B non-T cell lineage ALL. Long-term survivors (LTS), defined as survival in CR > or =3 years, represented 23% of evaluable patients. Eighty-three patients remain alive in initial CR at >3 years, while only three were LTS after a second CR. Overall, no significant improvement was shown in terms of CR achievement and survival duration over the years. However, regarding survival, a significant improvement was demonstrated in T cell lineage ALL (P = 0.03). Furthermore, patients (aged less than 50 years) transplanted while in first CR did significantly better than those receiving only chemotherapy as post-remission therapy (P < 0.0001). The 3-year OS, after allogeneic transplantation in first CR, was 74% in T cell lineage ALL, while it was less than 50% in B cell lineage ALL. This single center study on a large cohort of ALL patients reflects the degree to which ALL treatment remains unsuccessful in adults. Only T cell lineage ALL outcomes have improved over the years. The results suggest a time (3 years) at which it becomes reasonable to speak of potential cure, provided the patient is in CR.
Adolescent↗
[Acute myeloid leukemia in the elderly: a review].
The diagnosis and management of acute myeloid leukemia (AML) in the elderly is reviewed, including the basic aspects of epidemiology, cytogenetics, and prognostic factors. AML at higher ages is associated with several unique biologic and clinical characteristics. It generally arise from an early level of hematopoietic stem cells, and has a particularly high incidence of poor prognostic karyotypes. Effective treatment of the elderly patient with AML remains a challenging task. The importance of therapeutic approaches and promising new drugs is summarized. Prospective randomized studies clearly demonstrate that elderly patients benefit from intensive induction therapy. Hematopoietic growth factors accelerate the recovery from treatment-induced neutropenia and may improve the outcome. In patients not eligible for intensive chemotherapy, prospective studies testing different palliative or moderately intensive treatments are needed to improve quality of life and survival. New treatment strategies need to be developed to further improve on the therapeutic perspectives for elderly patients with AML.
Acute Disease↗
[Effectiveness of combined vancomycin and pefloxacine in gastrointestinal decontamination for preventing infections after chemotherapy-induced bone marrow aplasia. A randomized double-blind study].
OBJECTIVE: To test the value of the combination of pefloxacin and vancomycin as gastro-intestinal tract decontamination for the prevention of infections in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Oral pefloxacin plus vancomycin (48 patients), pefloxacin alone (51 patients), or placebo (52 patients) were administered in a randomized double-blind study. Evaluation was done by determining site and documentation of infections, organisms responsible for bacteriologically documented infections, organisms acquired in surveillance cultures and number of days with fever during aplasia. RESULTS: Patients receiving pefloxacin had significantly fewer episodes of bacteremia with enterobacteriacae. No differences were noted between patients treated by pefloxacin and those who received a combination of pefloxacin with vancomycin regarding gram-positive (Gram+) infections and infections with gram-negative (Gram-) organisms usually resistant to pefloxacin. However, placebo gave similar results. There was no induction of resistance to pefloxacin during the study. Tolerance of treatment was excellent. Only a prolonged aplasia has been observed in patients receiving pefloxacin. CONCLUSION: Thus, the combination of vancomycin with pefloxacin was not more efficacious than pefloxacin only for the prevention of Gram+ infections in the neutropenic patient. The systematic use of antibiotics as gastrointestinal tract decontamination for the prevention of infections in patients with aplasia may be questionable.
Adult↗
Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis.
Acute myeloid leukemia (AML) presenting with hyperleukocytosis is generally of poor prognosis due to an increased early death rate and a lower response to initial chemotherapy. Between April 1985 and December 1995, all patients with newly diagnosed AML admitted to our institution with an initial white blood cell (WBC) count greater than 100 x 10(9)/l were scheduled to undergo leukapheresis. This represented 53 patients (median age 59 years, range 16-78 years) who underwent from 1 to 4 sets of leukapheresis (median 1). The median initial WBC count was 160 x 10(9)/l (range 100-480 x 10(9)/l). Morphologic subtypes, according to the French-American-British classification, showed 3 M0, 16 M1, 6 M2, 10 M4, 16 M5, and 2 unclassified cases of AML. In 21 patients (40%), leukapheresis did not reduce their WBC counts significantly, while 32 patients (60%) achieved a WBC count of less than 100 x 10(9)/l (median 71 x 10(9)/l) after leukapheresis. Analysis of cell cycle was performed on bone marrow (BM) and peripheral blood leukemic cells before and after leukapheresis in three cases. In two of those cases, a recruitment of BM leukemic cells in the S phase was observed after leukapheresis. The median WBC count at the time of starting chemotherapy was 85 x 10(9)/l (range 23-264 x 10(9)/l). Complete remission was achieved in 55% (95% confidence interval 40-68%). Early death occurred in two cases. Median disease-free survival was 10 months, while median overall survival was 8 months. In this study, early death rate is lower than data previously published in the literature and almost all patients could receive chemotherapy. This might suggest a benefit of initial leukapheresis in the treatment of AML presenting with hyperleukocytosis.
Adolescent↗