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Results for “Remission Induction”

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PubMed1996

Therapy of untreated acute myeloid leukemia in the elderly: remission-induction using a non-cytarabine-containing regimen of mitoxantrone plus etoposide.

PURPOSE: The University of Manitoba Adult Acute Leukemia Study Group sought to examine the safety, efficacy, and impact on quality of life of a non-cytarabine-containing remission-induction regimen followed by intermediate-dose cytarabine (IDARA-C) postremission therapy for the management of untreated acute myeloid leukemia (AML) in patients age 60 to 80 years. PATIENTS AND METHODS: Eligible patients received mitoxantrone 10 mg/m2 and etoposide 100 mg/m2 on days 1 to 5. Complete remitters received a single course of cytarabine 0.5 mg/m2 every 12 hours on days 1 to 6. Cytogenetic and immunophenotyping studies were performed at diagnosis and were examined for prognostic importance. The Functional Living Index-Cancer (FLI-C) was used in the longitudinal assessment of quality of life. RESULTS: A total of 37 (55%) of 67 eligible patients achieved remission, 34 (92%) of whom did so with a single course. The induction mortality rate was 12%. The median disease-free and overall survival times were 8.4 and 9.2 months, respectively. CD34 stem-cell phenotype, poor performance status, and high cytogenetic complexity score were independent covariates of failure to achieve remission. Very complex karotype combined with CD34 stem-cell phenotype to predict induction death in 67% of cases (P = .0003). Cytotoxic therapy-related gut epithelial damage was maximal during weeks 2 and 3 of therapy. Complete remitters and partial responders exhibited significantly improved global FLI-C scores following completion of therapy. CONCLUSION: Mitoxantrone plus etoposide was an effective and well-tolerated first-line induction regimen for AML in the elderly that should be studied further in comparison to the standard cytarabine/anthracycline-based therapy.

Acute Disease↗

PubMed1998

Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukemia.

We conducted a prospective, randomized, multicentre clinical trial comparing the effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly patients with acute myeloid leukaemia (AML). The patients were randomized to either daunomycin-cytosine arabinoside (control arm: n = 161) or daunomycin-cytosine arabinoside with GM-CSF (GM-CSF arm: n = 157). The primary end-point was the effect of GM-CSF on the percentage of complete remissions (CR). Survival duration, disease-free survival, quality of life and costs were evaluated separately. CR after remission induction treatment was achieved in 55% of the patients in the control group and in 56% of the patients in the GM-CSF group (P = NS). The duration of survival and disease-free survival at 2 years after randomization were estimated at 22% and 19% for the control group and 22% and 14% for the GM-CSF group (P = NS). Considering the short-term quality of life, the administration of GM-CSF resulted in more problems with regard to depressed mood, diarrhoea and rash/eczema. With regard to the long-term quality of life there were no significant differences between the two groups. The average costs of the primary treatment were higher in GM-CSF-treated patients than in the control group, i.e. US$40782 and US$34465, respectively (P < 0.01). The costs during the follow-up period did not differ between the two groups. The results of this randomized clinical trial indicate that daunomycin-cytosine arabinoside plus GM-CSF is not a cost-effective treatment strategy when compared with daunomycin-cytosine arabinoside alone.

Acute Disease↗

PubMed1994

Acute myeloid leukemia in Manitoba. The consequences of standard "7 + 3" remission-induction therapy followed by high dose cytarabine postremission consolidation for myelosuppression, infectious morbidity, and outcome.

BACKGROUND: To the authors' knowledge, the natural history of myelosuppression and infectious complications associated with the use of standard cytarabine (ARA-C) plus daunorubicin ("7 + 3") remission-induction therapy for adult acute myeloid leukemia (AML) and high dose ARA-C (HDARA-C) consolidation has not been described completely. METHODS: A retrospective study of untreated adult AML patients receiving standard 7 + 3 induction followed by "5 + 2" and HDARA-C consolidation was undertaken to describe the relationship of the myelosuppression profiles, blood product use, and infectious morbidity, and to correlate this finding with the outcome of antileukemic therapy. Multivariate techniques were used to evaluate variables of prognostic importance. RESULTS: Fifty-nine percent of the patients achieved remission after a median of 35 days; almost half (48%) of these patients required more than one 7 + 3 induction course. For one, two, and three induction courses, the mean number of days the patients experienced severe neutropenia (< 0.5 x 10(9)/l) were 22.5 +/- 10.9, 39.3 +/- 14.3, and 47.4 +/- 9.7 days (P < 0.001), respectively, and the infection rates were 1.45, 2.45, and 3 infections per course (P < 0.0001), respectively. The pattern of blood product use was similar. HDARA-C consolidation was the most significant factor related to prolonged disease free survival, however the myelosuppression profiles and infection rates were surprisingly similar to those for the single 7 + 3 induction courses. CONCLUSIONS: The 7 + 3 induction regimen used in this center provided only limited antileukemic activity, while requiring multiple induction courses in a high proportion of patients. The use of multiple induction courses had consequences of prolonged myelosuppression, increased blood product use, and incremental risks of infectious complications. HDARA-C consolidation for those who experienced complete remission appeared to improve disease free survival with myelosuppression comparable with that of patients who received primary induction therapy. The infection risk was acceptable, with only a marginal increase in bacteremic and fungal infections.

Adult↗

PubMed1997

Acyclovir prophylaxis and fever during remission-induction therapy of patients with acute myeloid leukemia: a randomized, double-blind, placebo-controlled trial.

PURPOSE: A randomized, double-blind, placebo-controlled trial was performed to estimate the preventive effect of the antiherpetic drug acyclovir on fever, incidence of bacteremia, use of antibiotics, and presentation of infections in patients with acute myeloid leukemia (AML). PATIENTS AND METHODS: Ninety herpes simplex virus (HSV)-seropositive patients aged 18 to 84 years were included. Forty-five patients received acyclovir (800 mg by mouth daily) and 45 placebo. The patients were examined daily for 28 days from the initiation of remission-induction chemotherapy. RESULTS: Fever developed in all patients in both groups. Acyclovir prophylaxis postponed the development of an oral temperature > or = 38.0 degrees C by 3 days (95% confidence interval [CI], 1 to 4 days; P = .03) and the initiation of antibacterial treatment by 3 days (95% CI, 1 to 5 days; P = .008). The duration of fever, use of antibacterial treatment, incidence of bacteremia, and need for systemic antifungal therapy were not affected by acyclovir prophylaxis. At fever development, acyclovir prophylaxis affected the incidence and localization pattern of oral ulcers. Thus, in the acyclovir group, the number of nonfungal oral infections was reduced (relative risk, 0.45 [95% CI, 0.24 to 0.85]) and mainly located on the soft palate (relative risk, 2.49 [95% CI, 1.19 to 5.22]). CONCLUSION: Acyclovir prophylaxis has an impact on fever development, but not on the duration of fever or the need for antibiotics. It does not reduce the incidence of bacteremia, but the presentation of acute oral infections is changed.

Acyclovir↗

PubMed2001

Intensive timed sequential remission induction chemotherapy with high-dose cytarabine for childhood acute myeloid leukemia.

BACKGROUND: Timed sequential chemotherapy and high-dose cytarabine (cytosine arabinoside, Ara-C; HDAC) are both effective treatments for acute myeloid leukemia (AML). We review our institutional experience with timed sequential induction chemotherapy consisting of daunorubicin/Ara-C/-thioguanine (DAT) or idarubicin/Ara-C/-thioguanine (IAT) followed on day 14 by HDAC regardless of the degree of marrow aplasia for children with newly diagnosed AML. PROCEDURE: Children presenting with newly diagnosed AML were treated with induction chemotherapy consisting of idarubicin (12 mg/m/day on days 1-3 or daunorubicin at 45 mg/m(2)/day for the first five patients), Ara-C (100 mg/m(2)/day by continuous infusion on days 1-7), and thioguanine (100 mg/m(2)/day on days 1-7). HDAC (1 g/m(2)/dose every 12 hr for 10 doses) was administered beginning on day 14, regardless of the results of bone marrow examination. RESULTS: Thirteen children received timed sequential HDAC. Only one child received HDAC later than Day 18. Eleven of the children achieved a complete remission. All patients experienced grade 4 hematologic toxicity, and all had fever as well. There were 11 children with documented infections. Ten had grade 3 or 4 GI toxicity. One patient died of sepsis. CONCLUSIONS: HDAC administered as a part of timed sequential therapy yields an excellent remission induction rate with manageable toxicity.

Adolescent↗

PubMed1989

Remission induction in children with acute non-lymphocytic leukemia using cytosine arabinoside and doxorubicin or daunorubicin: a report from the Childrens Cancer Study Group.

Four hundred ninety evaluable patients were treated on an induction regimen consisting of two to four courses of cytosine arabinoside plus an anthracycline. Overall, 78% of patients went into remission, 10% died during induction, and 12% were induction failures. For the first 152 patients, courses consisted of 7 days continuous infusion with cytosine arabinoside (Ara-C, 100 mg/m2) and 3 days of doxorubicin (30 mg/m2). Because of unacceptable toxicity, particularly for children less than 3 years of age, the anthracycline was changed to daunorubicin, and the doses of both induction drugs for children under 3 was reduced. For children aged 3 years and older the change in anthracycline was associated with a significant increase in induction failures (7% to 16%, P = .04) and a decrease in deaths (15% to 8%, P = .09). For younger children, for whom doses were also changed, the effect was greater; Mortality decreased from 29% to 1% (P less than .0001), and the remission induction rate increased from 66% to 88% (P = .005). The therapy modifications also influenced survival following remission induction: Daunorubicin-treated patients, aged 3 years and over, did significantly better than those given doxorubicin (P = .03), but the opposite was seen in younger children (P = .06). Gastrointestinal and skin toxicities and septicemia were significantly more common when doxorubicin was being used, but the extent of myelosuppression was similar for the two anthracyclines.

Age Factors↗

PubMed1995

[Electrolytic changes in children with acute lymphoblastic leukemia during remission induction].

The alterations of the water-electrolyte balance are among the commonest early complications of treatment in children with acute lymphoblastic leukaemia (ALL). A study was carried out in thirteen patients with ALL aged between 1.5 and 14 years. Four had high risk ALL and nine had standard risk ALL. All patients received intravenous epirubicin and vincristine, per os prednisone, allopurinol and bicarbonate, and intrathecal methotrexate and hydrocortisone. Venous blood was drawn before starting therapy and on days second and sixth of treatment in order to assay sodium, potassium, calcium, phosphate, magnesium, albumin, urea nitrogen, creatinine and uric acid concentrations. The following alterations were found: hyponatraemia in 4 cases, hypokalemia in 9, hypomagnesaemia in 9, hypocalcaemia in 11, hypophosphataemia in 9, hypouricemia in 3 and hyperuricaemia in 3 others. None of the patients developed acute renal insufficiency. These abnormalities could be due to the leukaemia itself or appear as a consequence of the remission induction treatment.

Adolescent↗

PubMed1998

Adjuvant treatment with cyclosporin A increases the toxicity of chemotherapy for remission induction in acute non-lymphocytic leukemia.

P-glycoprotein (Pgp)-related multidrug resistance (MDR) is frequently observed in acute non-lymphocytic leukemia (ANLL) and is associated with a poor response to standard chemotherapy. Cyclosporin A (CsA) is an effective downmodulator of Pgp-related MDR in vitro and has already been tested for that purpose in vivo also. Since Pgp is expressed in several normal cells and tissues, the modulation of Pgp can also modify total body exposure to antileukemic drugs and can alter and increase the toxicity of the antileukemic treatment. We report here the results of a study where 46 consecutive adult patients with ANLL were assigned to receive the same standard chemotherapy regimen of arabinosyl cytosine and idarubicin (IDA) for remission induction or consolidation, without or with CsA. Twenty-eight patients received 36 courses of chemotherapy without CsA and 18 patients received 32 courses of chemotherapy with CsA. CsA dose was 10-12.5 mg/kg/day and was given as a continuous i.v. infusion for 72 h. Whole blood CsA steady-state concentration ranged between 0.61 and 1.14 microM. The IDA area-under-the-curve was about twice as high in the cases that received CsA than in the other cases. CsA had no detectable effects on renal function and fluid balance, but significantly increased systemic blood diastolic pressure and conjugated bilirubine concentration. Furthermore, CsA-treated patients had greater, and more severe, oral and intestinal mucosal toxicity, with more severe adverse events, including more cases of gram-negative bacteremia, and with a delayed hemopoietic recovery. In conclusion, this study showed that an attempt at an effective downmodulation of Pgp-mediated MDR would substantially increase the hemopoietic and mucosal toxicity of antileukemic treatment and that the increase is accounted for, at least in part, by an increase of total body exposure to IDA.

Adult↗

PubMed1978

[Clinical and cell kinetic data on the combination of cytosine arabinoside with daunorubicin, isosfamide, thioguanine, and vincristine for remission induction and maintenance in patients with acute myelocytic leukaemia (author's transl)].

31 adult patients (study A) with acute myelocytic leukaemia were treated for remission induction with cytosine arabinoside (ARA-C, 100 mg/m2/day) by a 7 (5) day continuous infusion. 3 (2) doses of daunorubicin (DNR, 45 mg/m2 i.v.) were added at daily intervals. For maintenance 5 day ARA-C was given monthly in sequential combination with DNR, thioguanine (TG), or ifosfamide (IFOS). 16 (52%) patients achieved complete remission (C.R.) after 1.8 (1-3) courses and 6.7 (3-10) weeks from treatment start. The median survival for responders and non-responders was 11.5 months, early death rate within 6 weeks was 3 (10%). Median remission duration was 13.5 months. Among 11 patients surving for 7-22 months 7 patients are in first remission for 5.5-20.5 months. DNR, IFOS and TG were given before the 3rd day of ARA-C infusion. In a previous group of 34 leukaemic patients and in 44 therapy courses DNA histograms of bone marrow cells using pulse cytophotometry showed marked accumulation in S-phase for 75% of courses. Also (G2 + M)-cells in the DNA distribution and thymidine pulse labelling indices were markedly increased in most cases, whereas thymidine uptake by scintillation counter was diminished and mitotic indices had not changed significantly. In now 15 patients (study B) the induction regimen was intensified by adding vincristine (VCR, 2 mg i.v.) and 3 doses of IFOS (600 mg/m2 i.v.). Preliminary results are 50% C.R. after 1,7 (1-2) courses and 6.8 (5-10) weeks from initiation of therapy. 2 patients died in the first 6 weeks.

Adolescent↗

PubMed1984

Relationship between the per cent of marrow cells in S phase and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia.

The relationship between the pretherapy cell cycle characteristics of leukaemic marrow cells and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia was studied in newly diagnosed and relapsed patients who were then treated with either combination chemotherapy consisting of cytosine arabinoside/anthracycline antibiotic +/- 6 thioguanine or with single agent high-dose cytosine arabinoside therapy. The outcome of high-dose cytosine arabinoside therapy was highly dependent upon the per cent of pretherapy cells in S phase with no remissions occurring in patients in whom the 3H-TdR labelling index was less than 6%. In contrast, the outcome of cytosine arabinoside/anthracycline antibiotic therapy was independent of the pretherapy cell cycle characteristics of the leukaemic cells.

Acute Disease↗

PubMedDate not supplied

Infectious toxicity of dexamethasone during all remission-induction chemotherapy: report of two cases and literature review.

Traditionally, children with acute lymphoblastic leukemia receive prednisone, as part of multiagent remission-induction chemotherapy. Recently, many cooperative groups use dexamethasone instead of prednisone during induction. We describe the infectious toxicities experienced by the first two patients in our institution treated with dexamethasone (10 mg/m(2)/day for 4 weeks with gradual tapering) during induction according to the dexamethasone arm of BFM 2000 and review the relevant literature that suggests an increased risk of infectious complications with dexamethasone. Only a prospective two-arm ALL dexamethasone study at two dose levels (6 and 10 mg/m(2)/day) will clarify if indeed the higher dose of dexamethasone during induction is more effective and without unacceptable toxicity.

Adolescent↗

PubMed1984

Pathologic data of prognostic significance for remission induction in advanced ovarian carcinoma.

Sixty-eight patients with "advanced ovarian carcinoma" were entered into an ongoing phase-II trial for remission induction with cis-platinum (DDP) 80 mg/m2 i.v. on day 1 followed by forced saline diuresis, melphalan (L-PAM) 12 mg/m2 i.v. on day 2 and hexamethylmelamine (HMM) 130 mg/m2 p.o. X 14 days from days 8-21 in six monthly cycles following operative resection and/or staging. Fifty-one patients were evaluable for response, ten had not completed six courses and could not be assessed, two patients died early (one probably of toxicity), and five patients refused treatment and follow-up. Thirty-Two patients had serous, endometrioid or undifferentiated carcinomas of the ovary. Of these, 11 (35%) achieved a pathologically proven complete remission (CR), five (16%) were NED after second-look (residual disease in ovary or removed omentum with all other biopsies and cytology washings negative), eight (32%) achieved a partial remission (PR), and three (12%) had progressive disease. None of the seven patients with clear-cell carcinoma and none of the three patients with Mullerian tumor of the ovary responded. Six of nine patients with tumors of uncertain origin or proven metastasis to ovary did not respond to treatment. These preliminary results indicate that advanced ovarian carcinomas form a heterogeneous group of recognizable neoplastic diseases with striking variation in response to treatment.

Adenocarcinoma↗

PubMed1988

Intermediate and high dose Ara-C and m-AMSA for remission induction and consolidation treatment of patients with acute myeloid leukemia: an EORTC Leukemia Cooperative Group phase II study.

Seventy-nine patients (aged 17-76 years) with acute myelogenous leukemia in first (56) or second (3) relapse, primary refractory leukemia (15) or leukemia occurring as secondary malignancy that developed after a preleukemic phase (3) or after another tumor (2) were given remission induction therapy consisting of cytosine arabinoside (Ara-C, 1 g/m2 as a 2-h infusion every 12 h for 6 days) and m-AMSA (120 mg/m2, i.v. on days 5, 6, 7). In total 45 patients (57%) achieved complete remission. Younger patients and those with a relatively low initial white blood cell count, a good performance status or in first relapse had a higher response rate. Thirty-five patients were given one or two courses of consolidation chemotherapy consisting of Ara-C (3 g/m2 as a 2-h infusion every 12 h for 4 days) and m-AMSA (120 mg/m2 i.v. on day 5). Three patients received an allogeneic bone marrow graft after the induction courses and four patients received an autologous bone marrow transplantation after consolidation therapy. The median of the disease-free survival curve was 21 weeks. The median duration of survival was 25 weeks. The response rate for this intermediate dose Ara-C regimen is satisfactory and does not differ from that reported for high dose Ara-C. The impact of consolidation chemotherapy in bad risk acute myelogenous leukemia is questionable.

Adult↗

PubMed1984

Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia.

Plasma adriamycin and adriamycinol levels were measured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels as found. Plasma levels increased after the administration of each of the three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.

Acute Disease↗

PubMed1980

Evaluation of hypercoagulability after remission induction chemotherapy of acute leukemia.

In 20 patients with acute leukemia the thrombin-mediated fibrin monomer complexes (SFMC) were determined before and after remission induction chemotherapy for several weeks to assess the extent of hypercoagulability. Increased levels of SFMC were observed in patients with high leukocyte cell counts after induction chemotherapy which may reflect the release of thromboplastic material from destructed leukemic cells. Patients with low leukocyte counts showed only a moderate increase in SFMC. A low concentration of antithrombin III (< 20 mg/100 ml) or a drop from a previously normal value was a prognostic unfavorable sign. An elevated level of plasmin-mediated fibrin-split-products could not be related to the course of therapy.

Acute Disease↗

PubMed1985

Ciprofloxacin for selective decontamination of the alimentary tract in patients with acute leukemia during remission induction treatment: the effect on fecal flora.

Ciprofloxacin, a new quinolone derivative, was given prophylactically (500 mg twice a day) to 15 patients with acute leukemia during remission induction treatment for a mean duration of 42 days. The effect on the microbial flora of the alimentary tract was evaluated. A rapid elimination of Enterobacteriaceae within three to five days was observed. Bacteroides and Clostridium species were not affected, but the number of anerobic nonsporeforming gram-positive bacilli and anaerobic cocci was decreased. Nine ciprofloxacin-resistant gram-negative rods (Pseudomonas and Acinetobacter species) were isolated but without colonization or subsequent infection. Four of the five bacteriologically documented infections in these patients were caused by gram-positive cocci. Ciprofloxacin was well tolerated, and no side effects were noticed.

Acinetobacter↗

PubMed1986

Remission-induction of acute lymphoblastic transformation of chronic myeloid leukaemia, followed by long-term maintenance therapy.

Acute lymphoblastic transformation of chronic myeloid leukaemia (LT-CML) of 7 consecutive patients was treated according to a remission-induction and maintenance therapy used for de novo acute lymphoblastic leukaemia (ALL). All 7 patients achieved a second chronic phase with a median remission duration of 15 months. Two patients showed an isolated central nervous system (CNS) relapse. This did not occur in the 4 patients, who received prophylactic therapy with intrathecal methotrexate. The second transformation was nonlymphoblastic in nature in 4 out of the 5 patients. A treatment protocol similar to that of a bad risk ALL, including long-term maintenance therapy and CNS-prophylaxis is indicated in lymphoblastic transformation of CML.

Adult↗

PubMed1983

[Herpes virus infections during a remission induction treatment in acute leukemias].

Herpes virus hominis infection was observed in 28% (diagnosis assessed on viral examination) to 33% (clinical suspicion) of 36 adult patients prospectively studied during remission induction chemotherapy for acute leukaemia. Symptoms are non specific so that diagnosis relies upon viral isolation. All infected patients but one survived the viral infection and the prognosis of the underlying acute leukaemia was unaffected.

Acute Disease↗