Combined drug treatment of Hodgkin's disease: remission induction, remission duration, and survival; an appraisal.
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Adult↗
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Results for “Remission Induction”
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Oscillations of marrow culture growth in acute myeloid leukemia during remission induction and remission.
Sequential studies in acute myeloid leukemia of bone marrow cells in agar culture showed striking fluctuations of colony and cluster formation during induction of remission. These oscillations may be initiated by recruitment of resting leukemic and normal cells upon chemotherapeutic perturbation. Striking oscillations of the colony and cluster formation occurred also during remission with or without maintenance therapy, but with a longer periodicity as compared sto the phase of induction of remission. Oscillations of the marrow growth capacity during remission may reflect potential relapses where the outcome depends on proliferative advantages of the normal or leukemic cell clone.
Adult↗
Remission induction and remission duration with primary radiotherapy in advanced lymphosarcoma.
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Adult↗
Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen.
Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.
Acute Disease↗
[Therapy of acute leukemia. 4. Remission induction and remission maintenance therapy].
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Acute Disease↗
Fibrinopeptide A changes during remission induction treatment with L-asparaginase in acute lymphoblastic leukemia: evidence for activation of blood coagulation.
L-Asparaginase, a widely used antileukemic agent, inhibits liver protein synthesis leading to hypofibrinogenemia and hypoprothrombinemia together with a severe reduction of antithrombin III and protein C. An increased risk of thrombosis has been reported in leukemic patients treated with this agent. We measured fibrinopeptide A (FPA) changes in 14 patients with acute lymphoblastic leukemia during induction remission treatment with a protocol including L-Asparaginase (10,000 U/m2/daily intravenous for 14 days). At diagnosis, 9/14 patients had FPA level above upper limit of normal range (mean = 4.1 ng/ml). After two days of therapy, FPA rose to 5.2 ng/ml and thereafter showed a slight increase throughout. Antithrombin III, protein C and fibrinogen dropped to its nadir on day 6 and 9. However, the ratio FPA/fibrinogen on a molar basis showed a three-fold increase during this days, demonstrating that the thrombin-dependent consumption of fibrinogen was also increased. In conclusion, our data show that activation of blood coagulation occurs in concomitance with the hemostatic derangement caused by L-Asparaginase. Replacement therapy with the recently available antithrombin III concentrates may be worthy of a clinical trial to test its effectiveness in preventing the thrombotic phenomena reported in these patients.
Adolescent↗
Vincristine and prednisone vs vincristine, L-asparaginase, and prednisone for second remission induction of acute lymphocytic leukemia in children.
Second remission induction rates for vincristine and prednisone alone (VP) and vincristine, L-asparaginase, and prednisone (VLP) are compared for children with acute lymphocytic leukemia. No evidence of a significant difference between the second induction complete remission rate for VP (78.6%) and VLP (73.7%) was found. Duration of first remission and prognostic group at initial diagnosis (defined on the basis of age and white blood count at initial diagnosis) are shown to be significant prognostic factors for second remission induction; and three second remission induction risk groups are defined on the basis of these two factors. Periodic reinforcement with prednisone in first remission does not appear to lower second induction complete response (CR) rates for VP. There was no evidence of a significant difference in the frequency of occurrence of severe toxicity between the VP and VLP regimens.
Adolescent↗
Apoptosis induction in peripheral leukemia cells by remission induction treatment in vivo: selective depletion and apoptosis in a CD34+ subpopulation of leukemia cells.
In vitro studies demonstrating the induction of programmed cell death by cytotoxic drugs used in anticancer chemotherapy suggested that antileukemic treatment eliminates leukemia cells by apoptosis. We therefore analyzed apoptosis induction and activation of apoptosis signaling molecules in patients receiving remission induction treatment for AML and ALL during the initial phase of leukemia cell reduction. A coexistence of distinct populations of CD34(+) and CD34(-) leukemia cells could be identified. During chemotherapy, CD34(+) leukemia cells were more rapidly depleted than CD34(-) cells. Furthermore, a significant increase in leukemia cell apoptosis ex vivo was detected in CD34(+) cells, while no such increase was observed in the CD34(-) subpopulation, suggesting that CD34(+) leukemia cells are the main targets for apoptosis induction through antileukemic treatment. No alterations in Bax and Bcl-2 expression were found during in vivo chemotherapy, and CD95 expression and sensitivity remained low, indicating the induction of apoptosis independent of the CD95 system or regulation of protein levels of Bax and Bcl-2. The data suggest that analysis of leukemia cell subpopulations is required for further identification of apoptosis signaling molecules relevant for response to treatment and assessment of drug efficacy in vivo and in vitro.
Adult↗
Use of the day 6 bone marrow to alter remission induction therapy in patients with acute myeloid leukaemia: a leukemia intergroup study.
Patients with acute myeloid leukaemia who fail to show substantial bone marrow cytoreduction by day 6 of induction therapy enter complete remission (CR) less frequently than patients with good bone marrow leukaemic cytoreduction. The objective of the current study was to determine whether an increase in the intensity of therapy on days 8, 9 and 10 ('augmentation' of remission induction therapy) for patients with poor bone marrow cytoreduction detected in the day 6 bone marrow could improve the complete remission rate without increasing the number of toxic deaths. Patients from six centres were entered and treated with standard dose ara-C for 7 or 10 d and an anthracycline for the first 3 d. Patients aged less than 60 years and with greater than 30% bone marrow biopsy cellularity or greater than 10% abnormal cells on the aspirate obtained 6 d after the start of therapy were augmented with cytosine arabinoside 3 g/m2 every 12 h on days 8, 9 and 10. Therapy was augmented in 116 of the 252 patients less than 60 years. There was a highly statistically significant difference between augmented and nonaugmented patients (P less than 0.001) for the per cent biopsy cellularity and per cent abnormal cells in the day 6 marrow. The CR rate for augmented patients was 69% and for nonaugmented patients 60% suggesting that augmentation therapy abrogated the prognostic significance of more extensive residual leukaemia in the day 6 bone marrow. The results suggest that augmentation of remission induction for patients with poor bone marrow cytoreduction detected 6 d after initiation of therapy, may salvage patients who are destined to fail remission induction because of resistant disease without producing excessive toxicity.
Adult↗
High-dose cytosine arabinoside remission induction for acute myelogenous leukemia: comparison of two regimens of remission maintenance.
We report a single institution sequential trial of two maintenance treatment regimens for patients with acute myelogenous leukemia (AML). A total of 175 consecutive patients with AML received initial remission induction therapy with high-dose cytosine arabinoside (ara-C) and glucocorticoids. For the initial 63 patients (group A), the control population, planned maintenance treatment was with conventional-dose ara-C given over 4 days for up to 18 months. The subsequent 107 patients (group B) had planned maintenance therapy of up to 6 courses of daunorubicin, ara-C and prednisone and daily cis-retinoic acid for up to two years. The presenting features of group A and B patients were similar as were the response to remission induction, 60 and 52%, respectively. Severe neurological toxicity was encountered once after high-dose ara-C; no drug-related deaths occurred during maintenance treatment. Median duration of remission for group B patients was 9.9 months compared with 5.5 for group A (p = 0.0685). Median survival duration for the two groups was similar, 9.1 months for group A and 10.4 for group B. Survival of patients in group B who attained a complete remission was significantly better than that of patients in group A (p = 0.0439). The studies confirm our initial experience with remission induction using single agent high-dose ara-C and suggest a positive role for maintenance therapy in AML.
Acute Disease↗
Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia.
With the recent pressure to control health care expenditures, the costs of patient participation in clinical trials, especially in their earliest phases, have come under increasingly intense scrutiny. We therefore reviewed our experience in patients with acute promyelocytic leukemia (APL) who were treated during the first US trial of a new experimental drug, all-trans retinoic acid (RA). The purpose of the review was to evaluate parameters of patient morbidity and financial cost associated with the use of all-trans RA compared with standard chemotherapy for induction of complete remission in newly-diagnosed patients with APL. We retrospectively compared outcomes of consecutive patients treated during the first 2 years of our studies that used all-trans RA for remission induction (1990-1992) with an identical number of patients consecutively treated with standard chemotherapy (cytosine arabinoside plus an anthracycline) during the immediately preceding period (1985-1990). Responding patients in both groups received post-remission chemotherapy. Evaluation parameters included transfusions of packed red blood cells and platelets, use of anti-bacterial and anti-fungal drugs, duration of fever, time to remission, length of hospital stay, hospital charges, and both overall and relapse-free survival. Thirty patients were evaluated in each group. Complete remission was achieved in 26 patients (87%) treated with all-trans RA, and 24 patients (77%) treated with chemotherapy (p = 0.5). In the chemotherapy group, there were five early deaths (four from hemorrhage, one from sepsis); one other patient was resistant to treatment and died at 6 months. Four patients in the all-trans RA group died prior to response from complications of the 'retinoic acid syndrome'. The median time to complete response by all criteria was 41 days (range, 18-78) for the all-trans RA group and 50 days (range, 24-121) for patients who received conventional chemotherapy (p = 0.2). Looking only at patients who achieved remission, chemotherapy-treated patients required a significantly greater number of platelet transfusions (medians, 14 vs. 4; p < 0.001) and packed red blood cell transfusions (15 vs. 4; p < 0.001). Patients who received chemotherapy also experienced a significantly larger number of days with fever (13 vs. 6; p = 0.01) that was reflected in a greater median number of days on combination antibiotics (35 vs. 21; p = 0.001) and Amphotericin B (20 vs. 0; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Combination therapy of M2-protocol and interferon-alpha as remission induction in refractory multiple myeloma.
A successful induction of remission in two patients with resistant multiple myeloma using a new combination therapy of modified M-2 protocol and interferon-alpha (IFN-alpha) is described. The first case was a 32-year-old man with K type urinary Bence-Jones protein who became resistant after treatment with melphalan and prednisone (MP protocol). IFN-alpha alone had a marginal response. The modified M-2 protocol proved insufficient. Therefore, IFN-alpha was administered in the interval of M-2 protocol. This combination therapy showed remarkable responses. The second case was a 59-year-old woman with advanced IgA myeloma who was treated with M-2 protocol and became resistant. IFN-alpha alone resulted in a slight response. After addition of IFN-alpha to the modified M-2 protocol, a rapid reduction in the level of serum IgA was found and clinical symptoms including bone pain, anaemia and so on were dramatically improved. No infection and/or intolerable side effects were observed in either case. This combination treatment appears worthy to try in cases of resistant or relapsing myeloma patients.
Adult↗
High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia.
We determined the incidence and complications of disseminated intravascular coagulation (DIC) at presentation and during remission induction of previously untreated adults with acute lymphoblastic leukemia (ALL) or de novo Philadelphia chromosome-positive ALL (PCALL) seen at Memorial Hospital between January 1, 1978 and December 31, 1989. DIC was diagnosed in the presence of (1) low fibrinogen (less than or equal to 160 mg/dL), (2) prolonged prothrombin time (PT) and falling fibrinogen, or (3) prolonged PT and positive fibrin split products (FSP). L-Asparaginase was not used during remission induction. Among adequately screened patients with ALL, DIC was detected in 7 of 58 (12%) before initiation of chemotherapy and in 35 of 45 (78%) during remission induction. DIC was not simply the result of infection because clinical and laboratory signs of infection were absent in 16 patients, whereas only 2 of the 22 febrile patients with DIC had positive cultures. Among the 38 patients with DIC at presentation or during remission induction, serious complications were seen in 13 in temporal association with DIC (pulmonary embolus in one, sagittal sinus thrombosis in three, and serious hemorrhage in nine) and were major factors in the deaths of three patients. Among the 10 patients with thorough screening but no evidence of DIC there was only one hemorrhage during the same time interval. In patients with PCALL, DIC was detected in 9% at presentation and in 80% during remission induction. We conclude that DIC is rare at presentation but common during remission induction of adult ALL and PCALL and may be associated with significant thrombotic and hemorrhagic complications. We suggest daily screening for DIC during the first 14 days of remission induction. The treatment of DIC in ALL and PCALL should be a subject of future clinical studies.
Adult↗
Remission induction therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines.
Remission induction therapy with vincristine, a corticosteroid, L-asparaginase and an anthracycline has been the mainstay of the initial phase of treatment for childhood acute lymphoblastic leukaemia (ALL) for the past 25 years. The speed and depth of the early response to remission induction therapy has become an important determinant of the intensity of subsequent therapy in many protocols worldwide. Moreover, the detection of significant levels of minimal residual disease at the end of remission induction may have an important bearing on subsequent outcome. Although these clinical observations may reflect, in part, the inherent sensitivity of lymphoblasts to remission induction therapy, the pharmacology of these agents in relation to childhood ALL may also play an important part in early response to therapy. In-vitro studies of human leukaemia cell lines indicate that both the extracellular fluid concentration and duration of exposure to vincristine and anthracyclines are important determinants of cytotoxicity. For L-asparaginase and corticosteroids, the cellular and molecular pharmacological determinants of chemosensitivity have been partially characterized, but further work is needed in this area. The clinical pharmacology of vincristine and L-asparaginase have been well characterized in relation to childhood ALL, and considerable interpatient pharmacokinetic variability exists for these drugs. For corticosteroids and anthracyclines, pharmacology studies are needed in order to fully characterize and understand the factors influencing interpatient pharmacokinetic variability for these agents in relation to childhood ALL. Whereas the relationship between the clinical pharmacology, and potentially important pharmacodynamic effects such as asparagine depletion, has been well characterized for therapy with L-asparaginase, similar studies have yet to be performed for the other drugs that form the mainstay of remission induction therapy for childhood ALL. Therefore, further studies are required to investigate the relative importance of the clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines in the speed and depth of response to remission induction therapy for childhood ALL. Where these have been studied, interindividual differences in the clinical and cellular pharmacology of anticancer agents have been shown to be important determinants of the long-term disease-free survival for children with ALL.
Antibiotics, Antineoplastic↗
[Chemotherapy of gastric and rectal cancers incorporating non-radical irradiation during remission induction. 1].
For the remission induction therapy of advanced gastric and rectal cancer, 25 cases were treated by non-radical irradiation (total doses: 3000-6000 rad) combined with tegafur, which minimized the tumor mass. For the reduction of tumor mass, a modified method of FAMT was employed and for the maintenance therapy of long-term chemotherapy a modified method of FAMT, MFE, MF or tegarfur alone were performed. Prolongation in survival was obtained with this combination therapy: Of 25 cases, 11 cases survived longer than one year and 6 cases longer then two years. One case of survived rectal cancer obtained disease-free for about 8 years with this treatment. But the observation period was too short to calculate one-year and two-year survival rates of all cases. The indications for application of this combination therapy were as follows; (1) Locally operable cases with myocardial infarct, heart insufficiency, poor risk or refusal of operation, (2) Very aged patients, (3) Locally inoperable cases without clinical metastasis, and (4) Primary lesion of gastric cancer with small metastasis controllable by tegafur. It was concluded that over 3000 rad of irradiation combined with tegafur was necessary to obtain the sufficient radiation effect. As for side effects, loss of appetite , leukopenia and a few case of gastric bleeding by radiation were noted. From the result this treatment modality appears to be valuable in the management of gastric and rectal cancer.
Antineoplastic Combined Chemotherapy Protocols↗
[Is cellular immunity not impaired after remission induction in acute lymphoblastic leukemia in children].
UNLABELLED: We examined immune system at the time of diagnosis and after remission induction in the group of 30 children (aged 6.5 +/- 3.6) with acute pre-B lymphoblastic leukaemia (ALL). The group was divided into standard risk group (treated with BFM protocol, n = 20) and high risk group (New York protocol, n = 10). We measured: episodes of infection, leukocytosis, immunoglobulin concentrations (G, M, A and E), lymphocytes and their subpopulations (CD19+, CD3+, CD3 + HLA-DR+, CD4+, CD8+, CD4 + CD45RA+, CD4 + CD45RO+, CD8 + CD45RA+, CD8 + CD45RO+, CD16 + CD56+). RESULTS: Immunoglobulin concentrations at the time of diagnosis were normal, and decreased after remission induction only reduction of IgG concentration was statistically significant (p = 0.008). At the time of diagnosis we noted the following differences in examined group compared to control group: higher leukocytosis (p = 0.03), lower lymphocyte count (p = 0.0008), significantly lower lymphocyte subpopulation count (for subpopulations CD19+; CD3+; CD4+; CD8+ and CD16 + 56+). After remission induction comparing to the time of diagnosis we observed: total leukocytosis reduction (p = 0.01), percentage and count CD19+ lymphocytes reduction (adequately p = 0.000007, p = 0.03), increase of lymphocyte CD3+ percentage (p = 0.002) and CD8+ lymphocyte percentage (p = 0.00003). CONCLUSIONS: 1. At the time of diagnosis of acute lymphoblastic leukaemia in children lower counts of all lymphocyte populations are observed. 2. Immune suppression after remission induction in this group of patients concerns mainly humoral response, particularly immunoglobulin G production. 3. Severe infections in patients treated for acute lymphoblastic leukaemia are indication to immunological system assessment and early immunoglobulin supplementations of deficits e.g. immunoglobulin infusions. 4. Humoral immunity impairment in children with ALL is an effect of treatment, not disease.
Adolescent↗
Benefit of high-dose methylprednisolone in comparison with conventional-dose prednisolone during remission induction therapy in childhood acute lymphoblastic leukemia for long-term follow-up.
Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group B). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together </=2 or >/=10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count >/=50 x 10(9)/l, the 8-year EFS was 38% in group A vs58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.
Adolescent↗
Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia.
BACKGROUND: The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS: The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS: Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes) during remission induction, including 4 toxic deaths (11%). In contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS: Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL.
Antineoplastic Agents, Hormonal↗