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PubMed1975

Combination chemotherapy for children with acute lymphocytic leukemia who fail to respond to standard remission-induction therapy.

Short courses of cytosine arabinoside (Ara-C), cyclophosphamide, and L-asparaginase were given to seven children with newly diagnosed acute lymphocytic leukemia, who had failed to remit on standard remission induction therapy. These 4-day courses of Ara-C and cyclophophamide followed by 4 days of L-asparaginase were repeated at 3- to 4-week intervals for two or four courses. Complete remission occurred in six patients. The median duration of remission was 94+ days, on various maintenance regimens. The most serious side effect was neutropenia. This combination of these three drugs appears to be effective remission-induction therapy for children with ALL with unfavorable prognostic features.

Asparaginase↗

PubMed2006

Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.

Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention (RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region (range 36-76%) and the two-year overall survival, with no censored observations (6-21%) (chi-squared for trend=11.3, P<0.001; r2=0.86, P<0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates (P=0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.

Acute Disease↗

PubMed1989

Correlation of morphology, immunophenotype, and flow cytometry with remission induction and survival in high grade non-Hodgkin's lymphoma.

A series of cases of high grade non-Hodgkin's lymphomas has been studied by morphology (110 cases), immunocytochemistry (90 cases), using reagents reactive in fixed paraffin-embedded tissue, and flow cytometry (77 cases). B-cell tumours constituted 67.0 per cent of the total, T-cell tumours 22.0 per cent, and unclassified cases 8.8 per cent. Immunocytochemistry revealed two anaplastic carcinomas. Of the 77 cases studied by flow cytometry, 67.5 per cent were diploid and 32.5 per cent DNA aneuploid. T-cell tumours were more likely to be diploid than B-cell tumours, though the difference did not reach statistical significance. T-cell tumours had a significantly lower proliferative index (%S + G2) than B-cell tumours (P = 0.002). The overall remission induction rate was 68 per cent and actuarial 3-year survival 47 per cent. There was a trend for cases with %S + G2 less than 22 per cent to survive longer (P = 0.07). This trend became statistically significant when aneuploid cases were added to the high PI group (P = 0.04). No correlation was seen between morphological or immunophenotypic groups and remission induction rates or survival.

Adolescent↗

PubMed1995

VAD chemotherapy as remission induction for multiple myeloma.

A total of 142 patients with multiple myeloma received VAD as remission induction therapy. Seventy-five were previously untreated and 67 had relapsed (31) or refractory disease (36). Vincristine (total dose 1.6 mg) was infused with doxorubicin 36 mg m-2 by continuous ambulatory pump over 4 days. In addition, oral dexamethasone 40 mg day-1 was given for 4 days. Intermittent dexamethasone was only given to 19 patients. Courses were repeated every 21 days. The overall response rate was 84% [27% complete response (CR)] in previously untreated patients and 61% (3% CR) in patients with relapsed and refractory disease. The median survival was 36 months for untreated patients and 10 months for those who had received prior therapy. VAD was well tolerated; however, despite prophylaxis, 54% patients received antibiotics at some time during therapy and 37% had dyspepsia. Twenty-three patients subsequently received a transplant (eight allografts, eight marrow autografts and seven peripheral blood stem cell transplants). Eight have died-four in the allogeneic group and four in the autologous group. The overall median survival of transplanted patients has not yet been reached. VAD is an effective, out-patient therapy for inducing remission in multiple myeloma. Post-remission therapy needs to be optimised, but it is likely that the needs of previously untreated patients may be different from those with relapsed and refractory disease.

Adult↗

PubMed1980

Selective use of daunorubicin for remission-induction chemotherapy in acute non-lymphoblastic leukemia.

Twenty-eight patients with acute non-lymphoblastic leukemia (ANLL) were started on induction chemotherapy consisting of Cytosine Arbinoside (Ara C) and 6 thioguanine (TG). Daunorubicin (DNR) was used selectively in 20 of 28 patients who failed to respond by day 14 to the Ara C and TG combination. Seven patients, or 25%, achieved complete remission (CR) without requiring DNR during remission induction. The overall response rate was 89% (64% CR and 25% PR). The median duration of survival for the CR group was 578 days. 189 days for the partial remission (PR) group (P = .02). Patients in the age groups of 18--40 years and with acute myelomonocytic leukemia subtype had the best response rate. There was no difference in the survival of the DNR treated group of complete responders as compared to DNR non-treated group. These results suggest that even though the majority of patients do require DNR for the remission induction, a significant number, perhaps as high as 25% of previously untreated patients, will achieve remission without the use of DNR. A significant minority of patients, therefore, be spared the toxicity of DNR early in the course of their disease.

Adolescent↗

PubMed1978

Acute promyelocytic leukemia. Management of the coagulopathy during daunorubicin-prednisone remission induction.

Seven adults with acute promyelocytic leukemia (APL) and disseminated intravascular coagulation were treated for remission induction with daunorubicin hydrochloride and prednisone. In all patients the coagulopathy was managed with continuous-infusion heparin sodium and vigorous transfusion with platelets, cryoprecipitate, and fresh frozen plasma. Five patients survived induction; they all achieved complete remission (CR). Median duration of CR was 27 + months; two patients presently survive in their initial CR at 28 and 48 months. Recognition of APL as a distinct type of acute leukemia and prompt initiation of treatment aimed at rapid cytoreduction and control of the coagulopathy has resulted in a prolonged disease-free survival for the majority of patients.

Adolescent↗

PubMed1977

High remission-induction rate in acute myeloid leukaemia.

28 adult patients with acute myeloid leukaemia (A.M.L.) received T.A.D., a high-dose sequential chemotherapeutic remission-induction regimen consisting of 7-day courses of cytosine arabinoside, 6-thioguanine, and daunorubicin. Overall response-rate was 82%. 22 patients (79%) achieved complete remission, and 1 had a partial remission. Median remission duration was 280 days and median survival 375 days. 10 patients remain in remission. These induction results are superior to those reported in most studies and indicate that disease remission can be achieved in a high proportion of patients with A.M.L. treated with an intensive multi-agent chemotherapeutic regimen, provided support facilities are adequate.

Administration, Oral↗

PubMed1989

[Remission induction treatment in adults with acute myeloid leukemia. 8-year experience with 2 successive protocols].

We report our eight year experience remission induction therapy in adult patients with acute myeloblastic leukemia. Overall 67 patients were treated, with a mean age of 43.3 years (range 15-75). Two treatment protocols were used. Complete remission (CR) was achieved in 23 patients of 39 receiving protocol A (58%). The 28 last patients were treated with the more aggressive protocol B, and CR was achieved in 23 patients (82%). CR was achieved in 68% of the overall group. The most outstanding predictive factors were age above 30 years, and M-5 morphology as indicating a poor prognosis.

Adolescent↗

PubMed1992

[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia].

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.

Adult↗

PubMed1977

Remission induction with daunomycin, vincristine, and prednisone in adult acute lymphocytic leukemia.

Prednisone plus vincristine plus daunomycin induced complete remission in nine adults with acute lymphocytic leukemia. The median duration of complete remission will be between 14 and 18 months, with three patients remaining in hematological remission at 10+, 11+, and 18+ months. The median survival will be between 19 and 23 months, with all patients surviving at least one year. This remission induction regimen produced rapid complete remission in adult acute lymphocytic leukemia (ALL) with minimal toxicity, and could be administered predominantly on an outpatient basis.

Adolescent↗

PubMed1986

Plasma adriamycin levels during remission induction therapy: RIA versus HPLC.

Plasma concentrations of adriamycin and adriamycinol were measured in patients with acute nonlymphocytic leukemia during remission induction therapy with araC adriamycin and cytosine arabinoside. Blood samples were analyzed at 10 min, 1, 3, 6 and 24 hrs after the end of the first, second and third daily injection of adriamycin, using high pressure liquid chromatography and a commercially available radioimmuno assay. Overall, 65 samples were compared, with the correlation coefficient r = 0.765-0.920 for the different time points. The combined correlation coefficient for 57 samples was 0.853. These correlations were significant at the p = 0.005 level.

Chromatography, High Pressure Liquid↗

PubMed1993

Idarubicin for remission induction of acute myeloid leukemia: United Kingdom multicenter experience.

Ninety-eight adult patients with acute myeloid leukemia were given variable remission induction/consolidation regimens containing idarubicin. Sixty-nine (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24) or had primary refractory disease (n = 5) (median age, 46 years). Complete remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed patients, with no difference for those below or above 55 years of age (56% v 59%) or for patients exhibiting white blood cell counts of less or more than 50 x 10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of the total number of patients) remain in CR with a median follow-up of 3 months (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24 patients) and 60% of the primary refractory disease cases (three of five patients) achieved CR. Of these 13 responders, six are alive (three continuing in CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20 months), and seven have died with a median survival of 7 months (range, 0 to 12 months). Of the 52 patients who have achieved CR, 84% did so with one course of treatment and 16% with two courses. The presence of normal cytogenetic analysis or favorable chromosomal aberrations significantly improved overall CR rates. The patients in this study had significantly more unfavorable cytogenetic abnormalities than the historic controls. Reported toxicity was hepatic in 13%, cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable efficacy of idarubicin to other anthracyclines in remission induction of acute myeloid leukemia, with a promising role in relapsed/refractory disease.

Acute Disease↗

PubMed1991

Alterations in oral microflora and pathogenesis of acute oral infections during remission-induction therapy in patients with acute myeloid leukaemia.

To investigate changes in the aerobic and facultatively anaerobic oral microflora during remission-induction chemotherapy in patients with acute myeloid leukaemia, 10 consecutive patients were studied during a period of 28 days. During antineoplastic treatment, the concentration of microorganisms in saliva doubled from day 0 to day 2, presumably as a result of a concurrent 64% decrease in the salivary flow rate. No changes in the relative proportion of individual microorganisms or acquisition of new microorganisms occurred during antineoplastic treatment. During antibacterial treatment, which was subsequently initiated in all patients, a 100-fold decline occurred in the median salivary concentration of microorganisms within the first 7 days. During this period, members of the normal flora became undetectable in 5 patients, and Enterobacteriaceae, Enterococcus faecalis or Candida spp. became parts of the quantitatively predominant oral microflora in 7 patients. Apart from Candida spp., these potentially pathogenic microorganisms were acquired only after the initiation of the antibacterial treatment. After termination of the antibacterial treatment, the median concentration of microorganisms increased again to the original level and normal flora became reestablished within a period of 8 days. Clinically, 10/20 acute oral infections emerged before day 8, i.e. within the period with increased concentrations of microorganisms in saliva. Specifically, the clinical diagnosis of acute oral candidiasis was associated with a rise in the concentration of Candida spp. above a critical value of 1,000 CFU/ml. Herpes simplex virus (HSV) type 1 was detected in 4/9 HSV-seropositive patients on days 14 and 21, and HSV-1 was in all 4 cases isolated simultaneously with the emergence of an intraoral ulcer. The results suggest that chemotherapy-induced xerostomia plays a significant role in the pathogenesis of acute oral infections and transmission of potentially pathogenic microorganisms is of importance mainly after initiated antibiotic treatment in these patients.

Aclarubicin↗

PubMedDate not supplied

A novel strategy for remission induction and maintenance in cancer therapy.

The p53 tumor suppressor gene plays an important role in protecting cells from developing undesirable proliferation. The mutant p53 gene or malfunctioning p53 protein found in more than 50% of cancer cells impedes DNA repair or apoptosis induction. This may be why some cancers gain resistance to chemotherapy and radiation and become more resistant after frequent cancer treatments. A non-toxic p53 gene activator would induce cancer cell apoptosis and help damaged cancer cells to recover. Therefore, the combination use of chemotherapeutics or radiation with a non-toxic p53 gene activator will be crucial in cancer therapy, damaging DNA with chemotherapeutics or radiation on the one hand and promoting apoptosis induction with p53 gene activator on the other. This strategy would be most efficient for remission induction and maintenance in cancer therapy. Antineoplastons are naturally occurring peptides and amino acid derivatives that control neoplastic growth. Antineoplaston A10 and AS2-1 are chemically identified and synthesized antineoplastons proven to inhibit cancer cell growth by arresting the cell cycle in the G1 phase and inhibiting tumor growth by reducing mitosis. These agents are thought to be good candidates for clinically easily applicable non-toxic p53 gene activators. Our cases of advanced cancer responded well to combination treatment using chemotherapeutics and irradiation with antineoplaston A10 and AS2-1 in clinical trials being conducted in Kurume University Hospital. We describe herein the clinical cases and discuss the possible mechanism of action of this combination therapy.

Adult↗

PubMed1977

Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone.

Fifty-six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA). The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p less than 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p less than 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p less than 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed. The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.

Child, Preschool↗

PubMed1989

[Effect of remission induction chemotherapy on blood coagulability in patients with gynecological malignancies].

In 12 patients (38 courses) with gynecological malignancies who had been treated with remission induction chemotherapy, we measured the levels of ESR, Platelet, PT, APTT, Hepa T, AT III, alpha 2 PI, FDP and D-dimer, and we also measured such molecular markers as Fibrinopeptide A (FPA), Fibrinopeptide B beta 1-42 (FPB beta 1-42), and Fibrinopeptide B beta 15-42 (FPB beta 15-42) before and after chemotherapy. Then the relation between the post chemotherapeutic trends and prognosis for patient with gynecological malignancies were investigated. 1) Before chemotherapy, the levels of ESR, FDP, D-dimer and FPB beta 1-42 were increased, PT and APTT were shortened significantly in cases on groups IIIrd and IVth stage compared with in cases on groups Ist and IInd stage (p less than 0.05). The levels of FPA were also high, but there was no significant differences. The levels of FPB beta 15-42 were almost same in both groups. However, the each markers indicated the existence of chronic DIC in cases of group IIIrd and IVth stage. 2) One week after chemotherapy, the levels of ESR, fibrinogen, FDP and FPA were decreased, while FPB beta 1-42 and FPB beta 15-42 were increased, suggesting elevated fibrinolytic activity. Two weeks after chemotherapy, there was stronger tendency to coagulation dominant again, but it was only temporary. Three weeks after chemotherapy, the hemostatic balance was regained. 3) In patient with complete remission after effective chemotherapy, their coagulability data were showed within normal range, however, some cases with poor prognosis were not able to obtain the recovery of hemostatic balance, and the levels of molecular markers were significantly elevated. Coagulative activity was more enhanced than fibrinolytic activity in patients with progressive gynecological malignancies, but hemostatic balance was maintained clinically. The hemostatic balance was disrupted by the chemotherapy, but this balance was regained for the IIIrd week. Accordingly, the recovery of hemostatic balance with effective chemotherapy is related to the prognosis for patients with gynecological malignancies, and the levels of molecular markers may be able to expect the prognosis for patients.

Adult↗

PubMed1992

[Disappearance of Philadelphia chromosomes after remission induction in lymphoid crisis of chronic myelogenous leukemia].

The authors report a rare case of chronic myelogenous leukemia (CML) in which the Ph1 clone disappeared after remission induction of lymphoid crisis. A 58-year-old man was admitted to our hospital because of fever in July 1988. The white cell count was elevated. Bone marrow aspirate showed hypercellularity with myeloid hyperplasia. In the chromosomal analysis, Ph1 chromosomes were detected in 100% of bone marrow cells analysed. Diagnosis of CML was made and treatment was initiated with recombinant interferon-alpha 2a. Hematological remission without cytogenetic improvement was achieved. In March 1990 he developed lymphoid crisis with proliferation of CD10-positive cells. The chromosomal analysis revealed additional abnormalities including, 45, X, -Y, t(9;22) (q34;q11), +1, -8. With vincristine 0.6 mgX4, pirarubicin 15 mgX4, dexamethasone 40 mgX4 therapy complete remission was obtained. In December 1990 the Ph1 positive clone completely disappeared judging from normal karyotypes in the chromosomal analysis and the disappearance of M-bcr gene rearrangement.

Blast Crisis↗

PubMed1995

Autologous stem cell transplantation after first remission induction treatment in multiple myeloma. A report of the French Registry on Autologous Transplantation in Multiple Myeloma.

Eighteen French centers reported 133 autologous stem cell transplantations performed after first remission induction in multiple myeloma. The source of stem cell was marrow (81 cases), blood (51 cases) or marrow plus blood (1 case). The immediate outcome after transplantation was 49 (37%) complete remissions (CR; 13 maintained, 36 achieved), 61 (46%) partial remissions, 17 failures and 5 toxic deaths. With a median follow up of 35 months, the median remission duration was 33 months, the median time to treatment failure was 22 months. The median overall survival was 46 months, 54 months for the 103 patients responding to primary treatment and 30 months for the 30 nonresponders. In univariate analysis, the outcome was influenced by age, Ig isotype, initial beta 2-Microglobulin level, response to initial chemotherapy, plasma cell marrow involvement at the time of harvest, albumin and beta 2-Microglobulin level at the time of transplantation and CR achievement after transplantation. In multivariate analysis, the most important prognostic factor was the quality of response after transplantation. The conditioning regimen and the source of stem cell had no significant impact on immediate and long-term results. Maintenance therapy with alpha interferon did not appear to prolong remission duration or survival. Autologous stem cell transplantation is an effective consolidation for patients responding to primary treatment and a salvage therapy for some nonresponding patients. This approach has to be compared to conventional chemotherapy in prospective randomized studies. The critical impact of CR achievement on survival implies new strategies in order to increase the CR rate.

Adult↗