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Results for “Remission Induction”

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PubMed2000

Acute myeloblastic leukemia secondary to myelodysplasia (MDS-AML): a comparison of remission induction with three drugs versus standard two-drugs induction.

To evaluate the addition of a third drug to standard induction chemotherapy in patients with MDS-AML, 23 patients (males/females 13/10, median age 54.3 years, range 24-74 years, median MDS duration 9.8 months, range 2-39 months) who received a standard 2-drugs induction were compared with 23 patients (males/females 11/12, median age 45.6 months, range 21-60 years, median MDS duration 8.3 months, range 2-29 months) who received an intensified 3-drugs induction with etoposide. CR rate, median CR duration and median OS were similar in both groups (48% vs 56%, 4.8 vs 5.9 months, 6.5 vs 7.0 months respectively). Among responding patients, all but one, who underwent allogeneic bone marrow transplantation, relapsed. In conclusion, addition of a third drug (etoposide) does not seem to significantly improve the poor prognosis of MDS-AML patients.

Adult↗

PubMed2001

The prognostic value of Bcl-XL gene expression for remission induction is influenced by cytogenetics in adult acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: There is growing evidence that altered expression of genes belonging to the BcL-2 family of apoptosis regulators might influence chemotherapy-induced apoptosis in malignant cells and therefore could confer multidrug resistance. So far expression studies of apoptosis-regulating genes on acute myeloid leukemia (AML) have mainly focused on Bcl-2 itself and most of them have not included other factors involved in drug resistance or apoptosis as parameters determining response to chemotherapy, disease progression and survival. DESIGN AND METHODS: We therefore examined Bcl-2, Bcl-XL and Bax gene expression in 235 adult patients with de novo or secondary myeloid leukemia. The expression levels were correlated with established prognostic factors such as age, cytogentic aberrations, mdr1 gene expression and clinical outcome in a multivariate analysis. RESULTS: Bcl-2 and Bcl-XL positive patients had a much lower white blood cell count than negative patients (p<0.001 and p=0.003, respectively). Bcl-2 expression correlated with FAB subtype M0 (p=0.03), Bax with M5b (p=0.02) and Bcl-XL with M6 (p=0.005). Mdr1 expression was more frequently seen in Bcl-2 and Bcl-XL positive patients (p=0.03 and p=0.02, respectively). Remarkably Bax was significantly less frequently expressed in de novo AML patients with high risk cytogenetics (p=0.007). No difference in expression was recognized for Bcl-2 or Bcl-XL when statistical analyses were done for cytogenetic risk groups. However, in the multivariate analysis regarding the group of de novo AML patients < or =60 years with intermediate risk cytogenetics, Bcl-XL expression was found to be an independent negative prognostic factor for response to induction therapy (p=0.04). In contrast, no prognostic impact of Bcl-XL expression on treatment response was seen within the group of patients with high risk cytogenetic findings. Neither Bcl-2 nor Bax nor Bcl-XL expression had a significant influence on overall or disease-free survival. INTERPRETATION AND CONCLUSIONS: These data indicate that the prognostic value of Bcl-XL gene expression for treatment response in AML patients < or =60 years is dependent on cytogenetics.

Acute Disease↗

PubMedDate not supplied

Retrospective study of the prognostic factors of remission induction for single-agent chemotherapy with cisplatin in advanced epithelial ovarian cancer.

A retrospective study to explore the prognostic factor was conducted in 39 patients with advanced epithelial ovarian cancer, FIGO stage III-IV, who underwent single-agent adjuvant chemotherapy with cisplatin following primary debulking surgery. The survival rate following the adjuvant chemotherapy was 50.9% after 3 years and 44. 7% after 5 years, with a median survival time of 40.4 months. The actual dose intensity of the cisplatin ranged from 14.38 to 46.30 mg/m2/week, and the total dose/m2 was 143.79 to 645.83 mg/m2. Under these therapeutic conditions, the actual dose intensity was found to correlate with survival time (p<0.05), but there was no correlation between the total dose/m2 and survival time.

Adult↗

PubMed1988

Remission induction in non-Hodgkin lymphoma with reshaped human monoclonal antibody CAMPATH-1H.

A genetically reshaped human IgG1 monoclonal antibody (CAMPATH-1H) was used to treat two patients with non-Hodgkin lymphoma. Doses of 1-20 mg daily were given intravenously for up to 43 days. In both patients lymphoma cells were cleared from the blood and bone marrow and splenomegaly resolved. One patient had lymphadenopathy which also resolved. These effects were achieved without myelosuppression, and normal haemopoeisis was restored during the course of treatment, partially in one patient and completely in the other. No antiglobulin response was detected in either patient. CAMPATH-1H is a potent lympholytic antibody which might have an important use in the treatment of lymphoproliferative disorders and additionally as an immunosuppressive agent.

Aged↗

PubMed2006

Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of imatinib treatment on remission induction and allogeneic stem cell transplantation.

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has been associated with the worst patient survival rates of the various acute leukemias. Imatinib mesylate is a novel therapeutic agent that targets the BCR-ABL tyrosine kinase, the molecular abnormality associated with Ph+ ALL. The combination of imatinib with chemotherapy has led to improved and durable treatment responses in adult patients with Ph+ ALL, including the elderly population. Hematopoietic stem cell transplantation has also integrated imatinib into its transplant strategies, with early data suggesting improved progression-free survival without clearly identifiable augmented toxicity. Second-generation tyrosine kinase inhibitors offer potentially even greater improvements on these excellent imatinib-associated outcomes. This review addresses the evolution of the management of Ph+ ALL and is intended to assist in the description of its new natural history.

Antineoplastic Agents↗

PubMed1991

Remission induction of adjuvant arthritis in rats by total body irradiation and autologous bone marrow transplantation.

Following the demonstration that adjuvant arthritis in rats can be cured with total body irradiation (TBI) and allogeneic or syngeneic bone marrow, the efficacy of autologous bone marrow was investigated in the experiments reported here. Bone marrow from arthritic rats, harvested at the same time that the recipients were irradiated, and real autologous bone marrow were found to be similarly effective as bone marrow grafts from naive syngeneic donors. Sublethal TBI with lower doses was less effective, but the highest tolerated doses of 8 Gy approached the effect of 9 Gy and bone marrow rescue. In contrast, partial body irradiation of either the affected limbs, or of the whole body except the limbs, resulted in only partial and temporary regression of the arthritis.

Animals↗

PubMed1989

Prophylaxis of fungal infections with itraconazole during remission-induction therapy.

Deep fungal infections are an increasing problem in the treatment of acute leukemias and malignant lymphomas. Risk factors are known but unavoidable. Because of diagnostic difficulties most patients are treated empirically with intravenous amphotericin B. This drug's toxicity increases morbidity and mortality. An orally absorbable triazole derivative, itraconazole, may offer effective and safe prophylaxis against deep candidosis and aspergillosis in these patients. Such infections have been treated successfully with oral itraconazole even when resistant to intravenous amphotericin B. In retrospective comparative studies there are significantly less deep fungal infections in patients given itraconazole. The significance of the difference varies between studies. Pharmacokinetic data confirm therapeutic plasma levels of itraconazole but with wide variation within and between patients. The current large, multi-centre, randomised, double-blind, prospective trial of oral itraconazole versus placebo in the U.K. will test its prophylactic efficacy against deep fungal infections during treatment of haematological malignancies.

Adolescent↗

PubMed1992

Remission induction with carboplatin-epirubicin-prednimustine followed by consolidation radiotherapy in advanced ovarian cancer.

Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no clinical evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. This protocol was discontinued for five (23%) patients because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of ten stage-III ovarian cancer patients, who received chemoradiotherapy and were evaluable for assessment of treatment efficacy, was retrospectively compared with the survival of 11 stage-III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no evidence of disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Invasive fungal disease in adults undergoing remission-induction therapy for acute myeloid leukemia: the pathogenetic role of the antileukemic regimen.

Using multivariate techniques, we studied the relationships of cytotoxic regimen, intestinal mucosal damage, and fungal colonization in the pathogenesis of invasive fungal disease in 138 patients undergoing induction therapy for untreated acute myeloid leukemia (AML) according to three institutional protocols: AML-84 (cytarabine/daunorubicin), AML-87 (high-dose cytarabine/etoposide/daunorubicin), and AML-88 (mitoxantrone/etoposide). Invasive fungal disease occurred in 36%, 6%, and 2.6% of patients participating in protocols AML-87, AML-84, and AML-88, respectively (chi 2 = 23.465; P < .0001). Protocol AML-87 was the strongest independent predictor in the multivariate model (RR = 26.7; P < .0001). Cytotoxic therapy-related epithelial damage in the gut, as measured by D-xylose malabsorption, correlated with invasive fungal disease and protocol AML-87. Fungal colonization, a predictor of invasive fungal disease, correlated with frequent modifications of antibiotic regimens. These results demonstrate the role of cytotoxic regimen-related gut epithelial damage, antibiotic-prescribing behavior, and fungal colonization in the pathogenesis of invasive fungal disease in patients with leukemia.

Adolescent↗

PubMed1998

Adoptive immunotherapy for leukemia: donor lymphocytes transduced with the herpes simplex thymidine kinase gene for remission induction. HGTRI 0103.

This study will evaluate the safety and efficacy of allogenic donor lymphocyte infusions in patients who have relapsed hematologic malignancies after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow for retention of the anti-leukemia response of transfused donor lymphocytes while allowing for the adverse effects of GVHD to be mitigated. Patients with relapsed hematologic malignancies after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The Herpes Simplex thymidine kinase (HStk) gene will be transduced into the cells ex vivo using LTKOSN. 1 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effect of graft versus host disease, if it develops.

Clinical Protocols↗

PubMed2007

Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia.

In contrast to that in children, pharmacokinetic, pharmacodynamic, and safety information on pegaspargase in adults is very limited. We administered a single intravenous dose of pegaspargase (2000 IU/m2) as part of a standard frontline induction regimen to 25 adults with newly diagnosed acute lymphoblastic leukemia (ALL), and obtained serum samples on several time points. The population mean peak serum concentration of asparaginase enzymatic activity was 1 IU/mL, the elimination half-life was 7 days, and the volume of distribution was 2.43 L/m2. After the single dose, asparagine deamination was complete in all patients after 2 hours, and in 100%, 81%, and 44% on days 14, 21, and 28, respectively. A pharmocodynamic correlation model showed minimal enzymatic activity of 0.2 IU/mL for optimal asparagine depletion. The kinetic posthoc analyses demonstrated enzymatic activity for 3 weeks or more. One patient developed neutralizing antiasparaginase antibodies on day 22 after administration. Pegaspargase was well tolerated, with few grade 3/4 side effects. No allergic reactions or pancreatitis were observed. In adults aged 55 years or younger, pegaspargase produces a long duration of asparagine depletion and can be given intravenously, with a safety profile that is similar to equivalent multiple doses of intramuscular Escherichia coli asparaginase.

Adolescent↗

PubMed1997

Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: effects, role of patient pretreatment characteristics, and costs.

An early intensive anthracycline therapy can improve therapeutic outcome in adult acute lymphoblastic leukaemia (ALL) but is usually associated with marked myelosuppressive effects and significant morbidity by infections. To reduce this risk, we employed granulocyte colony-stimulating factor (G-CSF, filgrastim 5 microg/kg/d) as an adjunct to a myelotoxic, 14-day long induction regimen with idarubicin-vincristine-L-asparaginase-prednisone (IVAP). Owing to changes in study design, patients received 'late' (n = 28) or 'early' (n = 37) G-CSF from days 15 or 4 of IVAP, respectively, until resolution of severe neutropenia. Study endpoints included time to recovery from neutropenic nadir, duration of neutropenia <0.5 x 10(9)/l, incidence of infectious complications, assessment of variables affecting G-CSF response, clinical outcome and costs. Sixty-five consecutive cases were evaluable. Patients in early G-CSF group recovered significantly faster from the neutropenic nadir (p < 0.002), contracted less infectious complications (p = 0.007), and required less intravenous antibiotic (p = 0.008) and antifungal (p = 0.002) medications. Although these reductions did not compensate for the increased G-CSF treatment cost, the overall supportive care cost was not significantly increased by early G-CSF. Interestingly, T-ALL phenotype (p = 0.02) and higher neutrophil presentation count (p = 0.03) were associated with a shorter neutropenic course even with late G-CSF. Early G-CSF may be a valid approach to mitigate chemotherapy-induced neutropenia of IVAP and other similarly myelosuppressive adult ALL regimens.

Adolescent↗

PubMedDate not supplied

Response to multimodal treatment in advanced neuroblastomas. Factors associated with complete remission induction, and factors associated with prolonged survival.

The influence of patient and treatment variables upon the probabilities of response to chemotherapy in advanced neuroblastomas was investigated in 71 children with stages III-IV disease treated in Denmark between 1965-1980. The therapeutic regimens consisted of various combinations of chemotherapeutic agents with or without surgical excision of the primary tumour and irradiation. Complete response (CR) was achieved by 75% of patients in stage III, and another 17% showed partial response. In stage IV 60% responded, 19% with CR. Relationships between patient and treatment variables and the probability of being alive in CR 22 weeks after initiation of the treatment were examined by logistic regression analysis. The probability of CR was not related to age at diagnosis, the addition of an anthracycline to the chemotherapeutic regimens, or to irradiation. Factors related to the maintenance of CR could not be statistically examined due to the small number of complete responders at 22 weeks. Only age below 2 years seems, however, to have positive impact on the response duration. The influence of patient characteristics was further suggested by the result of secondary treatment attempts. 42% of the patients selected for secondary treatment responded, and 17% achieved CR. 1/25 (4%) had survived disease-free for more than 8 years. Factors related to the duration of survival were subsequently examined in the 71 children using Cox's regression analysis. Only children below 2 years of age at diagnosis had survived for more than 8 years. Resection of the tumour at diagnosis, irradiation and the addition of an anthracycline appear not to influence the length of survival in this patient population.

Child↗

PubMed2001

Remission induction therapy: the more intensive the better?

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

Acute Disease↗

PubMed1990

Low dose 5-azacytidine is ineffective for remission induction in patients with acute myeloid leukemia.

Low dose 5-azacytidine was administered to 11 patients with acute myeloid leukemia (AML) in hopes of achieving complete remissions by inducing differentiation of leukemic blasts. The patient population included both patients who had received no prior therapy (two patients), as well as patients refractory to primary therapy (five patients) and patients who had relapsed after achieving complete remission (four patients). Both previously untreated patients had a history of myelodysplastic syndrome, and two of the primarily refractory patients had leukemia following chemotherapy for other malignancies. The median age was 55 years (range 36-78 years). Twenty-one courses of 5-azacytidine were administered as 7-day continuous infusions at a dose of 75 mg/m2/day. Significant nonhematologic toxicity was not observed. No patient had a response as defined by bone marrow remission or improvement in transfusion requirement for red blood cells or platelets. Although some patients developed bone marrow hypocellularity (six courses in five patients), none became aplastic, and eight courses in six patients were associated with increased bone marrow cellularity percentage of blasts. Five courses in three patients were inevaluable (one central nervous system hemorrhage, one central nervous system leukemia, three courses in one patient who refused bone marrow aspiration). It is unlikely that low dose 5-azacytidine will be of benefit to patients with AML, and there was no evidence of clinically significant induction of differentiation noted.

Adult↗

PubMedDate not supplied

Intensive alternating drug pairs after remission induction for treatment of infants with acute lymphoblastic leukemia: A Pediatric Oncology Group Pilot Study.

PURPOSE: Infants with acute lymphoblastic leukemia (ALL) often enter remission; however, they have a high rate of relapse. To prevent relapse, infants' tolerance of and benefits from early intensive rotating drug pairs as part of therapy were studied. METHODS: After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were administered in 30 weeks: A, intermediate dose methotrexate (MTX) and intermediate dose mercaptopurine (MP); B, cytosine arabinoside (Ara-C) and daunorubicin (DNR); C, Ara-C and teniposide (VM-26). Triple intrathecal chemotherapy (Ara-C, MTX, and hydrocortisone) was administered for central nervous system prophylaxis. Continuation therapy consisted of weekly MTX and daily MP for a total of 130 weeks of continuous complete remission. RESULTS: Thirty-three infants (1 year old or younger) with newly diagnosed ALL were treated. Two infants did not respond to induction, 1 died from sepsis during continuation, 1 received a bone marrow transplant, and 24 relapsed. Median time to relapse was 39 weeks. The event-free survival rate at 5 years was 17% (standard error +/- 7.7%). The most significant toxicities occurred during intensification and included fever-neutropenia and bacterial sepsis. CONCLUSION: Although early intensive rotating therapy is tolerable, the relapse-free survival rate remains poor for infants treated with the schedule on this protocol.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811.

The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL.

Adolescent↗

PubMed1994

In vitro all-trans retinoic acid (ATRA) sensitivity and cellular retinoic acid binding protein (CRABP) levels in relapse leukemic cells after remission induction by ATRA in acute promyelocytic leukemia.

The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is focused on differentiating agents such as the vitamin A derivative all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy for this disease characterized cytogenetically by a translocation t(15;17)(q21;q22) involving the alpha retinoic acid receptor on chromosome 17 and the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA followed by or combined with conventional chemotherapy may be more beneficial than chemotherapy for inducing complete remission. Unfortunately, ATRA as a single agent, does not appear able to maintain patients in remission (median 5 months), and when relapse occurs resistance to a second induction of ATRA therapy is observed in almost all cases. Recently our laboratory investigated whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed. We have demonstrated that AML3 patients' cells (from four patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding protein and this protein was not detected prior to ATRA therapy. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with 'virgin'-AML3 cells. Results from this study suggest that CRABP could modulate ATRA cellular concentrations reaching the nucleus. This induced ATRA hypercatabolytic state should be monitored during consolidation therapy and at relapse by evaluating CRABP and RA metabolite levels, in order to detect ATRA resistance in patients with AML3.

Drug Screening Assays, Antitumor↗