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At least 217 records · Page 12Linked to original sources
PubMed1985

Remission induction of meningeal leukemia with high-dose intravenous methotrexate.

Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.

Adolescent↗
PubMed2003

Remission induction in Behçet's disease following lymphocyte depletion by the anti-CD52 antibody CAMPATH 1-H.

OBJECTIVE: Behçet's disease (BD) is a multisystem vasculopathy of unknown cause with variable clinical presentation and the outcome of current treatments is often unsatisfactory. There is evidence for T-cell autoreactivity in BD and this study explores the therapeutic response to lymphocyte depletion with a humanized anti-CD52 antibody, CAMPATH-1H. METHODS: Eighteen patients with active BD received a single course of 134 mg of CAMPATH-1H. Immunosuppressives were withdrawn and prednisolone reduced according to clinical status. Treatment response was assessed by remission of clinical features of disease activity, erythrocyte sedimentation rate, C-reactive protein, prednisolone dose, the need for subsequent immunosuppressives and disease relapse. RESULTS: By 6 months, 13/18 (72%) had entered remission and average, daily prednisolone dose was reduced from 17.7 to 6.7 mg/day (P < 0.005). At patient follow-up after 37 (6-60) months, seven had relapsed after an average of 25 months, five had required the introduction of an immunosuppressive drug and two had been retreated with CAMPATH-1H; 10 were in stable remission and six were receiving no therapy. Moderate infusion-related adverse effects occurred in five and two developed hypothyroidism. Circulating CD4+ T cells fell to low levels after CAMPATH-1H and remained depressed for at least 1 yr; no opportunistic infections were seen. CONCLUSIONS: The therapeutic response to CAMPATH-1H suggests a central role for autoreactive lymphocytes in BD. The potential of CAMPATH-1H to induce sustained treatment-free remission in BD poorly controlled by conventional therapy requires further evaluation.

Adolescent↗
PubMed1997

[Lymphomatoid granulomatosis--remission induction with interferon-alpha 2b].

HISTORY AND ADMISSION FINDINGS: A 72-year-old woman was admitted to hospital because of nonproductive cough, acrodistal sensorimotor axonal polyneuropathy, fatigue and 10 kg weight loss over the preceding 9 months. INVESTIGATIONS: Chest radiogram showed multiple round foci in both lungs. No organs other than the lungs and the peripheral nervous system were affected. Open lung biopsy revealed a pleomorphic angioinvasive lymphocytic infiltrations. DIAGNOSIS, TREATMENT AND COURSE: The findings indicated lymphomatoid granulomatosis (LG). Wegener granulomatosis was excluded on the basis of the clinical, serological and histopathological findings. Treatment with alpha-interferon (IFN-alpha) produced complete remission within 4 months. Interruption of treatment immediately resulted in a recurrence. CONCLUSION: Together with previously reported cases this patient's response to IFN-alpha suggests that IFN-alpha is a less toxic alternative to cyclophosphamide and corticosteroid administration in the early stages of LG.

Aged↗
PubMed2002

BCRP gene expression is associated with a poor response to remission induction therapy in childhood acute myeloid leukemia.

Breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MRX) or placenta ABC protein (ABC-P), is the second member of the ABCG subfamily of ABC transport proteins (gene symbol ABCG2). Transfection and enforced expression of BCRP in drug-sensitive cells confers resistance to mitoxantrone, doxorubicin, daunorubicin and topotecan. In this study the expression of BCRP gene was measured using TaqMan real-time PCR in 59 children with newly diagnosed AML. Nine patients were also analyzed in relapse. The median of BCRP gene expression was more than 10 times higher in patients who did not achieve remission after the first phase of chemotherapy (n = 24) as compared to patients who did achieve remission at this stage (n = 21; P = 0.012). In first relapse the expression of the BCRP gene was higher than at diagnosis (P = 0.038). Although high levels of BCRP gene expression were more frequent in subtypes of AML with a favorable prognosis, we found that within both risk groups (high and low risk), patients who expressed high levels of BCRP had a worse prognosis (P = 0.023). Our results strongly suggest that the expression of the BCRP gene reduces the response to chemotherapy in AML and that BCRP expression is higher at the time of relapse.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1995

A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group.

406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III patients were randomised to receive MP or VBAMDex (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36 months in both groups without a detectable difference. 117 responders of stage II and III with stable disease were randomised to receive either IFN-alpha (5 x 10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The relapse rate in both groups was 50% after 13 months. No survival benefit for IFN alpha treated patients was observed (50% TRS: 45 months).

Aged↗
PubMed1991

Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (Protocol 81-01 update).

We evaluated event-free survival (EFS) and leukemia-free interval (LFI) of children treated for acute lymphoblastic leukemia (ALL). Patients were randomized to receive either a low dose or high dose of methotrexate (MTX) as a single agent at the time of diagnosis. Five days later, multidrug therapy was begun. We assessed the early antileukemic efficacy of the two doses of MTX, as well as toxicity and long-term efficacy. An increase in cell kill, as indicated by a larger decrease in the percentage of viable cells in the bone marrow between days 0 and 5, was observed for the high-dose MTX group when compared with the low-dose MTX group (P = .04). At 7.1 years of median follow-up, the 38 children randomized to receive high-dose MTX had a better EFS and LFI compared with the 39 patients randomized to receive low-dose MTX. The 7-year percentages (+/- SE) for EFS were 82% +/- 6% for high-dose MTX and 69% +/- 7% for low-dose MTX (P = .13). The 7-year percentages for LFI were 91% +/- 5% and 69% +/- 7%, respectively (P = .01). We recommend that high-dose MTX be considered as an effective addition to induction therapy in childhood ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia.

A total of 622 consecutive patients with acute promyelocytic leukaemia (APL) treated within the Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) group during 1989-97 have been reviewed to assess the clinical effectiveness of all-trans retinoic acid (ATRA) on the incidence of early haemorrhagic deaths and on APL-associated coagulopathy. Of them, 499 were treated with idarubicin plus ATRA (study A) and 123 with Idarubicin alone (study B). In both studies, similar guidelines for supportive treatment were used. Haemorrhagic symptoms were evaluated according to a reproducible score system. Deaths occurring within 10 d of starting treatment were 19 (3.8%) in study A and nine (7.3%) in study B (P = 0.09), with 15 (3%) and five (4.1%) (P not significant) due to haemorrhage. Overall, induction mortality was 7.6% and 16.2% respectively (P < 0.003). In study A, days with platelet counts </= 20 x 109/l or with fibrinogen </= 1 g/L were reduced by about 30%, the haemorrhagic score by 50% and the consumption of blood products by about 40%, and fewer patients were treated with antihaemorrhagic drugs (39% vs. 61%; P < 0.001). On multivariate analysis, early deaths were influenced by blast count at diagnosis > 30 x 109/l (P < 0.001) in both studies, and by a haemorrhagic score of 3 in study A (P < 0.001). Although the reduction of early fatal haemorrhages was not significant, a substantial clinical improvement was evident in terms of reduction of the severity of bleeding symptoms, blood product consumption and overall induction mortality when ATRA was combined with idarubicin.

Adolescent↗
PubMed1999

Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia.

We have used a combination of flow cytometric assays to define multidrug resistance (MDR) positive and negative blasts in cryopreserved samples from 47 MRC trial patients with acute myeloblastic leukaemia (AML). Our primary test is a standardized assay for daunorubicin accumulation. Confirmatory assays for MDR comprised the cyclosporin modulation assay for rhodamine-123 uptake as a measure of functional P-glycoprotein and the measurement of lung resistance protein and multidrug resistance associated protein (with LRP-56 and MRPr1 respectively). 57% of samples had both low accumulation and at least one positive confirmatory test. 32% were MDR negative in all four assays. 15% of patients had primary chemo-resistant disease. Resistant disease rates were 22% for confirmed MDR-positive patients and 0% for confirmed MDR-negative patients (P=0.07). Complete remission was achieved in 74% of patients, with rates of 63% in confirmed MDR-positive patients and 93% in confirmed MDR-negative patients (P=0.06). The use of a standardized method for daunorubicin uptake, combined with the use of confirmatory tests, should reduce the uncertainty that is currently characteristic of MDR evaluation in leukaemia. In comparison with daunorubicin uptake, p-gp expression, measured using MRK-16 antibody, was more closely associated with remission rates (P =0.01). This suggests an additional role for p-glycoprotein in mediating drug resistance beyond that of a drug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Remission induction after pentoxifylline treatment in a patient with rheumatoid arthritis].

Pentoxifylline (POF) has been shown to have anti-inflammatory and immunomodulatory effects. including suppression of TNF-alpha production by activated macrophages, Th-1 response of T cells, and fibroblasts' proliferation and metalloproteinase production. Pentoxifylline was also reported to possess therapeutic properties in 50% of severe refractory RA in an open study. We experienced a 64 year-old man with seronegative RA, stage 2, class 3. He showed 23 swollen joints, 32 painful joints, ADL score 37/40, and ESR 135 mm/h. All these parameters were dramatically improved 3 weeks after administration of POF 300 mg/d and prednisolone 5 mg/d. Discontinuation of POF resulted in rapid exacerbation of RA. POF was restarted and the patient showed complete recovery from arthritis with normalization of ESR within 3 months and was maintained a complete remission for another 1 year. This case further supports a potential antirheumatic effect of POF on some patients with RA.

Anti-Inflammatory Agents↗
PubMed2006

Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia.

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of > or = 100 x 10(9)/L, a value characteristically associated with "hyperleukocytosis" (HL). In this patient cohort, a presenting leukocyte count of > or = 30 x 10(9)/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.

Adolescent↗
PubMed1996

Complete remission induction with combined VBMCP chemotherapy and interferon (rIFN alpha 2b) in patients with multiple myeloma.

The purpose of this study was to evaluate a new regimen for the treatment of multiple myeloma based on alternating 3-week cycles of chemotherapy and interferon (rIFN alpha 2). In this prospective phase II clinical trial the Eastern Cooperative Oncology Group evaluated a regimen consisting of 2 cycles of VBMCP (Vincristine 1.2 mg/M(2) IV d1, BCNU 20 mg/M(2) IV d1, Melphalan 8 mg/M(2) PO dl-4, Cyclophosphamide 400 mg/M2 IV d1, Prednisone 40 mg/M(2) PO d1-7) followed by alternating 3-week cycles of VBMCP and rIFN alpha2 5 Mu/M(2) SC 3x/week. Treatment was administered for 2 years. Fifty-eight patients with previously untreated multiple myeloma were entered. Objective response (OR) required 50% decrease in M-protein with correction of severe anemia and no progression of skeletal disease. Complete remission (CR) was defined by disappearance of M-protein and normalization of the bone marrow morphology. Life table analysis was utilized to express survival and response duration. Fifty-four patients were evaluable. Objective response was seen in 80% of patients including CR in 30% (16 patients). The median response duration is 35 months, 46 months for patients with CR. The median survival is 42 months for all patients. Five year survival is 42%. Although 78% of patients had neutrophil nadirs <1000 x 10(9)/L, the incidence of severe infection was only 9%. These data demonstrate that VBMCP + interferon is an effective new regimen combining chemotherapy with a biological response modifier for the treatment of multiple myeloma. The incidence of CR is high, and the response and survival durations appear to be 1 year longer than usually seen with standard chemotherapy. A current ECOG randomized trial compares VBMCP + interferon with VBMCP alone.

Aged↗
PubMed1998

IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial.

A phase II trial was designed to explore the potential feasibility and efficacy of a reinduction therapy consisting of fludarabine, cytarabine, idarubicin and granulocyte colony stimulating factor (G-CSF) for acute myelogenous leukaemia (AML) patients with poor prognosis. Twenty-three patients aged 1 2-17.5 years with refractory (n=3), relapsed (n=19) or secondary (n=11) AML were treated with the IDA-FLAG regimen, a combination therapy of idarubicin (days 2-4, 12 mg/m2/d), fludarabine (days 1-4, 30 mg/m2/d), cytarabine (days 1-4, 2000mg/ m2/d) and G-CSF (day 0 up to ANC > 1 x 10(9)/l, 400 microg/m2/ d). They received a total of 3 7 courses of IDA-FLAG and/or FLAG (IDA-FLAG without idarubicin). 17/23 patients achieved a complete remission (CR) with a median duration of 13.5 months (1-39 months), one patient showed a partial remission, and five were nonresponders while in CR, 11 patients underwent bone marrow or PBSC (peripheral blood stem cells) transplantation. Overall, nine patients remain in continuous complete remission with a median duration of 17.5 months (9.5-39 months). The toxicity of the IDA-FLAG courses was more severe than for the FLAG courses with marked neutropenia and thrombocytopenia (for IDA-FLAG: median 22.5 and 25 d respectively; for FLAG: median 10.5 and 14 d respectively). Pulmonary infections were the main nonhaematological toxicity. One patient died in CR from invasive aspergillosis. The IDA-FLAG regimen produced a CR of >12 months in more than half of the patients and can be recommended as a therapeutic option prior to allogeneic or autologous bone marrow transplantation.

Adolescent↗
PubMed1996

Pneumonia during remission induction chemotherapy in patients with AML or MDS.

We analyzed the 67 of 278 patients with newly-diagnosed AML or 'high-risk' MDS, treated in 1994 and 1995, who developed pneumonia during course 1 of their induction therapy. Pneumonia responded to treatment in 66%, but outcome depended on when pneumonia was diagnosed. Patients with pneumonia diagnosed during week 1 or 2 (group 2 patients) had the lowest response rate (43%). Patients who developed pneumonia in the 3rd week after treatment initiation had the best outcome with all 16 patients recovering. Patients presenting with pneumonia had an intermediate response rate (75%). The different patient groups were comparable with regard to age, underlying disease, prophylactic therapy, and G-CSF application. Although a lower CR rate was not entirely responsible for the lower response rate in group 2, failure to achieve CR predicted unsuccessful treatment of pneumonia in all groups. Fungal pathogens appeared more common in group 2 patients. However, in these patients, administration of amphotericin B was associated with a significantly higher failure rate (15/21 failures vs 2/9 who received no amphotericin B). We conclude that patients who develop pneumonia during week 1 or 2 are a high-risk group, and that use of amphotericin B indicates a particularly poor prognosis, although we present data suggesting that earlier use of amphotericin might be beneficial. Furthermore, since achievement of CR was an important prognostic factor in all groups, WBC transfusions particularly from donors given G-CSF should be considered as a therapeutic option. Finally, since time to failure of induction therapy and time to CR were similar in high-risk patients, new chemotherapy regimens could potentially improve both the CR rate and the outcome of pneumonia.

Acute Disease↗
PubMed2004

[Remission induction of refractory diffuse large B-cell lymphoma with allogeneic peripheral blood stem cell transplantation followed by interferon-alpha and donor lymphocyte infusion].

Graft-versus-lymphoma (GVL) effect has been described in patients with malignant lymphoma after allogeneic stem cell transplantation (alloSCT). The effect of interferon-alpha (IFN-alpha) on the GVL effect still remains unclear. Here we report on a 29-year-old woman with refractory diffuse large B-cell lymphoma (DLBL). Her clinical findings included multiple masses in the liver, stomach, bilateral kidneys, thyroid, vertebral bones and a bulky mediastinal mass. Since the patient did not respond to various combination chemotherapies and further developed superior vena cava syndrome, allogeneic peripheral blood stem cell transplantation (PBSCT) from a HLA-identical brother was carried out after a myeloablative TBI/CY-based conditioning regimen. DLIs have been also performed every 4 weeks since day +14. As a result, the lymphoma masses showed a partial response. In order to enhance the GVL effect, IFN-alpha was further given at a maximum of 3 MU four times per week. Although the patient only experienced graft-versus-host disease of the skin (grade II) even after both DLIs and IFN, complete clinical remission was observed. 200 days after transplantation, the patient is still disease-free and in good condition. This report suggests the curative potential of IFN-alpha combined with DLI after allogeneic SCT in refractory DLBL.

Adult↗
PubMed2004

A randomized trial of dexamethasone before remission induction, in de novo childhood acute lymphoblastic leukemia.

We evaluated the impact of adding dexamethasone before chemotherapy in 95 children with de novo standard-risk acute lymphoblastic leukemia (ALL). The children were randomly divided into 2 groups: one group was given dexamethasone, the other was not. The initial characteristics and mean follow-up of both groups were similar. Day +14 blast percentage was significantly lower in the dexamethasone group. Disease-free survival at 40-months follow-up was better (almost significantly so) in the dexamethasone group.

Antineoplastic Combined Chemotherapy Protocols↗