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S Rule

Publications and source records attributed to S Rule.

18 recordsLinked to original sources
PubMed2006

Fludarabine phosphate and melphalan: a reduced intensity conditioning regimen suitable for allogeneic transplantation that maintains the graft versus malignancy effect.

Reduced intensity conditioning (RIC) for allogeneic stem cell transplantation allows stable donor cell engraftment with the maintenance of a graft versus malignancy effect. Many different regimens exist employing various combinations of chemotherapy, radiotherapy and T-cell depletion. We examined the role of non-T-cell depleted RIC regimens in 56 patients with haematological malignancies. Patients received fludarabine phosphate for 5 days (30 mg/m2 in 35 patients, 25 mg/m2 in 21 patients) and melphalan for 1 day (140 mg/m2 in 36 patients, 100 mg/m2 in 20 patients). Immunosuppression was with CyA alone in 33 patients and CyA/MTX in 23 patients. Twenty-four of the 26 patients with chimerism data showed >95% donor chimerism at 3 months post transplant. aGVHD occurred in 18% of patients receiving CyA/MTX compared to 53% of patients receiving CyA. The 100-day mortality rate was 0.16 (95%CI 0.08-0.28) and 1-year nonrelapse mortality was 0.24 (95%CI 0.13-0.38). Thirty-three patients remained alive and in CR at a median of 19 months post transplant (range 3-38 months). We have shown that patients transplanted with fludarabine phosphate, melphalan 100 mg/m2 and with CyA/MTX as post transplant immunosuppression can achieve good disease control with an acceptable level of toxicity. Further studies are required to confirm these findings.

Adult↗
PubMed2000

FLUDAP: salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma.

The aim of this study was to investigate the combination of fludarabine phosphate, dexamethasone, cytosine arabinoside and cis-platinum (FLUDAP) in the treatment of patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). This regimen comprises: dexamethasone 100 mg/d continuous infusion (cont. inf.) d1-3; cytosine arabinoside (ara-C) 1 g/m2/d cont. inf. d 2,3; fludarabine phosphate 30 mg/m2 short inf. 4hr prior to each 24hr ara-C inf.; cis-platinum 50 mg/m2 4hr inf. at the start of each 24hr ara-C inf. G-CSF (lenograstim, Granocyte) is given at 263 microg s.c. daily from day 7 until the neutrophil count reaches 1.0x10(9)/l. The regimen repeats at 21 day intervals. A total of 33 patients were registered (median age 47 years; 24 males, 9 females); the majority (73%) were refractory to their previous treatment and most had advanced disease by Ann Arbor stage. Thirteen (39%) of the 33 enrolled patients (52% of the 25 fully evaluable patients who received at least 2 courses of FLUDAP) responded to treatment. A maximum response of complete remission was achieved in 5 patients, good partial remission in 3, and partial remission in 5. Twelve patients went on to successful stem cell supported intensification therapy. Median survival times were higher in the responding patients, and in those patients transplanted post-FLUDAP. The toxicity associated with the FLUDAP regimen was generally predictable; frequently reported severe events included haematological toxicity and infection. In conclusion, the FLUDAP regimen shows promise as a salvage regimen and increases the available therapeutic options in the treatment of recurrent/refractory aggressive NHL.

Adult↗
PubMed1999

Combination therapy with fludarabine and cyclophosphamide as salvage treatment in lymphoproliferative disorders.

Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven patients) were treated with a combination of fludarabine 25 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had previously received purine analogue therapy of which four had progressive disease during treatment. The overall response rate of patients with CLL was 71% (28% CR, 43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and vomiting which was maximal in the 3 d after therapy, infections and haematological suppression which was prolonged in some patients. This combination, which is based on a rational prediction of synergistic activity, is highly effective but associated with significant problems with tolerance.

Aged↗
PubMed1999

Interstitial pneumonitis following mitozantrone, chlorambucil and prednisolone (MCP) chemotherapy.

We describe two cases of interstitial lung disease in patients with non-Hodgkin's lymphoma who were treated with combination chemotherapy including mitozantrone. In both we had radiological and histological evidence of interstitial lung disease, with patterns of organizing pneumonia and hypersensitivity without a clear aetiological agent. Clinical resolution occurred on withdrawal of chemotherapy. One patient required a course of corticosteroid treatment. To date, both patients are well and in remission, and there has been no recurrence of their respiratory disease. We postulate that these observations are hitherto undescribed pulmonary abnormalities secondary to mitozantrone therapy.

Aged↗
PubMed1998

Vinorelbine in the treatment of lymphoma.

Seventeen patients with previously treated Hodgkin's disease or non-Hodgkin's lymphoma (NHL) were treated with single-agent vinorelbine (Navelbine Pierre-Fabre Medicament) in an open study to assess the activity of this new-generation vinca alkaloid. Responses were obtained in four out of eight patients with Hodgkin's disease and four out of nine patients with NHL, including four patients who had been previously treated with high-dose therapies. Toxicity was very mild. The study demonstrates worthwhile activity and justifies the inclusion of vinorelbine in combination therapies for lymphoma.

Adult↗
PubMed1997

Adult onset of acute myeloid leukaemia (M6) in patients with Shwachman-Diamond syndrome.

Three male patients (two of whom were brothers) with Shwachman-Diamond (SDS) syndrome presented with acute myeloid leukaemia in adulthood. In all three cases there was trilineage myelodysplasia and the morphology was consistent with FAB subtype M6. SDS is an inherited bone marrow failure syndrome with a high propensity to leukaemic transformation. Since this may not occur until adulthood, SDS should be considered in the differential diagnosis of adults presenting with acute myeloid leukaemia, particularly where features of myelodysplasia are prominent.

Adolescent↗
PubMed1995

Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient.

Between August 1985 and July 1994, we performed 115 volunteer unrelated donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Standard serologic HLA typing of potential donors and recipients was supplemented with one-dimensional isoelectric focusing (IEF) for class I proteins, allogenotyping for DR and DQ alleles using DNA restriction fragment length polymorphism (RFLP) analysis, and the measurement of antirecipient major histocompatibility complex (MHC) cytotoxic T-lymphocyte precursor cells in the donors' blood (CTLp assay). Recipients were conditioned for transplantation with a combination of high-dose chemotherapy and total body irradiation (n = 103) or high-dose chemotherapy alone (n = 12). Twenty eight recipients received ex vivo T-cell-depleted marrow, and 84 underwent some form of in vivo T-cell depletion. The probability of severe (grades III or IV) acute graft-versus-host disease (aGVHD) was 24%, and that of extensive chronic graft-versus-host disease (cGVHD), 38%. Proportional hazards regression analysis showed an association between low frequency CTLp and a reduced incidence of severe aGVHD (relative risk [RR], 0.28; P = .0035). The probability of relapse at 3 years was 23%, with first chronic phase disease being independently associated with a lower risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years was 37%; the LFS for the first chronic phase and advanced phase recipients was 41% and 26%, respectively. First chronic phase disease (RR, 0.56; P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity and an IEF-matched donor (RR, 0.48; P = .011) were both associated with improved LFS. The probabilities of survival and LFS for patients under 40 years of age transplanted in first chronic phase from an IEF-matched donor were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable option for patients with CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved in patients transplanted in chronic phase with marrow from donors without demonstrable class I HLA mismatch and a low CTLp frequency.

Adolescent↗
PubMed1993

Use of thrombolysis for acute myocardial infarction by general practitioners.

The early administration of thrombolytic agents significantly reduces mortality following a myocardial infarct and ideally they could be given by general practitioners when the patient is first seen. However, the diagnosis of myocardial infarction in the early stages can be very difficult especially if an electrocardiogram is not available. This may limit the use of thrombolytic drugs by general practitioners. We assessed the accuracy of diagnosis in general practice by asking general practitioners referring patients with chest pain, the likelihood that the event was due to a myocardial infarction and if they would use thrombolysis if it were available. Diagnostic accuracy and appropriate use of thrombolysis was analysed retrospectively, comparing the general practitioner with the admitting hospital doctor. One hundred consecutive patients were studied. The general practitioners accurately diagnosed myocardial infarctions in approximately 45% of cases and would have given thrombolysis inappropriately on 67% of occasions mainly because the final diagnosis in most of these patients was unstable angina rather than infarction. The hospital doctors administered streptokinase inappropriately to 33% of the patients and four had complications during treatment. Of those patients receiving thrombolysis, the average time delay from the general practitioner referring the patient to hospital to the patient being treated was 107 minutes. This study confirms that the diagnosis of myocardial infarction in the early stages is difficult and that thrombolytic therapy may be given inappropriately (mainly to patients with unstable angina). We conclude that until the accuracy of diagnosis of myocardial infarction can be improved in general practice it would seem inappropriate for thrombolysis to be given in the community at the moment.

Adult↗
PubMed1991

Fludarabine phosphate for the treatment of low grade lymphoid malignancy.

Thirty-four patients with previously treated, advanced, low grade NHL were treated with Fludarabine, a deamination-resistant analogue of adenosine arabinoside, at a dose of 25 mg m-2 intravenously, daily for 5 days (median number of cycles = 3, range 1-10). Complete remission (CR) was achieved in six and partial remission (PR) in a further seven. Overall, responses were seen in 11/23 patients (48%) with follicular lymphoma and in 2/11 (18%) with low grade, diffuse NHL. Fifteen patients with previously treated CLL and one patient with prolymphocytic leukaemia (PLL) were also treated as above (median no. of cycles = 3, range 1-6). A partial response was seen in three of the 11 evaluable patients with CLL and CR was achieved in the patient with PLL. There were four deaths due to infection and 19 further episodes requiring admission to hospital. No other significant toxicity was reported in a total of 164 cycles of Fludarabine. This agent is active in advanced low grade lymphoid malignancy. Further studies are required to assess its role in newly diagnosed patients.

Antineoplastic Agents↗
PubMedDate not supplied

Management of acute myeloid leukaemia. A regional audit in the south and west of the United Kingdom.

In a retrospective audit data were collected on all 231 patients from 26 hospitals diagnosed with AML in the south and west region of the UK in 1996. Their median age at diagnosis was 67 years. Sixty one percent (142/231) of patients were treated with chemotherapy; most of the rest received blood product support only; and 7% (15) had no treatment at all. Sixty eight percent of patients aged under 60 years were treated in a clinical trial compared with 24% of patients over 60. The major reasons given for not entering patients in a trial were ineligibility in the younger cohort and poor performance status in the older group. Twenty elderly patients (12.5%) refused to be entered in a trial. In an unselected cohort of patients with AML the accrual into clinical trials is impressively high for patients under 60 years. However, this is a disease of the elderly and comparable enrolment is not seen with elderly patients despite being managed by the same haematologists. If the percentage of patients entered into trials is to be defined as a quality standard, then it is important for those trials to be relevant to the population being treated.

Adolescent↗
PubMedDate not supplied

Non-Hodgkin's lymphoma.

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Antibodies, Monoclonal↗