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D Swirsky

Publications and source records attributed to D Swirsky.

34 records · Page 2Linked to original sources
PubMed1991

Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor.

Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhIL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the alpha chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the alpha chain increased from 15% to 61% (P less than 0.01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor alpha chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the alpha chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.

Adult↗
PubMed1991

Prognostic importance of Sudan Black positivity: a study of bone marrow slides from 1,386 patients with de novo acute myeloid leukaemia.

Analysis of bone marrow slides from 1,386 patients entered into the Medical Research Council's 8th and 9th trials in Acute Myeloid Leukaemia confirmed that features associated with differentiation in blast cells, in particular increasing Sudan Black (SB) positivity, were the most important morphological features for predicting remission achievement (P = 0.002) and hence survival (P less than 0.0001). SB positivity was also weakly predictive of remission duration (P = 0.05). A low complement of maturing granulocytes was associated with early induction death and a high percentage of blasts with shorter remissions. The few patients with acute promyelocytic leukaemia (FAB M3) had a high haemorrhagic death rate during induction and a low relapse rate. Apart from this, lineage involvement was not predictive of outcome. Multiple lineage leukaemias, in particular those with megakaryocytic and/or erythroid involvement, which had been reported previously to have a poor prognosis, did not have any worse remission rates in this series. When more than one cell line was involved, no combination with particularly good or poor prognosis could be identified. Multivariate analysis suggested that percentage SB positivity was adequate on its own to divide granulocytic leukaemias into poorly differentiated (less than 50% SB +ve) and well-differentiated groups (50% or more SB +ve) without the need for further measurements. This simple and reproducible test was strongly predictive of resistant disease but not of induction deaths. It was of considerably greater prognostic value--and was less open to inter-observer disagreement--than the FAB criteria which are usually used to classify granulocytic lineage leukaemias into the M1 and M2 subgroups. It is proposed that greater than or equal to 50% of blasts with SB positivity should replace blasts greater than 10% of maturing myeloid cells for this sub-categorization between M1 and M2.

Acute Disease↗
PubMed1990

HIV and AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Bone marrow transplantation for severe aplastic anaemia using cyclosporin: long-term follow-up.

Between 1980 and 1986 we transplanted 49 patients from genotypically identical sibling donors for severe aplastic anaemia (SAA). Patients were predominantly adults, median age 22 years (3-47). Forty-six were multiply transfused prior to referral. The median pre-transplant disease duration was 4 months (1-72). Pre-transplant conditioning was with cyclophosphamide (CY) 200 mg/kg. Cyclosporin A (CSA) was given from 1 day before the transplant and continued for 9-12 months. Eight of 48 evaluable patients did not achieve initial engraftment (early graft failure). Six of these episodes occurred in the eight cases transplanted more than 1 year after diagnosis, four of whom died. Thirteen of 44 (30%) evaluable patients (with stable engraftment after one or two transplants) had grade III-IV acute graft-versus-host disease (GVHD). Only three of 35 patients surviving more than 100 days with sustained engraftment developed generalized chronic GVHD; two died. An additional 10 patients developed localized chronic GVHD, which was very mild, transient and related to CSA withdrawal. Four long-term survivors are known to have autologous marrow function. All survivors have Karnofsky scores of greater than 90%. We conclude that the use of CSA after bone marrow transplantation for SAA is associated with good long-term survival and minimal on-going chronic GVHD. Early graft failure was frequent when transplantation was delayed beyond 1 year from diagnosis.

Anemia, Aplastic↗
PubMed1989

Bone marrow transplantation for Fanconi's anaemia: the Hammersmith experience 1977-89.

Twenty-one patients with Fanconi's anaemia (FA) were treated by allogeneic bone marrow transplantation (BMT). Two, transplanted before 1980, received high dose cyclophosphamide conditioning and both died. Subsequently 19 patients received conditioning with low dose cyclophosphamide 5 mg/kg x 4 and total body irradiation 200 cGy x 3. Ten of 19 received HLA identical sibling marrow (ID-BMT) and nine marrow from alternative donors (MM-BMT). Marrow was T cell depleted in 9/19 cases. Sustained engraftment was observed in 13 cases (eight ID-BMT, five MM-BMT). Nine patients developed greater than or equal to grade II acute graft-versus-host disease (GVHD) (six ID-BMT, nine MM-BMT). Chronic GVHD occurred in 5/11 evaluable patients. Overall survival of the low dose cyclophosphamide group was 9/19 (47%) at a median follow-up of 1257 days post-BMT (110-1825). Six of 10 (60%) survived after ID-BMT compared with two of nine (22%) after MM-BMT. We conclude that allogeneic BMT using a low dose cyclophosphamide protocol is a satisfactory treatment for FA patients who have a normal HLA identical sibling. The results of MM-BMT have been poor, and must improve before these transplants can be generally recommended for treatment of FA.

Adolescent↗
PubMed1987

Bone marrow in leukemia and aplastic anemia: MR imaging before, during, and after treatment.

Serial magnetic resonance (MR) studies of the cervical bone marrow were performed in five patients undergoing bone marrow transplantation for chronic granulocytic leukemia and in four patients with aplastic anemia who were treated with antilymphocytic globulin. Findings were compared with those from a group of healthy volunteers. Chemical shift imaging techniques were used to exploit the presence of protons in fat and water in the red marrow. Characteristic changes were seen in aplastic anemia before treatment, but derivation of images representing fat and water fractions was necessary to distinguish leukemic marrow. Acute changes during the treatment of leukemia may reflect the effects of chemotherapy and radiation therapy, whereas changes in the chronic phase of both diseases may prove useful in predicting treatment outcome. MR studies are likely to be useful in the assessment and treatment of hematologic disorders.

Adolescent↗
PubMed1986

Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial.

Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6-thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse-free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure-related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival.

Adolescent↗
PubMed1986

Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia.

We treated 14 patients by transplantation of marrow from unrelated volunteer donors. Eight patients had severe aplastic anemia, 3 had chronic granulocytic leukemia, and 3 had Fanconi's anemia. The results are compared with those of a group of 14 similar patients transplanted concurrently from human leukocyte antigen (HLA)-mismatched family members: Sustained engraftment was achieved in 8 of 14 patients in both groups; one additional patient survived with autologous marrow reconstitution following an unrelated donor transplant. In the unrelated donor group, 6 of 9 evaluable patients developed grade III through IV acute graft-v-host disease, as compared with 4 of 9 patients after family-mismatched transplants. Overall survival was similar in the two groups. In the unrelated donor group 4 of 14 (29%) patients survived (median survival 1,299 days) as compared with 5 of 14 (36%) in the mismatched-family donor group (median survival 808 days). In both groups, patients with HLA phenotypically matched donors fared better than those with donors who were mismatched for one or more HLA antigen. Of the patients transplanted from HLA phenotypically matched donors 6 of 12 patients (50%) survived, as compared with 3 of 16 patients (19%) transplanted from HLA-mismatched donors. We conclude that unrelated donor bone marrow transplantation (BMT) should be considered in those cases of leukemia or bone marrow failure in which the chance of cure using conventional therapy is remote and a HLA genotypically or phenotypically matched family donor is not available.

Anemia, Aplastic↗
PubMed1985

Reactivity of rat monoclonal antibody CAMPATH-1 with human leukaemia cells and its possible application for autologous bone marrow transplantation.

The rat monoclonal antibody CAMPATH-1 recognizes a hitherto undefined antigen present on virtually all normal lymphocytes and monocytes. Its reactivity with 105 samples of fresh leukaemic cells and 13 cell lines was measured by indirect fluorescence and peroxidase staining to define in more detail which stages of differentiation it recognizes. It was found to bind to cells from virtually all cases of lymphoid leukaemia (B cell CLL, T cell ALL, cALL and the few examples of HCL, PLL, Sezary syndrome and CGL in lymphoid blast crisis). The single case of cALL in relapse and four of six cases of null ALL were negative. Binding to non-lymphoid leukaemia cells (AML, AMML, AMoL, APL, AEL and CGL in blast crisis) was weaker or undetectable. Binding to established lymphoid cell lines was generally weak compared with fresh cells but some lines (MOLT4, DAUDI and X308) expressed adequate amounts of antigen to be lysed by CAMPATH-1 with human complement. Because CAMPATH-1 is very effective at killing lymphocytes in the presence of human complement, it has been used for removal of T cells in allogeneic transplants. The present results suggest that it might also have a role in purging bone marrow of leukaemia cells prior to autologous transplantation for acute lymphocytic leukaemia.

Animals↗
PubMed1985

Clostridium difficile in haematological malignancy.

Twenty patients with haematological malignancies who developed Clostridium difficile bowel infection or colonisation are described. All isolates of C difficile were toxigenic in vitro and faecal cytotoxin (toxin B) was detected in 20/26 episodes. Ten of 20 episodes with detectable faecal cytotoxin were associated with typical antibiotic associated diarrhoea. In the other 10 episodes (nine patients), there was a severe unusual illness which was associated with detection of C difficile. The unusual features of the illness were pronounced jaundice (total bilirubin greater than or equal to 44 mumol/l), abdominal pain and distension, and initial constipation followed either by diarrhoea or by large bowel stasis. Four of these patients died within seven days. Bacteraemia was often a presenting feature in neutropenic patients subsequently shown to have C difficile. This was not the case in non-neutropenic patients. Bacteraemia was commonly polymicrobial and in two cases C difficile was isolated from blood culture. The clinical implications of recognition of this atypical C difficile associated syndrome are discussed.

Adolescent↗
PubMed1982

Human myeloma cell line carrying a Philadelphia chromosome.

A new human plasmacytoma cell line (Karpas 707) has been established from a myeloma patient. The cultured cells are negative for Epstein-Barr viral nuclear antigen and free of mycoplasma. They are similar to plasma cells and secrete only lambda light chains. The cells are hypodiploid and contain the Philadelphia chromosome and other abnormalities. This cell line may be suitable for the production of human monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1982

Human plasmacytoma with an unusual karyotype growing in vitro and producing light-chain immunoglobulin.

A new human plasmacytoma line (Karpas 707) was established from the cells of the bone-marrow and peripheral blood of a patient with Bence-Jones-positive multiple myeloma. The cells of this line resembled the patient's malignant cells and fresh myeloma cells from nine other patients in being Epstein-Barr viral nuclear antigen negative. They looked like plasma cells and they secreted only lambda light chains. Both these cells and the patient's fresh cells were hypodiploid and contained the Philadelphia chromosome and several other markers. This line seems to be the first human plasmacytoma line since the IgE lambda-producing line (U266) established in 1968, and it may be suitable for the production of human monoclonal antibodies.

Antibodies, Monoclonal↗