PubMed Health⌕ Search

Biomedical subjects

H G Prentice

Publications and source records attributed to H G Prentice.

At least 217 records · Page 12Linked to original sources
PubMed1987

Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission.

Bone-marrow transplantation has been used in patients with acute lymphoblastic leukaemia (ALL) thought to be at high risk of relapse if managed with chemotherapy. Data from 444 ALL patients with one or more high-risk features at diagnosis were analysed to evaluate outcome after HLA-identical bone-marrow transplantation during first or during second remission. The 4-year actuarial probability of leukaemia-free survival was 45% (95% confidence interval 36-54%) for transplants in first remission compared with 22% (15-29%) for those in second remission (p less than 0.0002). The 4-year probabilities of relapse were 26% (14-38%) and 56% (45-67%) respectively (p less than 0.0001). For high-risk ALL, transplantation in first remission had clearly superior results to transplantation in second remission. Further studies are needed to determine whether patients with high-risk ALL should receive transplants during first remission or should initially receive chemotherapy, with transplantation being reserved for patients who relapse.

Adolescent↗
PubMed1987

Human large granular lymphocytes induce immunoglobulin synthesis after bone marrow transplantation.

Following T cell-depleted bone marrow transplantation, helper T cell numbers remain depressed for some months. Nonetheless, functional B cells can be adoptively transferred to the recipients of such grafts, where they continue to secrete antibody. We now show that immunoglobulin production by these transferred B cells is induced by activated large granular lymphocytes (LGL) which circulate in the recipients in substantial numbers during the immediate post-transplant period. The LGL are CD3 negative and therefore provide help in an antigen-unlinked manner. Helper effects for autologous (donor) B cells are augmented by the addition of anti-LFA-2 (anti-CD2) which appears to act by blocking recruitment of LGL inhibitory to developing B cells. In contrast antibody to the beta chain of LFA-1, which effectively reduces natural killer activity of LGL, does not influence their helper function. The peripheral blood LGL fraction thus contains both helper and cytotoxic activity, which can be distinguished by appropriate monoclonal antibodies.

Antibody Formation↗
PubMed1987

Regeneration of humoral immunity to herpes simplex virus following T-cell-depleted allogeneic bone marrow transplantation.

We investigated the adoptive transfer of immunity to herpes simplex virus (HSV) in 61 recipients of T-cell-depleted marrow allografts. Up to 3 months after bone marrow transplantation (BMT), high titres of HSV antibody (Ab) are passively acquired from blood products. This antibody has a half-life of 40.3 days, so that determination of recipient immunity to HSV cannot be made during the early post-transplant period. By 4 months after the allograft, seronegative recipients of seronegative donors had near-background levels of HSV Ab. Seropositive recipients, whether they were excreting virus or not, had high titres of HSV Ab regardless of donor status. Surprisingly, the seronegative recipients of HSV seropositive donors remained seronegative, a result at variance with observations made in the recipients allografts from which T-cells had not been removed. Thus, T-cell depletion modifies the adoptive transfer of humoral immunity to HSV, and an immune donor alone no longer ensures continued antibody production in the recipient.

Antibodies, Viral↗
PubMed1987

Cytotoxic effects of tumour necrosis factor and gamma-interferon on acute myeloid leukaemia blasts.

We have studied the cytotoxic effects of recombinant tumour necrosis factor and recombinant gamma interferon on primary cultures of leukaemia cells. The agents were added alone or in a combination to cells from 17 patients. Eleven had acute myeloblastic leukaemia (6 at presentation, 5 at relapse), 4 had acute lymphoblastic leukaemia, one had hairy cell leukaemia, and 2 had chronic myeloid leukaemia--one of whom was in myeloid blast transformation. Cells from patients with lymphoid malignancies or from the patient with chronic phase CML were not affected by either agent in any dose combination. In contrast, reduction of viability of myeloid blasts was weakly accelerated by TNF and gamma-interferon individually. Combination of the agents invariably produced enhanced killing and additive or synergistic effects were seen when 20-500 IU ml-1 of each cytokine was present. This sensitivity was also shown by blast cells from 5 patients with relapsed AML. We therefore suggest that trials of such combination therapy may be indicated in drug resistant or relapsed AML.

Cell Survival↗
PubMed1987

Interleukin 2 enhances cytotoxic cell function in vitro after T-cell depleted marrow transplantation.

After T-cell depleted marrow transplantation, there is a rapid recovery of cytotoxic effector cells, with activity against targets not susceptible to killing by 'resting' natural killer cells. These targets include Epstein-Barr virus transformed B cells and leukaemic cell lines. Activated killer cell function declines by 3 months after transplantation. We find that when CD3 negative effector cells are obtained from these patients and cultured in vitro with interleukin 2 there is a further enhancement of cytotoxic activity against a range of target cells in the early post-transplant period, and a restoration of high level cytotoxic activity to effector cells obtained 3 months or more after the procedure. These results may have relevance to attempts to reduce the incidence of leukaemic relapse, and EBV + ve lymphoma outgrowth after T-cell depleted BMT.

Adolescent↗
PubMed1987

Mitozantrone-induced toxicity and DNA strand breaks in leukaemic cells.

By applying the fluorometric analysis of DNA unwinding (FADU) the in vitro effect of mitozantrone on DNA strand breaks was studied in seven different human leukaemic/lymphoma cell lines and in fresh leukaemic samples from seven patients with acute myeloid leukaemia refractory to conventional treatment. Pulse exposure to mitozantrone for 30 min invariably caused strand breaks. In the cell lines JM 1, KM3 and RPM I 8420 DNA strand breakage was progressive upon further incubation in drug free medium. These cell lines were killed by pulse exposure to mitozantrone. In the cell lines Molt 4, Daudi, Raji and HL-60, the DNA strand breaks induced by mitozantone were only moderate and these cell lines were also resistant to killing by mitozantrone in vitro. The leukaemic cells of one of the seven patients behaved also like the cell lines that were sensitive and a complete remission was achieved in this patient using mitozantrone as single agent therapy. The other patients with a pattern similar to the resistant cell lines proved to be clinically refractory. Thus mitozantrone induces rapidly progressive DNA strand breaks as early as 30 min in leukaemic cells that are sensitive. The measurement of DNA strand breaks by the fluorometric analysis of DNA unwinding is a rapid method which might predict response to drugs whose major effect is on the induction of strand breaks.

Cell Line↗
PubMed1987

Role of bronchoalveolar lavage in the evaluation of interstitial pneumonitis in recipients of bone marrow transplants.

Forty episodes of pneumonitis in 30 recipients of allogeneic bone marrow transplants were investigated by fibreoptic bronchoscopy and bronchoalveolar lavage. A positive diagnosis was made in 32 episodes of pneumonitis (24 patients), giving a diagnostic yield of 80%. In 31 of these the diagnosis was made within 24 hours of bronchoscopy and this enabled the appropriate treatment to be instituted early. Eighteen patients recovered from their primary infection, although two died subsequently of respiratory failure due to postpneumonic lung destruction. Ten patients later developed a second episode of pneumonitis and a diagnosis was made in nine of these. Only three survived a second episode. Bronchoalveolar lavage was well tolerated by all patients and there was no morbidity or mortality that could be directly attributed to the procedure. Bronchoalveolar lavage is a safe and valuable early diagnostic procedure for the investigation of pulmonary complications in patients who have received bone marrow transplants.

Adolescent↗
PubMed1987

The role of mitozantrone in the treatment of acute leukaemia.

Mitozantrone (MTZ; Novantrone), 1,4-dihydroxy-5,8-bis-[(2-[(2-hydroxyethyl)amino]ethyl]amino)-9,10- anthracenedione dihydrochloride (NSC 302739), is a synthetic anthracenedione with intercalating properties. Activity has been shown in preclinical studies in mice bearing intraperitoneal P388 and L1210 leukaemias and a variety of solid tumours. Three sequential studies to examine the activity, toxicity and scheduling of MTZ in acute leukaemia or chronic granulocytic leukaemia in myeloid transformation were undertaken in relapsed and/or refractory disease in patients up to the age of 70. Single-dose treatment up to 32 mg/m2 showed little activity but in a 5-day schedule (10 mg/m2/day) MTZ gave a 24% complete remission rate in relapsed and/or resistant acute leukaemia. In a phase III study in which MTZ was given in a similar schedule combined with a 7-day infusion of cytosine arabinoside (Ara-C; 100 mg/m2/day), 68% of patients were rendered leukaemia-free. In studies from other centres, similar very encouraging results have been obtained where MTZ has been combined with high-dose Ara-C or VP16/213.

Acute Disease↗
PubMed1987

Bone marrow transplantation in acute or chronic leukaemia.

Using T-depleted BM from HLA-identical sibling donors we have performed 36 BMTs since 5/83 in first remission (CR1) of acute leukaemia (AL). Standard conditioning for BMT consisted of Cy 60 mg/kg X 2 and 7.5 Gy single fraction TBI (n = 27). Six patients received Ara-C 3 g/m2 X 6, Cy 45 mg/kg X 2 and 7.5 Gy, while 3 received Cy 60 mg/kg X 2 and 8 Gy radiation. T lymphocytes were depleted in vitro with 2 murine McAbs (MBG6 + RFT8, n = 17; or RFT8 + RFT12, n = 13; or RFT2, RFT8 + RFT12, n = 6) plus rabbit C'-mediated lysis. No immunosuppressive therapy was given in the absence of graft-versus-host disease (GvHD). Of 34 patients evaluable for a GvHD, 4 had grade I, 2 grade II and 1 grade III. Chronic GvHD occurred in 3 of 22 evaluable patients (greater than 150 days). There have been 13 deaths but only 1 from leukaemic relapse (CNS). The mean KS of surviving patients is 86% and actuarial disease-free survival is 53% at 40 months or 65% in those having 'standard conditioning'. The previous major problems of GvHD and leukaemic relapse appear to have been largely overcome. The major risk factor now is infection, particularly pneumonitis, and this problem is surmountable.

Acute Disease↗
PubMed1987

Pulmonary cryptosporidiosis occurring in a bone marrow transplant patient.

We describe what is believed to be the first bone marrow transplant patient, a 32-year-old man, in whom pulmonary cryptosporidiosis was associated with terminal respiratory failure. The diagnosis, treatment and postmortem histology are discussed together with a brief review of the literature.

Adult↗
PubMed1987

Rapid recovery of helper activity following T cell depleted allogeneic marrow transplant.

Within the first year after T cell depleted bone marrow transplantation, co-cultures of T cells and non-T cells from 32 individual recipients examined on 43 occasions generally failed to produce increased quantities of immunoglobulin in response to stimulation with pokeweed mitogen or B cell differentiation factors. Failure occurred even in the presence of significant numbers of CD20 + ve B cells. The non-production of Ig appears to be due to a functional B cell defect, since adding marrow donor (syngeneic) T cells to recipient B cells in the presence of PWM or conditioned medium did not lead to immunoglobulin production. This B cell deficit persisted for 1 year. In contrast helper activity in the recipient T cell enriched population returns rapidly and by 6 weeks after transplant co-cultures of marrow donor B cells and recipient T cells produce comparable amounts of Ig to co-cultures of donor T and B cells. This prolonged defect of B cell function in vitro correlates with a year long delay before humoral responses to novel vaccine antigens can be elicited in vivo.

Adolescent↗
PubMed1987

Haemorrhagic cystitis in bone marrow transplantation patients: possible increased risk associated with prior busulphan therapy.

Following bone marrow transplantation employing conditioning including 'high-dose' cyclophosphamide, 65 patients were studied for the subsequent development of symptomatic haemorrhagic cystitis. There was no protection from the urothelial toxicity of cyclophosphamide metabolites afforded by the concurrent administration of 2-mercaptoethane sodium sulphonate (mesna) if timing errors in administration were made. Other factors which might increase the risk of haemorrhagic cystitis due to cyclophosphamide administration include the prior administration of busulphan to patients with chronic granulocytic leukaemia, in whom the incidence of haemorrhagic cystitis was 36% compared with 4% in all other patients. We have also investigated the use of intravesical prostaglandin E2 as a treatment for haemorrhagic cystitis in eight patients, two of whom appeared to obtain major benefit.

Adolescent↗
PubMed1987

CD5-positive B cells after T cell depleted bone marrow transplantation.

CD5 is an antigen normally found on T cells and on a minority subpopulation of B cells in fetal spleen and tonsil and on the majority of cells in B-chronic lymphocytic leukaemia. Recent reports described the occurrence of large numbers of CD5-positive B cells in the peripheral blood after bone marrow transplantation (BMT). We examined the peripheral blood for CD5-positive B cells in 21 patients who underwent allogeneic BMT for leukaemia with marrow first depleted of T cells using anti-T monoclonal antibodies and complement mediated lysis. Twenty-six samples were obtained from patients 24-644 days after BMT and examined for the existence of blood-borne CD5-positive B cells by immunofluorescence analysis microscopically and by flow cytometry. The number of CD5-positive B cells was consistently lower than 2%. The absence of CD5-positive B cells in this series may be due to the method of T cell depletion of the marrow or to methodological differences in the analysis of the cells.

Adolescent↗
PubMed1987

Rearrangement of immunoglobulin and T cell antigen receptor genes in acute myeloid leukemia with lymphoid-associated markers.

Ten cases of adult acute myeloid leukemia (AML) displaying lymphoid-associated markers CD7 and/or terminal deoxynucleotidyl transferase (TdT) have been investigated for rearrangement of immunoglobulin and T cell antigen receptor beta and gamma genes. Two of six TdT+ cases had clonally rearranged Ig genes, whereas six of eight CD7+ AMLs, including three that were TdT+, had a germ line configuration of both immunoglobulin and T cell receptor beta and gamma genes. A single case of CD7+ TdT- AML had clonal rearrangement of all three genes. These results indicate that expression of TdT and/or CD7 is not accompanied by gene rearrangement in most cases of adult AML. A minority of cases, displaying lymphoid-associated phenotypic markers and accompanying gene rearrangement, may represent a distinct subgroup of AML that arises from a rare, primitive stem cell, possessing extensive multilineage potential.

Adult↗
PubMed1986

Transfer of a functioning humoral immune system in transplantation of T-lymphocyte-depleted bone marrow.

To test the effect of transplantation of T-cell-depleted bone marrow on recipient immune function the results of pre-transplantation immunisation with tetanus toxoid and hepatitis-B vaccine were studied in 38 donor-recipient pairs. Immunisation of the donor alone resulted in transfer of an antibody response to the recipient; immunisation of both donor and recipient resulted in potentiation of the antibody response in both magnitude and duration. These findings indicate that donor T-cell-depleted marrow can transfer humoral immunity to the recipient and that appropriate pre-transplant immunisation schedules may be of benefit to the recipient.

Adolescent↗
PubMed1986

Treatment of acute leukaemia with m-AMSA in combination with cytosine arabinoside.

A series of 46 patients with acute leukaemia were treated with amsacrine (m-AMSA) and cytosine arabinoside (ara-C). Complete remission (CR) was achieved in 15 of 38 (40%) patients with acute myelogenous leukaemia (AML) and 4 of 8 (50%) patients with acute lymphoblastic leukaemia (ALL). The CR rate was significantly higher (P less than 0.05) for the younger, previously treated patients with AML (9/16) than for the older previously untreated ones (6/22), because of higher treatment mortality in the latter group. Myelosuppression was prolonged and profound. Major nonhaematological toxicity affected the gastrointestinal tract (nausea, vomiting, mucositis, bleeding and ileus associated with severe diarrhoea). Many patients also developed reversible hepatic dysfunction and two elderly patients died of cardiac arrhythmia. Further trials of this combination are justified in patients with relapsed or resistant leukaemia, but for older patients dose reduction is recommended.

Aged↗