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J M Hows

Publications and source records attributed to J M Hows.

At least 91 records · Page 5Linked to original sources
PubMed1988

Auto-anti-Jka in Evans' syndrome with negative direct antiglobulin test.

A patient presented with haemolytic anaemia and a negative direct antiglobulin test (DAT), and was found to have an IgG antibody with anti-Jka specificity in his serum. His red cells were typed as Jk(a-b+). Later he developed idiopathic thrombocytopenic purpura (ITP), and had a positive DAT due to anti-Jka bound to his red cells, which now typed as Jk(a+b+). Family studies suggested that the patient's true type was Jk(a+b+). Splenectomy and immunosuppression were required to treat the thrombocytopenia. The autoanti-Jka was no longer detectable following therapy.

Adult↗
PubMed1988

Use of a hypervariable minisatellite DNA probe (33.15) for evaluating engraftment two or more years after bone marrow transplantation for aplastic anaemia.

We have studied long-term engraftment in 24 multiply transfused patients transplanted for severe aplastic anaemia (SAA) 2-7 years previously from HLA identical sibling donors. All 24 patients had engrafted initially; nine (38%) developed grade II-IV a-GVHD, but only 5 (21%) developed chronic GVHD, which was mild, localized and transient. In 22 cases DNA 'fingerprint' analysis using a hypervariable minisatellite DNA probe (33.15) confirmed the donor/recipient origin of patient peripheral blood (PB) nucleated cells. Red cell antigens and PB lymphocyte chromosomes were also analysed in informative cases. In 19 patients (79%) PB cells were of donor origin confirming sustained engraftment, whereas five (21%) had PB cells of recipient origin. In four of these five cases complete autologous reconstitution was demonstrated. In one case DNA fingerprinting revealed mixed haemopoietic chimaerism. In three of the four cases of autologous reconstitution there had been a previous episode of late graft failure. The low incidence of chronic GVHD in the study group was not explained by autologous reconstitution or mixed chimaerism. We conclude that the hypervariable minisatellite probes are valuable in the study of engraftment after BMT, especially when patient and donor are HLA identical, of the same sex, and have the same ABO-Rh blood type. Pre-transplant specimens from the patient are not necessary for interpretation of the results provided that DNA from the donor is available.

Adolescent↗
PubMed1987

Immunological reconstitution after bone marrow transplant with Campath-1 treated bone marrow.

Immunological reconstitution after allogeneic bone marrow transplant (BMT) was studied in 20 patients who received Campath-1 treated bone marrow. The peripheral blood lymphocyte phenotype was analysed with a panel of monoclonal antibodies at 3, 6 and 12 months. T cell proliferative capacity was evaluated by stimulation with PHA and Con A and in the mixed lymphocyte reaction (MLR). Natural killer (NK) cell activity was analysed against the K562 cell line at specified times after BMT in nine patients. Absolute numbers of T lymphocytes were reduced in all patients at 3 and 6 months. A marked decrease in the number of CD4+ cells persisted beyond 12 months. CD8+ cells regenerated more rapidly and reached normal at 6 months. No correlation was found between changes in lymphocyte subpopulations and the presence of graft-versus-host disease or cytomegalovirus infection. B cells recovered rapidly and maintained normal numbers throughout the study. A moderate increase in HNK1+ (Leu7) cells was observed at 3 and 6 months simultaneously with a low expression of NK15 (Leu11) and OKM1 antigens at 3 and 6 months, suggesting the presence of immature NK cells early after the transplant. A profound decrease of T cell proliferative capacity was observed both after mitogen stimulation and in the mixed lymphocyte reaction. NK cell activity was raised during the first month after transplant in all but one patient but no correlation was found with the presence of GVHD or cell marker analysis.

Adolescent↗
PubMed1987

Histocompatible unrelated donors for bone marrow transplantation.

Bone marrow transplantation using HLA one haplotype mismatched family donors has been associated with a high incidence of severe graft-versus-host disease, and an increased risk of graft failure. Recently, the use of histocompatible unrelated donors has been investigated when an HLA genotypically identical sibling is not available. Conventional histocompatibility testing of potential unrelated donors does not always predict alloreactivity in vivo. In this review, the preliminary results of histocompatible unrelated transplants are presented and methods of matching unrelated donors discussed.

Bone Marrow Transplantation↗
PubMed1987

Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity.

Sixty-four patients with aplastic anemia were treated with antilymphocyte globulin (ALG Merieux) between 1980 and 1985. The actuarial survival for all patients was 53% at 6 years, with 79% survival for nonsevere aplastic anemia (NSAA) and 36% for severe aplastic anemia (SAA). The neutrophil and platelet counts before treatment with ALG were highly predictive of survival, whereas sex, age, and etiology were not. Duration of disease prior to ALG treatment was inversely related to survival, although this was not statistically significant. Survival was closely associated with response to ALG, especially for patients with SAA. The response to one course of ALG was 33%. Eighteen patients who did not respond to an initial course of ALG received a second course; of these, four (22%) responded. The overall response to one or two courses of ALG was 40%. The mean RBC volume (MCV) measured after ALG treatment was a useful early indicator of response. Both the minimum lymphocyte count during ALG therapy and the mean lymphocyte count after therapy, however, were not significantly different between responders and nonresponders. The disappointing survival of patients with SAA in this study may reflect the poor clinical condition of severely affected patients referred to us and/or the presence of longstanding aplasia. The importance of studying a large series of patients with long-term follow-up to assess ALG in the treatment of aplastic anemia is shown by this investigation.

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↗
PubMed1984

Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study.

A prospective randomised study was carried out to compare the effect of mesna (2-mercaptoethane sulphonate sodium) with that of forced diuresis in preventing cyclophosphamide induced haemorrhagic cystitis in marrow transplant recipients. Sixty-one consecutive BMT recipients were randomised for treatment with forced diuresis or mesna. The incidence of macroscopic haematuria was significantly lower in the mesna treated group (chi 2 = 4.03, P less than 0.05). No specific side effects of mesna were detected. The lymphopenia induced by cyclophosphamide in the aplastic recipients was similar in the mesna and forced diuresis groups suggesting that mesna has no effect on the lymphocytotoxic activity of cyclophosphamide, although 6 out of 7 episodes of graft failure documented in the study occurred in mesna treated patients. As a result of this study our present policy is to use mesna in all BMT recipients but to continue careful documentation of the incidence of graft failure.

Adolescent↗
PubMed1984

Haematological reconstitution and severity of graft-versus-host disease after bone marrow transplantation for chronic granulocytic leukaemia: the influence of previous splenectomy.

Eighteen patients with chronic granulocytic leukaemia (CGL) were treated by chemoradiotherapy and transplantation of bone marrow (BMT) collected from their HLA-identical sibs; engraftment with donor marrow occurred in all cases. Ten of the patients had been subjected to splenectomy before BMT; recovery after BMT of granulocyte, lymphocyte and platelet numbers in the peripheral blood was more rapid in these patients than in the eight patients who retained their spleens. Acute graft-versus-host disease occurred in 12 of the 15 evaluable patients and appeared to be more severe in those who lacked their spleens at the time of transplant. Of the 12 patients surviving at follow-up times ranging from 59 to 207 weeks, six had been subjected to splenectomy before BMT and six retained their spleens. We conclude that engraftment was more rapid in the splenectomized patients and splenectomy might have increased the chance of eradicating the leukaemia, but these considerations must be balanced against the short-term and long-term risks associated with splenectomy.

Adolescent↗
PubMed1984

Airways obstruction associated with graft versus host disease after bone marrow transplantation.

Eight patients, five with chronic granulocytic leukaemia and three with severe aplastic anaemia, developed moderately severe airflow obstruction after allogeneic bone marrow transplantation. All eight had clinically and radiologically normal lungs before undergoing transplantation. Treatment in the patients with chronic granulocytic leukaemia before transplantation included high dose total body irradiation. All eight patients developed acute and chronic graft versus host disease after transplantation. The pulmonary syndrome consisted of cough, dyspnoea, and wheezing beginning six to 20 weeks after transplantation, with ratios of forced expiratory volume in one second (FEV1) to vital capacity (VC) falling to 60% or less of predicted values. The three patients with severe aplastic anaemia had relatively mild graft versus host disease and acute chest infection may have initiated or contributed to their airways obstruction, which subsequently resolved. The five patients with chronic granulocytic leukaemia had more severe graft versus host disease and more progressive respiratory problems; two died and three continued to have persistent airflow obstruction 11, 15, and 20 months after transplantation. None of those with chronic granulocytic leukaemia improved. Transfer factor (TLCO) was reduced in all patients after bone marrow transfer and did not improve; in the patients with chronic granulocytic leukaemia the reduction in TLCO preceded the fall in FEV1/VC ratio. Open lung biopsy in one of the patients with chronic granulocytic leukaemia showed obliterative bronchiolitis with lymphocytic infiltration consistent with graft versus host disease. Bronchodilators were of no benefit in the management of these patients, but prompt treatment of infection and early use of corticosteroids may have contributed to the improvement seen in the patients with severe aplastic anaemia.

Adolescent↗
PubMed1983

Regeneration of peripheral blood cells following ABO incompatible allogeneic bone marrow transplantation for severe aplastic anaemia.

The regeneration of peripheral blood cells in six patients receiving ABO incompatible bone marrow transplants for severe aplastic anaemia has been studied. The results are compared with those of 18 similar aplastic patients treated with ABO compatible transplants. Reticulocyte recovery in the ABO incompatible cases was significantly delayed (P less than 0.01) and associated with greatly prolonged red cell transfusion requirements (P less than 0.001). Peripheral blood regeneration of neutrophils, lymphocytes and platelets was also significantly delayed (P less than 0.01). Platelet support was required for longer in the ABO incompatible cases (P less than 0.001) but there was no increase in the incidence or severity of infections in the post transplant period.

ABO Blood-Group System↗
PubMed1983

Nephrotoxicity in bone marrow transplant recipients treated with cyclosporin A.

Cyclosporin A(CyA) is a valuable post graft immunosuppressive agent in allogeneic bone marrow transplantation. The use of CyA is associated with a reduction in severity of graft versus host disease and improved marrow engraftment. A major side effect of CyA is nephrotoxicity. In 33 patients studied during the first 4 weeks of therapy there is a close correlation between trough (12 h) serum cyclosporin A concentrations and plasma creatinine (r = 0.93, P less than 0.001) and urea (r = 0.88, P less than 0.001). Trough CyA serum concentrations of greater than 500 ng/ml are potentially nephrotoxic. Other risk factors for early nephrotoxicity in cyclosporin therapy are the concurrent use of aminoglycoside antibiotics (P = 0.01) and hyperbilirubinaemia (P = 0.01). Early nephrotoxicity can be prevented by maintaining trough CyA levels in the range 100-400 ng/ml. During prolonged CyA therapy, cumulative renal impairment can occur and nephrotoxic episodes associated with microangiopathic peripheral blood changes and hypertension are seen in a minority of patients.

Adolescent↗
PubMed1983

Stability of cyclosporin A in human serum.

Cyclosporin A (CyA), a new immunosuppressive drug, is used for the prevention of organ graft rejection in man. The main side effect of CyA is nephrotoxicity which is usually reversible when the drug is stopped. Nephrotoxicity may be avoided in patients by careful monitoring of serum CyA concentration by radioimmunoassay, in addition to the routine biochemical tests of renal function. There is a good correlation between trough (12 hour) serum concentrations of CyA and plasma creatinine. Cyclosporin A was stable in serum at room temperature for up to seven days and on storage at -20 degrees C for up to five months. Delayed separation of blood stored at room temperature led to increased serum CyA concentrations while blood stored at 4 degrees C before separation was much more stable. Blood samples should be separated as quickly as possible to avoid the release of CyA from the cellular fraction into the serum. Haemolysed samples should be avoided. CyA is sufficiently stable at room temperature for serum samples to be sent in the first class post to a control laboratory for CyA assay, after patients are discharged from the transplant centre. Control and patient serum samples should be stored for a maximum of five months at -20 degrees C prior to assay for CyA.

Cyclosporins↗
PubMed1982

Marrow transplantation for patients in the chronic phase of chronic granulocytic leukaemia.

In 1979 two patients with Philadelphia (Ph1)-chromosome-positive chronic granulocytic leukaemia (CGL) were treated with chemoradiotherapy and transplantation of bone marrow from their respective identical twins. Subsequently twelve patients with Ph1-positive CGL in chronic phase were treated with chemoradiotherapy followed by transplantation of bone marrow from their HLA-identical sibs. Two of the fourteen patients have died of complications of the transplant procedure; twelve patients are alive and well. All the survivors have normal or nearly normal blood counts; there is no evidence of recurrent leukaemia or Ph1-positive cells in any patient after follow-up periods ranging from 97 to 1112 days. Bone-marrow transplantation should be considered in the management of any young patient with CGL who has a suitable marrow donor.

Adolescent↗