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Biomedical subjects

J F Apperley

Publications and source records attributed to J F Apperley.

103 records · Page 6Linked to original sources
PubMed1988

Cytogenetic events after bone marrow transplantation for chronic myeloid leukemia in chronic phase.

Forty-eight patients treated by allogeneic bone marrow transplantation (BMT) for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia in chronic phase had serial cytogenetic studies of marrow performed at intervals after transplant. Twenty patients received marrow cells from donors of opposite sex. Ph+ marrow metaphases were identified in 24 of 48 (50%) of patients after BMT; they were first seen early (within 1 year) in 16 cases and late (greater than 1 year after BMT) in eight cases. Ph-positivity after BMT occurred more commonly in recipients of T-depleted than nondepleted marrow (19 of 28 v 5 of 20). In 4 cases the Ph+ metaphases were found only transiently after BMT; in 11 cases the Ph+ metaphases have persisted but hematologic relapse has not ensued; in 9 cases the finding of Ph+ metaphases coincided with or preceded hematologic relapse. Chromosomes in cells of donor origin had morphological abnormalities in two cases. No relapses were identified in cells of donor origin. Our data suggest that the relationship between cells of recipient and donor origin is complex: cure of leukemia may depend on factors that operate for some months or years after BMT.

Bone Marrow Transplantation↗
PubMed1987

Antibody titres to a rough-mutant strain of Escherichia coli in patients undergoing allogeneic bone-marrow transplantation. Evidence of a protective effect against graft-versus-host disease.

Much clinical and experimental evidence suggests that infection and graft-versus-host disease (GvHD) are commonly associated as complications of bone-marrow transplantation (BMT). A likely basis for this association is the gram-negative faecal flora,the origin of many septicaemias and a source of bacterial endotoxin, which has potent immunostimulatory effects. A rough-mutant strain, Escherichia coli J5, has only core determinants in its endotoxin,and antibodies to E coli J5 protect animals and human beings from the consequences of septic shock. Naturally occurring antibodies to E coli J5 ("anti-endotoxin") were assayed in serum from patients undergoing BMT, healthy controls, and patients with obstructive jaundice. BMT recipients had significantly lower titres than the other two groups. Furthermore, the titre of IgM class anti-J5 antibody was significantly associated with protection from GvHD.

Acute Disease↗
PubMed1987

Complete remission after autografting for chronic myeloid leukaemia.

A previously untreated 31-yr old female with Ph-positive chronic myeloid leukaemia (CML) received busulphan and melphalan at high dosage followed by an autograft of peripheral blood stem cells collected 4 weeks earlier. Though recovering haemopoiesis was at first mainly Ph-positive, Ph-negative haemopoiesis predominated at 12 months and has persisted until the most recent study (24 months post-autograft). Her haemopoietic cells now show no rearrangement of the bcr gene, unlike the cells collected at diagnosis. Autografting carried out soon after diagnosis could be valuable for obtaining cytogenetic remissions in other patients with CML.

Adult↗
PubMed1987

Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation.

Hemorrhagic cystitis is a well known complication of allogeneic bone marrow transplantation (BMT) and is normally attributed to the use of high-dose cyclophosphamide in the preparative regimen. Hemorrhagic cystitis occurring late after BMT is unlikely to be due to the effects of this conditioning, and probably has an infective etiology. Three patients undergoing BMT for chronic granulocytic leukemia (CGL) developed terminal dysuria and hematuria at 38, 56, and 149 days post-BMT. Electron microscopy (EM) of urine voided at these times revealed large numbers of papovavirions, which were subsequently identified as BK virus. Urine samples inoculated onto human embryonic lung fibroblasts induced infection of the cells and replication of the virus as detected by EM of tissue culture fluid. Urine from one of these patients was examined by standard cytological techniques, and EM of urothelial cells showed nuclear inclusions consisting of nonencapsulated virus particles of diameter 40 nm, consistent with papovavirus. Five further patients were found to be excreting BK virus without symptoms of cystitis, although one of these patients did experience abnormalities of liver function that were otherwise unexplained. BK virus has already been implicated in hepatic dysfunction posttransplant, and in cystitis in nonimmunosuppressed children. We postulate that it may also be involved in the etiology of late hemorrhagic cystitis after BMT.

Adult↗
PubMed1987

Identical twin marrow transplantation for 5 patients with chronic myeloid leukaemia: role of DNA finger-printing to confirm monozygosity in 3 cases.

5 patients with chronic myeloid leukaemia (CML) have been treated by BMT from identical twin donors. Syngeneity of the twins was established by conventional methods in the first 2 patients. These included the similarity of phenotype, dermatoglyphics and analysis of red cell isoenzymes and blood groups. 2 of the other patients had received multiple blood transfusions prior to referral for BMT thereby invalidating red cell analysis. However genetic identity was confirmed in these patients by the method of DNA 'finger-printing' which demonstrated identical restriction-fragment length polymorphisms. Conclusive proof of syngeneity in twins prior to BMT is important since it obviates the need for T-cell depletion and/or post-graft immunosuppression to prevent graft-versus-host disease (GVHD). All 5 patients were conditioned with high-dose chemoradiotherapy prior to BMT and all patients are alive and disease-free at a median follow-up of 12 months. In conclusion, we report a new, reliable method for determining syngeneity of twins which has bearing on the technical approach to BMT.

Adult↗
PubMed1987

HIV infection due to a platelet transfusion after allogeneic bone marrow transplantation.

A 30-yr-old man with chronic granulocytic leukaemia received a bone marrow transplant from his histocompatible sister in December 1982. His post-transplant course was complicated by Grade III graft-versus-host disease and multiple infectious episodes until his death from pneumonia on d + 190. He was later found to be seropositive for anti-HIV at the time of his death. Retrospective analysis of stored sera showed a transient period of seropositivity from d + 11 to d + 20 thought to reflect passive transfer of antibody from a blood product transfused prior to d + 11 when he was also exposed to infectious virus. He remained seronegative until d + 78 when anti-HIV was again found. Seropositivity persisted until his death and was attributed to endogenous antibody response. Although it is unclear whether his clinical course was due to AIDS, exposure of an immunosuppressed patient to HIV may be associated with more rapid development of clinical disease.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

Adult↗
PubMed1986

Bone marrow transplantation for patients with chronic myeloid leukemia.

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72 percent, and the actuarial risk of relapse was 7 percent. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18 percent, and the actuarial risk of relapse was 42 percent. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established.

Adolescent↗
PubMed1986

Philadelphia-positive metaphases in the marrow after bone marrow transplantation for chronic granulocytic leukemia.

A 28-year-old man with Ph-positive chronic granulocytic leukemia (CGL) was treated by high-dose chemoradiotherapy and transplantation of marrow cells harvested from his HLA-identical brother. One year after bone marrow transplantation (BMT) examination of his marrow showed a minority population of Ph-positive cells; their proportion subsequently fell such that 2 years after transplant analysis of marrow cells showed only cytogenetically normal cells. The patient remains clinically normal with a persisting mild lymphocytosis but without hematological evidence of leukemia. We cannot in this patient distinguish between persisting leukemia that later could no longer be recognized and relapse of leukemia that is now suppressed, perhaps only temporarily. This case emphasizes the need for caution in interpreting chromosomal finding after BMT for CGL.

Adult↗
PubMed1986

Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse.

Between December 1983 and November 1985 we treated 39 patients with chronic myeloid leukaemia by chemoradiotherapy and transplantation from HLA-identical sibling donors using bone marrow that had been depleted of T cells ex vivo with the rat monoclonal antibody Campath-1. Twenty-eight of the patients were in the chronic phase (good-risk group) and 11 patients were in more advanced phases of the disease (accelerated phase or blastic transformation; poor-risk group). Of the patients of good risk 23 (82%) survive; the median duration of follow-up is 461 (range 111-776) days; of the 11 patients of poor risk four survive; the median duration of follow-up is 280 (range 189-658) days. Acute graft-versus-host disease (GVHD) of grade II or greater occurred in three (11%) of the patients of good risk and in six (55%) of the patients of poor risk. In the patients of good risk haematological evidence of relapse was seen in four and cytogenetic evidence of persisting or relapsed leukaemia (based on the finding of Philadelphia-chromosome-positive marrow metaphases more than 6 months after transplant) was seen in three other patients. In comparison with the patients of good risk transplanted with untreated marrow between February 1981 and December 1983, the incidence of acute GVHD was reduced significantly (P less than 0.001) but the risk of leukaemic relapse (including patients with only cytogenetic evidence of relapse) was increased (P less than 0.005). We conclude that T-cell depletion used in this manner may be associated with an increased risk of leukaemic relapse.

Actuarial Analysis↗
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↗