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Biomedical subjects

R A Clift

Publications and source records attributed to R A Clift.

At least 91 records · Page 5Linked to original sources
PubMed1987

The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation.

The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission.

Bone Marrow Transplantation↗
PubMed1987

Treatment of preleukemic syndromes with marrow transplantation.

Thirty patients with advanced preleukemic syndromes were treated with marrow transplantation. Most cases were diagnosed by the presence of peripheral pancytopenia and a diagnostic marrow examination but in 6 of the 30 patients pretransplant chromosome studies were instrumental in establishing the diagnosis. Three patients prepared for transplantation with cyclophosphamide alone recurred with their disease within 6 months of transplantation. The other 27 patients were treated with cyclophosphamide and total body irradiation. Twenty of these 27 patients had preleukemia not associated with prior therapy or severe marrow fibrosis. Thirteen of these 20 are alive and well 9 to 56 months from transplant and 7 died, 4 of interstitial pneumonia, 2 of candida septicemia, and 1 of disseminated zoster. There have been no disease recurrences in this group. The remaining preleukemic patients, which include 3 patients transplanted for preleukemia secondary to prior therapy and 4 patients transplanted for preleukemia associated with severe marrow fibrosis, have all died. Major problems in these patients included disease recurrence (2 cases) and, in those with severe marrow fibrosis, graft failure (2 cases). These results suggest that for patients with life-threatening pancytopenia due to spontaneous preleukemia without severe marrow fibrosis, marrow transplantation can prolong disease-free survival and may result in cure of the disease.

Bone Marrow Transplantation↗
PubMed1986

The effects of splenectomy on engraftment and platelet transfusion requirements in patients with chronic myelogenous leukemia undergoing marrow transplantation.

Granulocyte and platelet recovery as well as platelet transfusion requirements following allogeneic marrow transplantation were analyzed in 67 patients with chronic myelogenous leukemia in the chronic phase. Twenty patients had splenectomy prior to transplantation. Forty-seven patients were transplanted without splenectomy, 21 of whom had splenic enlargement by physical examination. There were no differences in the proportion of patients with granulocyte recovery, but the recovery of peripheral granulocytes to levels of 200, 500 and 1,000/mm3 occurred more rapidly in the splenectomy group than in the no-splenectomy group. Patients with splenectomy received platelet transfusions for a mean of 10 (2-36) days as compared to 20 (3-82) days for patients without splenectomy (p less than .001). Eighteen (90%) patients with splenectomy became platelet transfusion independent at a median of 16 (2-32) days after transplantation as compared to 40 (85%) patients without splenectomy who became transfusion independent at a median of 28 (15-86) days (p less than .001). The proportion of patients achieving platelet levels of 50 and 100 X 10(3)/mm3 did not differ between the two groups (p = .07), but patients in the splenectomy group achieved these levels more rapidly following transplant (p less than .001). One of 17 evaluable patients in the splenectomy group and 31 of 46 in the no-splenectomy group became refractory to random platelets (p less than .001) and required platelets from family members or unrelated completely or partially HLA matched donors. In the no-splenectomy group, splenic size did not affect the speed of granulocyte or platelet recovery or platelet transfusion requirements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Prevention of nosocomial infections in marrow transplant patients: a prospective randomized comparison of systemic antibiotics versus granulocyte transfusions.

One hundred twelve patients with hematologic malignancies underwent marrow transplantation from HLA-matched sibling donors and were randomized to receive either prophylactic granulocyte transfusions (PG, 67 patients) or prophylactic systemic antibiotics (PSA, 45 patients) as prophylaxis against nosocomial infections. Patients were treated in conventional hospital rooms and studied until day 100 post-transplant. For the entire study period, 26 patients (39%) in the PG group developed septicemia compared to 15 patients (33%) in the PSA group. Twenty-eight patients (42%) in the PG group developed local major infections compared to 19 patients (42%) in the PSA group. Ten patients (15%) in the PG group developed viral interstitial pneumonitis compared to 6 patients (13%) in the PSA group. None of these differences were statistically significant. There was no difference in the incidence of bacterial or fungal infections or viral interstitial pneumonitis between the two groups during the granulocytopenic or post-engraftment period. There was no difference in the incidence and severity of graft-versus-host-disease (GVHD). Inability to carry out the prophylaxis was frequent in the PG group, with complications necessitating discontinuance of transfusion in 24% of the recipients and 13% of the donors. The use of PG as an infection prophylaxis modality in marrow transplantation is not supported by this study, as it is difficult to carry out and because PG did not show any advantage over the use of PSA in preventing nosocomial infections.

Adolescent↗
PubMed1986

Plasma exchange for platelet alloimmunization.

We studied the effectiveness of plasma exchange for reversing antiplatelet alloimmunization in 18 patients undergoing marrow transplantation. Patients received one-to-three daily exchanges. Most exchanges occurred during the pretransplant conditioning phase. Overall, eleven of 18 patients had a beneficial response to plasma exchange, defined as an improvement in post-platelet-transfusion increments. More patients responded who had received two or more exchanges. Patients who had lymphocytotoxic antibodies pretransplant were more likely to benefit from the exchange. Our results show that plasma exchange may improve the posttransfusion platelet increments in alloimmunized patients undergoing marrow transplant.

Adolescent↗
PubMed1986

Marrow transplantation for the treatment of chronic myelogenous leukemia.

One hundred ninety-eight patients with chronic myelogenous leukemia received marrow transplants after intensive chemotherapy and total body irradiation. Multivariate analysis showed disease status at time of transplantation to be the most powerful predictor of survival. The probability of long-term survival for allogeneic graft recipients was 49% for 67 patients in the first chronic phase, 58% for 12 in the second chronic phase, 15% for 46 in the accelerated phase, and 14% for 42 in the blastic phase. The major cause of death was interstitial pneumonia for patients in the chronic phase, and relapse for those in the blastic or accelerated phases. Factors favoring survival were early transplantation, age less than 30 years, and absence of severe graft-versus-host disease. Splenectomy or spleen size did not influence survival. For recipients of syngeneic grafts survival probability was 87% for 16 patients in the chronic phase, 27% for 7 in the accelerated phase, and 12% for 8 in the blastic phase. Of the 198 patients, 71 are alive without Philadelphia chromosomes 1 to 9 years after receiving their graft. All but 4 long-term disease-free survivors have Karnofsky performance scores of 80% or better.

Adult↗
PubMed1986

Marrow transplantation for severe aplastic anemia. Long-term outcome in fifty "untransfused" patients.

Fifty patients with severe aplastic anemia had no transfusions of blood products until just before marrow transplantation from HLA-identical family members. Of the 50, 42 are still alive 1 to 12 years after transplantation (median, 7 years). By actuarial standards, the 10-year probability of survival is 82%. Of the 42 surviving patients, 37 have Karnofsky performance status scores of 100% and 5 with chronic graft-versus-host disease have scores ranging from 50% to 90% (median, 80%). The 8 deaths were caused by early infection in 1, graft rejection in 1, acute graft-versus-host disease in 3, and chronic graft-versus-host disease in 3. All deaths occurred within two years after transplantation. The incidence of graft failure was 10%. Acute graft-versus-host disease developed in 14 of 44 patients at risk and chronic graft-versus-host disease, in 15 of 41. Risk factors for development of chronic graft-versus-host disease included increased age (p = 0.008) and presence of acute graft-versus-host disease (p = 0.001). The only factor associated with increased risk of death was development of acute graft-versus-host disease (p = 0.05). Results of this study extend our previous finding that patients with severe aplastic anemia who have transplants before the onset of transfusion-induced sensitization have an excellent probability of long-term survival and a normal life.

Acute Disease↗
PubMed1986

Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation.

Seventy-five patients with acute nonlymphoblastic leukemia (ANL) in first remission were treated with cyclophosphamide, 60 mg/kg on each of two consecutive days followed by total body irradiation (TBI) at an exposure rate of 4-6 cGy/min from two opposing 60Co sources. The first 22 patients were given 9.2 Gy of TBI as a single dose. Subsequently 53 patients were randomized to receive either 10 Gy single dose TBI (n = 27) or 6 x 2 Gy fractionated TBI (n = 26). All patients received marrow transplants from HLA-identical siblings and all had sustained engraftment. Patients given 10 Gy of TBI had more early toxicity, especially veno-occlusive disease of the liver, than patients given 9.2 or 6 x 2 Gy of TBI. Idiopathic interstitial pneumonitis appeared to be more frequent in patients given 9.2 or 10 Gy single-dose TBI than in patients given 6 x 2 Gy fractionated TBI. Patients have now been followed from 5 to 9 years. Survival (+/- 95% confidence limits) at 5 years is 54 +/- 31% among patients given 9.2 Gy single dose TBI, 33 +/- 31% among patients given 10 Gy single dose TBI, and 54 +/- 26% among patients given 6 x 2 Gy fractionated TBI (P = 0.04). These results indicate that about half the patients with ANL transplanted while in first chemotherapy-induced remission can be expected to become long-term survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Bone marrow transplantation experience for children with aplastic anemia.

From May 1971 through December 1981, 81 children (22 months to 17 years of age) received allogeneic bone marrow grafts for severe aplastic anemia. All donors were HLA-identical family members. Fifty-seven of the 81 (70%) are still alive. Twenty-three untransfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, and 19 (83%) have survived from 5 to 12 years. All 58 transfused patients were conditioned with cyclophosphamide, 50 mg/kg/d, for four days, 11 received additional immunosuppression, and 19 received posttransplantation donor buffy coat cells. Thirty-eight (65%) have survived from 3 to 13 years (P = .1). In a multivariate analysis, the only factor significantly associated with increased survival among patients with sustained grafts was the absence of significant graft v host disease (P less than .0001). The factors significantly related to increased rejection were low bone marrow cell dose (P less than .05) and positive relative response in mixed leukocyte culture (P less than .0001), but the addition of buffy coat cells did not significantly influence graft rejection. The development of grades II to IV acute graft v host disease was associated with random donor platelet refractoriness (P less than .05) and donor/recipient sex differences (P less than .05). Patients at highest risk for chronic graft v host disease were those patients who developed significant acute graft v host disease (P less than .01) and who received buffy coat infusions (P less than .025). All patients who were untransfused had a negative relative response and were not refractory to random donor platelets.

Acute Disease↗
PubMed1986

Adverse effect of severe marrow fibrosis on hematologic recovery after chemoradiotherapy and allogeneic bone marrow transplantation.

We reviewed the records and marrow biopsy specimens of 75 patients with leukemic, myelodysplastic, or myeloproliferative disorders to determine whether the presence of marrow fibrosis affected engraftment after allogeneic marrow transplantation. While 28 control patients without fibrosis achieved prompt engraftment, two of 32 patients (6%) with mild and five of 15 patients (33%) with severe fibrosis failed. The rate of myeloid recovery was significantly slower and the dependence on platelet and red blood cell transfusions was significantly longer in patients with severe fibrosis than in patients with no fibrosis. A finding of severe marrow fibrosis should therefore be taken into account when evaluating the risks and benefits of marrow transplantation.

Adolescent↗
PubMed1986

Allogeneic marrow transplantation for chronic granulocytic leukemia.

A retrospective analysis is presented of results obtained with allogeneic bone marrow transplantation (BMT) in three phases of Philadelphia chromosome-positive chronic granulocytic leukemia. At BMT, 23 patients were in blastic phase (BP), 33 were in accelerated phase (AP), and 45 were in chronic phase (CP). With a follow-up time of 1-8 years after BMT, the probability of long-term survival was 14, 10, and 58%, respectively, for patients transplanted in BP, AP, or CP. The probability of cytogenetic relapse with or without clinical hematologic relapse at 3 years after BMT was 80, 38, and 31%, respectively, for patients transplanted in BP, AP, or CP. Splenectomy did not influence posttransplant survival. Given the dismal prognosis on conventional therapy, patients younger than 50 in BP or AP should be considered for BMT. For the patient in CP, BMT offers the possibility of cure but with a significant risk of early death. Patients under 40 who fully understand the risks and potential benefits of BMT should be offered BMT early in CP before any change to AP occurs.

Adolescent↗
PubMed1985

Marrow transplantation from related donors other than HLA-identical siblings.

Marrow transplantation has generally been limited to patients with a sibling who is genotypically identical for HLA. In a study of the acceptable limits of HLA incompatibility, 105 consecutive patients with hematologic cancers who received marrow grafts from haploidentical donors (study group) were compared with 728 similar patients concurrently receiving grafts from HLA genotypically identical siblings (control group). The unshared haplotypes differed variably: 12 were phenotypically but not genotypically identical for HLA-A, HLA-B, and HLA-D; 63 differed at one locus (A, B, or D); 24 at two loci; and 6 at three. A higher proportion of study patients had delayed engraftment, granulocytopenia, or graft rejection. Acute graft versus host disease occurred earlier and with greater frequency in study patients. The risk of the disease did not correlate with disparity for Class I (A or B) versus Class II (D-region) loci. Thus, incompatibility for HLA has an important effect on the course after clinical marrow transplantation. In spite of these complications, there was no statistically significant difference in the survival of the study patients and control patients who received their transplants during remission.

Acute Disease↗
PubMed1985

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease.

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Adolescent↗
PubMed1985

Whole blood immunoadsorption of anti-A or anti-B antibodies.

Immunoadsorption columns capable of specifically removing antibodies show promise as an alternative treatment to plasma exchange. Most columns are designed to be perfused with plasma and it is necessary to use a plasma separation device (filtration or centrifugation) for the procedure. This increases the cost and complexity of the immunoadsorption procedure. We have adapted immunoadsorption columns capable of removing anti-A or anti-B red cell antibody from plasma to a whole blood perfusion system by coating the silica with a thin layer of collodion and incubating with albumin (1%). Patients were given heparin, 25 units/kg intravenously, followed by a continuous infusion of 3% citrate and heparin, 10 units/ml, to achieve a ratio of 1:16-1:20 (anticoagulant to whole blood) before delivery through the columns. Effective and specific removal of anti-A or anti-B antibody was achieved with this technique. Effects on coagulation parameters and the complement system were acceptably small.

ABO Blood-Group System↗
PubMed1985

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.

Adult↗
PubMed1985

Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporine versus methotrexate for prophylaxis of graft-versus-host disease.

Forty-eight patients with chronic myelocytic leukemia, aged 11 to 47, were treated with high-dose cyclophosphamide and fractionated total body irradiation, followed by infusion of marrow from HLA-identical siblings. They were randomized to receive either methotrexate (MTX) (n = 23) or cyclosporine (CSP) (n = 25) as postgrafting prophylaxis for graft-v-host disease (GVHD). All patients had evidence of sustained hematopoietic engraftment. Seventeen of the 25 patients receiving CSP and 17 of the 23 patients receiving MTX are alive between one and almost four (median, 1.7) years, with an actuarial survival rate at three years of 62% and 66%, respectively (P = .60). Also, with respect to most other parameters studied, the two drugs were identical. The probability of acute GVHD was .42 and .46, respectively (P = .70), that of chronic GVHD, .50 and .63 (P = .44), and that of death from transplant-related causes, .30 and .24 (P = .51). There were no differences in the speed of granulocyte and platelet engraftment (P = .82 and .94, respectively), and the duration of hospitalization was comparable (P = .58). Patients receiving MTX required red cell transfusions for a shorter period of time (P = .02), but had a slightly increased morbidity from early oral mucositis. The leukemia recurrence rates were comparable (P = .60). With the regimens used in this study, we conclude that CSP failed to reduce the incidence of GVHD and improve the survival of patients with chronic myelocytic leukemia when compared to results with standard MTX.

Adolescent↗