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Biomedical subjects

R A Clift

Publications and source records attributed to R A Clift.

At least 145 records · Page 8Linked to original sources
PubMed1982

Allogeneic marrow transplantation for acute lymphoblastic leukemia in remission using fractionated total body irradiation.

Twelve patients with acute lymphoblastic leukemia in second to fourth remission received allogeneic marrow transplants following preparation with cyclophosphamide, 120 mg/kg and 1400 rad of fractionated total body irradiation. Two patients died of interstitial pneumonitis 32 and 62 days post-transplantation. Six patients relapsed between days 59 and 659 and four died of leukemia-related problems. Two patients who relapsed are currently alive, one in remission and one in relapse. Four patients are alive and free of disease 657 to 991 days following transplantation. This disease-free survival was not significantly better than the six of 22 disease-free survivors previously observed following cyclophosphamide and 1000 rad of total body irradiation given in a single exposure.

Adolescent↗
PubMed1982

ABO-incompatible marrow transplants.

We analyzed data from 81 ABO-incompatible marrow transplants performed between 1972 and 1980. Patients with high anti-red blood cell antibody levels pretransplant had a significantly increased probability of antibody return post-transplant. This was true for IgG and for IgM as independent variables. However, the return of antibody post-transplant had no effect on engraftment, survival, or blood product requirements posttransplant. Patients who received ABO-incompatible marrow had a similar time to engraftment, survival, and incidence of rejection and graft-versus-host disease as patients receiving ABo-compatible transplants. Neither pretransplant treatment regimen nor the development of graft-versus-host disease had an effect on post-transplant antibody levels. ABO-incompatible marrow transplants can be performed with no greater morbidity or mortality than ABO-compatible grafts. The procedures for antibody removal may be useful in other organ transplant settings.

ABO Blood-Group System↗
PubMed1982

Immediate and delayed neurotoxicity after mechlorethamine preparation for bone marrow transplantation.

Twenty-four patients, including two with aplastic anemia and 22 with malignancy, underwent marrow transplantation after preparation with mechlorethamine, 0.3 to 2.0 mg/kg body weight. Fourteen of the 21 neurologically evaluable recipients developed immediate neurotoxicity a median of 4 days after treatment (range, 0 to 34 days). Confusion and disorientation were observed in six patients, headache in six, hallucinations n four, lethargy in four, tremors in three, paraplegia in one, seizure in one, and vertigo in one. Whereas acute symptoms cleared in 11 patients, three remained symptomatic until death. Twelve evaluable patients survived more than 60 days; all six with previous acute toxicity subsequently developed delayed onset of new neurologic findings (personality change, confusion, seizure, diplopia, or dementia) a median of 169 days (range, 70 to 248 days) after treatment. Cerebrospinal fluid analysis was usually normal but cerebral computed tomographic scans showed ventricular enlargement and electroencephalograms showed diffuse slowing. Postmortem histologic examination of brain showed neuronal degenerative changes with increased vascularity, gliosis, and perivascular fibrosis. Neurotoxicity appeared to increase with age and mechlorethamine dose and was commoner in patients given additional procarbazine or cyclophosphamide.

Adolescent↗
PubMed1982

Prophylactic granulocyte transfusions.

Prophylactic granulocyte transfusions prevent infections in granulocytopenic marrow transplant recipients. In this setting the selection of a single "compatible" related donor for each recipient removes many of the immunologic problems inherent in utilizing multiple random volunteer donors. Graft-versus-host disease is a real risk from granulocyte transfusions and can probably be prevented by irradiation prior to infusion. The problem of cytomegalovirus acquisition through granulocyte and other blood product donors remains to be solved.

Anemia, Aplastic↗
PubMed1982

Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients.

Sixty-five multiply transfused patients with severe aplastic anemia were given cyclophosphamide followed by grafts anemia were given cyclophosphamide followed by grafts from HLA-identical siblings. The effect of the administration of viable donor buffy coat cells following the marrow inoculum was evaluated with regard to graft rejection and survival. Results in 43 patients so treated are presented along with those in 22 concurrent patients given marrow alone. Most patients given buffy coat had positive in vitro tests of sensitization indicating a high risk for graft rejection, while all but one of the patients given marrow alone had negative tests. Thirty of the 43 (70%) patients given marrow and buffy coat are alive between 10 and 61 mo (median 36) after grafting; 4 died after graft rejection and 6 with acute or chronic graft-versus-host disease (GVHD). Eleven of the 22 (50%) patients given marrow alone are alive between 29 and 65 mo (median 52); 7 died after graft rejection and 3 with GVHD. The addition of buffy coat cell infusions to the marrow inoculum reduced the risk of rejection and increased survival in the currently reported transfused patients when compared to patients grafted before 1976. However, there was an increased risk of chronic GVHD. Recipients of marrow from female donors survived slightly better (73%) than recipients of male marrow (58%).

Adolescent↗
PubMed1982

Immune adsorption of anti-A and anti-B antibodies.

Plasma exchange is an effective technique for removal of antibodies prior to ABO incompatible marrow grafting. However, expense and hepatitis risk make alternative methods desirable. A solid phase immunoadsorbent column using blood group A trisaccharide has been demonstrated to specifically remove anti-A antibody from human plasma in vitro and immunized dogs in vivo with no toxicity. Preliminary results in patients are encouraging.

ABO Blood-Group System↗
PubMed1981

Marrow transplantation from donors other than HLA identical siblings.

As of 31 December 1979, 39 patients in Seattle have received marrow grafts from donors other than HLA genotypically identical siblings. Sixteen transplants were between siblings, 21 from a parent to a child, one from a paternal uncle, and one from an unrelated donor. Ten patients had aplastic anemia and 29 had a hematological malignancy. As of 1 February 1980, only one of the ten patients transplanted for aplastic anemia is currently alive (greater than 1048 days) with a normal marrow and without graft-versus-host disease. This surviving patient was untransfused and received marrow from an HLA phenotypically identical mother. There were five episodes of graft rejection among the ten aplastic patients. Among the 29 patients transplanted for hematological malignancy, 12 (42%) are surviving from greater than 64 to greater than 995 days. Twelve of 29 patients were transplanted while in remission and eight (75%) are alive from greater than 148 to greater than 790 days. The two most frequent causes of death were relapse of leukemia and interstitial pneumonia. Only two patients died from complications clearly related to graft-versus-host disease. Five of the surviving patients were phenotypically identical with their donor for HLA, while seven were incompatible for some HLA determinants. One patient--donor pair was incompatible for HLA-D and DR as a result of HLA-B/D recombination, and six pairs were incompatible for HLA-A and/or B.

Anemia, Aplastic↗
PubMed1981

Studies of the response in mixed leukocyte culture of cells from patients with aplastic anemia to cells from HLA-identical siblings.

We have studied the mixed leukocyte culture (MLC) reactions of 64 patients with severe aplastic anemia. Their peripheral blood mononuclear cells showed an increased relative response (RR) to cells from HLA-identical siblings as compared to cells from normal HLA-identical siblings, confirming the results reported in an earlier series of 34 patients. Elevated RRs were associated with patient antidonor lymphocyte antibodies as detected by the antibody-dependent cell-mediated cytotoxicity assay, but were not associated with antidonor complement-dependent cytotoxic antibodies or with antidonor cytotoxic T lymphocytes. Among 98 patients receiving marrow grafts from HLA-identical sibling donors, those with elevated RRs before transplantation were more apt to reject the transplant than those without (P less than 0.0001). There was no elevation of the RR in 10 untransfused patients, although positive RRs were noted in 2 patients within 12 to 24 hr of their first transfusions. Five patients with identical twins were also tested, and elevated RRs were noted in three. Although blood transfusion appears to be responsible for the increased RRs observed in some aplastic patients, genetic differences between donor and recipient were not always necessary for eliciting an increased MLC response, suggesting that mechanisms other than alloimmunization are involved.

Adolescent↗
PubMed1981

Bone marrow transplantation for refractory acute leukemia in 34 patients with identical twins.

Thirty-four patients aged 4-67 yr (median 17) with acute lymphocytic leukemia (ALL) (18 patients) or acute nonlymphocytic leukemia (ANL) (16 patients) who failed to enter complete remission (CR) or relapsed on conventional chemotherapy were treated with cyclophosphamide (CY), 60 mg/kg/day for 2 days, 1000 rad total body irradiation, and a marrow transplant from a genotypically identical normal twin. Sixteen of the patients received additional chemotherapy within the week before CY. After the transplant, 23 patients received immunotherapy consisting of killed autologous leukemic cells and/or normal twin peripheral blood lymphocytes, 16 as part of a prospectively randomized study. One moribund patient died before engraftment. Nine patients (6 ALL, 3 ANL) continued to have detectable leukemic cells. Twenty-four patients (70%) achieved CR. One of them died of viral hepatitis at 1 mo and another of viral interstitial pneumonitis at 4 mo in CR. Fourteen patients (7 ALL, 7 ANL) relapsed 2-16 mo (median 4) after transplantation. However, 8 patients (24%) (3 ALL, 5 ANL) remain in CR without any maintenance chemotherapy at 29-103 mo (median 80) after the transplant. The end results were not signficantly influenced by the type of leukemia, the immediated pre-CY chemotherapy, or the immunotherapy. The results show that this approach, even when applied to endstage patients with acute leukemia in relapse, causes tolerable morbidity, rare nonleukemic deaths, and frequent remissions, some of which represent cures.

Acute Disease↗
PubMed1981

Allogeneic bone marrow transplantation for chronic granulocytic leukemia.

Eighteen patients with chronic granulocytic leukemia underwent allogeneic marrow transplantation from HLA-identical sibling donors. The preparative regimen included cyclophosphamide and 1000-1500 rad total body irradiation in either single or fractionated doses. Eleven patients were transplanted in blast crisis. One died too early to evaluate. Five had recurrent leukemia, three died of interstitial pneumonia (IP), and two are living in remission after 20 and 39 months. One additional patient with blast crisis was transplanted while in remission after chemotherapy and is living in remission 28 months after transplantation. Two patients were transplanted in the accelerated phase; one died early of infection and one died of IP. Four were transplanted in the chronic phase; one died of IP, one with graft-versus-host disease, and two are living in remission 11 and 25 months after transplantation.

Adolescent↗
PubMed1980

Marrow transplantation in thirty "untransfused" patients with severe aplastic anemia.

Thirty patients with severe aplastic anemia had no transfusions of blood products until just before marrow transplantation from HLA-identical family members. They were conditioned for grafting with cyclophosphamide, 50 mg/kg body weight on each of 4 successive days. All 30 had prompt initial marrow engraftment, which was sustained in 27. Twenty-five of the 30 are alive between 9 to 84 (median, 19.5) months. The actuarial projection of survival for 2 to 6 years is 75%. Twenty of the 25 surviving patients have no problems. Five have chronic graft-versus-host disease, resolving in two and active in three. Five patients died with infection or hemorrhage, four of whom had graft-versus-host disease. These data show that early transplantation should be carried out before transfusions are given for any patient with severe aplastic anemia who has an HLA-identical family member. If sensitization to minor transplantation antigens contained in blood products is avoided, the incidence of marrow-graft rejection will decrease, and survival will improve.

Adolescent↗