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Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 361 records · Page 20Linked to original sources

Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia.

Seventy-six patients, aged 2 to 17 years, were treated with bone marrow transplantation for severe aplastic anaemia or acute leukaemia refractory to conventional therapy. 16 of the 22 patients (73%) who received marrow transplantations for aplastic anaemia are surviving, 12 of these for over one year. In acute leukaemia, using preparation with cyclophosphamide and total body irradiation, 8 of 33 patients (24%) receiving allogeneic and 5 of 8 (63%) receiving syngeneic transplantations are continuing in remission from 3 months to beyond 2 years. The longest continuing remission off therapy is now over 4 1/2 years after preparation with total body irradiation. The major causes of failure remain graft-versus-host disease, infection, graft rejection (aplastic anaemia), and leukaemic relapse.

Adolescent↗

Failure of isogeneic marrow engraftment in a patient with acute leukemia.

Marrow transplantation was carried out in a patient with acute myelogenous leukemia using a healthy identical twin as donor. The patient was prepared for grafting with combination chemotherapy, high dose cyclophosphamide, and 1,000 rad total body irradiation. Repopulation of marrow did not occur despite a second marrow infusion 21 days following the first attempt. The patient died 44 days after the initial marrow infusion. To our knowledge this is the first patient transplanted from an identical twin who did not achieve engraftment after high dose chemotherapy and supralethal irradiation. The survival time was well in excess of that required for evaluation of engraftment. The possible mechanisms for graft failure are discussed. The use of prophylactic interferon against viral infections is considered as the most likely cause of failure of engraftment.

Bone Marrow Cells↗

Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle.

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

Adolescent↗

Marrow transplantation in aplastic anemia and leukemia.

Human marrow transplantation has resulted in observations of fundamental significance in understanding both aplastic anemia and acute leukemia. For example, the observation that transplanted marrow can grow successfully in patients with aplastic anemia indicates that the disease is due to a defect in the marrow precursor cells and not in the marrow microenvironment. Similarly, the observation of recurrent leukemia in donor cells has important implications. Nonetheless, marrow transplantation is sufficiently established therapeutically to be considered the treatment of choice for patients with severe aplastic anemia, and a realistic alternative for patients with recurrent acute leukemia. We suggest that patients be managed with regard to marrow transplantation according to the general approach outlined in Table 3. Marrow transplantation and histocompatibility typing are available at increasing numbers of institutions throughout the world. More and more patients with either severe aplastic anemia or recurrent acute leukemia should have marrow transplantation available to them when it is indicated as part of optimal management of these no longer hopeless diseases.

Adult↗

Recovery from aplastic anemia following attempted marrow transplantation.

A 23-year-old man with severe idiopathic aplastic anemia was prepared for marrow transplantation by the administration of cyclophosphamide (CY) 50 mg/kg on each of 4 days. He then received an intravenous infusion of 9.5 x 10(9) marrow cells from an HL-A matched and mixed leukocyte culture non-reactive sister. The graft was successfully established as shown by cytogenetic studies but was rejected after approximately 4 weeks. In preparation for a second transplant he was given procarbazine 12.5 mg/kg and goat antihuman thymocyte globulin (ATG) 7 mg/kg administered on alternate days for a total of 4 doses of each agent. At the end of this therapy his white blood cell count was noted to be going up and the second transplant was not carried out. Complete hematologic recovery of host type marrow ensued and persists now 20 months later. The various pathophysiologic mechanisms that may be involved are discussed.

Adult↗

Autologous marrow recovery following allogeneic marrow transplantation in a patient with severe aplastic anemia.

A 45-year-old woman with severe idiopathic marrow failure was prepared for marrow transplantation by administration of cyclophosphamide (cy) 50 mg/kg on each of four successive days. She then received an intravenous infusion of 20 X 10(9) nucleated marrow cells from an HL-A matched and mixed lymphocyte culture (MLC) non-reactive sister. There was evidence for minimal marrow recovery in 1-2 months and a second marrow infusion was carried out 69 days after the first without additional immunosuppression. There was a continued slow recovery of peripheral blood counts with complete reconstitution of erythropoiesis, return of the white blood cell count to between 3 and 4000/mm3, with 50% granulocytes, and platelets to 60--70,000/mm3, 11 months after the initial grafting attempt. Red cell antigens and gamma globulin allotypes were of recipient type. The MLC and the indirect cell mediated lympholysis (CML) test became positive possibly indicating cellular sensitization to non HL-A antigens. This report of a patient with severe marrow failure documents autologous recovery of marrow function after receiving a large dose of cy and allogeneic marrow. The implications of this are discussed.

Anemia, Aplastic↗

Experience with second marrow transplants.

This report summarizes the experience with 25 patients who received a second marrow transplant. The marrow donor for the first transplant was an identical twin in four cases and a sibling matched at the major histocompatibility complex in 21 instances. The donor for the second transplant was the same as the first except for three patients whose second donor was another matched sibling. Nine patients with aplastic anemia rejected their first graft. Four of these patients were prepared for the second graft with a regimen of procarbazine and antithymocyte globulin (ATG) followed by cyclophosphamide or total body irradiation and were successfully regrafted. One rejected the second graft, two died of septicemia and one is alive and well 10 months after the second graft. Twelve patients with hematologic malignancy had a recurrence of disease after the first transplant. Despite preparation for the second graft with a variety of intensive chemotherapeutic regimens, the five patients who did not succumb to infection showed an early recurrence of disease. Four patients with hematologic malignancy had a failure of the first graft for unknown reasons, possibly related to the administration of ATG or methotrexate. One patient prepared for the second graft with procarbazine and ATG showed evidence of engraftment but died of infection. Two out of three patients given no additional preparation were successfully grafted. One died of recurrent central nervous system leukemia after 18 months and one is alive and well 26 months after the second graft.

Anemia, Aplastic↗

Allogeneic marrow grafting for treatment of aplastic anemia: a follow-up on long-term survivors.

Eleven of twenty-four patients with severe aplastic anemia given marrow grafts from HLA-identical siblings between October 1970 and March 1973 are alive with normal marrow function and continued evidence of engraftment 3-5 yr later. Ten have been leading normal lives with no immunosuppressive or other drug therapy since day 100 postgrafting. One has had chronic graft-versus-host disease of the skin which is now slowly improving with no therapy. He returned to full-time employment in the summer of 1975. The long-term well-being of almost half of our initial patients emphasizes the importance of marrow transplantation for the treatment of severe aplastic anemia.

Anemia, Aplastic↗

[Experiences with allogeneic and isogeneic bone marrow transplantations in aplastic anemia and acute leukemia].

A report is presented on 13 clinical bone marrow transplantations (BMT). Six of 6 patients with refractory aplastic anemia are presently alive with partial to complete hemopoetic reconstitution now lasting up to 3 years and more. It is shown that after immunosuppression with ALG and cyclophosphamide, followed by BMT, the patient's own hemopoetic system can recover. Two failures occurred in patients over 50 years of age and in one who had donor transfusions before the graft. Two of 4 patients grafted for acute refractory leukemia are alive, one being in complete remission on day 140. One died from interstitial pneumonia and one had no take although the donor was an identical twin. This patient had been on a maintenance program which included active immunotherapy.

Adolescent↗