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Biomedical subjects

C D Buckner

Publications and source records attributed to C D Buckner.

At least 325 records · Page 18Linked to original sources

Bone marrow transplantation for acute leukemia.

Since the results of bone marrow transplantation for acute leukemia in relapse have been poor (less than 20% long term survival), an attempt of bone marrow transplantation for acute leukemia in remission has been performed since 1976 by the Seattle Group. The results are very encouraging. In ANL transplanted in first remission, 56 per cent of the patients became long term survivors and were disease-free. The number of relapse was very low (less than 10%). IN ALL transplanted in second or subsequent remission, 40 per cent of the patients became long term survivors but the number of relapse was high (50%). Some attempts of bone marrow transplantation using a non-HLA identical sibling have been performed with most encouraging results.

Acute Disease↗

Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins.

Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.

Adolescent↗

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↗

Treatment of severe aplastic anemia using antithymocyte globulin with or without an infusion of HLA haploidentical marrow.

Nineteen patients with severe aplastic anemia were treated with a 4-day course of horse-anti-human thymocyte globulin (ATG). Thirteen of these patients also received an infusion of HLA one haplotype-identical bone marrow. Toxicity of ATG included fever, chills, rash, arthralgias and elevated liver function tests. Platelet transfusion requirements increased during therapy. Eleven patients died 0.2-9.4 months after beginning ATG therapy. None of the 11 patients had any improvement in hematologic status prior to death. The eight surviving patients have been followed for at least 24 months. Six had evidence of hematologic improvement within 6-8 weeks after ATG therapy and are transfusion-independent. The other two patients improved more than one year after treatment. Survival after ATG therapy did not correlate with the presumed etiology of aplasia, duration of aplasia, patient age or sex, prior therapy, or admission granulocyte count. Addition of bone marrow infusion to ATG treatment also did not affect survival. This study demonstrated the necessity for a randomized trial of ATG versus supportive care alone for the treatment of severe aplastic anemia.

Adolescent↗

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↗

Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts.

To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.

Acute Disease↗

Disappearance of Ph1-positive cells in four patients with chronic granulocytic leukemia after chemotherapy, irradiation and marrow transplantation from an identical twin.

Four patients (21, 41, 13 and 38 years of age) with a history of chronic granulocytic leukemia for 12, 10, 11, and 106 months, respectively, were treated with dimethyl busulfan, cyclophosphamide, 920 rads of total-body irradiation and intravenous marrow infusion from normal, genetically identical twins. Serial chromosome analyses were performed on marrow aspirates cultured without mitotic stimulants. No Ph1-positive cells were detected in the marrows from the normal twins, whereas just before therapy, all 100 metaphases examined from each patient were Ph1-positive. Chromosome analyses were performed three to five times per patient after transplantation, and not a single Ph1-positive cell was detected. The patients remain hematologically normal 22, 23, 26 and 31 months after transplantation. The results show that the Ph1-positive clone can be eradicated by vigorous therapy and that the marrow in chronic granulocytic leukemia can be repopulated by stem cells from normal twins.

Adult↗

Successful treatment of juvenile chronic granulocytic leukemia with marrow transplantation.

A 46-month-old boy with juvenile chronic granulocytic leukemia was treated intensively with hydroxyurea, dimethyl myleran, cyclophosphamide, and total body irradiation. He then received a marrow transplant from an HL-A matched brother. Thirty-two months after the transplantation, he is hematologically normal and remains disease free on no-maintenance therapy. The successful outcome of this case suggests that a bone marrow transplant for any patient with a suitable histocompatible donor should be considered in the treatment of this disease.

Bone Marrow Transplantation↗