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.

Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse.

Six fractionated total body irradiation (TBI) regimens given over 2-7 days to a total midline dose of between 1200 and 1750 rads were evaluated in 41 patients with acute lymphoblastic leukemia in relapse. Cyclophosphamide 120 mg/kg was given prior to TBI in all cases, and dimethylbusulphan was added to cyclophosphamide and 1500 rad TBI in one regimen. Relapses occurred in all regimens.

Allogeneic marrow transplantation for patients with acute non-lymphoblastic leukemia in second remission.

Twenty-four patients with acute non-lymphoblastic leukemia (ANL) in second remission were transplanted from HLA-matched siblings. Twelve patients died of non-leukemic causes and four of recurrent leukemia. One patient is alive after relapse and seven patients are alive and free of disease 114-1907 days after transplantation.

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation.

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756-1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment.

Allogeneic marrow transplantation for acute leukemia in relapse.

The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin.

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.

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.

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.

In vitro and in vivo removal of anti-A erythrocyte antibody by adsorption to a synthetic immunoadsorbent.

A solid-phase immunoadsorbent column using blood group A trisaccharide was tested in vitro and in vivo in dogs. This column was demonstrated to specifically remove anti-A antibody from human plasma in vitro and in vivo dogs specifically immunized with synthetic human blood group A trisaccharide. These studies indicate that this technique will be useful in removing anti-A and B antibody in marrow transplant recipients of incompatible marrow.

Characterization of a thrombocytopoietic-stimulating factor from kidney cell culture medium.

The chemical characteristics of a thrombocytopoietic-stimulating factor (TSF or thrombopoietin) found in serum-free kidney cell culture medium were further delineated by subjecting the TSF-rich medium to varying temperatures, different pH, and trypsin digested; the ability of TSF to bind lectins on affinity chromatography was also determined. After treatment, the TSF was assayed in immunothrombocythemic mice by its ability to increase the incorporation of 35S-sodium sulfate into newly formed platelets. TSF appeared to be relatively heat stable; incubation of TSF for 16 h at temperatures of 4, 37, and 56 degrees C showed no loss of TSF activity.

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.

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.

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.

Allogeneic marrow grafting for acute leukemia: a follow-up of long-term survivors.

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years.

Assay for thrombopoietin: a comparison of time of isotope incorporation into platelets and the effects of different strains and sexes of mice.

Several workers have used mice for thrombocytopoiesis-stimulating factor (TSF) assays, but the methods have differed. In quest of the optimum TSF assay conditions, we investigated the effects of interval between isotope injection and measurement of 35S incorporation into platelets, different mouse strains and sexes of mice. The 35S incorporation into platelets of mice increased with increase of the interval after isotope injection.